CN1241212A - Compound and methods for immunotherapy and diagnosis of tuberculosis - Google Patents

Abstract

This invention discloses the compounds and methods for inducing protective immunity against tuberculosis are disclosed. The compounds provided include polypeptides that contain at least one immunogenic portion of one or more M. tuberculosis proteins and DNA molecules encoding such polypeptides. Such compounds may be formulated into vaccines and/or pharmaceutical compositions for immunization against M. tuberculosis infection, or may be used for the diagnosis of tuberculosis.

Description

The Compounds and methods for of immunotherapy and diagnosis of tuberculosis

Technical field

The present invention relates generally to detect, treatment and prevention mycobacterium tuberculosis (Mycobacteriumtuberculosis) infect.The present invention relates more particularly to comprise antigen of mycobacterium tuberculosis, and the perhaps polypeptide of its part or its other variant, and such polypeptide is diagnosed and vaccinated purposes m tuberculosis infection.

Background of invention

Tuberculosis is the chronic infection disease, and it is generally caused by m tuberculosis infection.It is a kind of main disease of developing country, and increasing problem occurs in the development area in the world, and annual about 800 ten thousand new cases and 300 are die ten thousand deaths and died.Although infecting to be asymptomatic in the quite a while, this disease is usually expressed as lung's acute inflammation most, causes fever and dry cough.If do not treated, generally cause severe complications and death.

Although tuberculosis generally can use the antibiotic therapy of expansion to control, what such treatment was not enough to ward off disease spreads.The individuality that infects may be asymptomatic, is contagious at certain hour still.In addition, although the conformability of treatment plan is strict, patient's behavior is difficult to monitor.Some patients do not finish the treatment phase, and this causes not having the treatment of effect and developing immunity to drugs.

Suppress lungy spreading and need the accurate of effective vaccine inoculation and disease, early stage diagnosis.Recently, be the effective means of inducing protective immunity with the microbionation of living.The prevailing mycobacterium that is used for this purpose is genus bacillus Calmette-Guerin (BCG), the attenuated strain of a kind of Mycobacterium bovis (Mycobacterium bovis).But the security of BCG and effectiveness are the topics of arguement, and in some countries, for example in the U.S., general public does not inoculate.Diagnosis is generally finished with skin test, and it relates to intradermal and is exposed to tuberculin PPD (derivative of protein purification).The scleroma that generation can be surveyed is replied at the injection point T cells with antigenic specificity in injection back 48-72 hour, and it shows and is exposed under the antigen of mycobacterium.But the problem of this test is susceptibility and specificity, and the individuality of inoculation BCG can not make a distinction with the individuality that infects.

Scavenger cell shows as the main effects of mycobacterium tuberculosis immunity and works, and the T cell is the main inductor of such immunity.The main effect of T cell in the protection that Killing Mycobacterium Tuberculosis infects illustrates by owing to infecting the disappearance of relevant CD4 T cell with human immunodeficiency virus (HIV) mycobacterium tuberculosis taking place frequently in AIDS patient.It is the potential producer of gamma-interferon (IFN-γ) that mycobacterium-reactive CD4 T cell shows, and the latter then shows the anti-mycobacterium effect at mouse internal trigger scavenger cell.Although IFN-γ is still not fully aware of in the intravital effect of people, studies show that 1,25-dihydroxyl-Vitamin D3 500,000 I.U/GM makes up individually or with IFN-γ or α-Zhong Liuhuaisiyinzi, activates human macrophage and suppresses m tuberculosis infection.In addition, known IFN-γ stimulating macrophage produces 1,25-dihydroxyl-Vitamin D3 500,000 I.U/GM.Similarly, IL-12 shows in the resistance that stimulates m tuberculosis infection and works.About the immunologic summary of m tuberculosis infection referring to Chan and Kaufmann, tuberculosis: pathogeny, the protection and the treatment Tuberculosis; Pathogenesis, Protect and Control, Bloom (writing), ASM publishes, Washington, DC, 1994.

Therefore, this area exists for improved vaccine and prevention, the needs of the method for treatment and diagnosis of tuberculosis.The present invention has satisfied these needs, and other relevant advantage further is provided

Summary of the invention

In brief, the invention provides the Compounds and methods for that is used to prevent with diagnosis of tuberculosis.On the one hand, the polypeptide that provides comprises the immunogenicity part of solubility antigen of mycobacterium tuberculosis or such antigenic variant, and described antigenic variant is just different on conservative property is replaced and/or modified.In the embodiment aspect this, this soluble antigen has it (a) Asp-Pro-Val-Asp-Ala-Val-Ile-Asn-Thr-Thr-Cys-Asn-Tyr-Gly-of following N-end sequence

Gln-Val-Val-Ala-Ala-Leu；(SEQ?ID?No.120)(b)????Ala-Val-Glu-Ser-Gly-Met-Leu-Ala-Leu-Gly-Thr-Pro-Ala-Pro-

Ser；(SEQ?ID?No.121)(c)????Ala-Ala-Met-Lys-Pro-Arg-Thr-Gly-Asp-Gly-Pro-Leu-Glu-Ala-

Ala-Lys-Glu-Gly-Arg；(SEQ?ID?No.122)(d)????Tyr-Tyr-Trp-Cys-Pro-Gly-Gln-Pro-Phe-Asp-Pro-Ala-Trp-Gly-

Pro；(SEQ?ID?No.123)

(e)????Asp-Ile-Gly-Ser-Glu-Ser-Thr-Glu-Asp-Gln-Gln-Xaa-Ala-Val；

(SEQ?ID?No.124)

(f)????Ala-Glu-Glu-Ser-Ile-Ser-Thr-Xaa-Glu-Xaa-Ile-Val-Pro；(SEQ?ID

No.125)

(g)????Asp-Pro-Glu-Pro-Ala-Pro-Pro-Val-Pro-Thr-Thr-Ala-Ala-Ser-

Pro-Pro-Ser；(SEQ?ID?No.126)

(h)????Ala-Pro-Lys-Thr-Tyr-Xaa-Glu-Glu-Leu-Lys-Gly-Thr-Asp-Thr-

Gly；(SEQ?ID?No.127)

(i)????Asp-Pro-Ala-Ser-Ala-Pro-Asp-Val-Pro-Thr-Ala-Ala-Gln-Leu-

Thr-Ser-Leu-Leu-Asn-Ser-Leu-Ala-Asp-Pro-Asn-Val-Ser-Phe-

Ala-Asn；(SEQ?ID?No.128)

(j)????Xaa-Asp-Ser-Glu-Lys-Ser-Ala-Thr-Ile-Lys-Val-Thr-Asp-Ala-

Ser；(SEQ?ID?No.134)

(k)????Ala-Gly-Asp-Thr-Xaa-Ile-Tyr-Ile-Val-Gly-Asn-Leu-Thr-Ala-

Asp; (SEQ ID No.135) or

(l)????Ala-Pro-Glu-Ser-Gly-Ala-Gly-Leu-Gly-Gly-Thr-Val-Gln-Ala-

Gly; (SEQ ID No.136) wherein Xaa can be any amino acid.

At related aspect, the polypeptide that provides comprises the immunogenicity part of antigen of mycobacterium tuberculosis or such antigenic variant, and described antigenic variant is just different on conservative property is replaced and/or modified.Antigen has one of following N-end sequence:

(m)???Xaa-Tyr-Ile-Ala-Tyr-Xaa-Thr-Thr-Ala-Gly-Ile-Val-Pro-Gly-Lys-

Ile-Asn-Val-His-Leu-Val; (SEQ ID No.137) or

(n)???Asp-Pro-Pro-Asp-Pro-His-Gln-Xaa-Asp-Met-Thr-Lys-Gly-Tyr-

Tyr-Pro-Gly-Gly-Arg-Arg-Xaa-Phe; (SEQ ID No.129) wherein Xaa can be any amino acid.

In another embodiment, this solubility antigen of mycobacterium tuberculosis comprises and is selected from SEQID Nos.:1,2,4-10,13-25,52,99 and 101 sequences of listing, the complementary sequence of described sequence and under medium stringent condition with SEQ ID Nos.:1,2,4-10,13-25, the aminoacid sequence of the dna sequence encoding of the dna sequence dna of 52,99 and 101 sequences of listing or its complementary sequence hybridization.

At related aspect, this polypeptide comprises the immunogenicity part of antigen of mycobacterium tuberculosis or such antigenic variant, described antigenic variant is just different on conservative property is replaced and/or modified, wherein antigen comprises and is selected from SEQ ID Nos.:26-51,138,139, the sequence that 163-183 and 201 lists, the complementary sequence of described sequence and under medium stringent condition with SEQ ID Nos.:26-51,138,139, the aminoacid sequence of the dna sequence encoding of the sequence that 163-183 and 201 lists or the dna sequence dna of its complementary sequence hybridization.

At related aspect, the dna sequence dna of coding aforementioned polypeptides also is provided, comprise the expression vector of these dna sequence dnas and with the such expression vector conversion or the host cell of transfection.

On the other hand, the invention provides the protein of fusion, it comprises first and second polypeptide of the present invention, polypeptide perhaps of the present invention and known antigen of mycobacterium tuberculosis.

In others, the invention provides and contain one or more aforementioned polypeptides, perhaps the encode dna molecular of such polypeptide and the pharmaceutical composition of pharmaceutical acceptable carrier.The present invention also provides and comprises one or more vaccines of polypeptide and nonspecific immune response toughener as mentioned above, and contains the dna sequence dna of the such polypeptide of one or more codings and the vaccine of nonspecific immune response toughener.

Aspect another, the method for inducing patient's protective immunity is provided, comprise one or more aforementioned polypeptides that give patient's significant quantity.

In another aspect of the invention, provide and check patient's method lungy and diagnosis box.This method comprises the chrotoplast with one or more aforementioned polypeptides contact patients, and checks the immune response on the patient skin.Diagnosis box comprises that one or more aforementioned polypeptides make polypeptide contact the equipment of patient's chrotoplast with being enough to.

