CN1423697A

CN1423697A - Virulence genes and proteins and their use

Info

Publication number: CN1423697A
Application number: CN 00818356
Authority: CN
Inventors: E·E·克拉克; 周立庆; J·E·谢伊; R·G·费尔德曼; D·W·霍尔登
Original assignee: VAMAX Ltd
Current assignee: VAMAX Ltd
Priority date: 1999-12-23
Filing date: 2000-12-22
Publication date: 2003-06-11

Abstract

A series of genes from <i>Streptococcus pyogenes</i> are shown to encode products which are implicated in virulence. The identification of these genes therefore allows attenuated microorganisms to be produced. Furthermore, the genes or their encoded products can be used in the manufacture of vaccines for therapeutic application.

Description

Virulence gene, protein and uses thereof

Invention field

The present invention relates to virulence gene and protein, and uses thereof.More particularly, the present invention relates to from the gene and the proteins/peptides of streptococcus pyogenes (Streptococcus pyogenes) acquisition, and the purposes aspect treatment and screening of medicaments.

Background of invention

A group streptococcus (GAS) is the cause of disease of most of suis diseases.Making us interested a kind of biology especially is streptococcus pyogenes, and it relates to a lot of Non-Invasives and aggressive infects, for example purulence kitchen sore, pharyngitis, necrotizing fasciitis, microbemia, suis toxic shock syndrome (STSS), pneumonia and rheumatic fever.

Some GAS infect can use antibiotic therapy, comprises penicillin and erythromycin.Yet, because the problem relevant with the microbiotic allergy patient with antibiotics resistance need can be used for the therapy for the treatment of or preventing GAS to infect in addition.

Summary of the invention

The present invention is based on the discovery of virulence gene in the streptococcus pyogenes.

According to a first aspect of the invention, peptide of the present invention is by the operon coding, and it comprises any nucleotide sequence from streptococcus pyogenes as follows: SEQ ID NO:1,3,5,7,9,11,13,15,17,19,21,23,25,27,29,31,33,35,37,39,41,43,45,47,49,51,53,55,57,59 and 61, or its homologue in gram positive bacterium, or its function fragment, be used for the treatment of or diagnose.

Described peptide infects treatment A group streptococcus can have many therepic use, is included in the purposes in the prophylactic applications vaccine.

According to second aspect, the polynucleotide of peptide as defined above of encoding also can be used for the treatment of or diagnose.

According to the third aspect, the gene of the described peptide of encoding can be used for preparing attenuated microorganisms.Attenuated microorganisms has a sudden change usually, and this sudden change destroys the expression of one or more this paper genes identified, and the bacterial strain that lacks virulence is provided.These microorganisms also can be used for the treatment of and diagnose.

According to fourth aspect, according to the illness that peptide of the present invention, gene and attenuated microorganisms can be used for treating or prevention is relevant with suis or gram positive bacteria infection.

Detailed Description Of The Invention

The discovery of the gene of the peptide that the present invention is based on encodes relates to virulence.Therefore peptide of the present invention and gene can be used for preparing the therapeutical agent that treatment is infected.The treatment that should be appreciated that indication also comprises prophylactic treatment, for example, and vaccination.In addition, although product of the present invention mainly is intended to treat the infection of human patients, the animal doctor uses and also is considered within the scope of the invention.

The present invention is described with reference to streptococcus pyogenes, yet all A group streptococcus bacterial strains and many other Gram-positive bacteria strains also may comprise related peptides or the protein that the protein identified with this paper has amino acid sequence identity or similarity.The biology that may comprise described peptide includes but not limited to lactococcus (Lactococcus), enterococcus spp (Enterococcus), streptococcus (Streptococcus) and Staphylococcus (Staphylococcus).

The peptide that the peptide that can be used for all respects of the present invention is preferably identified with this paper has the similarity greater than 40%.More preferably described peptide has the sequence similarity greater than 60%.Most preferably described peptide has the sequence similarity greater than 80%, for example 95% similarity.About this paper identified polynucleotides sequence, the related polynucleotides sequence that can be used for all respects of the present invention can have the identity greater than 40% with the sequence that this paper identifies.More preferably described polynucleotide sequence has the sequence identity greater than 60%.Most preferably described polynucleotide sequence has the sequence identity greater than 80%, for example 95% identity.

Term " similarity " and " identity " are known in the art.Used term " identity " is meant based on identical paired sequence between the corresponding same position of institute's comparative sequences relatively.Term " similarity " is meant the comparison between the aminoacid sequence, and not only considers also to consider intimate amino acid on correspondence position at the identical amino acid of correspondence position.Therefore the similarity between the peptide sequence represents also have functional similarity except that sequence similarity.

Identity between between identity level between the gene order and aminoacid sequence or similarity level can use known method to calculate.For the present invention, the computer based that can openly obtain determines that the method for identity and similarity comprises BLASTP, BLASTN and FASTA (Atschul etc., molecular biology magazine (J.Molec.Biol.), 1990; 215:403-410), available from the BLASTX program of NCBI with available from Genetics Computer Group, the Gap program of Madison WI.Similarity provided herein and identity level are to use the Gap program to obtain, with Gap penalize be 12 and Gap length to penalize be 4 to determine aminoacid sequence relatively, with Gap penalize be 50 and Gap length to penalize be 3 to carry out the polynucleotide sequence comparison.

Characterized according to gene of the present invention, thereby described gene order may be used at other microorganism search genes involved or peptide.This can be undertaken by searching in existing database, for example, and EMBL or GenBank.

Can carry out purifying and separate with method well known in the art according to peptide of the present invention or protein.Specifically, identify described gene order, thereby may use recombinant technology expressing said gene in appropriate host.But identified activity fragment and associated molecule are also used it for treatment.For example, peptide or its active fragments can be used for vaccine as antigenic determinant, excite immunne response.Also they can be used for Antibody Preparation, carry out passive immunization or be used for diagnosis.Suitable antibody comprises monoclonal antibody, or its fragment, comprises strand Fv fragment.The method for preparing antibody it will be apparent to those skilled in the art that.

The active fragments of described peptide is those fragments that keep the biological function of described peptide.For example, when being used to excite immunne response, this fragment has enough sizes, and the feasible antibody capable that is generated by this fragment is distinguished other peptides on described peptide and the bacterial micro-organism.Usually this segmental size is at least 30 Nucleotide (10 amino acid), and preferred 60 Nucleotide (20 amino acid) are most preferably greater than 90 Nucleotide (30 amino acid).

Be appreciated that also that except associated molecule the present invention includes the modification that the peptide and the polynucleotide of this paper evaluation are done, described modification does not significantly change its biological function from other microorganisms.The genetic code degeneracy can produce to have to compare with the indicated sequence of this paper has only little sequence change but still the polynucleotide of the identical peptide of encoding, and this it will be apparent to those skilled in the art that.The complementary polynucleotide are also included within the present invention.Conservative substitution on amino acid levels also can be infered, and promptly different acidity or basic aminoacids can be replaced, and function does not have substantial loss.

Preparation is known based on the vaccine of attenuated microorganisms to those skilled in the art.Available suitable carriers or adjuvant, for example alum as composition necessity or desirable, is prepared vaccine composition, to provide effective immunity to anti-infective.The preparation of vaccine preparation it will be apparent to those skilled in the art that.Can prepare attenuated microorganisms, it has the sudden change of any expression of gene of destroying this paper evaluation.The method that the known destruction specific gene of those skilled in the art is expressed.Adoptable technology comprises inactivation or the genetically deficient technology inserted.Also can comprise the other sudden change of other genes according to attenuated microorganisms of the present invention, for example, second gene identifying at this paper or on the needed independent gene of microorganism growth suddenlys change as aro.Attenuated microorganisms can also be used as the carrier system of sending heterologous antigen, therapeutic protein or nucleic acid (DNA or RNA).In this embodiment, described attenuated microorganisms is used to send heterologous antigen, protein or nucleic acid specific site to the body.Can heterologous antigen, peptide or nucleic acid be introduced attenuated microorganisms by traditional technology, these technology comprise utilizes recombinant precursor, and as carrier, it comprises the polynucleotide of expressing heterologous antigen or therapeutic protein, also comprises suitable promoter sequence.Perhaps, coding heterologous antigen or proteinic gene can be mixed in the genome of organism, and use endogenesis promoter control to express.

More generally, also be well known to those skilled in the artly to be, can select the activeconstituents of the present invention of appropriate amount, and suitable carriers or vehicle and route of administration, be used for the treatment of.Can select or definite these factors according to known index, as sanatory character/severity, curee's type and/or healthy state etc.

At one independently in the embodiment, product of the present invention can be used for identifying effective antimicrobial agents, or detects the shaker test of virulence.Conventional shaker test is well known by persons skilled in the art, also can make an amendment, and uses product of the present invention with appropriate means.For example, can be with the target of product of the present invention as active drug, described medicine energy deactivation or combining target show that then medicine has the potential antimicrobial acivity.

Various product of the present invention also can be used for the animal doctor and use.

Be the brief overview that is used to identify the test method of virulence gene below.In the streptococcus pyogenes mutant library, screen the attenuation mutant by use characteristic mark mutagenesis (STM) and identify the virulence gene of streptococcus pyogenes (Hensel etc., 1995. science (Science) 269 (5222): 400-3).

Use plasmid vector, insert by the Tn917 transposon and produce mutant.Except that the Tn917 fragment, used carrier also comprises streptomycin resistance gene, has the paraxin drug resistant gene (CAT gene) of synthetic promoter, the cloning site of Gram-negative bacteria replication orgin (rop.ori) and STM mark.After mark connected into carrier, carry out the intestinal bacteria conversion, select 96 plasmids with initial flagging hybridization.

Transform streptococcus pyogenes bacterial strain B514-SM (M50 type) respectively with each of 96 marker plasmids of gained, go out transformant by resistance screening to Streptomycin sulphate and paraxin.To each streptococcus pyogenes bacterial strain, insert 20 mutant of generation by the Tn917 transposon and create a mutant library through transforming.

In the skin aggressive damage model of mouse infection, screen mutant library (Schrager etc., Journal of Clinical Investigation (J.Clinical Investigation) 1996; 98:1954-1958), or from the throat field planting model discrimination mutant library of mouse infection (Husmann etc. infect and immune (Infection and Immunity) 1997; 65 (4): 935-944).

In skin model, be used in 1 * 10 in the 50 μ l volumes ⁸Cell carries out intradermal vaccination separately to five CD1 mouse, and these cells are represented the set of 96 mutant different and that be easy to distinguish.In inoculation back 48 hours, bacterium was also reclaimed in sampling.Skin decreased being immersed in 2 * BHI substratum, bacterium discharged from skin decreases by in bacterium separator, handling 10 minutes.With the bacterium bed board that discharges, reclaim minimum 10,000 bacterium colonies from minimum 3 mouse.DNA isolation and the being used for DNA of the mark in reclaiming bacterium that increases from these samples.To reclaim the storehouse separated DNA as hybridization probe from each, be presented at can not reclaim from animal in each storehouse, therefore those mutant of attenuation this animal infection modal.

In throat field planting model, with 2 * 10 ⁸Individual bacterium intranasal vaccination to 6 a C57BL/6 mouse, sampling after 48 hours.The same with skin model, the bacterium that contains transposon Tn917 insertion in virulence gene can not be reclaimed from the mouse that mixes group's inoculation with mutant, may be attenuation therefore.

Mutant by the STM Screening and Identification is carried out additional test, determined competitive index (CI).Each mutant of test in the polyinfection of carrying out with the wild type strain in the skin damage model that infects.(Chiang, S.L. and Mekalanos, J.J. molecular microbiology (MolecularMicrobiology) 1998; 27 (4) 797-805). for initial screening, with the wild-type and the mutant cell of equal number, to ading up to 1 * 10 ⁸Cell inoculation contains the group of 4 CD1 mouse.The bacterium of reclaiming after 48 hours is taped against on the selective medium flat board, thereby can distinguishes wild-type bacterium colony and mutant bacterium colony.The ratio of mutant bacteria and wild-type bacterium and the ratio that reclaims this ratio in the bacterium are competitive index (in the inoculum mutant to the ratio of wild-type divided by the ratio of the mutant that reclaims from animal model to wild-type bacterium) in inoculum

The following example describes the present invention in detail.

Embodiment 1

Identify first mutant, and the clone is right after the nucleotide sequence that transposon inserts.

Described nucleotide sequence, nucleotide level show with the streptococcus pyogenes genome in the identity of encoding sequence 100% shown in SEQID NO.1, this encoding sequence infer protein sequence shown in SEQ ID NO.2.

The aminoacid sequence of protein of prediction shows that (preserving number: the NAD that SW:Q57431) infers (P) H nitroreductase has 43% identity with hemophilus influenzae (H.influenzae).

Similarity in view of this gene of the NAD that infers (P) the H nitroreductase gene of streptococcus pyogenes and hemophilus influenzae it will be appreciated by those skilled in the art that the similar sequence in other suis and gram-positive microorganism also may relate to virulence.

In the virulence attenuation of test, mutant microbial demonstrates virulence attenuation of, and its competitive index (CI) is 0.644.

Embodiment 2

Identify another mutant, and the clone is right after the nucleotide sequence that transposon inserts.

Described nucleotide sequence, nucleotide level show with the streptococcus pyogenes genome in sequence shown in SEQID NO.3 98% identity is arranged.Its aminoacid sequence of inferring is shown in SEQ ID NO.4.

Described aminoacid sequence shows that (preserving number: TREMBL:069155) possible intergrase has 81% identity with Streptococcus mutans (S.mutans).

This proof, the possible integrase gene of ruined gene and Streptococcus mutans is identical to small part.Yet this gene before had been unknown in streptococcus pyogenes, did not think that it works in virulence.

Similarity in view of the possible integrase gene of described streptococcus pyogenes gene and Streptococcus mutans it will be appreciated by those skilled in the art that the similar sequence in other suis and gram-positive microorganism also is a virulence determinant.

In the virulence attenuation of test, mutant microbial demonstrates virulence attenuation of, and its competitive index (CI) is 0.229.

Embodiment 3

Described nucleotide sequence, nucleotide level show with the streptococcus pyogenes genome in sequence shown in SEQID NO.5 97% identity is arranged.The aminoacid sequence of its prediction is shown in SEQ ID NO.6.

Described aminoacid sequence shows at amino acid levels that (preserving number: GlgP albumen TREMBL:P73511) has 37% identity with unicellular cyanobacteria Synechocystis.spp.

This proof, ruined gene is identical to small part with the glgP gene of Synechocystis.spp.

Similarity in view of the glgP gene of described streptococcus pyogenes gene and Synechocystis.spp it will be appreciated by those skilled in the art that the similar sequence in other suis and gram-positive microorganism also is a virulence determinant.

In the virulence attenuation of test, mutant microbial demonstrates virulence attenuation of, and its competitive index (CI) is 0.011.

Embodiment 4

Described nucleotide sequence, nucleotide level show with the streptococcus pyogenes genome in sequence shown in SEQID NO.7 97% identity is arranged.The aminoacid sequence of its prediction is shown in SEQ ID NO.8.

Described aminoacid sequence shows at amino acid levels that (preserving number: BraB albumen TREMBL:034545) has 35% identity with subtilis (B.subtilis).。

This proof, ruined gene is identical to small part with the braB gene of subtilis.

Similarity in view of the braB gene of the braB gene of described streptococcus pyogenes and subtilis it will be appreciated by those skilled in the art that the similar sequence in other suis and gram-positive microorganism also may relate to virulence.

In the virulence attenuation of test, mutant microbial demonstrates virulence attenuation of, and its competitive index (CI) is 0.88.

Embodiment 5

Described nucleotide sequence, nucleotide level show with the streptococcus pyogenes genome in sequence shown in SEQID NO.9 99% identity is arranged.The aminoacid sequence of its prediction is shown in SEQ ID NO.10.

Also identified another attenuation mutant, its nucleotides sequence is listed in that the sequence shown in SEQ ID NO.11 has 98% identity in nucleotide level and the streptococcus pyogenes genome.The aminoacid sequence of its prediction is shown in SEQ ID NO.12.

(preserving number: AdcR albumen TREMBL:033703) has 53% identity to the predicted protein matter of first mutant amino acid levels and streptococcus pneumoniae (S.pneumoniae).(preserving number: AdcC albumen TREMBL:087862) has 79% identity to the predicted protein matter of second mutant amino acid levels and streptococcus pneumoniae.

This proof, ruined gene is identical to small part with adcR gene and the adcC gene of streptococcus pneumoniae.AdcR gene and adcC gene are the parts of (comprising adcR, adcC, adcB and adcA) of adc operon in the streptococcus pneumoniae.Therefore the virulence attenuation of of streptococcus pyogenes adcR and adcC mutant may be by due to the downstream gene that can not express adcR and adcC gene or its prediction (adcB and adcA homologous gene).Before do not think that these genes worked in the virulence of streptococcus pyogenes.

Similarity in view of adcR gene and the adcC gene of described streptococcus pyogenes gene and streptococcus pneumoniae it will be appreciated by those skilled in the art that the similar sequence in other suis and gram-positive microorganism may relate to virulence.

In the virulence attenuation of test, mutant microbial demonstrates virulence attenuation of, and its competitive index (CI) is 0.548 (adcR) and 0.028 (adcC).

Embodiment 6

Described nucleotide sequence, nucleotide level show with the streptococcus pyogenes genome in sequence shown in SEQID NO.13 99% identity is arranged.The aminoacid sequence of its prediction is shown in SEQ ID NO.14.

Described aminoacid sequence shows at amino acid levels that (preserving number: dna repair protein radC homologue (orfB) SW:Q02170) has 39% identity with subtilis.

This proof, ruined gene is identical to small part with the orfB gene of subtilis.

Similarity in view of the orfB gene of the orfB gene of described streptococcus pyogenes and subtilis it will be appreciated by those skilled in the art that the similar sequence in other suis and gram-positive microorganism may relate to virulence.

In the virulence attenuation of test, mutant microbial demonstrates virulence attenuation of, and its competitive index (CI) is 0.766.

Embodiment 7

Described nucleotide sequence, nucleotide level show with the streptococcus pyogenes genome in sequence shown in SEQID NO.15 98% identity is arranged.The aminoacid sequence of its prediction is shown in SEQ ID NO.16.

Described aminoacid sequence shows at amino acid levels that (preserving number: biotin carboxyl carrier protein SW:P29337) (BCCP) has 54% identity with Streptococcus mutans.

This proof, ruined gene is identical to small part with the gene of coding Streptococcus mutans BCCP.This gene before had been unknown in streptococcus pyogenes, did not think that it works in virulence.

Similarity in view of the streptococcus pyogenes gene and the Streptococcus mutans BCCP of described translation it will be appreciated by those skilled in the art that the similar sequence in other suis and gram-positive microorganism may relate to virulence.

In the virulence attenuation of test, mutant microbial demonstrates virulence attenuation of, and its competitive index (CI) is 0.044.

Embodiment 8

Identify that a series of and the gene that relates to citric acid fermentation have the mutant of sequence similarity.The nucleotide sequence of eight mutant show with the streptococcus pyogenes genome in the identity of sequence 100% shown in SEQ ID NO.17.The aminoacid sequence of its prediction is shown in SEQ ID NO.18.

(preserving number: citF albumen SW:P75726), citrate lyase α chain has 58% identity to the predicted protein of described streptococcus pyogenes gene amino acid levels and intestinal bacteria (E.coli).

In addition the nucleotide sequence of three mutant show with the streptococcus pyogenes genome in different sequences 99% identity is arranged.Described nucleotide sequence is shown in SEQ ID NO.19, and the aminoacid sequence of its prediction is shown in SEQ ID NO.20.

(preserving number: citE albumen SW:P77770), citrate lyase β chain has 55% identity to described aminoacid sequence amino acid levels and intestinal bacteria.

In addition the nucleotide sequence of two mutant show with streptococcus pyogenes in nucleotides sequence shown in SEQ ID NO.21 show 99% identity.The aminoacid sequence of its prediction is shown in SEQ ID NO.22.

(preserving number: CitD albumen SW:P77618), citrate lyase acyl carrier protein (citrate lyase γ chain) has 46% identity to described aminoacid sequence amino acid levels and intestinal bacteria.

Identified in addition two mutant, its nucleotide sequence show with streptococcus pyogenes in nucleotides sequence shown in SEQ IDNO.23 show 99% identity.The aminoacid sequence of its prediction is shown in SEQ IDNO.24.

(preserving number: CitC albumen SW:P77390), citric acid (pro-3s)-lyase (ligase enzyme) has 34% identity to described aminoacid sequence amino acid levels and intestinal bacteria.

Identified another mutant, its nucleotide sequence show with streptococcus pyogenes in nucleotides sequence shown in SEQ IDNO.25 show 99% sequence identity.The aminoacid sequence of its prediction is shown in SEQID NO.26.

(preserving number: CitX albumen SW:P77563) has 37% identity to described aminoacid sequence amino acid levels and intestinal bacteria.

Identified in addition three mutant, its nucleotide sequence show with streptococcus pyogenes in nucleotides sequence shown in SEQ IDNO.27 show 100% identity.The aminoacid sequence of its prediction is shown in SEQ IDNO.28.

Described aminoacid sequence shows at amino acid levels that (preserving number: OadA albumen SW:P13187), oxaloacetic decarboxylase α subunit has 59% identity with Klebsiella pneumonia (K.pneumoniae).

The predicted protein matter sequence table of all said mutation bodies reveal with intestinal bacteria or Klebsiella pneumonia in the required gene product of citric acid fermentation have in various degree identity.

This proof, the citF of ruined gene and intestinal bacteria or Klebsiella pneumonia, E, D, C, X is identical to small part with the oadA gene.The single site of gene co on intestinal bacteria and Klebsiella pneumonia karyomit(e) that relates to citric acid fermentation.Therefore, the virulence attenuation of of streptococcus pyogenes mutant may be by not expressing due to its citFEDCX and oadA gene or the downstream gene.Do not thought before that these genes worked in virulence.

In view of the similarity of those genes that exist in described streptococcus pyogenes gene and intestinal bacteria or the Klebsiella pneumonia, it will be appreciated by those skilled in the art that the similar sequence in other suis and gram-positive microorganism may relate to virulence.

To each citF, E, D, the mutant of X and oadA is tested weakening of virulence.Mutant microbial shows virulence attenuation of, and its competitive index (CI) is 0.122 (citF), 0.064 (citE), 0.078 (citD), 0.025 (citX) and 0.251 (oadA).

Embodiment 9

Identified another mutant, and the clone is right after the nucleotide sequence that transposon inserts.

Described nucleotides sequence be listed in nucleotide level show with the streptococcus pyogenes genome in sequence shown in SEQID NO.29 98% identity is arranged.The aminoacid sequence of its prediction is shown in SEQ ID NO.30.

Described aminoacid sequence shows at amino acid levels that (preserving number: femB albumen TREMBL:Q9X9D7) has 27% identity with streptococcus aureus (S.aureus).

This proof, ruined gene is identical to small part with the femB gene of streptococcus aureus.Yet this gene before had been unknown in streptococcus pyogenes, did not think that it works in virulence.

Similarity in view of the femB gene of described streptococcus pyogenes gene and streptococcus aureus it will be appreciated by those skilled in the art that the similar sequence in other suis and gram-positive microorganism may relate to virulence.

Embodiment 10

Sequence in described nucleotide sequence and the streptococcus pyogenes genome shown in SEQ ID NO.31 has significant identity.The aminoacid sequence of its prediction is shown in SEQ ID NO.32.

In the virulence attenuation of test, mutant microbial demonstrates virulence attenuation of, and its competitive index (CI) is 0.160.

Embodiment 11

Sequence in described nucleotide sequence and the streptococcus pyogenes genome shown in SEQ ID NO.33 has 100% identity.The aminoacid sequence of its prediction is shown in SEQ ID NO.34.

Embodiment 12

Described nucleotide sequence, the sequence in nucleotide level and streptococcus pyogenes genome shown in SEQ IDNO.35 has 98% identity.The aminoacid sequence of its prediction is shown in SEQ ID NO.36.

Described aminoacid sequence shows at amino acid levels that (preserving number: SW:P33116) subtilyne transhipment ATP is conjugated protein 46% identity with subtilis.