In the aspect, provide and check patient's method lungy in addition, this method comprises with being selected from SEQID Nos.:3,11,12,140,141,156-160,189-193,199,200 and 203 sequence, the complementary sequence of described sequence, with with SEQ ID Nos.:3,11,12,140,141,156-160,189-193, one or more polypeptide of the dna sequence encoding of 199,200 and 203 sequence hybridizations of listing contact patient's chrotoplast; And the immune response on the inspection patient skin.The diagnosis box that uses in such method also is provided.

With reference to following detailed and accompanying drawing, these and other aspect of the present invention will become apparent.Disclosed herein all incorporated by reference with reference to it, incorporated by reference separately as it.

The brief description of accompanying drawing and Sequence Identification

Figure 1A and B describe the 14Kd that embodiment 1 describes in detail, and 20Kd and 26Kd antigen are respectively to from the propagation of the T cell of first and second mycobacterium tuberculosis immunity donor and the hormesis that interferon-produces.

Fig. 2 describes two kinds of representative peptide T bRa3 and the TbRa9 hormesis to producing from the propagation in the T cell of mycobacterium tuberculosis immune body and interferon-in detail.

Fig. 3 A-D describes mycobacterium tuberculosis lysate (swimming lane 2) in detail, mycobacterium tuberculosis secretory protein (swimming lane 3), recombinant chou Tb38-1 (swimming lane 4), recombinant chou TbH-9 (swimming lane 5) and recombinant chou 85b (swimming lane 5) be the antisecretory mycobacterium tuberculosis protein respectively, known antigen of mycobacterium tuberculosis 85b and antigen Tb38-1 of the present invention and TbH-9 antiserum(antisera) reactivity.

Fig. 4 A describes secretion property mycobacterium tuberculosis protein in detail, and recombinant chou TbH-9 and contrast antigen TbRa11 are to the hormesis of TbH-9-specific T-cells clonal expansion.

Fig. 4 B describes secretion property mycobacterium tuberculosis protein in detail, the hormesis that PPD and recombinant chou TbH-9 produce interferon-among the TbH-9-specific T-cells clone.

Fig. 5 A and B describe the hormesis that fusion rotein TbH9-Tb38-1 produces propagation and interferon-in the TbH-9-specific T-cells in detail.

Fig. 6 A and B describe the hormesis of fusion rotein TbH9-Tb38-1 to Tb38-1-specific T-cells propagation and interferon-generation in detail.

Fig. 7 A and B describe fusion rotein TbH9-Tb38-1 in detail to before showing the hormesis that T cell proliferation that TbH-9 and Tb38-1 are replied and interferon-produce

Fig. 8 A and B describe representative polypeptide XP-1 in detail, RDIF6, RDIF8, the hormesis that RDIF10 and RDIF11 produce T cell proliferation and interferon-from the first mycobacterium tuberculosis immune body.

Fig. 9 A and B describe representative polypeptide XP-1 in detail, RDIF6, RDIF8, the hormesis that RDIF10 and RDIF11 produce T cell proliferation and interferon-from the second mycobacterium tuberculosis immune body.

SEQ.ID NO.1 is the dna sequence dna of TbRa1.

SEQ.ID NO.2 is the dna sequence dna of TbRa10.

SEQ.ID NO.3 is the dna sequence dna of TbRa11.

SEQ.ID NO.4 is the dna sequence dna of TbRa12.

SEQ.ID NO.5 is the dna sequence dna of TbRa13.

SEQ.ID NO.6 is the dna sequence dna of TbRa16.

SEQ.ID NO.7 is the dna sequence dna of TbRa17.

SEQ.ID NO.8 is the dna sequence dna of TbRa18.

SEQ.ID NO.9 is the dna sequence dna of TbRa19.

SEQ.ID NO.10 is the dna sequence dna of TbRa24.

SEQ.ID NO.11 is the dna sequence dna of TbRa26.

SEQ.ID NO.12 is the dna sequence dna of TbRa28.

SEQ.ID NO.13 is the dna sequence dna of TbRa29.

SEQ.ID NO.14 is the dna sequence dna of TbRa2A.

SEQ.ID NO.15 is the dna sequence dna of TbRa3.

SEQ.ID NO.16 is the dna sequence dna of TbRa32.

SEQ.ID NO.17 is the dna sequence dna of TbRa35.

SEQ.ID NO.18 is the dna sequence dna of TbRa36.

SEQ.ID NO.19 is the dna sequence dna of TbRa4.

SEQ.ID NO.20 is the dna sequence dna of TbRa9.

SEQ.ID NO.21 is the dna sequence dna of TbRaB.

SEQ.ID NO.22 is the dna sequence dna of TbRaC.

SEQ.ID NO.23 is the dna sequence dna of TbRaD.

SEQ.ID NO.24 is the dna sequence dna of YYWCPG.

SEQ.ID NO.25 is the dna sequence dna of AAMK.

SEQ.ID NO.26 is the dna sequence dna of TbL-23.

SEQ.ID NO.27 is the dna sequence dna of TbL-24.

SEQ.ID NO.28 is the dna sequence dna of TbL-25.SEQ.ID NO.29 is the dna sequence dna of TbL-28.SEQ.ID NO.30 is the dna sequence dna of TbL-29.SEQ.ID NO.31 is the dna sequence dna of TbH-5.SEQ.ID NO.32 is the dna sequence dna of TbH-8.SEQ.ID NO.33 is the dna sequence dna of TbH-9.SEQ.ID NO.34 is the dna sequence dna of TbM-1.SEQ.ID NO.35 is the dna sequence dna of TbM-3.SEQ.ID NO.36 is the dna sequence dna of TbM-6.SEQ.ID NO.37 is the dna sequence dna of TbM-7.SEQ.ID NO.38 is the dna sequence dna of TbM-9.SEQ.ID NO.39 is the dna sequence dna of TbM-12.SEQ.ID NO.40 is the dna sequence dna of TbM-13.SEQ.ID NO.41 is the dna sequence dna of TbM-14.SEQ.ID NO.42 is the dna sequence dna of TbM-15.SEQ.ID NO.43 is the dna sequence dna of TbH-4.SEQ.ID NO.44 is the dna sequence dna of TbH-4-FWD.SEQ.ID NO.45 is the dna sequence dna of TbH-12.SEQ.ID NO.46 is the dna sequence dna of Tb38-1.SEQ.ID NO.47 is the dna sequence dna of Tb38-4.SEQ.ID NO.48 is the dna sequence dna of TbL-17.SEQ.ID NO.49 is the dna sequence dna of TbL-20.SEQ.ID NO.50 is the dna sequence dna of TbL-21.SEQ.ID NO.51 is the dna sequence dna of TbH-16.SEQ.ID NO.52 is the dna sequence dna of DPEP.SEQ.ID NO.53 is the deduced amino acid of DPEP.SEQ.ID NO.54 is the terminal antigenic protein sequence of DPV N-.SEQ.ID NO.55 is the terminal antigenic protein sequence of AVGS N-.SEQ.ID NO.56 is the terminal antigenic protein sequence of AAMK N-.SEQ.ID NO.57 is the terminal antigenic protein sequence of YYWC N-.SEQ.ID NO.58 is the terminal antigenic protein sequence of DIGS N-.SEQ.ID NO.59 is the terminal antigenic protein sequence of AEES N-.SEQ.ID NO.60 is the terminal antigenic protein sequence of DPEP N-.SEQ.ID NO.61 is the terminal antigenic protein sequence of APKT N-.SEQ.ID NO.62 is the terminal antigenic protein sequence of DPAS N-.SEQ.ID NO.63 is the deduced amino acid of TbRa1.SEQ.ID NO.64 is the deduced amino acid of TbRa10.SEQ.ID NO.65 is the deduced amino acid of TbRa11.SEQ.ID NO.66 is the deduced amino acid of TbRa12.SEQ.ID NO.67 is the deduced amino acid of TbRa13.SEQ.ID NO.68 is the deduced amino acid of TbRa16.SEQ.ID NO.69 is the deduced amino acid of TbRa17.SEQ.ID NO.70 is the deduced amino acid of TbRa18.SEQ.ID NO.71 is the deduced amino acid of TbRa19.SEQ.ID NO.72 is the deduced amino acid of TbRa24.SEQ.ID NO.73 is the deduced amino acid of TbRa26.SEQ.ID NO.74 is the deduced amino acid of TbRa28.SEQ.ID NO.75 is the deduced amino acid of TbRa29.SEQ.ID NO.76 is the deduced amino acid of TbRa2A.SEQ.ID NO.77 is the deduced amino acid of TbRa3.SEQ.ID NO.78 is the deduced amino acid of TbRa32.SEQ.ID NO.79 is the deduced amino acid of TbRa35.SEQ.ID NO.80 is the deduced amino acid of TbRa36.SEQ.ID NO.81 is the deduced amino acid of TbRa4.SEQ.ID NO.82 is the deduced amino acid of TbRa9.SEQ.ID NO.83 is the deduced amino acid of TbRaB.SEQ.ID NO.84 is the deduced amino acid of TbRaC.SEQ.ID NO.85 is the deduced amino acid of TbRaD.SEQ.ID NO.86 is the deduced amino acid of YYWCPG.SEQ.ID NO.87 is the dna sequence dna of TbAAMK.SEQ.ID NO.88 is the deduced amino acid of Tb38-1.SEQ.ID NO.89 is the deduced amino acid of TbH-4.SEQ.ID NO.90 is the deduced amino acid of TbH-8.SEQ.ID NO.91 is the deduced amino acid of TbH-9.SEQ.ID NO.92 is the deduced amino acid of TbH-12.SEQ.ID NO.93 is the aminoacid sequence of Tb38-1 peptide 1.SEQ.ID NO.94 is the aminoacid sequence of Tb38-1 peptide 2.SEQ.ID NO.95 is the aminoacid sequence of Tb38-1 peptide 3.SEQ.ID NO.96 is the aminoacid sequence of Tb38-1 peptide 4.SEQ.ID NO.97 is the aminoacid sequence of Tb38-1 peptide 5.SEQ.ID NO.98 is the aminoacid sequence of Tb38-1 peptide 6.SEQ.ID NO.99 is the dna sequence dna of DPAS.SEQ.ID NO.100 is the deduced amino acid of DPAS.SEQ.ID NO.101 is the dna sequence dna of DPV.SEQ.ID NO.102 is the deduced amino acid of DPV.SEQ.ID NO.103 is the dna sequence dna of ESAT-6.SEQ.ID NO.104 is the deduced amino acid of ESAT-6.SEQ.ID NO.105 is the dna sequence dna of TbH-8-2.SEQ.ID NO.106 is the dna sequence dna of TbH-9FL.SEQ.ID NO.107 is the deduced amino acid of TbH-9FL.SEQ.ID NO.108 is the dna sequence dna of TbH-9-1.SEQ.ID NO.109 is the deduced amino acid of TbH-9-1.SEQ.ID NO.110 is the dna sequence dna of TbH-9-4.SEQ.ID NO.111 is the deduced amino acid of TbH-9-4.SEQ.ID NO.112 is the dna sequence dna of Tb38-1F2IN.SEQ.ID NO.113 is the dna sequence dna of Tb38-2F2RP.SEQ.ID NO.114 is the deduced amino acid of Tb37-FL.SEQ.ID NO.115 is the deduced amino acid of Tb38-IN.SEQ.ID NO.116 is the dna sequence dna of Tb38-1F3.SEQ.ID NO.117 is the deduced amino acid of Tb38-1F3.SEQ.ID NO.118 is the dna sequence dna of Tb38-1F5.SEQ.ID NO.119 is the dna sequence dna of Tb38-1F6.SEQ.ID NO.120 is the-terminal amino acid sequence of the derivation of DPV.SEQ.ID NO.121 is the-terminal amino acid sequence of the derivation of AVGS.SEQ.ID NO.122 is the-terminal amino acid sequence of the derivation of AAMK.SEQ.ID NO.123 is the-terminal amino acid sequence of the derivation of YYWC.SEQ.ID NO.124 is the-terminal amino acid sequence of the derivation of DIGS.

SEQ.ID NO.125 is the-terminal amino acid sequence of the derivation of AEES.

SEQ.ID NO.126 is the-terminal amino acid sequence of the derivation of DPEP.

SEQ.ID NO.127 is the-terminal amino acid sequence of the derivation of APKT.

SEQ.ID NO.128 is the deduced amino acid of DPAD.

SEQ.ID NO.129 is the terminal antigenic protein sequence of DPPD N-.

SEQ.ID NO.130-133 is four segmental protein sequences of DPPD cyanogen bromide.

SEQ.ID NO.134 is the antigenic N-terminal protein of an XDS matter sequence.

SEQ.ID NO.135 is the antigenic N-terminal protein of an AGD matter sequence.

SEQ.ID NO.136 is the antigenic N-terminal protein of an APE matter sequence.

SEQ.ID NO.137 is the antigenic N-terminal protein of an XYI matter sequence

SEQ.ID NO.138 is the dna sequence dna of TbH-29.

SEQ.ID NO.139 is the dna sequence dna of TbH-30.

SEQ.ID NO.140 is the dna sequence dna of TbH-32.

SEQ.ID NO.141 is the dna sequence dna of TbH-33.

SEQ.ID NO.142 is the aminoacid sequence of the indication of TbH-29.

SEQ.ID NO.143 is the aminoacid sequence of the indication of TbH-30.

SEQ.ID NO.144 is the aminoacid sequence of the indication of TbH-32.

SEQ.ID NO.145 is the aminoacid sequence of the indication of TbH-33.

SEQ.ID NO.146-151 is that preparation comprises TbRa3, the PCR primer that uses in the fusion rotein of 38kD and Tb38-1.

SEQ.ID NO.152 comprises TbRa3, the dna sequence dna of the fusion rotein of 38kD and Tb38-1

SEQ.ID NO.153 comprises TbRa3, the aminoacid sequence of the fusion rotein of 38kD and Tb38-1.

SEQ.ID NO.154 is the dna sequence dna of antigen of mycobacterium tuberculosis 38kD.

SEQ.ID NO.155 is the aminoacid sequence of antigen of mycobacterium tuberculosis 38kD.

SEQ.ID NO.156 is the dna sequence dna of XP14.

SEQ.ID NO.157 is the dna sequence dna of XP24.

SEQ.ID NO.158 is the dna sequence dna of XP31.

SEQ.ID NO.159 is 5 ' dna sequence dna of XP32.

SEQ.ID NO.160 is 3 ' dna sequence dna of XP32.

SEQ.ID NO.161 is the aminoacid sequence of the indication of XP14.

SEQ.ID NO.162 is the aminoacid sequence of indication of the reverse complementary sequence coding of XP14.

SEQ.ID NO.163 is the dna sequence dna of XP27.

SEQ.ID NO.164 is the dna sequence dna of XP36.

SEQ.ID NO.165 is 5 ' dna sequence dna of XP4.

SEQ.ID NO.166 is 5 ' dna sequence dna of XP5.

SEQ.ID NO.167 is 5 ' dna sequence dna of XP17.

SEQ.ID NO.168 is 5 ' dna sequence dna of XP30.

SEQ.ID NO.169 is 5 ' dna sequence dna of XP2.

SEQ.ID NO.170 is 3 ' dna sequence dna of XP2.

SEQ.ID NO.171 is 5 ' dna sequence dna of XP3.

SEQ.ID NO.172 is 3 ' dna sequence dna of XP3.

SEQ.ID NO.173 is 5 ' dna sequence dna of XP6.

SEQ.ID NO.174 is 3 ' dna sequence dna of XP6.

SEQ.ID NO.175 is 5 ' dna sequence dna of XP18.

SEQ.ID NO.176 is 3 ' dna sequence dna of XP18.

SEQ.ID NO.177 is 5 ' dna sequence dna of XP19.

SEQ.ID NO.178 is 3 ' dna sequence dna of XP19.

SEQ.ID NO.179 is 5 ' dna sequence dna of XP22.

SEQ.ID NO.180 is 3 ' dna sequence dna of XP22.

SEQ.ID NO.181 is 5 ' dna sequence dna of XP25.

SEQ.ID NO.182 is 3 ' dna sequence dna of XP25.

SEQ.ID NO.183 is the full length DNA sequence of TbH4-XP1.

SEQ.ID NO.184 is the aminoacid sequence of the indication of TbH4-XP1.

SEQ.ID NO.185 is the aminoacid sequence of indication of the reverse complementary sequence coding of TbH4-XP1.

SEQ.ID NO.186 is the aminoacid sequence of first indication of XP36 coding.

SEQ.ID NO.187 is the aminoacid sequence of second indication of XP36 coding.

SEQ.ID NO.188 is the aminoacid sequence of indication of the reverse complementary sequence coding of XP36.

SEQ.ID NO.189 is the dna sequence dna of RDIF2.

SEQ.ID NO.190 is the dna sequence dna of RDIF5.

SEQ.ID NO.191 is the dna sequence dna of RDIF8.

SEQ.ID NO.192 is the dna sequence dna of RDIF10.

SEQ.ID NO.193 is the dna sequence dna of RDIF11.

SEQ.ID NO.194 is the aminoacid sequence of the indication of RDIF2.

SEQ.ID NO.195 is the aminoacid sequence of the indication of RDIF5.

SEQ.ID NO.196 is the aminoacid sequence of the indication of RDIF8.

SEQ.ID NO.197 is the aminoacid sequence of the indication of RDIF10.

SEQ.ID NO.198 is the aminoacid sequence of the indication of RDIF11.

SEQ.ID NO.199 is 5 ' dna sequence dna of RDIF12.

SEQ.ID NO.200 is 3 ' dna sequence dna of RDIF12.

SEQ.ID NO.201 is the dna sequence dna of RDIF7.

SEQ.ID NO.202 is the aminoacid sequence of the indication of RDIF7.

SEQ.ID NO.203 is the dna sequence dna of DIF2-1.

SEQ.ID NO.204 is the aminoacid sequence of the indication of DIF2-1.

SEQ.ID NO.205-212 is that preparation comprises TbRa3, the PCR primer that uses among the 38kD, the fusion rotein of Tb38-1 and DPEP (hereinafter being referred to as TbF-2).

SEQ.ID NO.213 is the dna sequence dna of fusion rotein TbF-2.

SEQ.ID NO.214 is the aminoacid sequence of fusion rotein TbF-2.

Detailed description of the invention

As mentioned above, the present invention relates generally to prevention, composition and the method for the treatment of and diagnosis of tuberculosis. The present composition contains and comprises at least a kind of antigen of mycobacterium tuberculosis, is perhaps the polypeptide of the immunogenicity part of conservative replacement and/or the variant of modifying different such antigen. Polypeptide in the scope of the invention includes but not limited to immunogenicity solubility antigen of mycobacterium tuberculosis. " solubility antigen of mycobacterium tuberculosis " is the protein in the Much's bacillus source that exists in Much's bacillus culture filtrate. As used herein, term " polypeptide " comprises that wherein amino acid residue, by the amino acid chain of any length of covalency peptide bond connection, comprises full length protein (being antigen). Therefore, the polypeptide that comprises the immunogenicity part of one of above-mentioned antigen can all partly be comprised of immunogenicity, perhaps can comprise other sequence. Other sequence can or can be allos from natural antigen of mycobacterium tuberculosis, and such sequence can (but not must) be immunogenic.