Similarity in view of the gene of the gene of described streptococcus pyogenes and subtilis it will be appreciated by those skilled in the art that the similar sequence in other suis and gram-positive microorganism may relate to virulence.

In the virulence attenuation of test, mutant microbial demonstrates virulence attenuation of, and its competitive index (CI) is 0.128.

Embodiment 13

Sequence in described nucleotide sequence and the streptococcus pyogenes genome shown in SEQ ID NO.37 has 98% identity.The aminoacid sequence of its prediction is shown in SEQ ID NO.38.

Embodiment 14

Sequence in described nucleotide sequence and the streptococcus pyogenes genome shown in SEQ ID NO.39 has 98% identity.The aminoacid sequence of its prediction is shown in SEQ ID NO.40.

Described aminoacid sequence shows at amino acid levels that (preserving number: 36.9kDa hypothetical protein SW:P33019) has 29% identity with intestinal bacteria.

This proof, ruined gene is identical to small part with colibacillary described gene.Other similar sequences may relate to virulence.

In the virulence attenuation of test, mutant microbial demonstrates virulence attenuation of, and its competitive index (CI) is 0.747.

Embodiment 15

Sequence in described nucleotide sequence and the streptococcus pyogenes genome shown in SEQ ID NO.41 has 99% identity.The aminoacid sequence of its prediction is shown in SEQ ID NO.42.

Described aminoacid sequence shows and glimmers that (preserving number: 89kDa hypothetical protein TREMBL:028455) has 29% identity to ancient green-ball bacterium (A.fulgidus) at amino acid levels.

In the virulence attenuation of test, mutant microbial demonstrates virulence attenuation of, and its competitive index (CI) is 0.588.

Embodiment 16

Sequence in described nucleotide sequence and the streptococcus pyogenes genome shown in SEQ ID NO.43 has 99% identity.The aminoacid sequence of its prediction is shown in SEQ ID NO.44.

Embodiment 17

Sequence in described nucleotide sequence and the streptococcus pyogenes genome shown in SEQ ID NO.45 has 98% identity.The aminoacid sequence of its prediction is shown in SEQ ID NO.46.

Embodiment 18

Sequence in described nucleotide sequence and the streptococcus pyogenes genome shown in SEQ ID NO.47 has 97% identity.The aminoacid sequence of its prediction is shown in SEQ ID NO.48

Embodiment 19

Described nucleotide sequence, the sequence in nucleotide level and streptococcus pyogenes genome shown in SEQ IDNO.49 has 98% identity.The aminoacid sequence of its prediction is shown in SEQ ID NO.50.

Described aminoacid sequence shows at amino acid levels that (preserving number: ciaH albumen SW:Q54955) has 47% identity with streptococcus pneumoniae.

This proof, ruined gene is identical to small part with the ciaH gene of streptococcus pneumoniae.

Similarity in view of the ciaH gene of the ciaH gene of described streptococcus pyogenes and streptococcus pneumoniae it will be appreciated by those skilled in the art that the similar sequence in other suis and gram-positive microorganism may relate to virulence.

In the virulence attenuation of test, mutant microbial demonstrates virulence attenuation of, and its competitive index (CI) is 0.205.

Embodiment 20

Described nucleotide sequence, the sequence in nucleotide level and streptococcus pyogenes genome shown in SEQ IDNO.51 has 98% identity.The aminoacid sequence of its prediction is shown in SEQ ID NO.52.

Described aminoacid sequence shows at amino acid levels that (preserving number: mucA homologous protein TREMBL:Q9ZBB1) has 39% identity with streptococcus pneumoniae.

This proof, ruined gene is identical to small part with the mucA gene of streptococcus pneumoniae.

Similarity in view of the mucA gene of the gene of described streptococcus pyogenes and streptococcus pneumoniae it will be appreciated by those skilled in the art that the similar sequence in other suis and gram-positive microorganism may relate to virulence.

In the virulence attenuation of test, mutant microbial demonstrates virulence attenuation of, and its competitive index (CI) is 0.547.

Embodiment 21

Described nucleotide sequence, the sequence in nucleotide level and streptococcus pyogenes genome shown in SEQ IDNO.53 has 98% identity.The aminoacid sequence of its prediction is shown in SEQ ID NO.54.

Described aminoacid sequence shows at amino acid levels that (preserving number: gidA albumen SW:P39815) has 69% identity with subtilis.

This proof, ruined gene is identical to small part with the described gene of subtilis.

Similarity in view of the gidA gene of the gene of described streptococcus pyogenes and subtilis it will be appreciated by those skilled in the art that the similar sequence in other suis and gram-positive microorganism may relate to virulence.

In the virulence attenuation of test, mutant microbial demonstrates virulence attenuation of, and its competitive index (CI) is 0.444.

Embodiment 22

Described nucleotide sequence, the sequence in nucleotide level and streptococcus pyogenes genome shown in SEQ IDNO.55 has 98% identity.The aminoacid sequence of its prediction is shown in SEQ ID NO.56.

Described aminoacid sequence shows at amino acid levels that (preserving number: dltA albumen SW:Q53526) has 74% identity with Streptococcus mutans.

This proof, ruined gene is identical to small part with the dltA gene of Streptococcus mutans.

Similarity in view of the dltA gene of the gene of described streptococcus pyogenes and Streptococcus mutans it will be appreciated by those skilled in the art that the similar sequence in other gram-positive microorganisms may relate to virulence.

Embodiment 23

Described nucleotide sequence, the sequence in nucleotide level and streptococcus pyogenes genome shown in SEQ IDNO.57 has 98% identity.The aminoacid sequence of its prediction is shown in SEQ ID NO.58.

Described aminoacid sequence shows and glimmers that (preserving number: hmgA albumen SW:028538) has 41% identity to ancient green-ball bacterium at amino acid levels.

This proof, ruined gene is identical to small part with the described gene of the ancient green-ball bacterium of flicker.

In view of the gene of described streptococcus pyogenes similarity, it will be appreciated by those skilled in the art that the similar sequence in other suis and gram-positive microorganism may relate to virulence with the hmgA gene of the ancient green-ball bacterium of flicker.

Embodiment 24

Sequence in described nucleotide sequence and the streptococcus pyogenes genome shown in SEQ ID NO.59 has 99% identity.The aminoacid sequence of its prediction is shown in SEQ ID NO.60.

Described aminoacid sequence shows at amino acid levels that (preserving number: the JAG albumen of inferring TREMBL:Q9X1H1) has 34% identity with Thermotoga maritima (T.maritima).

This proof, the gene of ruined streptococcus pyogenes is identical to small part with the described gene of Thermotoga maritima (T.maritima).Similar sequence in other Gram-negative bacterias may relate to virulence.

Embodiment 25

Sequence in described nucleotide sequence and the streptococcus pyogenes genome shown in SEQ ID NO.61 has 99% identity.The aminoacid sequence of its prediction is shown in SEQ ID NO.62.

Described aminoacid sequence shows at amino acid levels that (preserving number: 49.4kDa hypothetical protein TREMBL:Q9X4U3) has 49% identity with swine streptococcus (S.suis).

This proof, the gene of ruined streptococcus pyogenes is identical to small part with the described gene of swine streptococcus.Similar sequence in other Gram-negative bacterias also may relate to virulence.

＜110〉Microscience Limited＜120〉、＜130〉REP06309WO＜140〉 ( )＜141〉2000-12-22＜150〉9930462.8＜151〉1999-12-23＜150〉9930463.6＜151〉1999-12-23＜150〉9930464.4＜151〉1999-12-23＜150〉9930466.9＜151〉1999-12-23＜150〉9930467.7＜151〉1999-12-23＜150〉9930469.3＜151〉1999-12-23＜150〉9930471.9＜151〉1999-12-23＜150〉9930472.7＜151〉1999-12-23＜150〉9930473.5＜151〉1999-12-23＜150〉9930474.3＜151〉1999-12-23＜150〉9930475.0＜151〉1999-12-23＜150〉9930476.8＜151〉1999-12-23＜150〉0003735.8＜151〉2000-02-17＜150〉0003733.3＜151〉2000-02-17＜150〉0003732.5＜150〉0003733.3＜151〉2000-02-17＜150〉0003732.5＜151〉2000-02-17＜150〉0003731.7＜151〉2000-02-17＜150〉0003736.6＜151〉2000-02-17＜150〉0003730.9＜151〉2000-02-17＜150〉0003729.1＜151〉2000-02-17＜150〉0003728.3＜151〉2000-02-17＜150〉0003727.5＜151〉2000-02-17＜150〉0003726.7＜151〉2000-02-17＜150〉0003725.9＜151〉2000-02-17＜150〉0010587.4＜151〉2000-05-02＜150〉0010585.8＜151〉2000-05-02＜160〉62＜170〉PatentIn Ver.2.1＜210〉1＜211〉666＜212〉DNA＜213〉＜400〉1atggatcaaa ccattcatca ccaaatacag caagcactac actttagaac agccgttcgt 60gtttataagg aagaaaagat ttctgatgag gatttagccc ttatccttga tgctgcttgg 120ttaagccctt cttctattgg cttagaaggc tggcgctttg tcgttttaga caacaagcct 180attaaagaag aaatcaagcc ctttgcctgg ggagcccagt atcaactgga aacagctagt 240cactttattc ttttaatagc cgaaaaacat gcaagatacg atagccctgc tatcaaaaat 300agccttttac ggcgtggtat caaagaaggt gatggtctca acagccgcct aaaactctat 360gaatctttcc aaaaagagga catggatatg gcagataatc ctcgggcact ctttgattgg 420acagctaaac aaacctatat cgctcttggt aatatgatga tgacagctgc tcttttgggc 480attgatactt gccctattga aggctttcat tatgataagg tcaatcatat cctagctaag 540cataatgtga ttgatttaga aaaagaaggc attgctagca tgttatccct aggctatcgt 600ttgcgagatc ccaaacatgc tcaagttcgt aagcctaaag aagaagtgat ttcagtcgtt 660aaatga 666＜210〉2＜211〉221＜212〉PRT＜213〉＜400〉2Met Asp Gln Thr Ile His His Gln Ile Gln Gln Ala Leu His Phe Arg 1 5 10 15Thr Ala Val Arg Val Tyr Lys Glu Glu Lys Ile Ser Asp Glu Asp Leu

20 25 30Ala?Leu?Ile?Leu?Asp?Ala?Ala?Trp?Leu?Ser?Pro?Ser?Ser?Ile?Gly?Leu

35 40 45Glu?Gly?Trp?Arg?Phe?Val?Val?Leu?Asp?Asn?Lys?Pro?Ile?Lys?Glu?Glu

50 55 60Ile?Lys?Pro?Phe?Ala?Trp?Gly?Ala?Gln?Tyr?Gln?Leu?Glu?Thr?Ala?Ser?65 70 75 80His?Phe?Ile?Leu?Leu?Ile?Ala?Glu?Lys?His?Ala?Arg?Tyr?Asp?Ser?Pro

85 90 95Ala?Ile?Lys?Asn?Ser?Leu?Leu?Arg?Arg?Gly?Ile?Lys?Glu?Gly?Asp?Gly

100 105 110Leu?Asn?Ser?Arg?Leu?Lys?Leu?Tyr?Glu?Ser?Phe?Gln?Lys?Glu?Asp?Met

115 120 125Asp?Met?Ala?Asp?Asn?Pro?Arg?Ala?Leu?Phe?Asp?Trp?Thr?Ala?Lys?Gln

130 135 140Thr?Tyr?Ile?Ala?Leu?Gly?Asn?Met?Met?Met?Thr?Ala?Ala?Leu?Leu?Gly145 150 155 160Ile?Asp?Thr?Cys?Pro?Ile?Glu?Gly?Phe?His?Tyr?Asp?Lys?Val?Asn?His

165 170 175Ile?Leu?Ala?Lys?His?Asn?Val?Ile?Asp?Leu?Glu?Lys?Glu?Gly?Ile?Ala

180 185 190Ser?Met?Leu?Ser?Leu?Gly?Tyr?Arg?Leu?Arg?Asp?Pro?Lys?His?Ala?Gln

195 200 205Val?Arg?Lys?Pro?Lys?Glu?Glu?Val?Ile?Ser?Val?Val?Lys

210 215 220＜210〉3＜211〉1071＜212〉DNA＜213〉＜400〉3atgagacgcg aattattact agaaaaaatt gaaacctaca aggctatcat gccctggtat 60gttttagatt attaccaatc caaattagct gttccataca gctttaccac cttatatgag 120tatttaaaag aatacaaacg cttttttgat tggctgatgg atgctgattt aacgcaggcg 180ccaaagattg ctgatattga cttgagcacg cttgagcacc ttaccaagaa ggatttagag 240gcctttgtgc tttatttgcg ggaacgacct tctctcaaca cctattccac caaagagggg 300ctttctcaaa ccactattaa tcggaccttg tctgccttat caagccttta caagtacttg 360actgaagagg ttgaaaatga ccaaggggag ccttattttt atcggaatgt tatgaaaaaa 420gtgtcaacaa aaaagaaaaa agaaaccctg gcttccagag cggaaaatat taagcagaaa 480ctgtttttag gtgatgaaac tctagctttc ttggattatg tggataagga atatgagcaa 540aaattgtcta atcgtgccaa atcttctttc cgtaaaaata aggagaggga tttggctatt 600attgctctac tacttgcttc tggtgttcgt ttgtctgaag cagtgaatct tgatttaaaa 660gatgtcaatc taaatatgat gattatcgaa gttattcgca aaggcggaaa acgtgattca 720gtcaatgtag caggttttgc gaaaggttat ttggagtctt atttagctgt tcgtcagaga 780cgttacaagg ctgaaaaaca ggatcttgct ttctttttaa cagaataccg tggcgttcca 840aatcgaatgg atgcttctag tatagaaaag atggttggca agtactctga ggattttaaa 900attcgtgtga ctcctcacaa attgcgtcat acgctagcga caagactata tgatgctact 960aaatctcagg tgttagttag tcatcaatta ggccattcct ctactcaagt cacggatctt 1020tatacccata ttgtcaatga tgagcaaaaa aatgctttag ataaccttta a 1071＜210〉4＜211〉356＜212〉PRT＜213〉＜400〉4Met Arg Arg Glu Leu Leu Leu Glu Lys Ile Asp Glu Leu Lys Glu Leu 1 5 10 15Met Pro Trp Tyr Val Leu Glu Tyr Tyr Gln Ser Lys Leu Thr Val Pro

20 25 30Tyr?Ser?Phe?Thr?Thr?Leu?Tyr?Glu?Tyr?Leu?Lys?Glu?Tyr?Arg?Arg?Phe

35 40 45Phe?Glu?Trp?Leu?Ile?Asp?Ser?Gly?Val?Ser?Asn?Ala?Asn?Lys?Leu?Ala

50 55 60Asp?Ile?Pro?Leu?Glu?Thr?Leu?Glu?His?Leu?Ser?Lys?Lys?Asp?Met?Glu?65 70 75 80Ser?Phe?Ile?Leu?Tyr?Leu?Arg?Glu?Arg?Thr?Leu?Leu?Asn?Thr?Lys?Asn

85 90 95Lys?Arg?Gln?Gly?Val?Ser?Gln?Thr?Thr?Ile?Asn?Arg?Thr?Leu?Ser?Ala

100 105 110Leu?Ser?Ser?Leu?Tyr?Lys?Tyr?Leu?Thr?Glu?Glu?Val?Glu?Asn?Ala?Asp

115 120 125Gly?Glu?Pro?Tyr?Phe?Tyr?Arg?Asn?Val?Met?Lys?Lys?Val?Ser?Thr?Lys

130 135 140Lys?Lys?Lys?Glu?Thr?Leu?Ala?Ala?Arg?Ala?Glu?Asn?Ile?Lys?Gln?Lys145 150 155 160Leu?Phe?Leu?Gly?Asn?Glu?Thr?Met?Glu?Phe?Leu?Glu?Tyr?Val?Asp?Cys

165 170 175Glu?Tyr?Glu?Gln?Lys?Leu?Ser?Lys?Arg?Ala?Leu?Ser?Ser?Phe?Arg?Lys

180 185 190Asn?Lys?Glu?Arg?Asp?Leu?Ala?Ile?Ile?Ala?Leu?Leu?Leu?Ala?Ser?Gly

195 200 205Val?Arg?Leu?Ser?Glu?Ala?Val?Asn?Leu?Asp?Leu?Lys?Asp?Val?Ash?Leu

210 215 220Asn?Met?Met?Ile?Ile?Glu?Val?Thr?Arg?Lys?Gly?Gly?Lys?His?Asp?Ser225 230 235 240Val?Asn?Val?Ala?Gly?Phe?Ala?Lys?Pro?Tyr?Leu?Glu?Asn?Tyr?Ile?Thr

245 250 255Ile?Arg?Arg?Gly?Arg?Tyr?Lys?Ala?Lys?Lys?Thr?Asp?Leu?Ala?Phe?Phe

260 265 270Leu?Ser?Glu?Tyr?Arg?Gly?Val?Pro?Asn?Arg?Met?Asp?Ala?Ser?Ser?Ile

275 280 285Glu?Lys?Met?Val?Ala?Lys?Tyr?Ser?Gln?Asp?Phe?Lys?Ile?Arg?Val?Thr

290 295 300Pro?His?Lys?Leu?Arg?His?Thr?Leu?Ala?Thr?Arg?Leu?Tyr?Asp?Ala?Thr305 310 315 320Lys?Ser?Gln?Val?Leu?Val?Ser?His?Gln?Leu?Gly?His?Ala?Ser?Thr?Gln

325 330 335Val?Thr?Asp?Leu?Tyr?Thr?His?Ile?Val?Asn?Asp?Glu?Gln?Lys?Asn?Ala

340 345 350Leu?Asp?Lys?Leu

355＜210〉5＜211〉2265＜212〉DNA＜213〉＜400〉5atgacacgct ttacagaata tgttgaaact aaactaggaa aatcacttac gcaagccagc 60aatgaagaga tttatctatc attattaaac tttgtcaaag aagaagctag ccacaaggct 120aaaaattctg ctaaacgcaa agtttactat atctcagcag agtttttgat tggtaaatta 180ctatcaaaca acctgattaa cctaggaatt tacaaggaca tcaaagaaga attggcagct 240gctggcaagt ctatcgcaga agtcgaagat gttgaattag aaccatcact aggtaatggt 300ggtttaggac gccttgcttc atgttttatt gactctattg catctcttgg gattaatggt 360gaaggggttg gtttaaacta tcattgtggg ttgtttaagc aagtcttcaa acacaatgag 420caagaagctg agccaaactt ctggattgaa gatgactcat ggttggttcc aacagacatt 480tcttacgatg tgccttttaa gaacttcacc ttgaaatctc gtcttgatcg tattgatgtt 540ttgggttaca aacgcgacac taaaaactac cttaacttgt ttgatatcga gggcgttgat 600tacgggttaa tcaaagacgg catttctttt gataaaacgc aaattgctaa aaacttgacc 660ttgttcctct acccagacga ttctgacaaa aatggggaat tgctccgtat ttaccaacag 720tactttatgg tgtcaaatgc agcgcaatta atcattgatg aagctatcga acgtggttca 780aaccttcatg accttgcaga ctacgcttac gtgcaaatta atgacacgca tccatcaatg 840gtcatcccag aattaattcg tctcttgact gaaaaacatg gctttgactt tgatgaagcg 900gtagctgttg tgaaaaatat ggttggttac actaaccaca ctattcttgc agaagccctt 960gaaaaatggc caactgctta cttaaacgaa gtagtgccac acttggtaac catcattgaa 1020aaattggatg ctcttgttcg ttcagaagtg tctgatccag ctgttcaaat tattgacgaa 1080tcaggtcgtg tgcacatggc ccatatggat attcattttg caacaagtgt caatggggta 1140gcagcactcc acacagaaat cttgaaaaac agcgaattaa aagctttcta tgacctttac 1200ccagaaaaat tcaacaacaa aaccaacggg attactttcc gtcgttggct agaatttgct 1260aaccaagact tggctgatta cattaaagaa cttattggcg atgagtactt gactgacgca 1320acaaaattag aaaaattgat ggcctttgca gatgacaaag ctgttcatgc taaattggct 1380gaaatcaaat tcaacaacaa attagctctt aaacgttacc ttaaagacaa taaagacatt 1440gagcttgatg aacattctat tattgatacc caaatcaaac gtttccacga gtacaaacgt 1500caacagatga atgctcttta cgtgattcac aaatatttgg aaattaaaaa aggcaacctt 1560ccaaaacgta aaatcactgt tatctttgga ggtaaagcag cgcctgctta cattattgcg 1620caagacatca ttcacttgat cctttgcttg tctgaattga ttaacaatga ccctgaagta 1680agcccatacc ttaatgtgca tctagttgaa aattacaacg tgacagtagc agagcacttg 1740attccagcaa ctgatatttc tgagcaaatt tcactagcat ccaaagaagc ttctggaact 1800ggtaatatga aattcatgct taacggtgct ttaacacttg gtacaatgga cggtgctaac 1860gtagaaatcg ctgagcttgc aggcatggag aatatctata cctttggtaa agattctgac 1920accatcatca acctttatgc gactgcttct tatgtagcaa aagattacta tgataaccac 1980cctgctatta aagcagcagt gaactttatt atcagtccag aattgctagc atttggcaac 2040gaagaacgtc ttgatcgtct ttataaagaa ttgatttcaa aagactggtt catgactttg 2100attgaccttg aagagtacat tgaagtgaaa gaaaaaatgt tagcagacta tgaagaccaa 2160gatttatgga tgacaaaagt ggtccataac atcgcaaaag ctggattctt ctcatctgac 2220cgtaccattg agcagtataa cgaagatatt tggcattcac gataa 2265＜210〉6＜211〉754＜212〉PRT＜213〉＜400〉6Met Thr Arg Phe Thr Glu Tyr Val Glu Thr Lys Leu Gly Lys Ser Leu 1 5 10 15Thr Gln Ala Ser Asn Glu Glu Ile Tyr Leu Ser Leu Leu Asn Phe Val

20 25 30Lys?Glu?Glu?Ala?Ser?His?Lys?Ala?Lys?Asn?Ser?Ala?Lys?Arg?Lys?Val

35 40 45Tyr?Tyr?Ile?Ser?Ala?Glu?Phe?Leu?Ile?Gly?Lys?Leu?Leu?Ser?Asn?Asn

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

85 90 95Leu?Gly?Asn?Gly?Gly?Leu?Gly?Arg?Leu?Ala?Ser?Cys?Phe?Ile?Asp?Ser

100 105 110Ile?Ala?Ser?Leu?Gly?Ile?Asn?Gly?Glu?Gly?Val?Gly?Leu?Asn?Tyr?His

115 120 125Cys?Gly?Leu?Phe?Lys?Gln?Val?Phe?Lys?His?Asn?Glu?Gln?Glu?Ala?Glu

130 135 140Pro?Asn?Phe?Trp?Ile?Glu?Asp?Asp?Ser?Trp?Leu?Val?Pro?Thr?Asp?Ile145 150 155 160Ser?Tyr?Asp?Val?Pro?Phe?Lys?Asn?Phe?Thr?Leu?Lys?Ser?Arg?Leu?Asp

165 170 175Arg?Ile?Asp?Val?Leu?Gly?Tyr?Lys?Arg?Asp?Thr?Lys?Asn?Tyr?Leu?Asn

180 185 190Leu?Phe?Asp?Ile?Glu?Gly?Val?Asp?Tyr?Gly?Leu?Ile?Lys?Asp?Gly?Ile

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

210 215 220Pro?Asp?Asp?Ser?Asp?Lys?Asn?Gly?Glu?Leu?Leu?Arg?Ile?Tyr?Gln?Gln225 230 235 240Tyr?Phe?Met?Val?Ser?Asn?Ala?Ala?Gln?Leu?Ile?Ile?Asp?Glu?Ala?Ile