Here " immunogenicity " used refer to the patient, people for example, and/or the ability of bringing out immune response (for example cell) in biological sample. Especially, that immunogenic antigen (with immunogenicity part or other variant of such antigen) can be selected from the T cell containing one or more, the NK cell, the biological sample moderate stimulation cell proliferation of the cell of B cell and macrophage, interleukin 12 produces and/or interferon-γ produces, and wherein cell is from the individuality of Much's bacillus immunity. At least the polypeptide that comprises the immunogenicity part of one or more antigen of mycobacterium tuberculosis generally can be used for checking tuberculosis or bringing out the antituberculotic protective immunity of patient.

The present composition and method also relate to the variant of above-mentioned polypeptide. " variant ", as used herein, be that just conservative replacement and/or modification are different from native antigen, make the reservation polypeptide bring out the polypeptide of the ability of immune response. Such variant generally can be by modifying one of above-mentioned polypeptide, and example as described herein the immunogenicity of the polypeptide modified of exemplary process evaluation identify.

" conservative replacement " is that wherein amino acid is had the amino acid substitution of similar character by another kind, makes the chemistry of peptides those skilled in the art can predict the secondary structure of polypeptide and the replacement that hydrophily there is no variation. Generally, the amino acid represent conservative of below organizing changes: (1) ala, pro, gly, glu, asp, gln, asn, scr, thr; (2) cys, ser, tyr, thr; (3) val, ile, leu, met, ala, phe; (4) lys, arg, his; (5) phe, tyr, trp, his.

Variant also can (perhaps) by for example to the immunogenicity of polypeptide, secondary structure and hydrophily have the amino acid whose disappearance of minimal effects or add and modify. For example, instruct signal (or leading) coupling sequence of the protein N-end of Protein transfer after polypeptide is translated together or translated. Polypeptide can also be coupled to and be easy to polypeptide (many-His) synthetic for example, purifying or evaluation, perhaps strengthen joint or other sequence that polypeptide is combined with solid carrier. For example, polypeptide can with IgF c district's coupling.

At related aspect, the combination polypeptide is disclosed. " combination polypeptide " be comprise at least a by the above-mentioned immunogenicity part on amino acid chain of peptide bond joint and the polypeptide of one or more other immunogenicity Much's bacillus sequences. Sequence can directly connect (namely not interleaving amino acid) or can connect by the not obvious immunogenic joint sequence (for example Gly-Cys-Gly) that reduces to form polypeptide.

Generally, antigen of mycobacterium tuberculosis, the DNA sequence dna of this antigen of encoding can prepare with various methods. For example soluble antigen can separate by well known to a person skilled in the art method from Much's bacillus culture filtrate, comprises anion-exchange and reverse-phase chromatography. Then use-case as described herein exemplary process the antigen of purifying estimated it elicit the ability of suitable immune response (for example cell). Then can use-case such as the Edman chemical technology of routine the immunogenicity antigen part is checked order. Referring to Edman and Bcrg, european journal of biological chemistry (Eur.J.Biochem.) 80:116-132,1967.

Immunogenicity antigen also can produce with the DNA sequence dna restructuring of this antigen of coding that is inserted in expression vector and expresses in suitable host. The DNA molecular of coding soluble antigen can separate by the suitable Much's bacillus expression library of the antiserum with the anti-solubility antigen of mycobacterium tuberculosis of specificity (for example rabbit) screening. Coding may be soluble or may not be that the DNA sequence dna of soluble antigen can be differentiated by using suitable Much's bacillus genome or the cDNA expression library of serum screening that obtains from the patient who infects Much's bacillus. Such screening generally can be carried out with the technology of well known to a person skilled in the art, such as being described in Sambrook etc., molecular cloning: laboratory manual, cold spring harbor laboratory, cold spring port, NY, those methods of 1989.

The DNA sequence dna of coding soluble antigen also can obtain with the DNA sequence dna of the degenerate oligonucleotide hybridization of the partial amino-acid series of the soluble antigen that carrys out self-separation by the Much's bacillus cDNA to suitable or genome dna library screening. Can design and synthesize the degenerate oligonucleotide sequence that uses in such screening, screening can according to (such as) Sambrook etc., molecular cloning: laboratory manual, cold spring harbor laboratory, the cold spring port, NY, the description of 1989 (with the reference of quoting wherein) is carried out. Also can use polymerase chain reaction (PCR), use the above-mentioned oligonucleotides in approach well known, come from cDNA or genomic library isolated nucleic acid probe, then can carry out the library screening with the probe that separates.

Perhaps, can be directly with the PMBC (PBMCs) that derives from or several Much's bacillus immune bodies or T clone or colony screening genome or the cDNA library from Much's bacillus. Generally, the PBMCs that uses in such screening and/or T cell can be according to following description preparations. Direct library is screened the ability of bringing out propagation and/or interferon-γ generation in the T cell that generally can be determined at by the set liquid of the recombinant protein to expressing from the Much's bacillus immune body and is carried out. Perhaps, as mentioned above, potential T cellular antigens can screen as basis first take antibody response.

Do not consider the preparation method, antigen as described herein (with its immunogenicity part) (it may be soluble or may not be soluble) has the ability that immunogenicity is replied of bringing out. More specifically, antigen has the T cell that brings out from the Much's bacillus immune body, the NK cell, and the propagation in B cell and/or macrophage and/or cell factor produce the ability of (for example interferon-γ and/or interleukin 12 produce). Certainly depend on the reaction of expectation for the selection for estimating the cell type that the immunogenicity of antigen is replied. For example, being suitable for estimating interleukin 12 most with the preparation that contains B cell and/or macrophage produces. The Much's bacillus immune body is to think to set up owing to having the effective t cell response to Much's bacillus (namely there is no disease symptoms) that places the people who tuberculosis is had resistance. Such individuality can and be that identify on basis without any tuberculosis signal or symptom according to (for example greater than approximately 10mm diameter scleroma) the intracutaneous skin test reaction of the strong positive to tuberculosis protein (PPD). From the T cell of Much's bacillus immune body, the NK cell, B cell and macrophage can be with well known to a person skilled in the art the method preparation. For example the prepared product of PBMCs (being PMBC) can further separate and forms cell and just can use. PBMCs generally can for example use and pass through Ficoll^TMThe centrifugal preparation of density of (Winthrop Laboratories, NY). The T cell that uses in test as described herein also can be directly from the PBMCs purifying. Perhaps, can use to the T clone of the enrichment of responding property of mycobacterium protein or to the T cell clone of individual responding property of mycobacterium protein. Such T cell clone can be by for example producing from PBMCs and the cultivation of mycobacterium protein of Much's bacillus immune body in 2-4 week. This makes only has the expansion of mycobacterium protein specific T cell, produces the clone that cell only in this way forms. Then can clone these cells and with individual proteins, test with the method for well known to a person skilled in the art, to define more accurately individual T cell specificity. Generally, use the T cell from the Much's bacillus immune body, what NK cell, B cell and/or macrophage carried out is considered to immunogenic to the positive antigen of test in the test of propagation and/or cell factor generation (being that interferon-γ and/or interleukin 12 produce). Such test can for example be carried out with the exemplary process that the following describes. The immunogenicity of such antigen part can be with similar Test Identification, and may reside in polypeptide as described herein.

The ability of polypeptide (for example immunogenicity antigen or its part, or its other variant) inducing cell propagation is estimated by the propagation with polypeptide exposing cell (for example T cell and/or NK cell) and mensuration cell. Generally, the weight range that is enough to estimate the polypeptide of about 105 cells is that about 10ng/mL is to about 100 μ g/mL, preferably about 10 μ g/mL. The incubation of polypeptide and cell generally carried out about 6 days under 37 ℃. After the polypeptide incubation, to cell test breeder reaction, this can be by well known to a person skilled in the art method evaluation, and the pulse and the mensuration mark that for example cell are exposed to radiolabeled thymidine enter mixing of cell DNA. Generally, producing propagation is considered to induce propagation than the polypeptide of three times of background (namely for the cell that there is no polypeptide, cultivating the propagation of finding) increases at least.

The ability that in the polypeptide irritation cell, interferon-γ and/or interleukin 12 produce is estimated by the level of the interferon-γ with polypeptide exposing cell and mensuration cell and/or interleukin 12 generation. Generally, be enough to estimate about 10⁵The weight range of the polypeptide of individual cell is that about 10ng/mL is to about 100 μ g/mL, preferably about 10 μ g/mL. Polypeptide can, but be not necessary, be fixed on solid carrier, described carrier is for example bead or biodegradable microsphere, those that for example describe in United States Patent(USP) Nos. 4897268 and 5075109. The incubation of polypeptide and cell generally carried out about 6 days under 37 ℃. After the polypeptide incubation, to cell Analysis interference element-γ and/or interleukin 12 (perhaps its one or more subunits), this can be by well known to a person skilled in the art method, for example enzyme linked immunosorbent assay (ELISA) (ELISA), perhaps in IL-12P70 subunit situation, for example measure the test biological test of T cell proliferation and estimate. Generally, cause every milliliter to cultivate supernatant and produce at least the 50pg interferon-γ (every milliliter contains 10⁴-10 ⁵Individual T cell) polypeptide is considered to stimulate the generation of interferon-γ. For every 10⁵Macrophage or B cell (perhaps every 3 * 10⁵PBMC) stimulate and to produce 10pg/mL IL-12P70 subunit at least, and/or the polypeptide of the 100pg/mL IL-12P70 subunit generation that is considered to stimulate IL-12 at least.

Generally, immunogenicity antigen is the T cell that stimulates from about at least 25% Much's bacillus immune body, the NK cell, in B cell and/or macrophage, propagation and/or cell factor produce those antigens of (being that interferon-γ and/or interleukin 12 produce). In these immunogenicity antigens, having the polypeptide of superior curative properties can be take the size of reacting in above-mentioned test as basis and take the percentage of the individuality of finding reaction, as basis, distinguished. In addition, external the stimulation from the propagation in the cell of the individuality that there is no the Much's bacillus immunity more than about 25% and/or cell factor of antigen with superior curative properties produces, thereby eliminated for Much's bacillus responsiveness cell, is not specific replying. At the high percentage T cell from the Much's bacillus immune body, the NK cell, induce those antigens of replying (with from replying on a small quantity in other individual preparation) to have superior curative properties in B cell and/or macrophage preparation.

Antigen with superior curative properties also can be with it in experimental animal, and when as vaccine, giving, the ability that reduces the order of severity of m tuberculosis infection is that identify on basis. The suitable vaccine preparation that experimental animal is used is discussed in more detail below. Can take provide after experimental infection about at least 50% bacterial population purpose to reduce and/or the antigenic capacity of the reduction of about at least 40% death rate as fundamental measurement effect. Suitable experimental animal comprises mouse, cavy and primate.

Antigen with superior curative properties generally can be to have suffering from the intracutaneous skin test that active individuality lungy carries out, and not having the ability of bringing out reaction in the test that the individuality to not infecting Much's bacillus carries out is that identify on basis. Skin test generally can be according to hereinafter described carrying out, and the reaction of 5mm scleroma is thought positive at least.

The immunogenicity part of antigen as described herein can and be identified with known method preparation, for example be summarized in Paul, basic immunology (Fundamental Immunology), the third edition, Raven publishes, those technology in 1993, pp.243-247 and the list of references wherein quoted. Such technology comprises the polypeptide portion screening immunogenicity character to native antigen. Representative propagation as described herein and cell factor produce to be measured generally and can use in these screenings. The immunogenicity of polypeptide is partly the part that produces the immune response (for example breed, interferon-γ and/or interleukin 12 produce) of the immune response that is substantially similar to the generation of total length antigen in such representativeness test. In other words, it is about at least 20% that the immunogenicity of antigen part can produce, preferably approximately the propagation of total length antigen induction in 100% described model proliferation test here. Immunogenicity part also can, perhaps, stimulates about at least 20%, the preferably approximately interferon-γ of total length antigen induction and/or interleukin 12 generation in 100% described model test here.

The part of antigen of mycobacterium tuberculosis and other variant can produce by synthetic or restructuring method. Have and be less than about 100 amino acid, and generally be less than about 50 amino acid whose synthetic polypeptide and can produce with the technology that well known to a person skilled in the art. For example such polypeptide can be with any commercial available solid phase technique, and for example wherein the amino acid Merrifield solid phase synthesis process that sequentially added to produce the amino acid chain of growth synthesizes. Referring to Merrifield, J.Am.Chem.Soc.85:2149-2146,1963. Automatically the equipment of synthetic polypeptide is from supplier Applied BioSystems for example, Inc., and Foster City, CA can buy, and can operate according to manufacturer's explanation. The variant of native antigen generally can with standard mutagenesis technology for example the site-specific mutagenesis that instructs of oligonucleotides prepare. Also can remove with the standard technique of the polypeptide that allows the preparation brachymemma fragment of DNA sequence dna.

Comprising the part of native antigen and/or the restructuring polypeptide of variant can easily use and well known to a person skilled in the art that multiple technologies prepare from the DNA sequence dna of this peptide of encoding. For example can be at first concentrated with the available filter of business from the supernatant that recombinant protein is secreted into the suitable host/carrier system in culture medium. After concentrated, concentrate can be applied to suitable purifying matrix, for example affine matrix or ion exchange resin. Finally, one or more reversed-phase HPLC steps can be used for being further purified recombinant protein.

Can be with well known to a person skilled in the art that any various expression vector expresses the present invention's polypeptide of recombinating. Expression can realize in any suitable host cell of the expression vector conversion with using the DNA molecular that comprises coding restructuring polypeptide or transfection. Suitable host cell comprises prokaryotic, yeast and more senior eukaryotic. Preferably, the host cell of use is Escherichia coli, and yeast or mammal cell line be COS or CHO for example. The DNA sequence dna of expressing with the method naturally occurring antigen of can encoding, natural part or its other variant that has antigen.

Generally, do not consider the preparation method, polypeptide disclosed herein prepares in basically pure mode. Preferably, polypeptide about at least 80% is pure, and more preferably about at least 90% is pure and mild most preferably about at least 99% pure. Below in more described preferred embodiments, pure polypeptide is incorporated in the pharmaceutical composition or vaccine that uses in disclosed one or more methods here basically.

In some specific embodiments, the invention discloses and comprise the solubility antigen of mycobacterium tuberculosis that has at least one of following N-end sequence, perhaps only have conservative to replace and/or modify the polypeptide of the immunogenicity part of its different variants:

(a)   Asp-Pro-Val-Asp-Ala-Val-Ile-Asn-Thr-Thr-Cys-Asn-Tyr-Gly-

      Gln-Val-Val-Ala-Ala-Leu；(SEQ ID No.120)

(b)   Ala-Val-Glu-Ser-Gly-Met-Leu-Ala-Leu-Gly-Thr-Pro-Ala-Pro-

      Ser；(SEQ ID No.121)

(c)   Ala-Ala-Met-Lys-Pro-Arg-Thr-Gly-Asp-Gly-Pro-Leu-Glu-Ala-

      Ala-Lys-Glu-Gly-Arg；(SEQ ID No.122)

(d)   Tyr-Tyr-Trp-Cys-Pro-Gly-Gln-Pro-Phe-Asp-Pro-Ala-Trp-Gly-

      Pro；(SEQ ID No.123)

(e)   Asp-Ile-Gly-Ser-Glu-Ser-Thr-Glu-Asp-Gln-Gln-Xaa-Ala-Val；

      (SEQ ID No.124)

(f)   Ala-Glu-Glu-Ser-Ile-Ser-Thr-Xaa-Glu-Xaa-Ile-Val-Pro；(SEQ ID

      No.125)

(g)   Asp-Pro-Glu-Pro-Ala-Pro-Pro-Val-Pro-Thr-Ala-Ala-Ala-Ser-

      Pro-Pro-Ser；(SEQ ID No.126)

(h)???Ala-Pro-Lys-Thr-Tyr-Xaa-Glu-Glu-Leu-Lys-Gly-Thr-Asp-Thr-

Gly；(SEQ?ID?No.127)

(i)???Asp-Pro-Ala-Ser-Ala-Pro-Asp-Val-Pro-Thr-Ala-Ala-Gln-Leu-

Thr-Ser-Leu-Leu-Asn-Ser-Leu-Ala-Asp-Pro-Asn-Val-Ser-Phe-

Ala-Asn；(SEQ?ID?No.128)

(j)???Xaa-Asp-Ser-Glu-Lys-Ser-Ala-Thr-Ile-Lys-Val-Thr-Asp-Ala-

Ser；(SEQ?ID?No.134)

(k)???Ala-Gly-Asp-Thr-Xaa-Ile-Tyr-Ile-Val-Gly-Asn-Leu-Thr-Ala-

Asp；(SEQ?ID?No.135)or

(l)???Ala-Pro-Glu-Ser-Gly-Ala-Gly-Leu-Gly-Gly-Thr-Val-Gln-Ala-

Gly; (SEQ ID No.136) wherein Xaa can be any amino acid, preferred cysteine residues.The antigenic dna sequence dna that coding is accredited as above-mentioned (g) provides in SEQ ID No.52, and SEQ ID No.52 encoded polypeptides provides in SEQ ID No.53.The antigenic dna sequence dna that coding is accredited as above-mentioned (a) provides in SEQ ID No.101, and its deduced amino acid provides in SEQ ID No.102.Dna sequence dna corresponding to above-mentioned antigen (d) provides in SEQ ID No.24, provides in SEQ ID No.25 and provides in SEQ ID No.99 corresponding to the dna sequence dna of above-mentioned antigen (i) corresponding to the dna sequence dna of above-mentioned antigen (c); Its deduced amino acid provides in SEQ IDNo.100.

In further specific embodiment, the invention discloses and comprise the antigen of mycobacterium tuberculosis that has one of following N-end sequence at least, perhaps have only conservative property to replace and/or modify the polypeptide of the immunogenicity part of its different variants:

(m)??Xaa-Tyr-Ile-Ala-Tyr-Xaa-Thr-Thr-Ala-Gly-Ile-Val-Pro-Gly-Lys-

Ile-Asn-Val-His-Leu-Val；(SEQ?ID?No?137)or

(n)??Asp-Pro-Pro-Asp-Pro-His-Gln-Xaa-Asp-Met-Thr-Lys-Gly-Tyr-

Tyr-Pro-Gly-Gly-Arg-Arg-Xaa-Phe; (SEQ ID No.129) wherein Xaa can be any amino acid, preferred cysteine residues.

In other specific embodiments, the invention discloses the polypeptide of the immunogenicity part of the solubility antigen of mycobacterium tuberculosis (perhaps so antigenic variant) that comprises the one or more aminoacid sequences that comprise following sequence encoding at least: (a) SEQ ID Nos.1,2,4-10,13-25 and 52 dna sequence dna; (b) complement of such dna sequence dna, perhaps (c) with (a) or the homologous dna sequence dna basically of the sequence (b).

In another specific embodiments, the invention discloses what comprise one or more aminoacid sequences of comprising following sequence encoding at least may be the polypeptide of the immunogenicity part of antigen of mycobacterium tuberculosis solubility or that may be insolubility (perhaps so antigenic variant): (a) SEQ ID Nos.26-51,138,139,163-183 and 201 dna sequence dna; (b) complementary sequence of such dna sequence dna, perhaps (c) with (a) or the homologous dna sequence dna basically of the sequence (b).

In the above in the specific embodiment of being discussed, antigen of mycobacterium tuberculosis comprise basically with here the variant of one or more dna sequence dna homologous dna sequence encodings of concrete citation." homology basically ", as used herein, refer to the dna sequence dna that under medium stringent condition, can hybridize.Suitable medium stringent condition is included in 5X SSC, 0.5%SDS, flushing in advance in 1.0mMEDTA (pH8, the 0) solution; At 50 ℃-65 ℃, among the 5X SSC hybridization spend the night, perhaps under hybridization-species (cross-species) homology situation at 45 ℃, 0.5X SSC; Then each with the 2X that contains 0.1%SDS, 0.5X and 0.2X SSC wash twice 65 ℃ of flushings 20 minutes.Such hybrid dna sequence also within the scope of the present invention, this is owing to the encode nucleotide sequence of immunogenic polypeptide of hybrid dna sequence encoding of degeneracy of the code.