245 250 255Glu?Arg?Gly?Ser?Asn?Leu?His?Asp?Leu?Ala?Asp?Tyr?Ala?Tyr?Val?Gln

260 265 270Ile?Asn?Asp?Thr?His?Pro?Ser?Met?Val?Ile?Pro?Glu?Leu?Ile?Arg?Leu

275 280 285Leu?Thr?Glu?Lys?His?Gly?Phe?Asp?Phe?Asp?Glu?Ala?Val?Ala?Val?Val

290 295 300Lys?Asn?Met?Val?Gly?Tyr?Thr?Asn?His?Thr?Ile?Leu?Ala?Glu?Ala?Leu305 310 315 320Glu?Lys?Trp?Pro?Thr?Ala?Tyr?Leu?Asn?Glu?Val?Val?Pro?His?Leu?Val

325 330 335Thr?Ile?Ile?Glu?Lys?Leu?Asp?Ala?Leu?Val?Arg?Ser?Glu?Val?Ser?Asp

340 345 350Pro?Ala?Val?Gln?Ile?Ile?Asp?Glu?Ser?Gly?Arg?Val?His?Met?Ala?His

355 360 365Met?Asp?Ile?His?Phe?Ala?Thr?Ser?Val?Asn?Gly?Val?Ala?Ala?Leu?His

370 375 380Thr?Glu?Ile?Leu?Lys?Asn?Ser?Glu?Leu?Lys?Ala?Phe?Tyr?Asp?Leu?Tyr385 390 395 400Pro?Glu?Lys?Phe?Asn?Asn?Lys?Thr?Asn?Gly?Ile?Thr?Phe?Arg?Arg?Trp

405 410 415Leu?Glu?Phe?Ala?Asn?Gln?Asp?Leu?Ala?Asp?Tyr?Ile?Lys?Glu?Leu?Ile

420 425 430Gly?Asp?Glu?Tyr?Leu?Thr?Asp?Ala?Thr?Lys?Leu?Glu?Lys?Leu?Met?Ala

435 440 445Phe?Ala?Asp?Asp?Lys?Ala?Val?His?Ala?Lys?Leu?Ala?Glu?Ile?Lys?Phe

450 455 460Asn?Asn?Lys?Leu?Ala?Leu?Lys?Arg?Tyr?Leu?Lys?Asp?Asn?Lys?Asp?Ile465 470 475 480Glu?Leu?Asp?Glu?His?Ser?Ile?Ile?Asp?Thr?Gln?Ile?Lys?Arg?Phe?His

485 490 495Glu?Tyr?Lys?Arg?Gln?Gln?Met?Asn?Ala?Leu?Tyr?Val?Ile?His?Lys?Tyr

500 505 510Leu?Glu?Ile?Lys?Lys?Gly?Asn?Leu?Pro?Lys?Arg?Lys?Ile?Thr?Val?Ile

515 520 525Phe?Gly?Gly?Lys?Ala?Ala?Pro?Ala?Tyr?Ile?Ile?Ala?Gln?Asp?Ile?Ile

530 535 540His?Leu?Ile?Leu?Cys?Leu?Ser?Glu?Leu?Ile?Asn?Asn?Asp?Pro?Glu?Val545 550 555 560Ser?Pro?Tyr?Leu?Asn?Val?His?Leu?Val?Glu?Asn?Tyr?Asn?Val?Thr?Val

565 570 575Ala?Glu?His?Leu?Ile?Pro?Ala?Thr?Asp?Ile?Ser?Glu?Gln?Ile?Ser?Leu

580 585 590Ala?Ser?Lys?Glu?Ala?Ser?Gly?Thr?Gly?Asn?Met?Lys?Phe?Met?Leu?Asn

595 600 605Gly?Ala?Leu?Thr?Leu?Gly?Thr?Met?Asp?Gly?Ala?Asn?Val?Glu?Ile?Ala

610 615 620Glu?Leu?Ala?Gly?Met?Glu?Asn?Ile?Tyr?Thr?Phe?Gly?Lys?Asp?Ser?Asp625 630 635 640Thr?Ile?Ile?Asn?Leu?Tyr?Ala?Thr?Ala?Ser?Tyr?Val?Ala?Lys?Asp?Tyr

645 650 655Tyr?Asp?Asn?His?Pro?Ala?Ile?Lys?Ala?Ala?Val?Asn?Phe?Ile?Ile?Ser

660 665 670Pro?Glu?Leu?Leu?Ala?Phe?Gly?Asn?Glu?Glu?Arg?Leu?Asp?Arg?Leu?Tyr

675 680 685Lys?Glu?Leu?Ile?Ser?Lys?Asp?Trp?Phe?Met?Thr?Leu?Ile?Asp?Leu?Glu

690 695 700Glu?Tyr?Ile?Glu?Val?Lys?Glu?Lys?Met?Leu?Ala?Asp?Tyr?Glu?Asp?Gln705 710 715 720Asp?Leu?Trp?Met?Thr?Lys?Val?Val?His?Asn?Ile?Ala?Lys?Ala?Gly?Phe

725 730 735Phe?Ser?Ser?Asp?Arg?Thr?Ile?Glu?Gln?Tyr?Asn?Glu?Asp?Ile?Trp?His

740 745 750Ser Arg＜210〉7＜211〉1371＜212〉DNA＜213〉＜400〉7atgaaacaaa aaaatgtata tatcgtcatt ggattcatgc tatttgcgct attttttgga 60gcagcaaacc tcatttaccc agctttttta ggcatctact caggtcatca gattctatgg 120tctatcattg gtttttgttt aactggtgtc tccttgcctt tactcggtgt cattgctgtt 180gctaaatctg gatcaggcga tgttgaaagt ttggcacgcc ccatctctaa atggtatgca 240atcttctatt cttccatttt gtatttatct attggcccat tttttgctat tccaagaaca 300ggagccactt ctttttcagt cggtatcgct cctatcttag gagataatac aaccaataaa 360gctatttatg ctatactatt ttttggtctg tcctacttcc ttgctatcaa acctagtaaa 420ctagctgaaa atatcggaaa atttttaacg ccaacgttgt tagttgttat ttctattttg 480gttatcgcgt cctttgtcca tcctgctgga aattacggtg atgcttttaa cgctggggtc 540ggtgttaata atgcctttaa agattttcct tttatagcag gattaattca aggttatggc 600actatggatg cactagcttc tcttgttttt gctattttag tcattgaggc taccaaacaa 660tttggcgcta agacggacaa agaaatgacc aaaataacac ttatttctgg ggctattgcc 720attttgctat tagcacttgt ctatatcttt gtcggtcgta ttggagcaac atcacaatca 780ttatttcctt ttattgatgg cagctttacc cttcatggta atccagttaa tggcggtcaa 840atcttaagtc atgcttctcg tttttaccta ggtggcatcg gacaagcatt tctagctgtt 900gtgattttcc tggcctgtct aaccacttca acaggcttaa tcacgtcaag tgctgaatac 960ttccataaat tagtgcctgc tttatctcat attgcttggg caactatctt tactttacta 1020tcagctttct tttattttgg tggcttatca gtcattatca actggtcagc tcctgtttta 1080ttccttttat acccattaac agtcgattta attttccttg ttttggcaca aaaatgcttc 1140aataatgatc ctattgtcta tcgaactaca attggtctaa cctttattcc tgccatattt 1200gatgcactcc taacactatc acaaatgact ggattatttc atttaccaga agccgttgta 1260acttttttcc aaaaaactgt tccactaggg caattctcaa tgggatggat tatctttgct 1320gctattggtt ttttaatagg gcttatacta agtaaaacga agaaaagcta a 137l＜210〉8＜211〉456＜212〉PRT＜213〉＜400〉8Met Lys Gln Lys Asn Val Tyr Ile Val Ile Gly Phe Met Leu Phe Ala 1 5 10 15Leu Phe Phe Gly Ala Ala Asn Leu Ile Tyr Pro Ala Phe Leu Gly Ile

20 25 30Tyr?Ser?Gly?His?Gln?Ile?Leu?Trp?Ser?Ile?Ile?Gly?Phe?Cys?Leu?Thr

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

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

85 90 95Ile?Pro?Arg?Thr?Gly?Ala?Thr?Ser?Phe?Ser?Val?Gly?Ile?Ala?Pro?Ile

100 105 110Leu?Gly?Asp?Asn?Thr?Thr?Asn?Lys?Ala?Ile?Tyr?Ala?Ile?Leu?Phe?Phe

115 120 125Gly?Leu?Ser?Tyr?Phe?Leu?Ala?Ile?Lys?Pro?Ser?Lys?Leu?Ala?Glu?Asn

130 135 140Ile?Gly?Lys?Phe?Leu?Thr?Pro?Thr?Leu?Leu?Val?Val?Ile?Ser?Ile?Leu145 150 155 160Val?Ile?Ala?Ser?Phe?Val?His?Pro?Ala?Gly?Asn?Tyr?Gly?Asp?Ala?Phe

165 170 175Asn?Ala?Gly?Val?Gly?Val?Asn?Asn?Ala?Phe?Lys?Asp?Phe?Pro?Phe?Ile

180 185 190Ala?Gly?Leu?Ile?Gln?Gly?Tyr?Gly?Thr?Met?Asp?Ala?Leu?Ala?Ser?Leu

195 200 205Val?Phe?Ala?Ile?Leu?Val?Ile?Glu?Ala?Thr?Lys?Gln?Phe?Gly?AlaLys

210 215 220Thr?Asp?Lys?Glu?Met?Thr?Lys?Ile?Thr?Leu?Ile?Ser?Gly?Ala?Ile?Ala225 230 235 240Ile?Leu?Leu?Leu?Ala?Leu?Val?Tyr?Ile?Phe?Val?Gly?Arg?Ile?Gly?Ala

245 250 255Thr?Ser?Gln?Ser?Leu?Phe?Pro?Phe?Ile?Asp?Gly?Ser?Phe?Thr?Leu?His

260 265 270Gly?Asn?Pro?Val?Asn?Gly?Gly?Gln?Ile?Leu?Ser?His?Ala?Ser?Arg?Phe

275 280 285Tyr?Leu?Gly?Gly?Ile?Gly?Gln?Ala?Phe?Leu?Ala?Val?Val?Ile?Phe?Leu

290 295 300Ala?Cys?Leu?Thr?Thr?Ser?Thr?Gly?Leu?Ile?Thr?Ser?Ser?Ala?Glu?Tyr305 310 315 320Phe?His?Lys?Leu?Val?Pro?Ala?Leu?Ser?His?Ile?Ala?Trp?Ala?Thr?Ile

325 330 335Phe?Thr?Leu?Leu?Ser?Ala?Phe?Phe?Tyr?Phe?Gly?Gly?Leu?Ser?Val?Ile

340 345 350Ile?Asn?Trp?Ser?Ala?Pro?Val?Leu?Phe?Leu?Leu?Tyr?Pro?Leu?Thr?Val

355 360 365Asp?Leu?Ile?Phe?Leu?Val?Leu?Ala?Gln?Lys?Cys?Phe?Asn?Asn?Asp?Pro

370 375 380Ile?Val?Tyr?Arg?Thr?Thr?Ile?Gly?Leu?Thr?Phe?Ile?Pro?Ala?Ile?Phe385 390 395 400Asp?Ala?Leu?Leu?Thr?Leu?Ser?Gln?Met?Thr?Gly?Leu?Phe?His?Leu?Pro

405 410 415Glu?Ala?Val?Val?Thr?Phe?Phe?Gln?Lys?Thr?Val?Pro?Leu?Gly?Gln?Phe

420 425 430Ser?Met?Gly?Trp?Ile?Ile?Phe?Ala?Ala?Ile?Gly?Phe?Leu?Ile?Gly?Leu

435 440 445Ile?Leu?Ser?Lys?Thr?Lys?Lys?Ser

450 455＜210〉9＜211〉441＜212〉DNA＜213〉＜400〉9atggggattt tagaaaaaaa acttgataac ttagtaaata ctattttatt aaaagcagaa 60aatcagcatg agttattatt tggagcttgt caaagtgacg ttaagcttac taatacgcaa 120gaacatattt taatgttact atctcagcaa cgtctcacta atacagattt ggctaaggca 180ttaaatatta gtcaggcggc agtaactaag gctatcaaga gtttggtcaa acaagacatg 240ttagcaggaa ctaaggatac ggttgatgct agggtgactt attttgaatt aaccgagtta 300gctaagccta ttgcgtcaga acatacccat catcatgatg aaaccttaaa tgtttacaac 360cgtttattac aaaaattctc cgcgaaagaa ttagagattg tagataagtt tgtaacagtt 420tttgctgagg aattagaagg g 441＜210〉10＜211〉147＜212〉PRT＜213〉＜400〉l0Met Gly Ile Leu Glu Lys Lys Leu Asp Asn Leu Val Asn Thr Ile Leu 1 5 10 15Leu Lys Ala Glu Asn Gln His Glu Leu Leu Phe Gly Ala Cys Gln Ser

20 25 30Asp?Val?Lys?Leu?Thr?Asn?Thr?Gln?Glu?His?Ile?Leu?Met?Leu?Leu?Ser

35 40 45Gln?Gln?Arg?Leu?Thr?Asn?Thr?Asp?Leu?Ala?Lys?Ala?Leu?Asn?Ile?Ser

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

85 90 95Leu?Thr?Glu?Leu?Ala?Lys?Pro?Ile?Ala?Ser?Glu?His?Thr?His?His?His

100 105 110Asp?Glu?Thr?Leu?Asn?Val?Tyr?Asn?Arg?Leu?Leu?Gln?Lys?Phe?Ser?Ala

115 120 125Lys?Glu?Leu?Glu?Ile?Val?Asp?Lys?Phe?Val?Thr?Val?Phe?Ala?Glu?Glu

130 135 140Leu Glu Gly145＜210〉11＜211〉815＜212〉DNA＜213〉＜400〉11atgcttgata ttttattcta tgatttcatg caacgggcgg taatggcggt agttgccatt 60agtatttttg ctccgatttt aggtattttc cttattttac gtcgtcaaag tttgatgagc 120gataccctta gtcatgtttc tttggctggg gtagcgcttg gggtagtcct tggtatttca 180ccaaccatca ctactattat tgttgtggtt ttagctgcta ttttgttaga atacctgcgt 240gtagtttaca aacactacat ggagatttca acggcgattt tgatgtcact tggcttggcc 300ctatctctga ttattatgag taagtcgcat agttcatcaa gcatgagttt agaacaatac 360ctttttggat cgatcatcac gattagtatg gaacaagttg tcgccttgtt tgctattgct 420gcgattattt taatcttgac cgttctcttc attagaccga tgtacattct gacctttgat 480gaagatactg cttttgtaga tggtttgccc gttcgcttga tgtctgttct attcaatatc 540gtcactgggg ttgctattgc tttgaccatt ccagcagcag gagcactttt ggtttctacc 600attatggtct tgccagcaag tatcgcaatg agattgggta aaaactttaa aacagttatc 660ttactgggaa ttgtcatcgg ttttagcggt atgttatctg gtattttctt atcttatttc 720tttgaaacgc cagctagtgc cactattacc atgattttca ttagtatttt cctcttagtt 780agtctaggtg gaatgcttaa aaaacggtta tttaa 815＜210〉12＜211〉239＜212〉PRT＜213〉＜400〉12Met Arg Tyr Ile Ser Val Lys Asn Leu Ser Phe Gln Tyr Glu Ser Glu 1 5 10 15Pro Val Leu Glu Gly Ile Thr Tyr His Leu Asp Ser Gly Glu Phe Val

20 25 30Thr?Met?Thr?Gly?Glu?Asn?Gly?Ala?Ala?Lys?Ser?Thr?Leu?Ile?Lys?Ala

35 40 45Thr?Leu?Gly?Ile?Leu?Gln?Pro?Lys?Ala?Gly?Arg?Val?Thr?Ile?Ala?Lys

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

85 90 95Lys?Ser?Gly?Arg?Tyr?Pro?Arg?Ser?Gly?Trp?Phe?Arg?His?Leu?Asn?Lys

100 105 110His?Asp?Glu?Glu?His?Val?Gln?Ala?Ser?Leu?Glu?Ala?Val?Gly?Met?Trp

115 120 125Glu?Asn?Arg?His?Lys?Arg?Ile?Gly?Ser?Leu?Ser?Gly?Gly?Gln?Lys?Gln

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

165 170 175Tyr?Glu?Leu?Met?His?His?Ser?Ala?His?Gln?His?Gly?Lys?Ser?Val?Leu

180 185 190Met?Ile?Thr?His?Asp?Pro?Glu?Glu?Val?Lys?Ala?Tyr?Ala?Asp?Arg?Asn

195 200 205Ile?His?Leu?Val?Arg?Asn?Gln?Lys?Leu?Pro?Trp?Arg?Cys?Phe?Asn?Ile

210 215 220His Glu Ala Glu Thr Asp Asp Glu Lys Gly Gly His Gly His Ala225 230 235＜210〉13＜211〉681＜212〉DNA＜213〉＜400〉13atgtattcta taaaatgtga tgataataaa gccatgccaa gagaacgttt gatgcgacta 60ggagcagagt ctctaagtaa tcaagaatta ttagcaattt tattacgaac aggtaataaa 120gaaaagcatg tcttagagct gtcatcctat cttttatcgc atttagacag tctggcagat 180tttaaaaaga tgtctttgca agaattacaa catttggcag gtataggaaa agttaaagcg 240attgaaatta aagctatgat tgagttggtt tcccgaattt tagcgacaga taagacatta 300actgatagcg tattaaccag tgttcaggtc gctgaaaaaa tgatggcagc tttaggagat 360aaaaaacaag agcatttagt cgtattgtat ttagataatc aaaatcgtat tattgaagaa 420aaaactattt ttattgggac tgtccgacgt tcacttgcag aaccaagaga aattttatac 480tatgcctgta aaaatatggc gactagtctc attgttattc ataatcatcc ttcaggaaat 540attgaaccta gttctaacga ttattgcttt actgaaaaaa taaaacgatc atgtgaagat 600ttaggcatta tctgtctaga tcacattatc gttagctata aagattatta tagttttcga 660gaaaaatcaa ccctttttta a 681＜210〉14＜211〉226＜212〉PRT＜213〉＜400〉14Met Tyr Ser Ile Lys Cys Asp Asp Asn Lys Ala Met Pro Arg Glu Arg 1 5 10 15Leu Met Arg Leu Gly Ala Glu Ser Leu Ser Asn Gln Glu Leu Leu Ala

20 25 30Ile?Leu?Leu?Arg?Thr?Gly?Asn?Lys?Glu?Lys?His?Val?Leu?Glu?Leu?Ser

35 40 45Ser?Tyr?Leu?Leu?Ser?His?Leu?Asp?Ser?Leu?Ala?Asp?Phe?Lys?Lys?Met

50 55 60Ser?Leu?Gln?Glu?Leu?Gln?His?Leu?Ala?Gly?Ile?Gly?Lys?Val?Lys?Ala?65 70 75 80Ile?Glu?Ile?Lys?Ala?Met?Ile?Glu?Leu?Val?Ser?Arg?Ile?Leu?Ala?Thr

85 90 95Asp?Lys?Thr?Leu?Thr?Asp?Ser?Val?Leu?Thr?Ser?Val?Gln?Val?Ala?Glu

100 105 110Lys?Met?Met?Ala?Ala?Leu?Gly?Asp?Lys?Lys?Gln?Glu?His?Leu?Val?Val

115 120 125Leu?Tyr?Leu?Asp?Asn?Gln?Asn?Arg?Ile?Ile?Glu?Glu?Lys?Thr?Ile?Phe

130 135 140Ile?Gly?Thr?Val?Arg?Arg?Ser?Leu?Ala?Glu?Pro?Arg?Glu?Ile?Leu?Tyr145 150 155 160Tyr?Ala?Cys?Lys?Asn?Met?Ala?Thr?Ser?Leu?Ile?Val?Ile?His?Asn?His

165 170 175Pro?Ser?Gly?Asn?Ile?Glu?Pro?Ser?Ser?Asn?Asp?Tyr?Cys?Phe?Thr?Glu

180 185 190Lys?Ile?Lys?Arg?Ser?Cys?Glu?Asp?Leu?Gly?Ile?Ile?Cys?Leu?Asp?His

195 200 205Ile?Ile?Val?Ser?Tyr?Lys?Asp?Tyr?Tyr?Ser?Phe?Arg?Glu?Lys?Ser?Thr

210 215 220Leu Phe225＜210〉15＜211〉410＜212〉DNA＜213〉＜400〉15atgatgttac gaaaatttaa aattaccatt gacggtaaag agtatcttgt agaaatggaa 60gaaatcggtg ctcctgccca agcagctgcc cccgctcaac caatatccac tccagtacct 120gtccctactg aagcaagccc acaagtggag gaagcgcaag caccacagcc agtagctgca 180gcgggagcgg atgccattcc atcaccaatg cctggaacca tcttaaaagt cttagtagca 240gtgggagacc aagtaactga aaatcagcca ctattgattt tagaagccat gaagatggaa 300aatgagattg tggcctcatc agcaggaacc attacagcta tccacgtcgg tccaggtcaa 360gtggtcaatc ctggtgatgg tctcattaca attggttaat agtactataa 410＜210〉16＜211〉134＜212〉PRT＜213〉＜400〉16Met Met Leu Arg Lys Phe Lys Ile Thr Ile Asp Gly Lys Glu Tyr Leu 1 5 10 15Val Glu Met Glu Glu Ile Gly Ala Pro Ala Gln Ala Ala Ala Pro Ala

20 25 30Gln?Pro?Ile?Ser?Thr?Pro?Val?Pro?Val?Pro?Thr?Glu?Ala?Ser?Pro?Gln

35 40 45Val?Glu?Glu?Ala?Gln?Ala?Pro?Gln?Pro?Val?Ala?Ala?Ala?Gly?Ala?Asp

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

85 90 95Met?Lys?Met?Glu?Asn?Glu?Ile?Val?Ala?Ser?Ser?Ala?Gly?Thr?Ile?Thr

100 105 110Ala?Ile?His?Val?Gly?Pro?Gly?Gln?Val?Val?Asn?Pro?Gly?Asp?Gly?Leu

115 120 125Ile?Thr?Ile?Gly?Tyr?Tyr

130＜210〉17＜211〉1533＜212〉DNA＜213〉＜400〉17atggtaacaa ataaactcgg tagagatatt cctcaaccat acgccgacca atacggtgtc 60tttgaaggag aactcgcaaa tatcaaacag tatgacgaat caagtcgccg tattaaacca 120gttaagcctg gagattctaa attactagga tctgttcgtg aagcgattga aaaaacaggt 180ttaacagatg gcatgaccat ttctttccac caccatttcc gtgaagggga tttcattatg 240aatatggtct tggaggaaat tgccaaaatg ggcattaaaa acctgtctat tgccccaagt 300tccatcgcta atgtacatga gcctttgatt gatcacatca aaaatggtgt ggtcactaac 360atcacttcat ctggtcttcg tgacaaagta ggggcagcca tctcagaagg actaatggaa 420aatcctgtgg ttattcgctc ccatggtggt cgcgctcgtg ccattgctag tggggatatc 480catattgatg ttgcctttct gggcgcccca agttcagatg cttacggaaa tgttaatggg 540acaaaaggga aagcaacctg tggttctttg ggctatgcca tgattgatgc caaatatgcg 600gatcaggtgg ttatcttgac agataatttg gttccttatc ctaatacccc aatcagcatt 660cctcaaacag atgttgacta tgtggtaaca gtggatgcta tcggagatcc tcaaggaatc 720gccaaagggg caactcgttt tacgaaaaat cctaaagaac tcttaattgc agaatacgcc 780gctaaagtaa tcaccaactc tccttatttt aaagaaggat tctctttcca aactggaaca 840ggtggcgctt ctttggcagt aacccgtttc atgcgtgaag ctatgattaa agaaaatatc 900aaagctagct ttgctcttgg tggtattacc aatgctatgg tggagttgct cgaagaagaa 960ctggttgaaa aaattcttga tgtccaagac tttgatcacc catcagctgt ttctcttggt 1020aagcatgctg aacattatga aattgatgcc aacatgtatg cctcaccttt gagcaagggt 1080gctgttatca atcaattaga cacttgtatt ttatcagccc ttgaagttga tactaacttc 1140aatgttaatg tgatgacagg atctgacggc gtgattcgtg gcgcttctgg aggacactgc 1200gacactgcct ttgcggctaa gatgagtttg gttatttcac cacttatccg cggacgcatc 1260ccaacttttg tagatgaggt taatacggtc attacaccag gaacaagtgt cgatgtgatc 1320gtcacagaag tgggaattgc cattaaccca aatcgtcaag acttagtaga ccatttcaaa 1380tccctcaatg tgccacaatt tagtattgag gagctaaaag agaaggctta cgccatcgtt 1440ggcacacctg agcgtattca atatggtgat aaggttgttg ctcttattga ataccgtgac 1500ggtagcctca tggatgtggt ttacaatgtg taa 1533＜210〉18＜211〉510＜212〉PRT＜213〉＜400〉18Met Val Thr Asn Lys Leu Gly Arg Asp Ile Pro Gln Pro Tyr Ala Asp 1 5 10 15Gln Tyr Gly Val Phe Glu Gly Glu Leu Ala Asn Ile Lys Gln Tyr Asp

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

35 40 45Leu?Gly?Ser?Val?Arg?Glu?Ala?Ile?Glu?Lys?Thr?Gly?Leu?Thr?Asp?Gly

50 55 60Met?Thr?Ile?Ser?Phe?His?His?His?Phe?Arg?Glu?Gly?Asp?Phe?Ile?Met?65 70 75 80Asn?Met?Val?Leu?Glu?Glu?Ile?Ala?Lys?Met?Gly?Ile?Lys?Asn?Leu?Ser

85 90 95Ile?Ala?Pro?Ser?Ser?Ile?Ala?Asn?Val?His?Glu?Pro?Leu?Ile?Asp?His

100 105 110Ile?Lys?Asn?Gly?Val?Val?Thr?Asn?Ile?Thr?Ser?Ser?Gly?Leu?Arg?Asp

115 120 125Lys?Val?Gly?Ala?Ala?Ile?Ser?Glu?Gly?Leu?Met?Glu?Asn?Pro?Val?Val

130 135 140Ile?Arg?Ser?His?Gly?Gly?Arg?Ala?Arg?Ala?Ile?Ala?Ser?Gly?Asp?Ile145 150 155 160His?Ile?Asp?Val?Ala?Phe?Leu?Gly?Ala?Pro?Ser?Ser?Asp?Ala?Tyr?Gly

165 170 175Asn?Val?Asn?Gly?Thr?Lys?Gly?Lys?Ala?Thr?Cys?Gly?Ser?Leu?Gly?Tyr

180 185 190Ala?Met?Ile?Asp?Ala?Lys?Tyr?Ala?Asp?Gln?Val?Val?Ile?Leu?Thr?Asp

195 200 205Asn?Leu?Val?Pro?Tyr?Pro?Asn?Thr?Pro?Ile?Ser?Ile?Pro?Gln?Thr?Asp

210 215 220Val?Asp?Tyr?Val?Val?Thr?Val?Asp?Ala?Ile?Gly?Asp?Pro?Gln?Gly?Ile225 230 235 240Ala?Lys?Gly?Ala?Thr?Arg?Phe?Thr?Lys?Asn?Pro?Lys?Glu?Leu?Leu?Ile

245 250 255Ala?Glu?Tyr?Ala?Ala?Lys?Val?Ile?Thr?Asn?Ser?Pro?Tyr?Phe?Lys?Glu

260 265 270Gly?Phe?Ser?Phe?Gln?Thr?Gly?Thr?Gly?Gly?Ala?Ser?Leu?Ala?Val?Thr

275 280 285Arg?Phe?Met?Arg?Glu?Ala?Met?Ile?Lys?Glu?Asn?Ile?Lys?Ala?Ser?Phe

290 295 300Ala?Leu?Gly?Gly?Ile?Thr?Asn?Ala?Met?Val?Glu?Leu?Leu?Glu?Glu?Glu305 310 315 320Leu?Val?Glu?Lys?Ile?Leu?Asp?Val?Gln?Asp?Phe?Asp?His?Pro?Ser?Ala

325 330 335Val?Ser?Leu?Gly?Lys?His?Ala?Glu?His?Tyr?Glu?Ile?Asp?Ala?Asn?Met

340 345 350Tyr?Ala?Ser?Pro?Leu?Ser?Lys?Gly?Ala?Val?Ile?Asn?Gln?Leu?Asp?Thr

355 360 365Cys?Ile?Leu?Ser?Ala?Leu?Glu?Val?Asp?Thr?Asn?Phe?Asn?Val?Asn?Val

370 375 380Met?Thr?Gly?Ser?Asp?Gly?Val?Ile?Arg?Gly?Ala?Ser?Gly?Gly?His?Cys385 390 395 400Asp?Thr?Ala?Phe?Ala?Ala?Lys?Met?Ser?Leu?Val?Ile?Ser?Pro?Leu?Ile

405 410 415Arg?Gly?Arg?Ile?Pro?Thr?Phe?Val?Asp?Glu?Val?Asn?Thr?Val?Ile?Thr

420 425 430Pro?Gly?Thr?Ser?Val?Asp?Val?Ile?Val?Thr?Glu?Val?Gly?Ile?Ala?Ile

435 440 445Asn?Pro?Asn?Arg?Gln?Asp?Leu?Val?Asp?His?Phe?Lys?Ser?Leu?Asn?Val

450 455 460Pro?Gln?Phe?Ser?Ile?Glu?Glu?Leu?Lys?Glu?Lys?Ala?Tyr?Ala?Ile?Val465 470 475 480Gly?Thr?Pro?Glu?Arg?Ile?Gln?Tyr?Gly?Asp?Lys?Val?Val?Ala?Leu?Ile

485 490 495Glu?Tyr?Arg?Asp?Gly?Ser?Leu?Met?Asp?Val?Val?Tyr?Asn?Val

500 505 510＜210〉19＜211〉888＜212〉DNA＜213〉＜400〉19atggaacgtt taagaagaac aatgatgttt gtgcctggtg ccaatgcagc catgcttcga 60gatgctcctt tatttggcgc tgattcaatc atgtttgact tggaagattc tgtttcactc 120aaagaaaaag acacctctag agctctcgtt cattttgcgc ttaaaacttt tgattattca 180agcgttgaaa cggttgttcg tgtgaatggt cttgattctt gtggggcttt agacatcgaa 240gctgttgttt tggcaggtgt caacgtgatt cgtcttccaa aaacagagac tgctcaagat 300attattgatg tggaggctgt tattgaacgt gtcgaacgcg agaacagcat tgaagttggt 360cgcacacgta tgatggcagc cattgaatca gccgaaggtg tcctaaatgc tcgtgagatt 420gccaaagctt ctaagcgctt gattggtatt gctcttggag cagaagacta tgtcacgaat 480atgaaaacgc gtcgttaccc agatggtcaa gaattattct ttgctcgtag catgatttta 540cacgctgctc gtgctgctgg aattgctgcc attgatactg tttattctga tgtcaataat 600accgaagggt tccaaaacga agttcgcatg atcaaacagt taggatttga tggtaaatcg 660gtcatcaacc ctcgccaaat tcctctggtc aatgagattt ataccccaac aaaaaaagaa 720attgaccatg ccaaacaagt catctgggca attcgtgaag ctgaaagcaa aggctctggc 780gttatttcct taaatggaaa aatggttgat aaaccaatcg ttgaacgtgc agaacgtgtg 840attgccctag caacagcagc aggtgtttta tctgaggagg atatttaa 888＜210〉20＜211〉295＜212〉PRT＜213〉＜400〉20Met Glu Arg Leu Arg Arg Thr Met Met Phe Val Pro Gly Ala Asn Ala 1 5 10 15Ala Met Leu Arg Asp Ala Pro Leu Phe Gly Ala Asp Ser Ile Met Phe

20 25 30Asp?Leu?Glu?Asp?Ser?Val?Ser?Leu?Lys?Glu?Lys?Asp?Thr?Ser?Arg?Ala

35 40 45Leu?Val?His?Phe?Ala?Leu?Lys?Thr?Phe?Asp?Tyr?Ser?Ser?Val?Glu?Thr

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

85 90 95Thr?Ala?Gln?Asp?Ile?Ile?Asp?Val?Glu?Ala?Val?Ile?Glu?Arg?Val?Glu

100 105 110Arg?Glu?Asn?Ser?Ile?Glu?Val?Gly?Arg?Thr?Arg?Met?Met?Ala?Ala?Ile

115 120 125Glu?Ser?Ala?Glu?Gly?Val?Leu?Asn?Ala?Arg?Glu?Ile?Ala?Lys?Ala?Ser

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

165 170 175Ser?Met?Ile?Leu?His?Ala?Ala?Arg?Ala?Ala?Gly?Ile?Ala?Ala?Ile?Asp

180 185 190Thr?Val?Tyr?Ser?Asp?Val?Asn?Asn?Thr?Glu?Gly?Phe?Gln?Asn?Glu?Val

195 200 205Arg?Met?Ile?Lys?Gln?Leu?Gly?Phe?Asp?Gly?Lys?Ser?Val?Ile?Asn?Pro

210 215 220Arg?Gln?Ile?Pro?Leu?Val?Asn?Glu?Ile?Tyr?Thr?Pro?Thr?Lys?Lys?Glu225 230 235 240Ile?Asp?His?Ala?Lys?Gln?Val?Ile?Trp?Ala?Ile?Arg?Glu?Ala?Glu?Ser

245 250 255Lys?Gly?Ser?Gly?Val?Ile?Ser?Leu?Asn?Gly?Lys?Met?Val?Asp?Lys?Pro

260 265 270Ile?Val?Glu?Arg?Ala?Glu?Arg?Val?Ile?Ala?Leu?Ala?Thr?Ala?Ala?Gly

275 280 285Val?Leu?Ser?Glu?Glu?Asp?Ile

290 295＜210〉21＜211〉309＜212〉DNA＜213〉＜400〉21atggatatta aacaaactgc cgttgctggt tcacttgaat caagtgacct aatgattaca 60gtatccccta atgacgagca aaccattaca ataaccctag acagtagtgt tgaaaaacaa 120tttggcaatc acattcgtca actcattcat caaaccctag tgaatttgaa ggtgacggct 180gctaaagtag aggctgttga taaaggtgca ttagattgca ccattcaagc gagaaccatc 240gcagctgttc atcgcgctgc tggtattgac caatacgatt ggaaggagat tgactcatgg 300aacgtttaa 309＜210〉22＜211〉102＜212〉PRT＜213〉＜400〉22Met Asp Ile Lys Gln Thr Ala Val Ala Gly Ser Leu Glu Ser Ser Asp 1 5 10 15Leu Met Ile Thr Val Ser Pro Asn Asp Glu Gln Thr Ile Thr Ile Thr

20 25 30Leu?Asp?Ser?Ser?Val?Glu?Lys?Gln?Phe?Gly?Asn?His?Ile?Arg?Gln?Leu

35 40 45Ile?His?Gln?Thr?Leu?Val?Asn?Leu?Lys?Val?Thr?Ala?Ala?Lys?Val?Glu

50 55 60Ala?Val?Asp?Lys?Gly?Ala?Leu?Asp?Cys?Thr?Ile?Gln?Ala?Arg?Thr?Ile?65 70 75 80Ala?Ala?Val?His?Arg?Ala?Ala?Gly?Ile?Asp?Gln?Tyr?Asp?Trp?Lys?Glu

85 90 95Ile?Asp?Ser?Trp?Asn?Val

100＜210〉23＜211〉1053＜212〉DNA＜213〉＜400〉23atgccttact acactatttc aaaagtcttt ccttcagata aaacgacaat ggctagtgta 60aagaacctgc ttcatcaaga aggtattcgt ttggatgctc atttagatta tacttgtgcc 120atcatgaatg cgcaaaatga tgtgattgct accggttctt actttggaaa tagcttgcgc 180tgtctttgcg tatccagtgc ctatcaaggt gaaggacttc ttaataggat tgtgagtcat 240ctcattgatg aagaatatgc ccttggcaac tatcatcttt ttgtttatac gaagacctct 300tctgctgctt ttttcaaaga tcttggtttt actgaaattg tccatatcga caatcacatc 360agtttcttgg aaaataaaaa aactggtttt caagattatc tgatgacact taataagcct 420gagcaaacac ctggtaaagt cgctgctatt gttatcaacg ctaacccctt taccttaggg 480catcaatttt tagtagagaa agctgcaaga gaaaatgatt gggttcatct gtttatggtc 540agtgaagacc gcagtctaat tcctttttcg gtgagaaaga ggttgattca agaaggtcta 600gctcatcttg ataatgtcat atatcatgaa acaggtcctt atttgattag ccaagcgact 660ttcccagcct atttccaaaa agaagacaat gacgtgatta agagccaagc tttgctggat 720actgctattt ttctaaagat tgctcaaacc ttacagatta caaaaagata cgttggagaa 780gagccaacca gccgagtaac tgctatttac aatgaaatta tggcagagca gttgcagcaa 840gctggtatcc tcctagatat tttgccaagg aaagctatca atcagcagca agatcctatc 900agtgcctcaa cggctaggca ggcattgaaa gataatgatt gggaccttct ggcaaaactc 960cttcccaaaa cgtctttaga ttatttttgt tcgctaaaag cccaacccat tattaaaaag 1020atacaagcca cttcatctgt caaacattac taa 1053＜210〉24＜211〉350＜212〉PRT＜213〉＜400〉24Met Pro Tyr Tyr Thr Ile Ser Lys Val Phe Pro Ser Asp Lys Thr Thr 1 5 10 15Met Ala Ser Val Lys Asn Leu Leu His Gln Glu Gly Ile Arg Leu Asp

20 25 30Ala?His?Leu?Asp?Tyr?Thr?Cys?Ala?Ile?Met?Asn?Ala?Gln?Asn?Asp?Val

35 40 45Ile?Ala?Thr?Gly?Ser?Tyr?Phe?Gly?Asn?Ser?Leu?Arg?Cys?Leu?Cys?Val

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

85 90 95Thr?Lys?Thr?Ser?Ser?Ala?Ala?Phe?Phe?Lys?Asp?Leu?Gly?Phe?Thr?Glu

100 105 110Ile?Val?His?Ile?Asp?Asn?His?Ile?Ser?Phe?Leu?Glu?Asn?Lys?Lys?Thr

115 120 125Gly?Phe?Gln?Asp?Tyr?Leu?Met?Thr?Leu?Asn?Lys?Pro?Glu?Gln?Thr?Pro

130 135 140Gly?Lys?Val?Ala?Ala?Ile?Val?Ile?Asn?Ala?Asn?Pro?Phe?Thr?Leu?Gly145 150 155 160His?Gln?Phe?Leu?Val?Glu?Lys?Ala?Ala?Arg?Glu?Asn?Asp?Trp?Val?His

165 170 175Leu?Phe?Met?Val?Ser?Glu?Asp?Arg?Ser?Leu?Ile?Pro?Phe?Ser?Val?Arg

180 185 190Lys?Arg?Leu?Ile?Gln?Glu?Gly?Leu?Ala?His?Leu?Asp?Asn?Val?Ile?Tyr

195 200 205His?Glu?Thr?Gly?Pro?Tyr?Leu?Ile?Ser?Gln?Ala?Thr?Phe?Pro?Ala?Tyr

210 215 220Phe?Gln?Lys?Glu?Asp?Asn?Asp?Val?Ile?Lys?Ser?Gln?Ala?Leu?Leu?Asp225 230 235 240Thr?Ala?Ile?Phe?Leu?Lys?Ile?Ala?Gln?Thr?Leu?Gln?Ile?Thr?Lys?Arg

245 250 255Tyr?Val?Gly?Glu?Glu?Pro?Thr?Ser?Arg?Val?Thr?Ala?Ile?Tyr?Asn?Glu

260 265 270Ile?Met?Ala?Glu?Gln?Leu?Gln?Gln?Ala?Gly?Ile?Leu?Leu?Asp?Ile?Leu

275 280 285Pro?Arg?Lys?Ala?Ile?Asn?Gln?Gln?Gln?Asp?Pro?Ile?Ser?Ala?Ser?Thr

290 295 300Ala?Arg?Gln?Ala?Leu?Lys?Asp?Asn?Asp?Trp?Asp?Leu?Leu?Ala?Lys?Leu305 310 315 320Leu?Pro?Lys?Thr?Ser?Leu?Asp?Tyr?Phe?Cys?Ser?Leu?Lys?Ala?Gln?Pro

325 330 335Ile?Ile?Lys?Lys?Ile?Gln?Ala?Thr?Ser?Ser?Val?Lys?His?Tyr

340 345 350＜210〉25＜211〉642＜212〉DNA＜213〉＜400〉25atggtgataa ggttgttgct cttattgaat accgtgacgg tagcctcatg gatgtggttt 60acaatgtgta aagacactta tttttcaggc gaagctatcc aacttagtga tatgttaaga 120gcccgcgaag aaagagctct gcgtcagctg catttattaa aggagtaccc agaaggtagc 180ttattatcgg tcaccatgaa tatccctgga ccaattaaaa cctctcctaa acttcttgaa 240gcttttgata tagtgattaa ggccattcaa actgccttag ctgacgataa gatttgttac 300cagttgcgat tactgcctac aacgggttat gagtattacc tcatcacaag tctacctagc 360cgcgacctga agttaaaaat gatagcctta gagacagagt tgccaatagg tcgtctcatg 420gatttagatg tcttggtctt gcaaaatgat ctgcctcatt caattagcag aaccgtatta 480ggaggctccc ctaggcaatg ttttatctgt tctaaagagg ccaaagtctg cggtcgccta 540cgtaagcaca gtgtcgagga gatgcagact gctatttcaa aattactcca ttcatttttc 600aataaagaca accaatcatc gtcatcagat aagacaggtt ga 642＜210〉26＜211〉213＜212〉PRT＜213〉＜400〉26Met Val Ile Arg Leu Leu Leu Leu Leu Asn Thr Val Thr Val Ala Ser 1 5 10 15Trp Met Trp Phe Thr Met Cys Lys Asp Thr Tyr Phe Ser Gly Glu Ala

20 25 30Ile?Gln?Leu?Ser?Asp?Met?Leu?Arg?Ala?Arg?Glu?Glu?Arg?Ala?Leu?Arg

35 40 45Gln?Leu?His?Leu?Leu?Lys?Glu?Tyr?Pro?Glu?Gly?Ser?Leu?Leu?Ser?Val

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

85 90 95Lys?Ile?Cys?Tyr?Gln?Leu?Arg?Leu?Leu?Pro?Thr?Thr?Gly?Tyr?Glu?Tyr

100 105 110Tyr?Leu?Ile?Thr?Ser?Leu?Pro?Ser?Arg?Asp?Leu?Lys?Leu?Lys?Met?Ile

115 120 125Ala?Leu?Glu?Thr?Glu?Leu?Pro?Ile?Gly?Arg?Leu?Met?Asp?Leu?Asp?Val

130 135 140Leu?Val?Leu?Gln?Asn?Asp?Leu?Pro?His?Ser?Ile?Ser?Arg?Thr?Val?Leu145 150 155 160Gly?Gly?Ser?Pro?Arg?Gln?Cys?Phe?Ile?Cys?Ser?Lys?Glu?Ala?Lys?Val

165 170 175Cys?Gly?Arg?Leu?Arg?Lys?His?Ser?Val?Glu?Glu?Met?Gln?Thr?Ala?Ile

180 185 190Ser?Lys?Leu?Leu?His?Ser?Phe?Phe?Asn?Lys?Asp?Asn?Gln?Ser?Ser?Ser

195 200 205Ser?Asp?Lys?Thr?Gly

210＜210〉27＜211〉1395＜212〉DNA＜213〉＜400〉27atgacgaaaa tccgtataac ggaaacagtt ttacgtgatg gtcaacaaag tcagattgcc 60acacgtatga caaccaagga aatgattcct attctcgaaa cgctagacaa tgctggttat 120catgcccttg aaatgtgggg aggagcaacc tttgattcct gcctacgctt tttaaatgaa 180gacccttggg aacggctaag agccatccgt aaagcagtga aaaagactaa acttcagatg 240ctcttacgcg gacaaaacct tcttggatat cgcaattatg ctgacgatgt ggtcagatcc 300tttattcaaa aatccattga aaatgggatt gatattgtcc gtattttcga tgctttaaac 360gacccacgca acttgcaaac agctgtttca gcgactaaaa aatttggagg gcatgctcaa 420gttgccattt cttacacgac aagtccggta cataccattg actactttgt tgaattggcg 480aaagcttacc aagctatcgg agcggactcc atttgtatca aagacatggc tggtgtctta 540actcctgaaa taggttacca attggtcaaa tgtatcaagg agaatacaac tatccctctt 600gaggttcata cccatgctac cagtggtatt tcagaaatga cttacttaaa agtagcagaa 660gcaggagctg atattattga tacggcgatt tcctcttttt cagggggaac cagtcagcct 720gccacagagt caatggcgat tgccttgacg gatttaggct ttgacacagg cttggatatg 780caagaggtgg ccaaagttgc agaatatttc aacactattc gtgaccacta tcgagaaata 840gggattttaa atcctaaagt caaagatact gagccaaaaa cattgattta ccaagttcca 900ggtggcatgc tatcaaacct attgagccaa ttaaccgagc aaggcctaac tgataaatac 960gaagaagtct tagcagaagt acctaaagta agggctgatc ttgggtatcc gccactcgta 1020acgccattat cacaaatggt tggcacacag gccttgatga atatcatctc aggggaacgt 1080tacaaggtag ttccaaatga aatcaaagac tatgttcgag ggctatacgg tcaatcacca 1140gcgccattag cagaaggtat caaagagaaa atcattggtg acgaagcagt tattacttgc 1200agaccagccg acctaatcga gcctcaaatg atttatctac gtgacgagat tgctccatac 1260gctcattcag aagaagacgt gttaagctat gcaagcttcc cgcaacaagc tagagatttc 1320ttgggacgcc gtgaagatcc tttctatgat gttccggttc aagaagttac tgtacaactg 1380gacattcaag actaa 1395＜210〉28＜211〉464＜212〉PRT＜213〉＜400〉28Met Thr Lys Ile Arg Ile Thr Glu Thr Val Leu Arg Asp Gly Gln Gln 1 5 10 15Ser Gln Ile Ala Thr Arg Met Thr Thr Lys Glu Met Ile Pro Ile Leu

20 25 30Glu?Thr?Leu?Asp?Asn?Ala?Gly?Tyr?His?Ala?Leu?Glu?Met?Trp?Gly?Gly

35 40 45Ala?Thr?Phe?Asp?Ser?Cys?Leu?Arg?Phe?Leu?Asn?Glu?Asp?Pro?Trp?Glu

50 55 60Arg?Leu?Arg?Ala?Ile?Arg?Lys?Ala?Val?Lys?Lys?Thr?Lys?Leu?Gln?Met?65 70 75 80Leu?Leu?Arg?Gly?Gln?Asn?Leu?Leu?Gly?Tyr?Arg?Asn?Tyr?Ala?Asp?Asp

85 90 95Val?Val?Arg?Ser?Phe?Ile?Gln?Lys?Ser?Ile?Glu?Asn?Gly?Ile?Asp?Ile

100 105 110Val?Arg?Ile?Phe?Asp?Ala?Leu?Asn?Asp?Pro?Arg?Asn?Leu?Gln?Thr?Ala

115 120 125Val?Ser?Ala?Thr?Lys?Lys?Phe?Gly?GIy?His?Ala?Gln?Val?Ala?Ile?Ser

130 135 140Tyr?Thr?Thr?Ser?Pro?Val?His?Thr?Ile?Asp?Tyr?Phe?Val?Glu?Leu?Ala145 150 155 160Lys?Ala?Tyr?Gln?Ala?Ile?Gly?Ala?Asp?Ser?Ile?Cys?Ile?Lys?Asp?Met

165 170 175Ala?Gly?Val?Leu?Thr?Pro?Glu?Ile?Gly?Tyr?Gln?Leu?Val?Lys?Cys?Ile

180 185 190Lys?Glu?Asn?Thr?Thr?Ile?Pro?Leu?Glu?Val?His?Thr?His?Ala?Thr?Ser

195 200 205Gly?Ile?Ser?Glu?Met?Thr?Tyr?Leu?Lys?Val?Ala?Glu?Ala?Gly?Ala?Asp

210 215 220Ile?Ile?Asp?Thr?Ala?Ile?Ser?Ser?Phe?Ser?Gly?Gly?Thr?Ser?Gln?Pro225 230 235 240Ala?Thr?Glu?Ser?Met?Ala?Ile?Ala?Leu?Thr?Asp?Leu?Gly?Phe?Asp?Thr