At related aspect, the invention provides the variant of the fused protein that comprises first and second polypeptide of the present invention or polypeptide of the present invention and known antigen of mycobacterium tuberculosis and such fusion rotein, wherein said known antigen of mycobacterium tuberculosis is for example Andersen and Hansen, Infect.Immun.57:2481-2488,1989, the middle 38kD antigen of describing, (gene pool registration number No.M30046) or ESAT-6 (SEQ ID Nos.103 and 104).Fusion rotein of the present invention also can comprise the joint peptide between first and second polypeptide.

The dna sequence dna of code book invention fusion rotein is to be assembled in the suitable expression vector and to make up with will the encode dna sequence dna that separates of first and second polypeptide of known recombinant DNA technology.Have or do not have under the peptide linker situation, 3 ' the end of dna sequence dna of first polypeptide of encoding is connected in 5 ' end of the dna sequence dna of coding second polypeptide, makes the frame of calling sequence be in the state that the bioactive single fusion rotein that keeps first and second polypeptide is translated into two dna sequence dna mRNA in permission.

The peptide linker sequence can be used for to separate first and second polypeptide with guaranteeing the distance that each polypeptide is folded into its secondary and tertiary structure.Such peptide linker sequence is inserted in the fusion rotein with standard technique well known in the art.Suitable peptide linker sequence can be that the basis is selected with following factor: it adopts the ability of flexible extensions conformation (1); (2) its can not form with first and second polypeptide on the interactional secondary structure of functional epitope; (3) cannot with the hydrophobic or charged residue of polypeptide functional epitope reaction.Preferred peptide linker sequence comprises Gly, Asn and Ser residue.Other is near neutral amino acid, and for example Thr and Ala also can use in joint sequence.The aminoacid sequence that can usefully be used as joint comprises Maratea etc., gene (Gene) 40:39-46,1985; Murphy etc., periodical (Pro.Natl.Acad.Sci.USA) 83:8258-8262 of institute of NAS, 1986; Those disclosed sequence in U.S. Patent number 4935233 and the U.S. Patent number 4751180.Joint sequence length can be about 1 to about 50 amino acid.When having the non-basic-terminal amino acid district that can be used for the divided function district and prevent spatial interference, first and second polypeptide do not need these peptide sequences.

The dna sequence dna that connects can be operatively connected in suitable transcribing or translation adjusting element.DNA is expressed 5 ' end that the regulatory element that works only is positioned at the dna sequence dna of coding first polypeptide.Stop translation similarly, and the required terminator codon of transcription termination signal just is present in 3 ' end of the dna sequence dna of second polypeptide of encoding.

On the other hand, the invention provides the method for inducing the antituberculotic protection immunity of patient with one or more aforementioned polypeptides or fusion rotein (dna molecular of such polypeptide of perhaps encoding).As used herein, " patient " refers to all warm-blooded animals, preferred people.The patient can be ill, and perhaps can be have disease and/or the infection that can find.In other words, can bring out the protection immunity and prevent or treat tuberculosis.

Aspect this, polypeptide, fusion rotein or dna molecular generally are present in pharmaceutical composition and/or the vaccine.Pharmaceutical composition can contain one or more polypeptide, and these polypeptide can comprise one or more above-mentioned sequences (perhaps its variant) separately and physiology can be accepted carrier.Vaccine can contain one or more aforementioned polypeptides and nonspecific immune response toughener, for example adjuvant or liposome (polypeptide is incorporated into wherein).Such pharmaceutical composition and vaccine can also contain other antigen of mycobacterium tuberculosis, perhaps are incorporated in the combination polypeptide or are present in separately the polypeptide.

Perhaps, vaccine can contain the DNA of aforesaid one or more polypeptide of encoding, and makes original position produce polypeptide.In such vaccine, DNA may reside in and well known to a person skilled in the art any various sending in the delivery system, comprises the expression of nucleic acid system, bacterium and virus expression systems.Suitable expression of nucleic acid system comprises and is used for the essential dna sequence dna (for example suitable promotor and termination signal) of expressing the patient.Bacterium send delivery system to comprise to give the bacterium (for example Bacillus-Calmette-Guerrin) in the immunogenicity part of its cell surface expression polypeptide.In preferred embodiments, can use virus expression systems (for example cowpox or other poxvirus.Retrovirus or adenovirus) introduce DNA, it can comprise (damaged) of using avirulence, replication-competent virus.The technology that DNA is inserted in such expression vector is well known to a person skilled in the art.DNA can be " exposing ", as for example Ulmer etc., and science 259:1745-1749,1993 and Cohen, science 259:1691-1692, described in 1993 summaries.By DNA is wrapped quilt to fully sending the absorption that can improve exposed DNA on the biodegradable pearl that is delivered in the cell.

At related aspect, dna vaccination described above can give simultaneously or give successively with polypeptide of the present invention or for example above-mentioned 38kD antigen of known antigen of mycobacterium tuberculosis.For example, as mentioned above, perhaps " expose " or in sending delivery system, give the DNA of code book invention polypeptide, can give antigen afterwards, in order to strengthen the vaccine protective immune effect.

Giving approach and frequency and dosage can be along with individual and individual and different, and those the parallel uses that can use in the immunization of use BCG with routine.Generally speaking, pharmaceutical composition and vaccine can be by injections (for example intracutaneous, intramuscular, intravenously or subcutaneous), (for example by sucking) or orally give in the nose.Can give 1-36 the cycle in week with 1 to 3 dose.Preferably, give 3 doses,, and after this can periodically give booster shot with 3-4 month interval.For each patient's change scheme is suitable.When giving as mentioned above, proper dosage be can in the patient of immunity, produce be enough to protect the patient at least 1-2 do not infect the polypeptide of immunne response of mycobacterium tuberculosis or the amount of DNA.Generally speaking, the amount of the polypeptide that exists in the dosage (perhaps in the dosage by the DNA original position produce amount) scope is every kilogram of about 1pg of host to about 100mg, generally is about 10pg to about 1mg, preferably from about 100pg to about 1 μ g.The proper dosage specification will be different along with patient's body weight, but general range is that about 0.1mL is to about 5mL.

Well known to a person skilled in the art any suitable carriers although can use in the pharmaceutical composition of the present invention, bearer type will depend on administering mode and change.For administered parenterally, for example subcutaneous injection, carrier preferably contains water, salt solution, alcohol, fat, wax or damping fluid.For oral administration, can use any above-mentioned carrier or solid carrier, for example mannitol, lactose, starch, Magnesium Stearate, soluble saccharin, talcum, Mierocrystalline cellulose, glucose, sucrose and magnesiumcarbonate.Biodegradable microsphere (for example polylactic galactide) also can be as the carrier of pharmaceutical composition of the present invention.Suitable biodegradable microsphere for example is disclosed in U.S. Patent number 4897268 and 5075109.

Can use any various adjuvant to come non-specific enhancing immunity to reply in the vaccine of the present invention.Most of adjuvants contain design protects the not quick catabolic material of antigen, for example nonspecific stimulation agent of aluminium hydroxide or mineral oil and immunne response, lipid A for example, Bortadella pertussis, or mycobacterium tuberculosis.Suitable adjuvant is commercial buying, for example Freund's incomplete adjuvant and Freund's complete adjuvant (Difco Laboratories) and Merck adjuvant 65 (Merk and Company, Inc., Rahway, NJ).Other suitable adjuvant comprises alum, biodegradable microsphere, a phosphoryl lipid A and a quilA.

On the other hand, the invention provides the method for above-mentioned one or more polypeptide of using with the skin test diagnosis of tuberculosis.As used herein, " skin test " is the test of directly patient being carried out, and wherein measures delaying type hypersensitivity (DTH) reaction (for example swelling reddens or dermatitis) after above-mentioned one or more polypeptide of intradermal injection.Such injection can be used and be enough to make any suitable device that polypeptide contacts with patient's chrotoplast for example tuberculin syringe or 1mL syringe are realized.Preferably, injected back 48 hours, more preferably 48-72 hour, check reaction.

The DTH reaction is a cell-mediated immune responses, is exposed to the patient of test antigen (i.e. the immunogenicity part of the polypeptide of Shi Yonging, perhaps its variant) in advance, and the DTH reaction is bigger.Reaction can be estimated with ruler.Generally speaking, diameter is greater than about 0.5cm, and preferred diameter is positive reaction greater than the reaction of about 1.0cm, and showing has tuberculosis infection, and it can show as active disease or not show as active disease.

Polypeptide of the present invention preferably is mixed with and uses in the skin test, contains the pharmaceutical composition that aforementioned polypeptides and physiology can be accepted carrier.Such composition generally contains scope in the 0.1mL volume be extremely about 100 μ g of about 1 μ g, and preferably approximately 10 μ g are to one or more aforementioned polypeptides of about 50 μ g amount.Preferably, the carrier that uses in such pharmaceutical composition is that suitable sanitas for example phenol and/or Tween80 are arranged ^TMSalts solution.

In preferred embodiments, the polypeptide that uses in the skin test has enough sizes, makes the time of being detained reaction time at injection point.Generally speaking, at least 9 amino acid whose polypeptide of length are enough.Polypeptide also preferably injection hour in decomposed to be by scavenger cell and to pass T-cell.Such polypeptide can contain one or more above-mentioned sequences of some multiple and/or other immunogenicity or non-immunogenic sequence.

Provide the following examples by detailed description, but whether limit the present invention.

Embodiment

Embodiment 1

Purifying and sign from the polypeptide of mycobacterium tuberculosis culture filtrate

This embodiment describes in detail and prepares the mycobacterium tuberculosis soluble polypeptide from culture filtrate.Except as otherwise noted, all per-cents in the following examples are weightmeasurement ratios.