245 250 255Gly?Leu?Asp?Met?Gln?Glu?Val?Ala?Lys?Val?Ala?Glu?Tyr?Phe?Asn?Thr

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

275 280 285Asp?Thr?Glu?Pro?Lys?Thr?Leu?Ile?Tyr?Gln?Val?Pro?Gly?Gly?Met?Leu

290 295 300Ser?Asn?Leu?Leu?Ser?Gln?Leu?Thr?Glu?Gln?Gly?Leu?Thr?Asp?Lys?Tyr305 310 315 320Glu?Glu?Val?Leu?Ala?Glu?Val?Pro?Lys?Val?Arg?Ala?Asp?Leu?Gly?Tyr

325 330 335Pro?Pro?Leu?Val?Thr?Pro?Leu?Ser?Gln?Met?Val?Gly?Thr?Gln?Ala?Leu

340 345 350Met?Asn?Ile?Ile?Ser?Gly?Glu?Arg?Tyr?Lys?Val?Val?Pro?Asn?Glu?Ile

355 360 365Lys?Asp?Tyr?Val?Arg?Gly?Leu?Tyr?Gly?Gln?Ser?Pro?Ala?Pro?Leu?Ala

370 375 380Glu?Gly?Ile?Lys?Glu?Lys?Ile?Ile?Gly?Asp?Glu?Ala?Val?Ile?Thr?Cys385 390 395 400Arg?Pro?Ala?Asp?Leu?Ile?Glu?Pro?Gln?Met?Ile?Tyr?Leu?Arg?Asp?Glu

405 410 415Ile?Ala?Pro?Tyr?Ala?His?Ser?Glu?Glu?Asp?Val?Leu?Ser?Tyr?Ala?Ser

420 425 430Phe?Pro?Gln?Gln?Ala?Arg?Asp?Phe?Leu?Gly?Arg?Arg?Glu?Asp?Pro?Phe

435 440 445Tyr?Asp?Val?Pro?Val?Gln?Glu?Val?Thr?Val?Gln?Leu?Asp?Ile?Gln?Asp

450 455 460＜210〉29＜211〉1224＜212〉DNA＜213〉＜400〉29atgacgaatt taacgtttta tgcaaaaatc ggtatttcag aagaagagca tgactctttt 60gttaaagaac atcagcaaat tagcgtttta caaggtagtg attgggcaaa aatcaaaaat 120caatggcaga atgagcgaat tggtatctat aaagaggaaa agcaggttgc ctctttatca 180cttttgatta agctattgcc acttggaaga agcattattt atattccaag agggccagtc 240atggattatc ttgaccgtga tttggtggca tttaccatga aaacactaaa ggattatggt 300aaaactaaaa aggccctctt tatcaaatat gatccagcta tcctgttaaa acaatacgca 360ctgggacagg aagaagaaga aaaaccttta gctttagcag ctattaagaa tctccaagaa 420gctggtgttc attggactgg tttaacaatg gagattgcag atagtatcca acctcgtttc 480caagctaata tttacactca agaaaacctt gagatgcaat ttcctaagca taccagacgt 540ttaataaaag atgctaagca gcgtggtgta aaaacatatc gtgtcagtca atcagaactt 600cacaaatttt ccaagattgt ctccttaaca gaaaaacgta aaaatatttc tttgcgtaac 660gaagcttact ttcaaaagtt gatgactact tatggggata aggcctactt acatctagca 720aaagtgaata ttcctcaaaa actagatcaa taccgccagc aattaattct tattaaccaa 780gatattactc gcacccaagc tcatcaaaag aagcgtttaa aaaaattaga agatcaaaaa 840gcttctttag aacgttatat aactgaattt gaaggcttta cagaccaata tcctgaggaa 900gttgttgtag caggtatatt atctatttct tatggaaatg ttatggaaat gctttatgct 960gggatgaatg atgattttaa gaagttttat cctcagtatc tgctgtatcc taatgttttt 1020caggatgctt atcaagatgg tattatttgg gctaacatgg gaggagtaga aggctcgctt 1080gatgatggac ttaccaaatt taaggccaac tttgctccga caatagaaga atttatagga 1140gaatttaatc tccctgtcag cccactttat catattgcta ataccatgta caaaatacga 1200aaacagttaa agaataaaca ttaa 1224＜210〉30＜211〉407＜212〉PRT＜213〉＜400〉30Met Thr Asn Leu Thr Phe Tyr Ala Lys Ile Gly Ile Ser Glu Glu Glu 1 5 10 15His Asp Ser Phe Val Lys Glu His Gln Gln Ile Ser Val Leu Gln Gly

20 25 30Ser?Asp?Trp?Ala?Lys?Ile?Lys?Asn?Gln?Trp?Gln?Asn?Glu?Arg?Ile?Gly

35 40 45Ile?Tyr?Lys?Glu?Glu?Lys?Gln?Val?Ala?Ser?Leu?Ser?Leu?Leu?Ile?Lys

50 55 60Leu?Leu?Pro?Leu?Gly?Arg?Set?Ile?Ile?Tyr?Ile?Pro?Arg?Gly?Pro?Val?65 70 75 80Met?Asp?Tyr?Leu?Asp?Arg?Asp?Leu?Val?Ala?Phe?Thr?Met?Lys?Thr?Leu

85 90 95Lys?Asp?Tyr?Gly?Lys?Thr?Lys?Lys?Ala?Leu?Phe?Ile?Lys?Tyr?Asp?Pro

100 105 110Ala?Ile?Leu?Leu?Lys?Gln?Tyr?Ala?Leu?Gly?Gln?Glu?Glu?Glu?Glu?Lys

115 120 125Pro?Leu?Ala?Leu?Ala?Ala?Ile?Lys?Asn?Leu?Gln?Glu?Ala?Gly?Val?His

130 135 140Trp?Thr?Gly?Leu?Thr?Met?Glu?Ile?Ala?Asp?Ser?Ile?Gln?Pro?Arg?Phe145 150 155 160Gln?Ala?Asn?Ile?Tyr?Thr?Gln?Glu?Asn?Leu?Glu?Met?Gln?Phe?Pro?Lys

165 170 175His?Thr?Arg?Arg?Leu?Ile?Lys?Asp?Ala?Lys?Gln?Arg?Gly?Val?Lys?Thr

180 185 190Tyr?Arg?Val?Ser?Gln?Ser?Glu?Leu?His?Lys?Phe?Ser?Lys?Ile?Val?Ser

195 200 205Leu?Thr?Glu?Lys?Arg?Lys?Asn?Ile?Ser?Leu?Arg?Asn?Glu?Ala?Tyr?Phe

210 215 220Gln?Lys?Leu?Met?Thr?Thr?Tyr?Gly?Asp?Lys?Ala?Tyr?Leu?His?Leu?Ala225 230 235 240Lys?Val?Asn?Ile?Pro?Gln?Lys?Leu?Asp?Gln?Tyr?Arg?Gln?Gln?Leu?Ile

245 250 255Leu?Ile?Asn?Gln?Asp?Ile?Thr?Arg?Thr?Gln?Ala?His?Gln?Lys?Lys?Arg

260 265 270Leu?Lys?Lys?Leu?Glu?Asp?Gln?Lys?Ala?Ser?Leu?Glu?Arg?Tyr?Ile?Thr

275 280 285Glu?Phe?Glu?Gly?Phe?Thr?Asp?Gln?Tyr?Pro?Glu?Glu?Val?Val?Val?Ala

290 295 300Gly?Ile?Leu?Ser?Ile?Ser?Tyr?Gly?Asn?Val?Met?Glu?Met?Leu?Tyr?Ala305 310 315 320Gly?Met?Asn?Asp?Asp?Phe?Lys?Lys?Phe?Tyr?Pro?Gln?Tyr?Leu?Leu?Tyr

325 330 335Pro?Asn?Val?Phe?Gln?Asp?Ala?Tyr?Gln?Asp?Gly?Ile?Ile?Trp?Ala?Asn

340 345 350Met?Gly?Gly?Val?Glu?Gly?Ser?Leu?Asp?Asp?Gly?Leu?Thr?Lys?Phe?Lys

355 360 365Ala?Asn?Phe?Ala?Pro?Thr?Ile?Glu?Glu?Phe?Ile?Gly?Glu?Phe?Asn?Leu

370 375 380Pro?Val?Ser?Pro?Leu?Tyr?His?Ile?Ala?Asn?Thr?Met?Tyr?Lys?Ile?Arg385 390 395 400Lys?Gln?Leu?Lys?Asn?Lys?His

405＜210〉31＜211〉483＜212〉DNA＜213〉＜400〉31atgccaaaga gaataagaaa agctctagga gtagttggga aactgatgtc aattgttcct 60gacactactg aaattattgg aaaaacgatt gataacagtc gaccaattat cgaaaaacgt 120atggaacaaa aacatgaaaa agagatgcaa ttacgcacga taaatgatgt gattaatctt 180cctgttgatc aggcacaagc tcatttggaa caacttggct ttgtagtagc cactatacct 240gctaagcctc ataaaaaatg gcttcatagt aatctcaatg aagtggttgc tatgtctcca 300aaatctggta aatataagat aggaagcctg atcaaactct actacattac tgttgatgtt 360ttggaaaaaa gtcaagactt attagaccaa gaaaacttgc ggactgtgga acgcaatcaa 420aaaatcgctg atacttttga gtctgtcaaa cacattcgat ttccttttaa aaaatggcgt 480taa 483＜210〉32＜211〉160＜212〉PRT＜213〉＜400〉32Met Pro Lys Arg Ile Arg Lys Ala Leu Gly Val Val Gly Lys Leu Met 1 5 10 15Ser Ile Val Pro Asp Thr Thr Glu lle Ile Gly Lys Thr Ile Asp Asn

20 25 30Ser?Arg?Pro?Ile?Ile?Glu?Lys?Arg?Met?Glu?Gln?Lys?His?Glu?Lys?Glu

35 40 45Met?Gln?Leu?Arg?Thr?Ile?Asn?Asp?Val?Ile?Asn?Leu?Pro?Val?Asp?Gln

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

85 90 95Ala?Met?Ser?Pro?Lys?Ser?Gly?Lys?Tyr?Lys?Ile?Gly?Ser?Leu?Ile?Lys

100 105 110Leu?Tyr?Tyr?Ile?Thr?Val?Asp?Val?Leu?Glu?Lys?Ser?Gln?Asp?Leu?Leu

115 120 125Asp?Gln?Glu?Asn?Leu?Arg?Thr?Val?Glu?Arg?Asn?Gln?Lys?Ile?Ala?Asp

130 135 140Thr Phe Glu Set Val Lys His Ile Arg Phe Pro Phe Lys Lys Trp Arg145 150 155 160＜210〉33＜211〉1345＜212〉DNA＜213〉＜400〉33atgatgttaa cgaaggggca acttccctat agtgctgctt ttacaacagg agggctcttt 60tactttgtta tcattgcatt aagttattat ttgggatcga cactttggct agtctttgtt 120caggtgtttt gtttttactt atctggttta tatctttata aactcattaa ttatatgaca 180ggctttcaaa aagtggcttt aactttttca attagctact atttattatc tgttagtctt 240ggttttgggg gattgtatcc tactcaactg gctatgccat ttatattaat atcggcttgg 300tttttaacta agtattttgc ctgtttagtg aaagatgagg catttattct ttttggcttt 360gtaggtgctc ttgcaatgct aattgacccg agtaccctta tcttttggtc ttttgcttgt 420gtgacagttt tttcttataa tataagccaa aagcatcttg caagaggttt ttatcaactg 480ctagcttcga tttttggaat gattttagtt ttttacacag caggatattt cattttgaac 540ttacaagtgc taaatcctta tttatcacaa acgatgattt atccttttac tttttttaaa 600tcaggaaact tatcgttgct ttttggactg gctattcagt tgttcttcgc tttggggctt 660ggtcttttga cgggaatgga gaatgtcatt aggcgattta aaaacaattc tgatagggtc 720gtcaagtggc tatttgtcat ggtcattcta gaatctatac ttgtggctat attttcacaa 780gactatcgcc cctatcatct tttacctctt ttaccttttg gattaatttt gactgctatt 840cctgttggct atcagtatgg tataggatta ggtcagagta gtcatcgcag acgtcatggt 900aaaaatggtg ttggtcgagt aatgatgatt tatcttaaga gacactttta tttgccaatt 960ttaattgtag ggacaatact aatctgttct acttattgtt tcattagtag tattcctctt 1020aatcaggagc gtgatcatat tgctagttat ttagaacaga aactaaataa aactcaatct 1080atttatgttt gggatgatac ttctaaaatt tatttggaca gtaaagctaa atctgtttct 1140caatttagtt ctcctgacat caatacgcaa aaagagagtc atcgaaaaat attagaagat 1200gaactattag aaaataaggc tgcttatatc gttgttaatc gctataaaaa cctgcctaaa 1260atcattcaaa aagtattatc tactaattac aaagtagata aacagataac gacaaaaagt 1320tttattgttt atcagaaaaa gtaat 1345＜210〉34＜211〉447＜212〉PRT＜213〉＜400〉34Met Met Leu Thr Lys Gly Gln Leu Pro Tyr Ser Ala Ala Phe Thr Thr 1 5 10 15Gly Gly Leu Phe Tyr Phe Val Ile Ile Ala Leu Ser Tyr Tyr Leu Gly

20 25 30Ser?Thr?Leu?Trp?Leu?Val?Phe?Val?Gln?Val?Phe?Cys?Phe?Tyr?Leu?Ser

35 40 45Gly?Leu?Tyr?Leu?Tyr?Lys?Leu?Ile?Asn?Tyr?Met?Thr?Gly?Phe?Gln?Lys

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

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

100 105 1l0Glu?Ala?Phe?Ile?Leu?Phe?Gly?Phe?Val?Gly?Ala?Leu?Ala?Met?Leu?Ile

115 120 125Asp?Pro?Ser?Thr?Leu?Ile?Phe?Trp?Ser?Phe?Ala?Cys?Val?Thr?Val?Phe

130 135 140Ser?Tyr?Asn?Ile?Ser?Gln?Lys?His?Leu?Ala?Arg?Gly?Phe?Tyr?Gln?Leu145 150 155 160Leu?Ala?Ser?Ile?Phe?Gly?Met?Ile?Leu?Val?Phe?Tyr?Thr?Ala?Gly?Tyr

165 170 175Phe?Ile?Leu?Asn?Leu?Gln?Val?Leu?Asn?Pro?Tyr?Leu?Ser?Gln?Thr?Met

180 185 190Ile?Tyr?Pro?Phe?Thr?Phe?Phe?Lys?Ser?Gly?Asn?Leu?Ser?Leu?Leu?Phe

195 200 205Gly?Leu?Ala?Ile?Gln?Leu?Phe?Phe?Ala?Leu?Gly?Leu?Gly?Leu?Leu?Thr

210 215 220Gly?Met?Glu?Asn?Val?Ile?Arg?Arg?Phe?Lys?Asn?Asn?Ser?Asp?Arg?Val225 230 235 240Val?Lys?Trp?Leu?Phe?Val?Met?Val?Ile?Leu?Glu?Ser?Ile?Leu?Val?Ala

245 250 255Ile?Phe?Ser?Gln?Asp?Tyr?Arg?Pro?Tyr?His?Leu?Leu?Pro?Leu?Leu?Pro

260 265 270Phe?Gly?Leu?Ile?Leu?Thr?Ala?Ile?Pro?Val?Gly?Tyr?Gln?Tyr?Gly?Ile

275 280 285Gly?Leu?Gly?Gln?Ser?Ser?His?Arg?Arg?Arg?His?Gly?Lys?Asn?Gly?Val

290 295 300Gly?Arg?Val?Met?Met?Ile?Tyr?Leu?Lys?Arg?His?Phe?Tyr?Leu?Pro?Ile305 310 315 320Leu?Ile?Val?Gly?Thr?Ile?Leu?Ile?Cys?Ser?Thr?Tyr?Cys?Phe?Ile?Ser

325 330 335Ser?Ile?Pro?Leu?Asn?Gln?Glu?Arg?Asp?His?Ile?Ala?Ser?Tyr?Leu?Glu

340 345 350Gln?Lys?Leu?Asn?Lys?Thr?Gln?Ser?Ile?Tyr?Val?Trp?Asp?Asp?Thr?Ser

355 360 365Lys?Ile?Tyr?Leu?Asp?Ser?Lys?Ala?Lys?Ser?Val?Ser?Gln?Phe?Ser?Ser

370 375 380Pro?Asp?Ile?Asn?Thr?Gln?Lys?Glu?Ser?His?Arg?Lys?Ile?Leu?Glu?Asp385 390 395 400Glu?Leu?Leu?Glu?Asn?Lys?Ala?Ala?Tyr?Ile?Val?Val?Asn?Arg?Tyr?Lys

405 410 415Asn?Leu?Pro?Lys?Ile?Ile?Gln?Lys?Val?Leu?Ser?Thr?Asn?Tyr?Lys?Val

420 425 430Asp?Lys?Gln?Ile?Thr?Thr?Lys?Ser?Phe?Ile?Val?Tyr?Gln?Lys?Lys

435 440 445＜210〉35＜211〉618＜212〉DNA＜213〉＜400〉35atgattaaag ctcagctaaa gaatctaata aaaacaattc atctcgtaaa agaggctggt 60ttctccctaa atggttcatt gtacatggag ttattgcatg attttacgca tgatgagtta 120gtacataacc ctataatcga aagtacggtt gatacaattc agtcagttga atttgaaagg 180gtttcttttt catataatgg taaggataat gtaataaacg atataagttt ttcaattaaa 240gcaggagaga ggttagcaat tgttggtgga aatggttctg gaaaaagtac gattttcaaa 300ttagcctgcg gtctttacga taattatgaa ggcaatatat atataaatgg tattaatctt 360tgttcaatac agaaaaagtc atactacaag agaatatccg cattgttcca agatttttta 420aagtatgaat tgacactgcg tgaaaatgtt ggattgggtg aattatcaaa gttatatagt 480gatgagtctt ataatacttc attttttacc acatcatggg attcagagaa tgaactgcga 540ttggaggata tttatataag atatagtgat ggtaagtttc attttacaac tatcgatgaa 600tcgattaaac gggattaa 618＜210〉36＜211〉205＜212〉PRT＜213〉＜400〉36Met Ile Lys Ala Gln Leu Lys Asn Leu Ile Lys Thr Ile His Leu Val 1 5 10 15Lys Glu Ala Gly Phe Ser Leu Asn Gly Ser Leu Tyr Met Glu Leu Leu

20 25 30His?Asp?Phe?Thr?His?Asp?Glu?Leu?Val?His?Asn?Pro?Ile?Ile?Glu?Ser

35 40 45Thr?Val?Asp?Thr?Ile?Gln?Ser?Val?Glu?Phe?Glu?Arg?Val?Ser?Phe?Ser

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

85 90 95Thr?Ile?Phe?Lys?Leu?Ala?Cys?Gly?Leu?Tyr?Asp?Asn?Tyr?Glu?Gly?Asn

100 105 110Ile?Tyr?Ile?Asn?Gly?Ile?Asn?Leu?Cys?Ser?Ile?Gln?Lys?Lys?Ser?Tyr

115 120 125Tyr?Lys?Arg?Ile?Ser?Ala?Leu?Phe?Gln?Asp?Phe?Leu?Lys?Tyr?Glu?Leu

130 135 140Thr?Leu?Arg?Glu?Asn?Val?Gly?Leu?Gly?Glu?Leu?Ser?Lys?Leu?Tyr?Ser145 150 155 160Asp?Glu?Ser?Tyr?Asn?Thr?Ser?Phe?Phe?Thr?Thr?Ser?Trp?Asp?Ser?Glu

165 170 175Asn?Glu?Leu?Arg?Leu?Glu?Asp?Ile?Tyr?Ile?Arg?Tyr?Ser?Asp?Gly?Lys

180 185 190Phe?His?Phe?Thr?Thr?Ile?Asp?Glu?Ser?Ile?Lys?Arg?Asp

195 200 205＜210〉37＜211〉1434＜212〉DNA＜213〉＜400〉37atgctaagaa aaaagagaat tttgggttta tttcgacttg ttgaattaat tttcctagga 60ttattgttga gtttagttgt ttcgtacctt gcgtggacca atagttttgc aacacttcat 120aatatattag caactgtcgg aatagtggaa cgaagcaaag atcaacagcc tcgctatcac 180attggacaag ctattcaagt acaaaaaagt ggtccatatc atcaatggat tggaactatt 240aataaacagg tagaagatat agccgaaaat taccgagtga gttatcatta tgaagtggta 300tttccaatag gaaaagtcac tgtttctttg ccagaacata acctgaaaga gcctgataaa 360ccgaggttta aaaaaggaga tatcgttaaa ttatcttcat taactaaaaa gccacatata 420aaagtatatc aaggtcaatt agcgactatt aaacaagtta aaaaatgcta tgactattcg 480ttaggaggat atcagtacga tattaatctg aaagataatc taagattaga tggaatttca 540gagcaagatt ttgttaaacc ttattatatt aggttcaata aaggaaattc ccctgagcaa 600aacaatcgtc ttttgcgaaa agctttcgct tatgcaaagc agcatccaaa tagcgttata 660tcttttccaa aggggcaatt tcacattggc tctttgcctt cacaaaaaga ttattttgag 720cttccatctg atacagctat tattggtcat cagacagagt tcattattca cggtaaaatg 780ttgtggtttg gattccctac aggaccaaag gctgaacaag gtgttcgtaa tctcgtgttg 840actggagtgc atttcaaagc aaatgatttg aaaaaaggag accactttat gattatggct 900gatcatggta ctgattggca tatttacgat aacaaattta ctatggttca taagcgtaat 960agtcatattt ttgatttagg atctctacaa aattcattgt ttgagaaaaa ccaatttatt 1020ggctatgcgc cagaattagt acaagaccaa cagctgctat caaaggctca agggcatgat 1080tttttttcag aagtcattca gtttgatgct gctgttcatc attttgcatg ggatggaggt 1140ctacttagta atattgctcc aaactatgaa gcatttaacc aaactcgaca tctatgtcac 1200aatattactg taagccaaaa tcaattttta ccttatatag atccgactgg ttgcctgaga 1260gcctatagtg gttctattgg tcagcattcc tcaaaagtag gagttattag ggttttaaat 1320aatgttttta cctcatccat tgttactaaa gcgaagctca ctagttggtt tatggaacct 1380attcattttc caccaaattc accggttatt gtcgcaggta atatcattaa ttga 1434＜210〉38＜211〉477＜212〉PRT＜213〉＜400〉38Met Leu Arg Lys Lys Arg Ile Leu Gly Leu Phe Arg Leu Val Glu Leu 1 5 10 15Ile Phe Leu Gly Leu Leu Leu Ser Leu Val Val Ser Tyr Leu Ala Trp

20 25 30Thr?Asn?Ser?Phe?Ala?Thr?Leu?His?Asn?Ile?Leu?Ala?Thr?Val?Gly?Ile

35 40 45Val?Glu?Arg?Ser?Lys?Asp?Gln?Gln?Pro?Arg?Tyr?His?Ile?Gly?Gln?Ala

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

85 90 95Tyr?Glu?Val?Val?Phe?Pro?Ile?Gly?Lys?Val?Thr?Val?Ser?Leu?Pro?Glu

100 105 110His?Asn?Leu?Lys?Glu?Pro?Asp?Lys?Pro?Arg?Phe?Lys?Lys?Gly?Asp?Ile

115 120 125Val?Lys?Leu?Ser?Ser?Leu?Thr?Lys?Lys?Pro?His?Ile?Lys?Val?Tyr?Gln

130 135 140Gly?Gln?Leu?Ala?Thr?Ile?Lys?Gln?Val?Lys?Lys?Cys?Tyr?Asp?Tyr?Ser145 150 155 160Leu?Gly?Gly?Tyr?Gln?Tyr?Asp?Ile?Asn?Leu?Lys?Asp?Asn?Leu?Arg?Leu