Mycobacterium tuberculosis (H37Ra, ATCC No.25177, perhaps H37Rv, one of ATCCNo.25618) was cultivated 14 days down at 37 ℃ in sterilization GAS substratum.Then by 0.45 μ strainer with substratum vacuum filtration (remove bulk cell) in sterilization 2.5L bottle.Then substratum is filled in the sterilization 4L bottle, and in culturing filtrate, adds NaN by 0.2 μ strainer ₃To 0.04% concentration.Then bottle is placed 4 ℃ of cold houses.

Cross and the 400mL Amicon agitated pool that comprises 10000kDa MWCO film concentrates culturing filtrate by filtrate being placed autoclaved 12L holder and filtrate being joined with alcohol flushing.Use nitrogen that pressure is remained on 60psi.This process reduces to about 50mL with the 12L volume.

, with two kinds of different ammonium bicarbonate solns culturing filtrate is carried out dialysis in 0.1% bicarbonate of ammonia with 8000kDa MWCO cellulose ester membrane.(Pierce, Rockford IL) measure protein concn by the commercial BCA test that gets then.

The culturing filtrate of freeze-drying dialysis then, polypeptide is suspended in distilled water again.Polypeptide is to 0.01mM1, two [three (hydroxymethyl)-methylaminos] propane of 3-, pH 7.5 (Bis-Tris propane damping fluid), the starting condition of anion-exchange chromatography, dialysis.(Perseptive BioSystems, Framingham MA) go up a large amount of chromatograms of use gel and carry out fractional separation equilibrated POROS 146 II Q/M anion-exchange column 4.6mm * 100mm in 0.01mM Bis-Tris propane pH of buffer 7.5.In above-mentioned buffering system with linear 0-0.5M NaCl gradient elution polypeptide.Monitoring post elutriant under wavelength 220nm.

The polypeptide set liquid and the freeze-drying that go out with distill water dialysis wash-out from the ion exchange column.With the substance dissolves that obtains in 0.1% trifluoroacetic acid (TFA) the pH1.9 aqueous solution, and the Delta-PakC18 pillar (Waters, Milford, MA) 300 dust cell sizes, (3.9 * 150mm) go up purified polypeptides to 5 micron particle degree.With linear gradient 0-60% dilution buffer liquid (acetonitrile solution of 0.1%TFA) wash-out polypeptide from the pillar.Flow velocity is 0.75mL/ minute, and at 214nm monitoring HPLC elutriant.Collection contains the fraction of the polypeptide that wash-out goes out, and makes the purity maximum of each sample.Obtain the polypeptide of about 200 purifying.

Then the polypeptide screening of purifying is induced the ability of T-cell proliferation in the PBMC preparation.Positive and its T-cell shows the PBMCs of the donor of replying PPD and breeding and cultivates in RPMI 1640 substratum that contain the human serum that is supplemented with 10% set and 50 μ g/mL gentamicins from the thick soluble protein of MTB from known PPD skin test.The polypeptide that adds the double purifying, concentration 0.5-10 μ g/mL.200 μ L volumes were cultivated after 6 days in 96-hole circle base plate, take out 50 μ L substratum and measure IFN-γ level from each hole, and are as described below.Contain the tritium thymidine to dull and stereotyped pulse 18 minutes again with 1 μ Ci/ hole then, results and the tritium that absorbs with gaseous scintillation counter mensuration.Cause in two repeat samples breeding ratio big triple fraction of the viewed propagation of cultured cells in the single culture base to think male.

IFN-γ measures with enzyme-linked immunosorbent assay (ELISA).(Pharmingen, San Diego CA) at room temperature wrap by elisa plate 4 hours with the mouse monoclonal antibody of anti-people IFN-γ among the PBS.The PBS that contains 5% (W/V) skim-milk then under the room temperature was with hole sealing 1 hour.Then flat board is washed in PBS/0.2%TWEEN-20 6 times, and the sample that diluted in substratum 1: 2 in the ELISA flat board is incubated overnight at room temperature.Washing plate once more, and in each hole, be added in the anti-people IFN-of the multi-clone rabbit γ serum that dilutes 1: 3000 times in the PBS/10% normal goats serum.Afterwards, flat board is incubation 2 hours at room temperature, flushing, and with in the PBS/5% skim-milk, dilute extraordinarily go at 1: 2000 horseradish peroxidase-link coupled anti--rabbit igg (SigmaChemical So., St.Louis, MO).2 hours post-flush of incubation are dull and stereotyped and add TMB matrix again under the room temperature.Use 1N sulfuric acid termination reaction after 20 minutes.Measure optical density(OD) as the reference wavelength at 450nm with 570nm.The OD that two repeat samples provide recently from the average OD big two of single culture base cultured cells extraordinarily the fraction of 3 standard deviations think male.

For order-checking, each drying of polypeptide is placed Biobrene ^TM(Perkin Elmer/AppliedBioSystems Division, Foster City, the glass fibre filter of CA) handling.The strainer that has polypeptide is downloaded on Perkin Elmer/Applied BioSystems Division Procise 492 protein sequencers.With traditional Ai Deman chemistry polypeptide is checked order from N-terminal.By relatively the residence time of PTH amino acid derivative and suitable PTH derivative standard are measured aminoacid sequence to every peptide species.

Use aforesaid method, separated antigen with following N-end sequence:

(a)???Asp-Pro-Val-Asp-Ala-Val-Ile-Asn-Thr-Thr-Xaa-Asn-Tyr-Gly-

Gln-Val-Val-Ala-Ala-Leu；(SEQ?ID?No.54)

(b)???Ala-Val-Glu-Ser-Gly-Met-Leu-Ala-Leu-Gly-Thr-Pro-Ala-Pro-

Ser；(SEQ?ID?No.55)

(c)???Ala-Ala-Met-Lys-Pro-Arg-Thr-Gly-Asp-Gly-Pro-Leu-Glu-Ala-

Ala-Lys-Glu-Gly-Arg；(SEQ?ID?No.56)

(d)???Tyr-Tyr-Trp-Cys-Pro-Gly-Gln-Pro-Phe-Asp-Pro-Ala-Trp-Gly-

Pro；(SEQ?ID?No.57)

(e)???Asp-Ile-Gly-Ser-Glu-Ser-Thr-Glu-Asp-Gln-Gln-Xaa-Ala-Val；

(SEQ?ID?No.58)

(f)???Ala-Glu-Glu-Ser-Ile-Ser-Thr-Xaa-Glu-Xaa-Ile-Val-Pro；(SEQ?ID

No.59)

(g)???Asp-Pro-Glu-Pro-Ala-Pro-Pro-Val-Pro-Thr-Ala-Ala-Ala-Ala-

Pro-Pro-Ala; (SEQ ID No. 60) and

(h)???Ala-Pro-Lys-Thr-Tyr-Xaa-Glu-Glu-Leu-Lys-Gly-Thr-Asp-Thr-

Gly; (SEQ ID No.61) wherein Xaa can be any amino acid.

In addition to the above methods, separate other antigen with microbore HPLC purification step.Particularly, 20 μ L contain fraction from the antigenic mixture of previously described chromatographic purification step in Perkin Elmer/Applied BioSystems Division Model 172 HPLC, 7 microns cell sizes, Aquapore C18 pillar (the PerkinElmer/Applied BioSystems Division of pillar specification 1mm * 100mm, Foster City CA) goes up purifying.With 1% of linear gradient/minute the aqueous solution (0.05%TFA) of acetonitrile (containing 0.05%TFA) with 80 μ L/ minute flow velocitys elutriated fraction from the pillar.At 250nm monitoring elutriant.The source class branch is divided into 4 main peaks adds other than small component, obtain polypeptide, it shows have 12.054Kd (passing through mass spectrum) molecular weight and following N-end sequence:

(i)??Asp-Pro-Ala-Ser-Ala-Pro-Asp-Val-Pro-Thr-Ala-Ala-Gln-Gln-

Thr-Ser-Leu-Leu-Asn-Asn-Leu-Ala-Asp-Pro-Asp-Val-Ser-Phe-

Ala-Asp (SEQ ID No.62). this polypeptide uses above-mentioned test chart to reveal and induce propagation and IFN-γ generation in the PBMC preparation.

Other soluble antigen is as described below to be separated from the mycobacterium tuberculosis culturing filtrate.Prepare the mycobacterium tuberculosis culturing filtrate as mentioned above.To Bis-Tris propane damping fluid, after the pH5.5 dialysis, be Bis-Tris propane damping fluid with anion-exchange chromatography, carry out fractional separation on PorosQE pillar 4.6 * 100mm (Perseptive Biosystems) that balance is crossed among the pH5.5.With the flow velocity wash-out polypeptide of above-mentioned buffering system neutral line 0-1.5M NaCl gradient with 10mL/ minute.In 214nm wavelength monitoring post elutant.

The fraction that set goes out from the ion exchange column wash-out, and carry out reverse-phase chromatography with Poros R2 post 4.6 * 100mm (Perseptive Biosystems).With linear gradient 0-100% acetonitrile (0.1%TFA) with 5mL/ minute flow velocity from pillar wash-out polypeptide.At 214nm monitoring elutriant.

Freeze-drying contains the fraction of the polypeptide that washes out and is suspended in again among the aqueous 0.1%TFA of 80 μ, further make (Western Analytical at Vydac C4 post 4.6 * 150mm, Temecula CA) carries out reverse-phase chromatography with linear gradient 0-100% acetonitrile (0.1%TFA) with 2mL/ minute flow velocity.At 214nm monitoring elutriant.