165 170 175Asp?Gly?Ile?Ser?Glu?Gln?Asp?Phe?Val?Lys?Pro?Tyr?Tyr?Ile?Arg?Phe

180 185 190Asn?Lys?Gly?Asn?Ser?Pro?Glu?Gln?Asn?Asn?Arg?Leu?Leu?Arg?Lys?Ala

195 200 205Phe?Ala?Tyr?Ala?Lys?Gln?His?Pro?Asn?Ser?Val?Ile?Ser?Phe?Pro?Lys

210 215 220Gly?Gln?Phe?His?Ile?Gly?Ser?Leu?Pro?Ser?Gln?Lys?Asp?Tyr?Phe?Glu225 230 235 240Leu?Pro?Ser?Asp?Thr?Ala?Ile?Ile?Gly?His?Gln?Thr?Glu?Phe?Ile?Ile

245 250 255His?Gly?Lys?Met?Leu?Trp?Phe?Gly?Phe?Pro?Thr?Gly?Pro?Lys?Ala?Glu

260 265 270Gln?Gly?Val?Arg?Asn?Leu?Val?Leu?Thr?Gly?Val?His?Phe?Lys?Ala?Asn

275 280 285Asp?Leu?Lys?Lys?Gly?Asp?His?Phe?Met?Ile?Met?Ala?Asp?His?Gly?Thr

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

325 330 335Asn?Gln?Phe?Ile?Gly?Tyr?Ala?Pro?Glu?Leu?Val?Gln?Asp?Gln?Gln?Leu

340 345 350Leu?Ser?Lys?Ala?Gln?Gly?His?Asp?Phe?Phe?Ser?Glu?Val?Ile?Gln?Phe

355 360 365Asp?Ala?Ala?Val?His?His?Phe?Ala?Trp?Asp?Gly?Gly?Leu?Leu?Ser?Asn

370 375 380Ile?Ala?Pro?Asn?Tyr?Glu?Ala?Phe?Asn?Gln?Thr?Arg?His?Leu?Cys?His385 390 395 400Asn?Ile?Thr?Val?Ser?Gln?Asn?Gln?Phe?Leu?Pro?Tyr?Ile?Asp?Pro?Thr

405 410 415Gly?Cys?Leu?Arg?Ala?Tyr?Ser?Gly?Ser?Ile?Gly?Gln?His?Ser?Ser?Lys

420 425 430Val?Gly?Val?Ile?Arg?Val?Leu?Asn?Asn?Val?Phe?Thr?Ser?Ser?Ile?Val

435 440 445Thr?Lys?Ala?Lys?Leu?Thr?Ser?Trp?Phe?Met?Glu?Pro?Ile?His?Phe?Pro

450 455 460Pro Asn Ser Pro Val Ile Val Ala Gly Asn Ile Ile Asn465 470 475＜210〉39＜211〉1020＜212〉DNA＜213〉＜400〉39atgtcaactc acttaagaaa acttccaggg ctgttacttt gcttattgtt agctcttcca 60gcctggtgtt tagggcgctt atttcccatt attggagcac ctgtttttgc tattctttta 120ggaatgttgt tagccttgtt ttatgaacat cgtgacaaga ctaaagaggg aattagtttt 180acatccaagt atattttaca aacagcagtg gttttgcttg gttttggatt aaacctaacc 240caagttatgg cagtgggcat gcagtcttta ccgattatca tttcaactat tgcgacagct 300cttttggtag cttatggctt acagaaatgg ctgcgcttag atgtcaatac agccaccttg 360gtaggtgtag gatcttccat ttgtgggggg tctgctgttg cagcgacagc tcctgtcatt 420aaggcaaagg atgacgaggt tgctaaggca atttcagtca tttttctctt taatatgtta 480gcagctttgc tatttccaag tttaggacaa ttactaggct tatctaatga aggttttgct 540atttttgccg ggacagctgt taacgacact tcttccgtga ctgcaacggc cacggcctgg 600gatgcccttc accattccaa tacactagat ggagcaacca ttgttaaatt gactcgcacc 660ttggctattc tcccaattac tttaggttta tccctttacc gagcgaaaaa agagcacgac 720atcgttacag aagaaaactt tagccttagg aagtcattcc ctcgtttcat cctcttcttt 780ttattagctt ctctcatcac aacattgatg accagtttgg gagtttctgc cgatagtttc 840cattacctaa aaaccttatc aaaattcttt atcgtgatgg ctatggcagc gattggttta 900aacacaaacc tggttaaact gattaagacg ggcggtcagg ctatcctttt aggagctatt 960tgctgggtag ctatcaccct tgtcagttta gccatgcaat taagtttggg catttggtaa 1020＜210〉40＜211〉339＜212〉PRT＜213〉＜400〉40Met Ser Thr His Leu Arg Lys Leu Pro Gly Leu Leu Leu Cys Leu Leu 1 5 10 15Leu Ala Leu Pro Ala Trp Cys Leu Gly Arg Leu Phe Pro Ile Ile Gly

20 25 30Ala?Pro?Val?Phe?Ala?Ile?Leu?Leu?Gly?Met?Leu?Leu?Ala?Leu?Phe?Tyr

35 40 45Glu?His?Arg?Asp?Lys?Thr?Lys?Glu?Gly?Ile?Ser?Phe?Thr?Ser?Lys?Tyr

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

85 90 95Ile?Ala?Thr?Ala?Leu?Leu?Val?Ala?Tyr?Gly?Leu?Gln?Lys?Trp?Leu?Arg

100 105 110Leu?Asp?Val?Asn?Thr?Ala?Thr?Leu?Val?Gly?Val?Gly?Ser?Ser?Ile?Cys

115 120 125Gly?Gly?Ser?Ala?Val?Ala?Ala?Thr?Ala?Pro?Val?Ile?Lys?Ala?Lys?Asp

130 135 140Asp?Glu?Val?Ala?Lys?Ala?Ile?Ser?Val?Ile?Phe?Leu?Phe?Asn?Met?Leu145 150 155 160Ala?Ala?Leu?Leu?Phe?Pro?Ser?Leu?Gly?Gln?Leu?Leu?Gly?Leu?Ser?Asn

165 170 175Glu?Gly?Phe?Ala?Ile?Phe?Ala?Gly?Thr?Ala?Val?Asn?Asp?Thr?Ser?Ser

180 185 190Val?Thr?Ala?Thr?Ala?Thr?Ala?Trp?Asp?Ala?Leu?His?His?Ser?Asn?Thr

195 200 205Leu?Asp?Gly?Ala?Thr?Ile?Val?Lys?Leu?Thr?Arg?Thr?Leu?Ala?Ile?Leu

210 215 220Pro?Ile?Thr?Leu?Gly?Leu?Ser?Leu?Tyr?Arg?Ala?Lys?Lys?Glu?His?Asp225 230 235 240Ile?Val?Thr?Glu?Glu?Asn?Phe?Ser?Leu?Arg?Lys?Ser?Phe?Pro?Arg?Phe

245 250 255Ile?Leu?Phe?Phe?Leu?Leu?Ala?Ser?Leu?Ile?Thr?Thr?Leu?Met?Thr?Ser

260 265 270Leu?Gly?Val?Ser?Ala?Asp?Ser?Phe?His?Tyr?Leu?Lys?Thr?Leu?Ser?Lys

275 280 285Phe?Phe?Ile?Val?Met?Ala?Met?Ala?Ala?Ile?Gly?Leu?Asn?Thr?Asn?Leu

290 295 300Val?Lys?Leu?Ile?Lys?Thr?Gly?Gly?Gln?Ala?Ile?Leu?Leu?Gly?Ala?Ile305 310 315 320Cys?Trp?Val?Ala?Ile?Thr?Leu?Val?Ser?Leu?Ala?Met?Gln?Leu?Ser?Leu

325 330 335Gly Ile Trp＜210〉41＜211〉2637＜212〉DNA＜213〉＜400〉41atgataaaga aaaccttatg gaaggatatt ttgagagcta tcaagaatag taaagggcga 60ttcatttcct tatttttcct aatggcctta ggctcctttg ctttagttgg acttaaagtc 120accggtccag atatggaacg aacagccagc cgttacctcg aaagacacca ggtgatggac 180ctaacggtac tggcttctca tcaattttcc caagccgata aacaagagtt agatacgtta 240aaaggggctc atttagaata tggtcattta cttgatgtca gtctaactag caaccagaaa 300tctcttaggc tctatagcgt gccaaagaaa gtgtctaagc cagtcttggt taaagggagt 360tggccaaagc gagagacaga tttggtttta tcctcctcac ttgctaaaaa ctatcagatt 420ggagatgaac tagcagtcac ctcacctatg gaaggtttgc tgacgacaac ccattttcaa 480gtggttggtt ttgcgaattc ttcagaagtt tggtccaagt ccaatttagg aagttcctca 540accggagatg gaagtctcta cgcttatgct tttgttaatc caaacgtttt taaaagtgcc 600tttaacctgc tgcgcatccg ttttagtcat cttcgtctga caaacgcttt ttccaaagac 660tatcaaaaaa gggtaaccca aaaccaagct catttggata atctacttaa agataatggc 720cagaagcgtt atgatgacct ccaaaatcag tatgaccttg ccttaaaaaa tggcagagca 780gcacttgcaa aggaaacagt gaaactagct gcgagtgagg agaacttaac ttttttagaa 840ggctctgctt tacaagaagc taagcatcag attgaacaag gcaaacaagc attagccaag 900gaggaaaagc agttagagca ggtgcaggct acaaaagata agctagaaaa acccagttac 960ctgacttata atcgctcgac cctaccagga ggagaaggat atcatactta tgcaacttca 1020acgacctcca tttcaaatgt tggaaatatt tttcctgttg ttctttatct cgtagctgct 1080ctagtagcct ttaccaccat gacacgttat gttgatgaag aaagaacaag ctctggtcta 1140ttaaaagcca ttggttattc taacaaggat atcagtttaa agtttcttat ctatgggctt 1200ttagccagtt ttttagggac aactttaggt attattgggg gaacttacct cttatctacc 1260ttgatttcag agatcttaac aggagctttg actattggaa agactcacct ttatagttat 1320tggttttata atggcatagc ttacttgctg gctatgttat ctgctgtttt accagcctac 1380ttaattgtca aaaaggaatt attcctcaat gcagctcagt tattgctgcc caaacctcct 1440agtaaggggg caaaaatctg gttggaacac cttacttttg tctggaaagc cctgtccttt 1500actcacaagg tgaccatacg taatattttt cgctataaac aaagaatgct gatgaccatt 1560gtaggcgttg caggctcagt agccctttta tttgcaggct tagggattca gtcgtcatta 1620gccaaagtag ttgagcatca atttggtgat ttaacgactt atgatatttt ggctgtcggt 1680tcggccaaag cgacagcgac agagcaaact gacttagcta gctatcttaa acaagaacct 1740attacagggt accaaaaggt atcttatgcc agcttaaccc ttcctgtaaa gggattacct 1800gataagcaaa gtatttccat tttatcaagt tcagctactt ctcttagtcc ctattttaat 1860ctgctggata gtcaggagca aaagaaggtt cccattccaa cctctggtgt tttgatttct 1920gagaaattag cctcctatta caaggtaaaa ccaggtgatc agttggtatt gactgatcgg 1980aaaggacagt cttataaagt gacgattaaa caggttattg acatgacagt tggccattac 2040ctgataatgt ctgataccta ttttaagaat cattttaaag gattggaggc tgctcctgcc 2100tatctgatta aggtaaaaga caaagatagc aagcacataa aggagacagc cagtgacttg 2160ttaaccttaa aagcgattag agcagtttca caaaacgtca atcatattaa atctgttcag 2220ctagtagtca cctctcttaa tcaggtcatg accctccttg tcttcttgtc tattttatta 2280gcaatcgtta tcctttataa cttaacgact attaatattg ctgagcgtat tcgagaatta 2340tccactatta aagttctggg attttacgat caggaggtca ccttatatat ttatcgagaa 2400actatttcgc tatccctagt aggcattctt ttaggtatct atttaggaaa aggcctgcat 2460acttatatca tgacaatgat ttcaactggg gatattcaat ttggtgtaaa ggttgatgct 2520tatgtttatc tagtgccaat tctagtaatc cttagcttgt tagcggtatt aggtatctgg 2580gttaatcgcc atttaaaaaa ggttgatatg ttagaagctt tgaaatccat agattga 2637＜210〉42＜211〉878＜212〉PRT＜213〉＜400〉42Met Ile Lys Lys Thr Leu Trp Lys Asp Ile Leu Arg Ala Ile Lys Asn 1 5 10 15Ser Lys Gly Arg Phe Ile Ser Leu Phe Phe Leu Met Ala Leu Gly Ser

20 25 30Phe?Ala?Leu?Val?Gly?Leu?Lys?Val?Thr?Gly?Pro?Asp?Met?Glu?Arg?Thr

35 40 45Ala?Ser?Arg?Tyr?Leu?Glu?Arg?His?Gln?Val?Met?Asp?Leu?Thr?Val?Leu

50 55 60Ala?Ser?His?Gln?Phe?Ser?Gln?Ala?Asp?Lys?Gln?Glu?Leu?Asp?Thr?Leu?65 70 75 80Lys?Gly?Ala?His?Leu?Glu?Tyr?Gly?His?Leu?Leu?Asp?Val?Ser?Leu?Thr

85 90 95Ser?Asn?Gln?Lys?Ser?Leu?Arg?Leu?Tyr?Ser?Val?Pro?Lys?Lys?Val?Ser

100 105 110Lys?Pro?Val?Leu?Val?Lys?Gly?Ser?Trp?Pro?Lys?Arg?Glu?Thr?Asp?Leu

115 120 125Val?Leu?Ser?Ser?Ser?Leu?Ala?Lys?Asn?Tyr?Gln?Ile?Gly?Asp?Glu?Leu

130 135 140Ala?Val?Thr?Ser?Pro?Met?Glu?Gly?Leu?Leu?Thr?Thr?Thr?His?Phe?Gln145 150 155 160Val?Val?Gly?Phe?Ala?Asn?Ser?Ser?Glu?Val?Trp?Ser?Lys?Ser?Asn?Leu

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

180 185 190Asn?Pro?Asn?Val?Phe?Lys?Ser?Ala?Phe?Asn?Leu?Leu?Arg?Ile?Arg?Phe

195 200 205Ser?His?Leu?Arg?Leu?Thr?Asn?Ala?Phe?Ser?Lys?Asp?Tyr?Gln?Lys?Arg

210 215 220Val?Thr?Gln?Asn?Gln?Ala?His?Leu?Asp?Asn?Leu?Leu?Lys?Asp?Asn?Gly225 230 235 240Gln?Lys?Arg?Tyr?Asp?Asp?Leu?Gln?Asn?Gln?Tyr?Asp?Leu?Ala?Leu?Lys

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

260 265 270Glu?Glu?Asn?Leu?Thr?Phe?Leu?Glu?Gly?Ser?Ala?Leu?Gln?Glu?Ala?Lys

275 280 285His?Gln?Ile?Glu?Gln?Gly?Lys?Gln?Ala?Leu?Ala?Lys?Glu?Glu?Lys?Gln

290 295 300Leu?Glu?Gln?Val?Gln?Ala?Thr?Lys?Asp?Lys?Leu?Glu?Lys?Pro?Ser?Tyr305 310 315 320Leu?Thr?Tyr?Asn?Arg?Ser?Thr?Leu?Pro?Gly?Gly?Glu?Gly?Tyr?His?Thr

325 330 335Tyr?Ala?Thr?Ser?Thr?Thr?Ser?Ile?Ser?Asn?Val?Gly?Asn?Ile?Phe?Pro

340 345 350Val?Val?Leu?Tyr?Leu?Val?Ala?Ala?Leu?Val?Ala?Phe?Thr?Thr?Met?Thr

355 360 365Arg?Tyr?Val?Asp?Glu?Glu?Arg?Thr?Ser?Ser?Gly?Leu?Leu?Lys?Ala?Ile

370 375 380Gly?Tyr?Ser?Asn?Lys?Asp?Ile?Ser?Leu?Lys?Phe?Leu?Ile?Tyr?Gly?Leu385 390 395 400Leu?Ala?Ser?Phe?Leu?Gly?Thr?Thr?Leu?Gly?Ile?Ile?Gly?Gly?Thr?Tyr

405 410 415Leu?Leu?Ser?Thr?Leu?Ile?Ser?Glu?Ile?Leu?Thr?Gly?Ala?Leu?Thr?Ile

420 425 430Gly?Lys?Thr?His?Leu?Tyr?Ser?Tyr?Trp?Phe?Tyr?Asn?Gly?Ile?Ala?Tyr

435 440 445Leu?Leu?Ala?Met?Leu?Ser?Ala?Val?Leu?Pro?Ala?Tyr?Leu?Ile?Val?Lys

450 455 460Lys?Glu?Leu?Phe?Leu?Asn?Ala?Ala?Gln?Leu?Leu?Leu?Pro?Lys?Pro?Pro465 470 475 480Ser?Lys?Gly?Ala?Lys?Ile?Trp?Leu?Glu?His?Leu?Thr?Phe?Val?Trp?Lys

485 490 495Ala?Leu?Ser?Phe?Thr?His?Lys?Val?Thr?Ile?Arg?Asn?Ile?Phe?Arg?Tyr

500 505 510Lys?Gln?Arg?Met?Leu?Met?Thr?Ile?Val?Gly?Val?Ala?Gly?Ser?Val?Ala

515 520 525Leu?Leu?Phe?Ala?Gly?Leu?Gly?Ile?Gln?Ser?Ser?Leu?Ala?Lys?Val?Val

530 535 540Glu?His?Gln?Phe?Gly?Asp?Leu?Thr?Thr?Tyr?Asp?Ile?Leu?Ala?Val?Gly545 550 555 560Ser?Ala?Lys?Ala?Thr?Ala?Thr?Glu?Gln?Thr?Asp?Leu?Ala?Ser?Tyr?Leu

565 570 575Lys?Gln?Glu?Pro?Ile?Thr?Gly?Tyr?Gln?Lys?Val?Ser?Tyr?Ala?Ser?Leu

580 585 590Thr?Leu?Pro?Val?Lys?Gly?Leu?Pro?Asp?Lys?Gln?Ser?Ile?Ser?Ile?Leu

595 600 605Ser?Ser?Ser?Ala?Thr?Ser?Leu?Ser?Pro?Tyr?Phe?Asn?Leu?Leu?Asp?Ser

610 615 620Gln?Glu?Gln?Lys?Lys?Val?Pro?Ile?Pro?Thr?Ser?Gly?Val?Leu?Ile?Ser625 630 635 640Glu?Lys?Leu?Ala?Ser?Tyr?Tyr?Lys?Val?Lys?Pro?Gly?Asp?Gln?Leu?Val

645 650 655Leu?Thr?Asp?Arg?Lys?Gly?Gln?Ser?Tyr?Lys?Val?Thr?Ile?Lys?Gln?Val

660 665 670Ile?Asp?Met?Thr?Val?Gly?His?Tyr?Leu?Ile?Met?Ser?Asp?Thr?Tyr?Phe

675 680 685Lys?Asn?His?Phe?Lys?Gly?Leu?Glu?Ala?Ala?Pro?Ala?Tyr?Leu?Ile?Lys

690 695 700Val?Lys?Asp?Lys?Asp?Ser?Lys?His?Ile?Lys?Glu?Thr?Ala?Ser?Asp?Leu705 710 715 720Leu?Thr?Leu?Lys?Ala?Ile?Arg?Ala?Val?Ser?Gln?Asn?Val?Asn?His?Ile

725 730 735Lys?Ser?Val?Gln?Leu?Val?Val?Thr?Ser?Leu?Asn?Gln?Val?Met?Thr?Leu

740 745 750Leu?Val?Phe?Leu?Ser?Ile?Leu?Leu?Ala?Ile?Val?Ile?Leu?Tyr?Asn?Leu

755 760 765Thr?Thr?Ile?Asn?Ile?Ala?Glu?Arg?Ile?Arg?Glu?Leu?Ser?Thr?Ile?Lys

770 775 780Val?Leu?Gly?Phe?Tyr?Asp?Gln?Glu?Val?Thr?Leu?Tyr?Ile?Tyr?Arg?Glu785 790 795 800Thr?Ile?Ser?Leu?Ser?Leu?Val?Gly?Ile?Leu?Leu?Gly?Ile?Tyr?Leu?Gly

805 810 815Lys?Gly?Leu?His?Thr?Tyr?Ile?Met?Thr?Met?Ile?Ser?Thr?Gly?Asp?Ile

820 825 830Gln?Phe?Gly?Val?Lys?Val?Asp?Ala?Tyr?Val?Tyr?Leu?Val?Pro?Ile?Leu

835 840 845Val?Ile?Leu?Ser?Leu?Leu?Ala?Val?Leu?Gly?Ile?Trp?Val?Asn?Arg?His

850 855 860Leu Lys Lys Val Asp Met Leu Glu Ala Leu Lys Ser Ile Asp865 870 875＜210〉43＜211〉1344＜212〉DNA＜213〉＜400〉43atgatgttaa cgaaggggca acttccctat agtgctgctt ttacaacagg agggctcttt 60tactttgtta tcattgcatt aagttattat ttgggatcga cactttggct agtctttgtt 120caggtgtttt gtttttactt atctggttta tatctttata aactcattaa ttatatgaca 180ggctttcaaa aagtggcttt aactttttca attagctact atttattatc tgttagtctt 240ggttttgggg gattgtatcc tactcaactg gctatgccat ttatattaat atcggcttgg 300tttttaacta agtattttgc ctgtttagtg aaagatgagg catttattct ttttggcttt 360gtaggtgctc ttgcaatgct aattgacccg agtaccctta tcttttggtc ttttgcttgt 420gtgacagttt tttcttataa tataagccaa aagcatcttg caagaggttt ttatcaactg 480ctagcttcga tttttggaat gattttagtt ttttacacag caggatattt cattttgaac 540ttacaagtgc taaatcctta tttatcacaa acgatgattt atccttttac tttttttaaa 600tcaggaaact tatcgttgct ttttggactg gctattcagt tgttcttcgc tttggggctt 660ggtcttttga cgggaatgga gaatgtcatt aggcgattta aaaacaattc tgatagggtc 720gtcaagtggc tatttgtcat ggtcattcta gaatctatac ttgtggctat attttcacaa 780gactatcgcc cctatcatct tttacctctt ttaccttttg gattaatttt gactgctatt 840cctgttggct atcagtatgg tataggatta ggtcagagta gtcatcgcag acgtcatggt 900aaaaatggtg ttggtcgagt aatgatgatt tatcttaaga gacactttta tttgccaatt 960ttaattgtag ggacaatact aatctgttct acttattgtt tcattagtag tattcctctt 1020aatcaggagc gtgatcatat tgctagttat ttagaacaga aactaaataa aactcaatct 1080atttatgttt gggatgatac ttctaaaatt tatttggaca gtaaagctaa atctgtttct 1140caatttagtt ctcctgacat caatacgcaa aaagagagtc atcgaaaaat attagaagat 1200gaactattag aaaataaggc tgcttatatc gttgttaatc gctataaaaa cctgcctaaa 1260atcattcaaa aagtattatc tactaattac aaagtagata aacagataac gacaaaaagt 1320tttattgttt atcagaaaaa gtaa 1344＜210〉44＜211〉447＜212〉PRT＜213〉＜400〉44Met Met Leu Thr Lys Gly Gln Leu Pro Tyr Ser Ala Ala Phe Thr Thr l 5 10 15Gly Gly Leu Phe Tyr Phe Val Ile Ile Ala Leu Ser Tyr Tyr Leu Gly

20 25 30Ser?Thr?Leu?Trp?Leu?Val?Phe?Val?Gln?Val?Phe?Cys?Phe?Tyr?Leu?Ser

35 40 45Gly?Leu?Tyr?Leu?Tyr?Lys?Leu?Ile?Asn?Tyr?Met?Thr?Gly?Phe?Gln?Lys

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

100 105 110Glu?Ala?Phe?Ile?Leu?Phe?Gly?Phe?Val?Gly?Ala?Leu?Ala?Met?Leu?Ile

115 120 125Asp?Pro?Ser?Thr?Leu?Ile?Phe?Trp?Ser?Phe?Ala?Cys?Val?Thr?Val?Phe

165 170 175Phe?Ile?Leu?Asn?Leu?Gln?Val?Leu?Asn?Pro?Tyr?Leu?Ser?Gln?Thr?Met

180 185 190Ile?Tyr?Pro?Phe?Thr?Phe?Phe?Lys?Ser?Gly?Asn?Leu?Ser?Leu?Leu?Phe

195 200 205Gly?Leu?Ala?Ile?Gln?Leu?Phe?Phe?Ala?Leu?Gly?Leu?Gly?Leu?Leu?Thr

245 250 255Ile?Phe?Ser?Gln?Asp?Tyr?Arg?Pro?Tyr?His?Leu?Leu?Pro?Leu?Leu?Pro

260 265 270Phe?Gly?Leu?Ile?Leu?Thr?Ala?Ile?Pro?Val?Gly?Tyr?Gln?Tyr?Gly?Ile

275 280 285Gly?Leu?Gly?Gln?Ser?Ser?His?Arg?Arg?Arg?His?Gly?Lys?Asn?Gly?Val

325 330 335Ser?Ile?Pro?Leu?Asn?Gln?Glu?Arg?Asp?His?Ile?Ala?Ser?Tyr?Leu?Glu

340 345 350Gln?Lys?Leu?Asn?Lys?Thr?Gln?Ser?Ile?Tyr?Val?Trp?Asp?Asp?Thr?Ser

355 360 365Lys?Ile?Tyr?Leu?Asp?Ser?Lys?Ala?Lys?Ser?Val?Ser?Gln?Phe?Ser?Ser

405 410 415Asn?Leu?Pro?Lys?Ile?Ile?Gln?Lys?Val?Leu?Ser?Thr?Asn?Tyr?Lys?Val

420 425 430Asp?Lys?Gln?Ile?Thr?Thr?Lys?Ser?Phe?Ile?Val?Tyr?Gln?Lys?Lys

435 440 445＜210〉45＜211〉324＜212〉DNA＜213〉＜400〉45atgcagtttt tacaaaaatg gtttaaacac tctaaaaaag agaagttgaa agaatcctcg 60tcccttagta cagaaataga accttctgaa aactgggcaa agattcccgc ttatattcct 120gcagacaaaa gtgattacaa aaaggttact ttaattacca gtgttattgc tgctgggcga 180tagacctaat agtcaattca aggttaaacg cattctcaag cgcaatcctg aggcaatcac 240tgtttcttta attgcttcaa gtatcgctgc aggtgtttac ccagaaagtc agtttcgggt 300gacatccatc tattgcaaaa gtaa 324＜210〉46＜211〉107＜212〉PRT＜213〉＜400〉46Met Gln Phe Leu Gln Lys Trp Phe Lys His Ser Lys Lys Glu Lys Leu 1 5 10 15Lys Glu Ser Ser Pro Leu Ser Thr Glu Ile Glu Pro Ser Glu Asn Trp

20 25 30Glu?Lys?Ile?Pro?Ala?Tyr?Ile?Pro?Ala?Asp?Lys?Ser?Asp?Tyr?Lys?Lys

35 40 45Val?Thr?Leu?Ile?Thr?Ser?Ala?Ile?Ala?Ala?Gly?Asp?Arg?Pro?Asn?Ser

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

85 90 95Gln?Phe?Arg?Val?Thr?Ser?Ile?Tyr?Cys?Lys?Arg

100 105＜210〉47＜211〉288＜212〉DNA＜213〉streptococcus pyogenes＜400〉47atgacaaaac gtaattcaaa agcctatata ttatggcaaa aaattatcaa aattttagga 60attattgcac taattggtac ttttttcctc gctttttggc tgtatagact aggtatatta 120aacgatagta atgctcttaa agacttagtg cagcgctata gattatgggg gccgtttgtt 180tttattgtcg tgcagatcat acagattgtt tttcctgtga ttcctggagg ccttacgaca 240gttgcaggtt ttttaatctt tggcccctgt aacaggtttt atttataa, 288＜210〉48＜211〉95＜212〉PRT＜213〉streptococcus pyogenes＜400〉48Met Thr Lys Arg Asn Ser Lys Ala Tyr Ile Leu Trp Gln Lys Ile Ile, 15 10 15Lys Ile Leu Gly Ile Ile Ala Leu Ile Gly Thr Phe Phe Leu Ala Phe

20 25 30Trp?Leu?Tyr?Arg?Leu?Gly?Ile?Leu?Asn?Asp?Ser?Asn?Ala?Leu?Lys?Asp

35 40 45Leu?Val?Gln?Arg?Tyr?Arg?Leu?Trp?Gly?Pro?Phe?Val?Phe?Ile?Val?Val

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

85 90 95＜210〉49＜211〉1311＜212〉DNA＜213〉＜400〉49atgaataaat taaaaaaaga gattttatca gataactata accacttttt tcattttttt 60gcggttttta caggtatttt tgtcattatg actattatta tcttacagat tatgcggttt 120ggcgtttatt cgtcagttga cagtagttta gtttctgtta gtaataatgc aagtagctat 180gctaatcgta cgatggctag aatatcttct ttttactttg atactgaaaa taacattatt 240aaggcgctgc ctgattcaga tagttctaag ttattaggaa cgcctgcagc taatacagat 300atcattttgt ttagtgctaa tggaacaatt ttaaatgctt ttgatgcgtt ttctaactat 360caaaattttc atttagataa acgccggttg gggagtattg aaaccaccag tttaatgaat 420ttttatggac aagaagaaaa ataccatacg ataactgtag gggttcatat caaaaattat 480cctgcagttg cctatatgat ggcagtagta aatgtggaac aattagaccg cgctaatgaa 540cgttatgagc gcattattat tatagttatg agtgtttttt ggctaatttc tattttagca 600agtatttatt tagccaagtg gagcagaaaa cctattttag aaagctatga aaaacaaaaa 660atgtttgttg aaaatgctag tcatgaatta aggacccctt tggcggtctt acagaatcgt 720ctggaatcgc tttttcgtaa gcccaacgaa acgatattag aaaatagtga gcatctcgct 780tctagtttag acgaggttcg caacatgcgc atcttaacaa ctaatttatt aaatttagca 840agacgagatg atggcattaa tccacagtgg actcatttag atacagattt ttttaatgct 900atttttgaga attatgaact agttgctaaa gaatatggaa aaatatttta ttttcagaac 960caagtcaata gatcgttaag aatggataag gctttactaa aacaattaat aacgatttta 1020tttgacaatg ctattaaata tacagataaa aatggtatta ttgaaattat agtgaaaaca 1080acggacaaaa atttattaat ttctgttatt gataatggtc cagggataac agatgaagaa 1140aagaaaaaga tttttgatcg tttttatcga gttgacaaag ctagaacacg gcaaacaggt 1200ggatttggct tggggttggc tttagctcag caaatcgtga tgtctttaaa aggaaatatt 1260acagtaaagg ataatgatcc taaaggtagt atttttgaag tcaaactata a 1311＜210〉50＜211〉436＜212〉PRT＜213〉＜400〉50Met Asn Lys Leu Lys Lys Glu Ile Leu Ser Asp Asn Tyr Asn His Phe 1 5 10 15Phe His Phe Phe Ala Val Phe Thr Gly Ile Phe Val Ile Met Thr Ile

20 25 30Ile?Ile?Leu?Gln?Ile?Met?Arg?Phe?Gly?Val?Tyr?Ser?Ser?Val?Asp?Ser

35 40 45Ser?Leu?Val?Ser?Val?Ser?Asn?Asn?Ala?Ser?Ser?Tyr?Ala?Asn?Arg?Thr

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

85 90 95Ala?Asn?Thr?Asp?Ile?Ile?Leu?Phe?Ser?Ala?Asn?Gly?Thr?Ile?Leu?Asa

100 105 110Ala?Phe?Asp?Ala?Phe?Ser?Asn?Tyr?Gln?Asn?Phe?His?Leu?Asp?Lys?Arg

115 120 125Arg?Leu?Gly?Ser?Ile?Glu?Thr?Thr?Ser?Leu?Met?Asn?Phe?Tyr?Gly?Gln

130 135 140Glu?Glu?Lys?Tyr?His?Thr?Ile?Thr?Val?Gly?Val?His?Ile?Lys?Asn?Tyr145 150 155 160Pro?Ala?Val?Ala?Tyr?Met?Met?Ala?Val?Val?Asn?Val?Glu?Gln?Leu?Asp

165 170 175Arg?Ala?Asn?Glu?Arg?Tyr?Glu?Arg?Ile?Ile?Ile?Ile?Val?Met?Ser?Val

180 185 190Phe?Trp?Leu?Ile?Ser?Ile?Leu?Ala?Ser?Ile?Tyr?Leu?Ala?Lys?Trp?Ser

195 200 205Arg?Lys?Pro?Ile?Leu?Glu?Ser?Tyr?Glu?Lys?Gln?Lys?Met?Phe?ValGlu

210 215 220Asn?Ala?Ser?His?Glu?Leu?Arg?Thr?Pro?Leu?Ala?Val?Leu?Gln?Asn?Arg225 230 235 240Leu?Glu?Ser?Leu?Phe?Arg?Lys?Pro?Asn?Glu?Thr?Ile?Leu?Glu?Asn?Ser

245 250 255Glu?His?Leu?Ala?Ser?Ser?Leu?Asp?Glu?Val?Arg?Asn?Met?Arg?Ile?Leu

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

275 280 285Gln?Trp?Thr?His?Leu?Asp?Thr?Asp?Phe?Phe?Asn?Ala?Ile?Phe?Glu?Asn

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

325 330 335Ile?Thr?Ile?Leu?Phe?Asp?Asn?Ala?Ile?Lys?Tyr?Thr?Asp?Lys?Asn?Gly

340 345 350Ile?Ile?Glu?Ile?Ile?Val?Lys?Thr?Thr?Asp?Lys?Asn?Leu?Leu?Ile?Ser

355 360 365Val?Ile?Asp?Asn?Gly?Pro?Gly?Ile?Thr?Asp?Glu?Glu?Lys?Lys?Lys?Ile

370 375 380Phe?Asp?Arg?Phe?Tyr?Arg?Val?Asp?Lys?Ala?Arg?Thr?Arg?Gln?Thr?Gly385 390 395 400Gly?Phe?Gly?Leu?Gly?Leu?Ala?Leu?Ala?Gln?Gln?Ile?Val?Met?Ser?Leu

405 410 415Lys?Gly?Asn?Ile?Thr?Val?Lys?Asp?Asn?Asp?Pro?Lys?Gly?Ser?Ile?Phe

420 425 430Glu?Val?Lys?Leu

435＜210〉51＜211〉699＜212〉DNA＜213〉＜400〉51atgttttctg gacatcaact aaaaacagca cgattatcaa agggaataac tcaatcagaa 60ttgggaagat tgttgcatgt caataaaatg acaatatcta attgggaaaa aggtaagaat 120ataccaaatg aaaaacattt aaatgcctta ttgcatctat tcaatgtgac atctgattat 180ttcgacccaa actatagatt gctaacgcct tataaccagc tgacaatatc taataaagaa 240aaagtaattg gctattcaga gcgattgtta aatcatcaaa tagacaaaaa atctaaagat 300ctcatagata aaccatcaca attatatgct tatcgggtct atgaaagttt atctgctggt 360actggttact cctattttgg tgatggtaac tttgatgttg tcttttacga tgaacaatta 420gaatacgatt ttgcgtcttg ggtttttgga gattctatgg agccaactta tttaaatggt 480gaagttgttc ttataaaaca aaatagtttt gattacgatg gagcaattta tgcagtcgaa 540tgggatgggc aaacatatat caaaaaggta tttcgtgaag atgagggatt acgtctagtg 600tccttaaata aaaaatattc tgataagttt gctccctata gcgaagaacc tcgcattatt 660ggcaaaatta tcgctaattt taggccctta gaaatttaa 699＜210〉52＜211〉232＜212〉PRT＜213〉＜400〉52Met Phe Ser Gly His Gln Leu Lys Thr Ala Arg Leu Ser Lys Gly Ile 1 5 10 15Thr Gln Ser Glu Leu Gly Arg Leu Leu His Val Asn Lys Met Thr Ile

20 25 30Ser?Asn?Trp?Glu?Lys?Gly?Lys?Asn?Ile?Pro?Asn?Glu?Lys?His?Leu?Asn

35 40 45Ala?Leu?Leu?His?Leu?Phe?Asn?Val?Thr?Ser?Asp?Tyr?Phe?Asp?Pro?Asn

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

85 90 95Lys?Ser?Lys?Asp?Leu?Ile?Asp?Lys?Pro?Ser?Gln?Leu?Tyr?Ala?Tyr?Arg

100 105 110Val?Tyr?Glu?Ser?Leu?Ser?Ala?Gly?Thr?Gly?Tyr?Ser?Tyr?Phe?Gly?Asp

115 120 125Gly?Asn?Phe?Asp?Val?Val?Phe?Tyr?Asp?Glu?Gln?Leu?Glu?Tyr?Asp?Phe

130 135 140Ala?Ser?Trp?Val?Phe?Gly?Asp?Ser?Met?Glu?Pro?Thr?Tyr?Leu?Asn?Gly145 150 155 160Glu?Val?Val?Leu?Ile?Lys?Gln?Asn?Ser?Phe?Asp?Tyr?Asp?Gly?Ala?Ile

165 170 175Tyr?Ala?Val?Glu?Trp?Asp?Gly?Gln?Thr?Tyr?Ile?Lys?Lys?Val?Phe?Arg

180 185 190Glu?Asp?Glu?Gly?Leu?Arg?Leu?Val?Ser?Leu?Asn?Lys?Lys?Tyr?Ser?Asp

195 200 205Lys?Phe?Ala?Pro?Tyr?Ser?Glu?Glu?Pro?Arg?Ile?Ile?Gly?Lys?Ile?Ile

210 215 220Ala Asn Phe Arg Pro Leu Glu Ile225 230＜210〉53＜211〉1497＜212〉DNA＜213〉＜400〉53ttgaaaaggg ttcccgtaga aagagacaaa cgcttagtct ctttcttttt ctttcttctc 60atttctgtta taataagtca ggtaactaca ttagaaagat ttgtgggtct gtcatctaag 120agatgtcatt cccgaagagg tattagtgac ttgtctcaat caactgcaac ttatattaat 180gttattggag ctgggctagc tggttctgaa gctgcctatc agattgctaa gcgcggtatc 240cccgttaaat tgtatgaaat gcgtggtgtc aaagcaacac cgcaacataa aaccactaat 300tttgccgaat tggtctgttc caactcattt cgtggtgata gcttaaccaa tgcagtcggt 360cttctcaaag aagaaatgcg gcgattagac tccattatta tgcgtaatgg tgaagctaac 420cgcgtacctg ctgggggagc aatggctgtt gaccgtgagg ggtatgcaga gagtgtcact 480gcagagttgg aaaatcatcc tctcattgag gtcattcgtg gtgaaattac agaaatccct 540gacgatgcta tcacggttat cgcgacggga ccgctgactt cggatgccct ggcagaaaaa 600attcacgcgc taaatggtgg cgacggattc tatttttacg atgcagcagc gcctatcatt 660gataaatcta ccattgatat gagcaaggtt taccttaaat ctcgctacga taaaggcgaa 720gctgcttacc tcaactgccc tatgaccaaa gaagaattca tggctttcca tgaagctctg 780acaaccgcag aagaagcccc gctgaatgcc tttgaaaaag aaaagtattt tgaaggctgt 840atgccgattg aagttatggc taaacgtggc attaaaacca tgctttatgg acctatgaaa 900cccgttggat tggaatatcc agatgactat acaggtcctc gcgatggaga atttaaaacg 960ccatatgccg tcgtgcaatt gcgtcaagat aatgcagctg gaagccttta taatatcgtt 1020ggtttccaaa cccatctcaa atggggtgag caaaaacgcg ttttccaaat gattccaggg 1080cttgaaaatg ctgagtttgt ccgctacggc gtcatgcatc gcaattccta tatggattca 1140ccaaatcttt taaccgaaac cttccaatct cggagcaatc caaacctttt ctttgcaggt 1200cagatgactg gagttgaagg ttatgtcgaa tcagctgctt caggtttagt agcaggaatc 1260aatgctgctc gtttgttcaa aagagaagaa gcacttattt ttcctcagac aacagctatt 1320gggagtttgc ctcattatgt gactcatgcc gacagtaagc atttccaacc aatgaacgtc 1380aactttggca tcatcaaaga gttagaaggc ccacgcattc gtgacaaaaa agaacgttat 1440gaagctattg ctagtcgtgc tttggcagat ttagacacct gcttagcgtc gctttaa 1497＜210〉54＜211〉498＜212〉PRT＜213〉＜400〉54Leu Lys Arg Val Pro Val Glu Arg Asp Lys Arg Leu Val Ser Phe Phe 1 5 10 15Phe Phe Leu Leu Ile Ser Val Ile Ile Ser Gln Val Thr Thr Leu Glu

20 25 30Arg?Phe?Val?Gly?Leu?Ser?Ser?Lys?Arg?Cys?His?Ser?Arg?Arg?Gly?Ile

35 40 45Ser?Asp?Leu?Ser?Gln?Ser?Thr?Ala?Thr?Tyr?Ile?Asn?Val?Ile?Gly?Ala

50 55 60Gly?Leu?Ala?Gly?Ser?Glu?Ala?Ala?Tyr?Gln?Asn?Ala?Lys?Arg?Gly?Ile?65 70 75 80Pro?Val?Lys?Leu?Tyr?Glu?Met?Arg?Gly?Val?Lys?Ala?Thr?Pro?Gln?His

85 90 95Lys?Thr?Thr?Asn?Phe?Ala?Glu?Leu?Val?Cys?Ser?Asn?Ser?Phe?Arg?Gly

100 105 110Asp?Ser?Leu?Thr?Asn?Ala?Val?Gly?Leu?Leu?Lys?Glu?Glu?Met?Arg?Arg

115 120 125Leu?Asp?Ser?Ile?Ile?Met?Arg?Asn?Gly?Glu?Ala?Asn?Arg?Val?Pro?Ala

130 135 140Gly?Gly?Ala?Met?Ala?Val?Asp?Arg?Glu?Gly?Tyr?Ala?Glu?Ser?Val?Thr145 150 155 160Ala?Glu?Leu?Glu?Asn?His?Pro?Leu?Ile?Glu?Val?Ile?Arg?Gly?Glu?Ile

165 170 175Thr?Glu?Ile?Pro?Asp?Asp?Ala?Ile?Thr?Val?Ile?Ala?Thr?Gly?Pro?Leu

180 185 190Thr?Ser?Asp?Ala?Leu?Ala?Glu?Lys?Ile?His?Ala?Leu?Asn?Gly?Gly?Asp

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

210 215 220Ile?Asp?Met?Ser?Lys?Val?Tyr?Leu?Lys?Ser?Arg?Tyr?Asp?Lys?Gly?Glu225 230 235 240Ala?Ala?Tyr?Leu?Asn?Cys?Pro?Met?Thr?Lys?Glu?Glu?Phe?Met?Ala?Phe

245 250 255His?Glu?Ala?Leu?Thr?Thr?Ala?Glu?Glu?Ala?Pro?Leu?Asn?Ala?Phe?Glu

260 265 270Lys?Glu?Lys?Tyr?Phe?Glu?Gly?Cys?Met?Pro?Ile?Glu?Val?Met?Ala?Lys

275 280 285Arg?Gly?Ile?Lys?Thr?Met?Leu?Tyr?Gly?Pro?Met?Lys?Pro?Val?Gly?Leu

290 295 300Glu?Tyr?Pro?Asp?Asp?Tyr?Thr?Gly?Pro?Arg?Asp?Gly?Glu?Phe?Lys?Thr305 310 315 320Pro?Tyr?Ala?Val?Val?Gln?Leu?Arg?Gln?Asp?Asn?Ala?Ala?Gly?Ser?Leu

325 330 335Tyr?Asn?Ile?Val?Gly?Phe?Gln?Thr?His?Leu?Lys?Trp?Gly?Glu?Gln?Lys

340 345 350Arg?Val?Phe?Gln?Met?Ile?Pro?Gly?Leu?Glu?Asn?Ala?Glu?Phe?Val?Arg

355 360 365Tyr?Gly?Val?Met?His?Arg?Asn?Ser?Tyr?Met?Asp?Ser?Pro?Asn?Leu?Leu

370 375 380Thr?Glu?Thr?Phe?Gln?Ser?Arg?Ser?Asn?Pro?Asn?Leu?Phe?Phe?Ala?Gly385 390 395 400Gln?Met?Thr?Gly?Val?Glu?Gly?Tyr?Val?Glu?Ser?Ala?Ala?Ser?Gly?Leu

405 410 415Val?Ala?Gly?Ile?Asn?Ala?Ala?Arg?Leu?Phe?Lys?Arg?Glu?Glu?Ala?Leu

420 425 430Ile?Phe?Pro?Gln?Thr?Thr?Ala?Ile?Gly?Ser?Leu?Pro?His?Tyr?Val?Thr

435 440 445His?Ala?Asp?Ser?Lys?His?Phe?Gln?Pro?Met?Asn?Val?Asn?Phe?Gly?Ile

450 455 460Ile?Lys?Glu?Leu?Glu?Gly?Pro?Arg?Ile?Arg?Asp?Lys?Lys?Glu?Arg?Tyr465 470 475 480Glu?Ala?Ile?Ala?Ser?Arg?Ala?Leu?Ala?Asp?Leu?Asp?Thr?Cys?Leu?Ala

485 490 495Ser Leu＜210〉55＜211〉1539＜212〉DNA＜213〉＜400〉55atgattaagg atatgattga cagtattgag cagtttgctc agacacaggc tgattttcca 60gtttatgatt gtttagggga acgccgcact tacggacaac tcaaaagaga ttctgatagc 120attgctgcat ttatagatag cttagcttta ctggcaaaat ctccagtttt ggtttttggg 180gcgcaaactt atgatatgtt agctactttt gtagctttaa ccaaatctgg tcatgcctat 240atcccagtag atgtgcattc agcaccagaa cgtattttag cgattattga gattgcaaag 300cccagtttaa tcattgctat tgaggaattc cctcttacta ttgaagggat ttcccttgtc 360tcactatcag agattgagtc agcaaaatta gcagaaatgc cctatgagcg aacacattct 420gttaaaggag atgataatta ttacattatt ttcacctctg gaacaacggg ccaaccaaaa 480ggggtgcaaa tttcacatga caatcttttg agctttacca actggatgat cgaagatgca 540gcatttgatg tacctaaaca gccacaaatg ctggcgcagc caccctattc ctttgacctt 600tctgtcatgt actgggcacc taccttggct ttaggtggaa ccttatttgc acttccaaaa 660gaattggtgg cagactttaa acagttattt acaacgattg cgcaacttcc agttggcatt 720tggacatcga ctccttcatt tgctgatatg gccatgctta gcgatgattt ttgccaggct 780aagatgccag ctttaacgca tttttatttt gatggcgaag aattaaccgt ttctacggct 840cgaaaactct ttgaacgttt cccgagtgcc aagattatca atgcctatgg accaacagaa 900gcgactgtag ccttatccgc tattgaaatt accagagaaa tggtggataa ttatacccgc 960ttgccgattg gctaccccaa accagattct ccgacctata ttattgatga agatggtaag 1020gagttatctt caggggagca gggtgaaatt attgttacag ggcctgctgt gtcaaaaggt 1080tacctcaaca atcctgagaa aaccgcagaa gctttcttta cttttaaagg acagcctgct 1140tatcatacag gggacattgg ctcactgaca gaagataata ttttgttgta tggtgggcgt 1200ttggattttc agattaaata tgctggttat cgtattgaac tagaagatgt ttcccaacag 1260ttgaatcaat caccaatggt agcatcggct gtggctgttc caaggtacaa taaagaacat 1320aaggttcaaa atctcttggc ctatatcgtt gtcaaagatg gggttaaaga gcgttttgat 1380agggaattgg agttaaccaa agctatcaaa gcctctgtta aggatcatat gatgagttat 1440atgatgcctt ctaagtttct ttatcgagat agtctaccat taactccaaa tggtaagata 1500gatattaaaa ctttgattaa tgaggtcaat aaccgataa 1539＜210〉56＜211〉512＜212〉PRT＜213〉＜400〉56Met Ile Lys Asp Met Ile Asp Ser Ile Glu Gln Phe Ala Gln Thr Gln 1 5 10 15Ala Asp Phe Pro Val Tyr Asp Cys Leu Gly Glu Arg Arg Thr Tyr Gly

20 25 30Gln?Leu?Lys?Arg?Asp?Ser?Asp?Ser?Ile?Ala?Ala?Phe?Ile?Asp?Ser?Leu

35 40 45Ala?Leu?Leu?Ala?Lys?Ser?Pro?Val?Leu?Val?Phe?Gly?Ala?Gln?Thr?Tyr

50 55 60Asp?Met?Leu?Ala?Thr?Phe?Val?Ala?Leu?Thr?Lys?Ser?Gly?His?Ala?Tyr?65 70 75 80Ile?Pro?Val?Asp?Val?His?Ser?Ala?Pro?Glu?Arg?Ile?Leu?Ala?Ile?Ile

85 90 95Glu?Ile?Ala?Lys?Pro?Set?Leu?Ile?Ile?Ala?Ile?Glu?Glu?Phe?Pro?Leu

100 105 110Thr?Ile?Glu?Gly?Ile?Ser?Leu?Val?Ser?Leu?Ser?Glu?Ile?Glu?Ser?Ala

115 120 125Lys?Leu?Ala?Glu?Met?Pro?Tyr?Glu?Arg?Thr?His?Ser?Val?Lys?Gly?Asp

130 135 140Asp?Asn?Tyr?Tyr?Ile?Ile?Phe?Thr?Ser?Gly?Thr?Thr?Gly?Gln?Pro?Lys145 150 155 160Gly?Val?Gln?Ile?Ser?His?Asp?Asn?Leu?Leu?Ser?Phe?Thr?Asn?Trp?Met

165 170 175Ile?Glu?Asp?Ala?Ala?Phe?Asp?Val?Pro?Lys?Gln?Pro?Gln?Met?Leu?Ala

180 185 190Gln?Pro?Pro?Tyr?Ser?Phe?Asp?Leu?Ser?Val?Met?Tyr?Trp?Ala?Pro?Thr

195 200 205Leu?Ala?Leu?Gly?Gly?Thr?Leu?Phe?Ala?Leu?Pro?Lys?Glu?Leu?Val?Ala

210 215 220Asp?Phe?Lys?Gln?Leu?Phe?Thr?Thr?Ile?Ala?Gln?Leu?Pro?Val?Gly?Ile225 230 235 240Trp?Thr?Ser?Thr?Pro?Ser?Phe?Ala?Asp?Met?Ala?Met?Leu?Ser?Asp?Asp

245 250 255Phe?Cys?Gln?Ala?Lys?Met?Pro?Ala?Leu?Thr?His?Phe?Tyr?Phe?Asp?Gly

260 265 270Glu?Glu?Leu?Thr?Val?Ser?Thr?Ala?Arg?Lys?Leu?Phe?Glu?Arg?Phe?Pro

275 280 285Ser?Ala?Lys?Ile?Ile?Asn?Ala?Tyr?Gly?Pro?Thr?Glu?Ala?Thr?Val?Ala

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

325 330 335Glu?Asp?Gly?Lys?Glu?Leu?Ser?Ser?Gly?Glu?Gln?Gly?Glu?Ile?Ile?Val

340 345 350Thr?Gly?Pro?Ala?Val?Ser?Lys?Gly?Tyr?Leu?Asn?Asn?Pro?Glu?Lys?Thr

355 360 365Ala?Glu?Ala?Phe?Phe?Thr?Phe?Lys?Gly?Gln?Pro?Ala?Tyr?His?Thr?Gly

370 375 380Asp?Ile?Gly?Ser?Leu?Thr?Glu?Asp?Asn?Ile?Leu?Leu?Tyr?Gly?Gly?Arg385 390 395 400Leu?Asp?Phe?Gln?Ile?Lys?Tyr?Ala?Gly?Tyr?Arg?Ile?Glu?Leu?Glu?Asp

405 410 415Val?Ser?Gln?Gln?Leu?Asn?Gln?Ser?Pro?Met?Val?Ala?Ser?Ala?Val?Ala

420 425 430Val?Pro?Arg?Tyr?Asn?Lys?Glu?His?Lys?Val?Gln?Asn?Leu?Leu?Ala?Tyr

435 440 445Ile?Val?Val?Lys?Asp?Gly?Val?Lys?Glu?Arg?Phe?Asp?Arg?Glu?Leu?Glu

450 455 460Leu?Thr?Lys?Ala?Ile?Lys?Ala?Ser?Val?Lys?Asp?His?Met?Met?Ser?Tyr465 470 475 480Met?Met?Pro?Ser?Lys?Phe?Leu?Tyr?Arg?Asp?Ser?Leu?Pro?Leu?Thr?Pro

485 490 495Asn?Gly?Lys?Ile?Asp?Ile?Lys?Thr?Leu?Ile?Asn?Glu?Val?Asn?Asn?Arg

500 505 510＜210〉57＜211〉1278＜212〉DNA＜213〉＜400〉57atgacaaaaa ctaatcttaa ctggagcggt ttttcaaaga aaacattcga agaacgcctc 60caacttatcg aaaaatttaa actacttaat gctgaaaact taaatcaact caaaacagac 120gttcttttgc ctatccaaac agctaatcaa atgactgaaa atgtcttagg acgattggct 180ttgcccttta gcatagctcc tgattttctt gtcaacggtt caacttatca gatgcctttt 240gtcacggaag aaccttctgt tgttgctgca gcatctttcg cagcaaaact aatcaaacgc 300tcaggtggtt ttaaagctca aaccctaaac cgacaaatga ttggtcaaat tgttctttac 360gatatcgacc aaatagataa cgctaaagcc gccatccttc ataaaacaaa aaagctaatt 420gcattggcaa ataaagctta tccttccatt gttaaaagag gtggaggcgc tagaaccatt 480catttggaag aaaaaggaga atttttgatt ttctatctga ctgttgatac ccaagaagct 540atgggagcaa atatggtcaa tactatgatg gaagctcttg ttcctgattt aacaagactg 600tctaaggggc attgtctaat ggcgatttta tctaattacg caacagagtc gcttgttact 660actagttgtg agattcccgt gcgcctttta gatcacgata aaacaaaatc cctacagtta 720gctcaaaaaa tagagctagc cagccgacta gctcaagtag atccttaccg ggctactact 780cataataaag gtatttttaa tggcattgat gcagtggtaa tagccacagg aaatgactgg 840cgtgctattg aagcaggggc ccatgcttat gcctcaagaa atggtagcta tcaaggactt 900agtcagtggc attttgacca agataaacaa gttctgcttg gccaaatgac cctccctatg 960cctattgcta gtaagggggg atctatcggg cttaacccta ctgtttctat cgcacatgat 1020cttcttaatc aacctgatgc caaaacatta gcccaattga ttgcatctgt ggggttagct 1080caaaactttg ctgcactaaa agctctgacc tcatctggca tccaagctgg tcacatgaaa 1140ctacatgcga aatcattagc tcttttggcg ggggcaaccc aagacgaaat tgctccttta 1200gttaatgctt tactagctga taaaccaata aatctagaaa aagcacattt ttacttatcc 1260cagctaagac agtcttaa 1278＜210〉58＜211〉425＜212〉PRT＜213〉＜400〉58Met Thr Lys Thr Asn Leu Asn Trp Ser Gly Phe Ser Lys Lys Thr Phe 1 5 10 15Glu Glu Arg Leu Gln Leu Ile Glu Lys Phe Lys Leu Leu Asn Ala Glu

20 25 30Asn?Leu?Asn?Gln?Leu?Lys?Thr?Asp?Val?Leu?Leu?Pro?Ile?Gln?Thr?Ala

35 40 45Asn?Gln?Met?Thr?Glu?Asn?Val?Leu?Gly?Arg?Leu?Ala?Leu?Pro?Phe?Ser

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

85 90 95Leu?Ile?Lys?Arg?Ser?Gly?Gly?Phe?Lys?Ala?Gln?Thr?Leu?Asn?Arg?Gln

100 105 110Met?Ile?Gly?Gln?Ile?Val?Leu?Tyr?Asp?Ile?Asp?Gln?Ile?Asp?Asn?Ala

115 120 125Lys?Ala?Ala?Ile?Leu?His?Lys?Thr?Lys?Lys?Leu?Ile?Ala?Leu?Ala?Asn

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

165 170 175Thr?Gln?Glu?Ala?Met?Gly?Ala?Asn?Met?ValAsn?Thr?Met?Met?Glu?Ala

180 185 190Leu?Val?Pro?Asp?Leu?Thr?Arg?Leu?Ser?Lys?Gly?His?Cys?Leu?Met?Ala

195 200 205Ile?Leu?Ser?Asn?Tyr?Ala?Thr?Glu?Ser?Leu?Val?Thr?Thr?Ser?Cys?Glu

210 215 220Ile?Pro?Val?Arg?Leu?Leu?Asp?His?Asp?Lys?Thr?Lys?Ser?Leu?Gln?Leu225 230 235 240Ala?Gln?Lys?Ile?Glu?Leu?Ala?Ser?Arg?Leu?Ala?Gln?Val?Asp?Pro?Tyr

245 250 255Arg?Ala?Thr?Thr?His?Asn?Lys?Gly?Ile?Phe?Asn?Gly?Ile?Asp?Ala?Val

260 265 270Val?Ile?Ala?Thr?Gly?Asn?Asp?Trp?Arg?Ala?Ile?Glu?Ala?Gly?Ala?His

275 280 285Ala?Tyr?Ala?Ser?Arg?Asn?Gly?Ser?Tyr?Gln?Gly?Leu?Ser?Gln?Trp?His

290 295 300Phe?Asp?Gln?Asp?Lys?Gln?Val?Leu?Leu?Gly?Gln?Met?Thr?Leu?Pro?Met305 310 315 320Pro?Ile?Ala?Ser?Lys?Gly?Gly?Ser?Ile?Gly?Leu?Asn?Pro?Thr?Val?Ser

325 330 335Ile?Ala?His?Asp?Leu?Leu?Asn?Gln?Pro?Asp?Ala?Lys?Thr?Leu?Ala?Gln

340 345 350Leu?Ile?Ala?Ser?Val?Gly?Leu?Ala?Gln?Asn?Phe?Ala?Ala?Leu?Lys?Ala

355 360 365Leu?Thr?Ser?Ser?Gly?Ile?Gln?Ala?Gly?His?Met?Lys?Leu?His?Ala?Lys

370 375 380Ser?Leu?Ala?Leu?Leu?Ala?Gly?Ala?Thr?Gln?Asp?Glu?Ile?Ala?Pro?Leu385 390 395 400Val?Asn?Ala?Leu?Leu?Ala?Asp?Lys?Pro?Ile?Asn?Leu?Glu?Lys?Ala?His

405 410 415Phe?Tyr?Leu?Ser?Gln?Leu?Arg?Gln?Ser

420 425＜210〉59＜211〉915＜212〉DNA＜213〉＜400〉59atggtattat ttacaggaaa aacagtcgaa gaagctatcg aaacaggact tcaagagtta 60gggttatcac gccttaaagc gcatatcaaa gtcatttcaa aagagaaaaa aggtttcctc 120gggtttggta aaaagccagc ccaagttgat atcgaaggta tcagcgacaa gacggtttat 180aaggctgata aaaaagccac tcgaggtgtt ccagaggata ttaatcgtca aaatactccc 240gcggtcaatt ctgctgatgt agaacctgaa gaaataaaag ccactcaaag gttagaagca 300gaagatacca aagtggttcc tctcatgtct gaagatagtc cagcgcaaac cccttctaat 360cttgctgaga cagtcactga aacaaaagca caacaaccgt caatcccagt cgaagaatca 420gaagtgcccc aagatgctgg taatgatggt ttcagcaaag atattgaaaa agctgctcag 480gaagtgtccg attatgtgac taaaattatc tatgaaatgg atatcgaagc taccgttgaa 540accagcaaca atcgtcgcca aatcaatttg cagattgaaa cgccagaggc gggacgtgtg 600attggttacc atggtaaggt cttgaaatcc ttgcagttgt tagctcaaaa tttcttgcac 660gaccgctatt caaaaaattt ttcagtatcc ttgaatgtcc atgattatgt ggaacatcga 720acagaaacct tgattgactt tacgcaaaaa gttgccaaac gcgttttgga atctggtcaa 780gattacacca tggatcccat gagtaacagt gagcgtaaaa tcgttcataa aaccgtttca 840tccattgaag gggttgatag ttattctgaa ggcaatgacc ctaaccgcta tgtggtagtc 900agtcttcaac gttaa 915＜210〉60＜211〉304＜212〉PRT＜213〉＜400〉60Met Val Leu Phe Thr Gly Lys Thr Val Glu Glu Ala Ile Glu Thr Gly 1 5 10 15Leu Gln Glu Leu Gly Leu Ser Arg Leu Lys Ala His Ile Lys Val Ile

20 25 30Ser?Lys?Glu?Lys?Lys?Gly?Phe?Leu?Gly?Phe?Gly?Lys?Lys?Pro?Ala?Gln

35 40 45Val?Asp?Ile?Glu?Gly?Ile?Ser?Asp?Lys?Thr?Val?Tyr?Lys?Ala?Asp?Lys

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

85 90 95Arg?Leu?Glu?Ala?Glu?Asp?Thr?Lys?Val?Val?Pro?Leu?Met?Ser?Glu?Asp

100 105 ll0Ser?Pro?Ala?Gln?Thr?Pro?Ser?Asn?Leu?Ala?Glu?Thr?Val?Thr?Glu?Thr

115 120 125Lys?Ala?Gln?Gln?Pro?Ser?Ile?Pro?Val?Glu?Glu?Ser?Glu?Val?Pro?Gln

130 135 140Asp?Ala?Gly?Asn?Asp?Gly?Phe?Ser?Lys?Asp?Ile?Glu?Lys?Ala?Ala?Gln145 150 155 160Glu?Val?Ser?Asp?Tyr?Val?Thr?Lys?Ile?Ile?Tyr?Glu?Met?Asp?Ile?Glu

165 170 175Ala?Thr?Val?Glu?Thr?Ser?Asn?Asn?Arg?Arg?Gln?Ile?Asn?Leu?Gln?Ile

180 185 190Glu?Thr?Pro?Glu?Ala?Gly?Arg?Val?Ile?Gly?Tyr?His?Gly?Lys?Val?Leu

195 200 205Lys?Ser?Leu?Gln?Leu?Leu?Ala?Gln?Asn?Phe?Leu?His?Asp?Arg?Tyr?Ser

210 215 220Lys?Asn?Phe?Ser?Val?Ser?Leu?Asn?Val?His?Asp?Tyr?Val?Glu?His?Arg225 230 235 240Thr?Glu?Thr?Leu?Ile?Asp?Phe?Thr?Gln?Lys?Val?Ala?Lys?Arg?Val?Leu

245 250 255Glu?Ser?Gly?Gln?Asp?Tyr?Thr?Met?Asp?Pro?Met?Ser?Asn?Ser?Glu?Arg

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

275 280 285Ser?Glu?Gly?Asn?Asp?Pro?Asn?Arg?Tyr?Val?Val?Val?Ser?Leu?Gln?Arg

290 295 300＜210〉61＜211〉1269＜212〉DNA＜213〉＜400〉61atgacaacaa aatatcaaac aatcatttcc aatatcgaac aagatatcca gaaacagcga 60ctaaaaaaag gggacaagct accttcaatt agggtactaa gtaaggttta ttattgtagc 120aaagatactg ttcagcgggc tcttttagaa ttaaaatatc gtcacttaat ttatgctgtt 180cctaaaagtg gttattatgt tttgggtaac gtaagcatgc ccgataatgt tcttaatcta 240agtcttgaag attataataa tatggcttat gaagatttcc gactctgctt aaatgaggcc 300ttaagtgcta aagacaaata cctctttcat tattatcaca aaaccgaagg actagaagaa 360ctaagggaag ctttgcttct ttacttagct gaaaatagtg tttacagtaa caaagaccaa 420ctattaatca cctctgggac gcaacaagcg ctttatattt tatcacaaat gccttttcct 480aatacgggca aaacaattct ccttgaaaag cctacttatc atcggatgga agctattgtt 540gctcagttag gattacccta tcaaactatc tctagacact ttaatggcct tgatttagaa 600ctcttagaat ctttatttca aactggcgat attaaatttt tttacacgat ttcacgattt 660tcacatcctc tgggactttc ttatagcact aaggaaaagg aagctattgt tcgtctagca 720caacgatacc aggtttatat tttagaagat gattatttag gagattttgt gaaacttaaa 780gagccaccaa ttcattatta tgacactcat caccgaatca tctacctaaa atctttttca 840atgagtgttt ttcctgcact ccgtatcgga gctctagttt taccgtcagg tttaaaacct 900cattttttaa cccaaaaatc attgattgat ttagacacga acttactaat gcaaaaagca 960ttagctcttt atttagaaaa tgggatgttt caaaaaaatc ttcgctttat taagcgttat 1020ctaaaacagc gggaacgtca attggctctc tttttaaaac aaaattgccc tgatattcac 1080tatcaactaa cccctactca tttagtgatt gattacacga catcagactc ttatagaaac 1140tttacattag ataaatctga tagaataata ataactggaa aaaaacgcta tctctctatt 1200actatcaatc aacaaataca aagcaaatta aactcactaa tcaaaaatac ttgtggaaag 1260agcaactaa 1269＜210〉62＜211〉422＜212〉PRT＜213〉＜400〉62Met Thr Thr Lys Tyr Gln Thr Ile Ile Ser Asn Ile Glu Gln Asp Ile 1 5 10 15Gln Lys Gln Arg Leu Lys Lys Gly Asp Lys Leu Pro Ser Ile Arg Val

20 25 30Leu?Ser?Lys?Val?Tyr?Tyr?Cys?Ser?Lys?Asp?Thr?Val?Gln?Arg?Ala?Leu

35 40 45Leu?Glu?Leu?Lys?Tyr?Arg?His?Leu?Ile?Tyr?Ala?Val?Pro?Lys?Ser?Gly

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

85 90 95Leu?Asn?Glu?Ala?Leu?Ser?Ala?Lys?Asp?Lys?Tyr?Leu?Phe?His?Tyr?Tyr

100 105 110His?Lys?Thr?Glu?Gly?Leu?Glu?Glu?Leu?Arg?Glu?Ala?Leu?Leu?Leu?Tyr

115 120 125Leu?Ala?Glu?Asn?Ser?Val?Tyr?Ser?Asn?Lys?Asp?Gln?Leu?Leu?Ile?Thr

130 135 140Ser?Gly?Thr?Gln?Gln?Ala?Leu?Tyr?Ile?Leu?Ser?Gln?Met?Pro?Phe?Pro145 150 155 160Asn?Thr?Gly?Lys?Thr?Ile?Leu?Leu?Glu?Lys?Pro?Thr?Tyr?His?Arg?Met

165 170 175Glu?Ala?Ile?Val?Ala?Gln?Leu?Gly?Leu?Pro?Tyr?Gln?Thr?Ile?Ser?Arg

180 185 190His?Phe?Asn?Gly?Leu?Asp?Leu?Glu?Leu?Leu?Glu?Ser?Leu?Phe?Gln?Thr

195 200 205Gly?Asp?Ile?Lys?Phe?Phe?Tyr?Thr?Ile?Ser?Arg?Phe?Ser?His?Pro?Leu

210 215 220Gly?Leu?Ser?Tyr?Ser?Thr?Lys?Glu?Lys?Glu?Ala?Ile?Val?Arg?Leu?Ala225 230 235 240Gln?Arg?Tyr?Gln?Val?Tyr?Ile?Leu?Glu?Asp?Asp?Tyr?Leu?Gly?Asp?Phe

245 250 255Val?Lys?Leu?Lys?Glu?Pro?Pro?Ile?His?Tyr?Tyr?Asp?Thr?His?His?Arg

260 265 270Ile?Ile?Tyr?Leu?Lys?Ser?Phe?Ser?Met?Ser?Val?Phe?Pro?Ala?Leu?Arg

275 280 285Ile?Gly?Ala?Leu?Val?Leu?Pro?Ser?Gly?Leu?Lys?Pro?His?Phe?Leu?Thr

290 295 300Gln?Lys?Ser?Leu?Ile?Asp?Leu?Asp?Thr?Asn?Leu?Leu?Met?Gln?Lys?Ala305 310 315 320Leu?Ala?Leu?Tyr?Leu?Glu?Asn?Gly?Met?Phe?Gln?Lys?Asn?Leu?Arg?Phe

325 330 335Ile?Lys?Arg?Tyr?Leu?Lys?Gln?Arg?Glu?Arg?Gln?Leu?Ala?Leu?Phe?Leu

340 345 350Lys?Gln?Asn?Cys?Pro?Asp?Ile?His?Tyr?Gln?Leu?Thr?Pro?Thr?His?Leu

355 360 365Val?Ile?Asp?Tyr?Thr?Thr?Ser?Asp?Ser?Tyr?Arg?Asn?Phe?Thr?Leu?Asp

370 375 380Lys?Ser?Asp?Arg?Ile?Ile?Ile?Thr?Gly?Lys?Lys?Arg?Tyr?Leu?Ser?Ile385 390 395 400Thr?Ile?Asn?Gla?Gln?Ile?Gln?Ser?Lys?Leu?Asn?Ser?Leu?Ile?Lys?Asn

405 410 415Thr?Cys?Gly?Lys?Ser?Asn

420

Claims

1. the peptide that is used for the treatment of or diagnoses, it is by comprising any nucleotide sequence from streptococcus pyogenes as follows: SEQ ID NO.1,3,5,7,9,11,13,15,17,19,21,23,25,27,29,31,33,35,37,39,41,43,45,47,49,51,53,55,57,59 and 61, or the associated molecule of at least 40% sequence similarity or identity is arranged on peptide level or nucleotide level in the gram positive bacterium, or the operon of its function fragment coding.

2. according to the peptide of claim 1, wherein said sequence similarity or identity are at least 60%.

3. according to the peptide of claim 1 or 2, wherein said sequence similarity or identity are at least 90%.

4. according to the peptide of claim 1, it comprises aminoacid sequence as follows: SEQ ID NO.2,4,6,8,10,12,14,16,18,20,22,24,26,28,30,32,34,36,38,40,42,44,46,48,50,52,54,56,58,60 or 62.

5. the coding that is used for the treatment of or diagnoses is according to the polynucleotide of the peptide of any aforementioned claim.

6. host, it is expressed according to each peptide of claim 1 to 4 through transforming.

7. attenuated microorganisms, it comprises the sudden change that nucleotide sequence of destroying any claim 1 definition is expressed.

8. according to the microorganism of claim 7, wherein sudden change is to insert inactivation or genetically deficient.

9. according to the microorganism of claim 7 or 8, wherein said microorganism is the A group streptococcus.

10. according to each microorganism in the claim 7 to 9, it is used for the treatment of or diagnoses.

11. according to each microorganism in the claim 7 to 10, it comprises sudden change in another nucleotide sequence.

12. according to each microorganism in the claim 7 to 11, it comprises heterologous antigen, therapeutic peptide or nucleic acid.

13. a vaccine, it comprises according to each peptide in the claim 1 to 4, or its phraseology.

14. a vaccine, it comprises according to each microorganism in the claim 7 to 12.

15. according to the purposes of each product in the claim 1 to 12, it is used to produce and is used for the treatment of or the medicine of the illness that prevention is relevant with suis or gram positive bacteria infection.

16. according to the purposes of claim 15, wherein said illness is a pneumonia.

17. according to the purposes of claim 15 or 16, it is used for veterinary treatment.

18. an antibody, its antagonism is according to each peptide in the claim 1 to 4.

19. according to the purposes of each product in the claim 1 to 12, it is used to identify the shaker test of antimicrobial agents.