The fraction of biologically active is divided into a main peak and adds other than small component.The western blotting of this peak on pvdf membrane provides 3 master tapes, and molecular weight is 14Kd, 20Kd and 26Kd.Measure these polypeptide, they have following N-end sequence respectively:

(j)??Xaa-Asp-Ser-Glu-Lys-Ser-Ala-Thr-Ile-Lys-Val-Thr-Asp-Ala-

Ser；(SEQ?ID?No.134)

(k)??Ala-Gly-Asp-Thr-Xaa-Ile-Tyr-Ile-Val-Gly-Asn-Leu-Thr-Ala-

Asp; (SEQ ID No.135) and

(l)??Ala-Pro-Glu-Ser-Gly-Ala-Gly-Leu-Gly-Gly-Thr-Val-Gln-Ala-

Gly; (SEQ ID No.136), wherein Xaa can be any amino acid.

Use above-mentioned test, these peptides show induces propagation and IFN-γ to produce in the PBMC preparation.Figure 1A and B provide such test result of using from the PBMC preparation of first and second donors respectively.

By ³²The obtaining coding corresponding to N-end sequence and the oligonucleotide screening-gene group mycobacterium tuberculosis library that comprises the degeneracy of mycobacterium tuberculosis codon bias and above be denoted as (a) of P end mark, (c), (d) and antigenic dna sequence dna (g).Screening is carried out with the probe corresponding to above-mentioned antigen (a) that the clone with sequence that SEQ IDNo.101 provides identifies.SEQID No.102 provides SEQ ID No.101 encoded polypeptides.Screening is carried out with the probe corresponding to above-mentioned antigen (g) that the clone with sequence that SEQ ID No.52 provides identifies.SEQ ID No.53 provides SEQ ID No.52 encoded polypeptides.Screening is carried out with the probe corresponding to above-mentioned antigen (d) that the clone with sequence that SEQ ID No.24 provides identifies, and screening is carried out with the probe corresponding to above-mentioned antigen (c) that the clone with sequence that SEQID No.25 provides identifies

With DNA STAR system above-mentioned aminoacid sequence is compared with known aminoacid sequence in the gene pool.The data retrieved storehouse comprises 173000 kinds of protein and is Swiss, the combination of the protein sequence of PIR database and translation (87 editions).Do not check out with antigen (a)-(h) and (l) the obvious homology of aminoacid sequence.

Find the aminoacid sequence of antigen (i) and sequence homology from leprosy mycobacterium (M.leprae).Total length leprosy mycobacterium uses the sequence that obtains from GENEBANK to increase from genomic dna.Use this sequence screening such as following embodiment 2 described mycobacterium tuberculosis libraries then, and obtain the total length copy (SEQ ID No.99) of mycobacterium tuberculosis homologue.

Find the aminoacid sequence and the known mycobacterium tuberculosis protein matter homology of translating from dna sequence dna of antigen (j).Known to the contriver, before do not disclose this protein and had the T-cell-stimulating activity.The amino acid of finding antigen (k) is with relevant from the sequence of leprosy mycobacterium.

In above-mentioned propagation and IFN-γ test with the positive donor of 3 PPD, the representative antigenic result who provides above has been provided table 1:

The result of table 1PBMC propagation and IFN-γ test

Sequence	Propagation	????IFN-γ
			????(a)	????+	????-
????(c)	????+++	????+++
			????(d)	????++	????++
????(g)	????+++	????+++
			????(h)	????+++	????+++

In table 1, provide stimulation index (SI) between 2 and 4 (comparing) with cultured cells in the independent substratum reply mark for+, concentration be 1 μ g or more a hour SI be that 4-8 or 2-4 mark are ++, SI greater than 8 marks is +++.In propagation and IFN-γ test, find that for a donor antigen of sequence (i) has high SI (+++), and provide low SI (++ with+) for other two donors.These results show that these antigens can induce propagation and/or interferon-to produce.

Embodiment 2

Separate antigen of mycobacterium tuberculosis with the patients serum

This embodiment describes in detail by using serum from the individuality of m tuberculosis infection to screen from the mycobacterium tuberculosis lysate and separates antigen.

In 2%NP40 solution, add exsiccant mycobacterium tuberculosis H37a (DifcoLaboratories), and alternately homogenizing and ultrasonic three times.The suspension that obtains is centrifugal and make supernatant liquor pass through 0.2 micron syringe filter with 13000rpm in little centrifuge tube.Filtrate and Macro Prep DEAE bead (BioRad, Hercules) combination.Bead fully washes with 20mM Tris pH7.5, and with the albumen of 1M sodium-chlor elution of bound.With 10mM Tris pH7.5 with 1M sodium-chlor elutriant dialysed overnight.The solution of dialysis was at room temperature handled 30 minutes with 0.05mg/mLDNase and RNase, used α-D-mannosidase then, and 0.5U/mg, pH4.5 at room temperature handle the solution of dialysis.Material passes through the FPLC fractional separation through Bio Scale-Q-20 pillar (BioRad) after returning pH7.5.Fraction is divided into 9 set, at Centriprep10 (Amicon, Beverley uses after centrifugal in MA) serum set liquid from the patient who other antigen of the present invention is not had immunoreactive m tuberculosis infection by western blotting screening serology activity.

Have most reactive fraction and carry out SDS-PAGE.And transfer to PVDF.Downcut the band of about 85Kd, obtain following sequences:

(m)??Xaa-Tyr-Ile-Ala-Tyr-Xaa-Thr-Thr-Ala-Gly-Ile-Val-Pro-Gly-Lys-

Ile-Asn-Val-His-Leu-Val; (SEQ ID No.137), wherein Xaa can be any amino acid.

This sequence is compared with the sequence in the aforesaid gene pool, and showing with known sequences does not have tangible homology.

By using oligonucleotide screening-gene group mycobacterium tuberculosis Erdman bacterial strain library to obtain the dna sequence dna that coding above is denoted as (m) corresponding to the degeneracy of the mark of SEQ ID NO:137.Through identifying that this clone has the dna sequence dna that SEQ ID NO:203 provides.Find the aminoacid sequence that this sequence encoding SEQ ID NO:204 provides.With these sequences compare with the sequence of gene pool show with before mycobacterium tuberculosis and Mycobacterium bovis (M.bovis).

Embodiment 3

The preparation of the dna sequence dna of coding antigen of mycobacterium tuberculosis

This embodiment describes the serum that obtains from the patient with m tuberculosis infection by using in detail, perhaps prepares the dna sequence dna of the antigen of mycobacterium tuberculosis of encoding with the antiserum(antisera) screening mycobacterium tuberculosis expression library of anti-solubility antigen of mycobacterium tuberculosis.A. the rabbit anti-serum with the Killing Mycobacterium Tuberculosis supernatant liquor prepares the mycobacterium tuberculosis soluble antigen

From mycobacterium tuberculosis bacterial strain H37Ra isolation of genomic DNA.Random shearing DNA also is used for making up use λ ZAP expression system (Stratagene, La Jolla, CA) D expression library.Produce Killing Mycobacterium Tuberculosis bacterial strain H37Ra, the rabbit anti-serum of the secreted protein of H37Rv and Erdman by concentrated supernatant immunize rabbit with the mycobacterium tuberculosis substratum.Particularly, with containing 10 μ g Muramyl dipeptides (Calbiochem, La Jolla, the 200 μ g proteantigen subcutaneous first time of immunize rabbits CA) and in the common 2mL volume of 1mL Freund's incomplete adjuvant.After 4 weeks, with the subcutaneous booster immunization of 100 μ g antigens in the Freund's incomplete adjuvant.At last, after 4 weeks with 50 μ g proteantigen intravenously immunity.As Sambrook etc., molecular cloning: laboratory manual, cold spring harbor laboratory, the cold spring port, NY, 1989 describedly screen expression library with antiserum(antisera).Purifying phage plaque is expressed immunoreactivity antigen.From plaque, reclaim phagemid and infer the nucleotide sequence of mycobacterium tuberculosis.

32 clones of purifying, 25 previous sequences of in the bacillus tuberculosis typus humanus, not identifying of representative.Express recombinant antigen, and in described immune analysis, use the antigen of purifying as embodiment.Protein is induced by IPTG and by gel wash-out purifying, as Skeiky etc., and J.Exp.Med.181:1527-1537,1995 is described.SEQ ID Nos:1-25 provides the representative series of the dna molecular of identifying in this screening.The aminoacid sequence of corresponding indication provides in SEQ IDNos:63-87.

With above-mentioned database these sequences are compared with the known sequences in the gene pool, find to be appointed as hereinafter TbRA2A, TbRA16, TbRA18 and TbRA29 (SEQ ID Nos.76,68,70,75) clone shows the homology in a way with the sequence of before identifying of still identifying in mycobacterium tuberculosis in the leprosy mycobacterium.TbRA11, TbRA26, TbRA28 and TbDPEP (SEQ ID Nos.65,73,74,53) before identified in mycobacterium tuberculosis.For TbRA1, TbRA3, TbRA4, TbRA9, TbRA10, TbRA13, TbRA17, TbRa19, TbRA29, TbRA32, TbRA36 and overlapping clone TbRA35 and TbRA12 (SEQ ID Nos.63,77,81,82,64,67,69,71,75,78,80,79,66) do not find significant homology.Clone TbRa24 and TbRa29 are overlapping.

The PBMC propagation that use is carried out representative recombinant antigen from the patient's of several different mycobacterium tuberculosis immunity T-cell preparation and the result of interferon-mensuration provide in table 2 and 3 respectively.

Table 2

Result to the PBMC of representative soluble antigen propagation

Antigen	The patient
															????1	????2	????3	????4	????5	????6	????7	????8	????9	????10	????11	????12	????13
TbRa1	????-	????-	????±	????++	????-	????-	????±	????±	????-	????-	????+	????±	????-
														TbRa3	????-	????±	????++	????-	????±	????-	????-	????++	????±	????-	????-	????-	????-
TbRa9	????-	????-	????nt	????nt	????++	????++	????nt	????nt	????nt	????nt	????nt	????nt	????nt
														TbRa10	????-	????-	????±	????±	????±	????+	????nt	????±	????-	????+	????±	????±	????-
TbRa11	????±	????±	????+	????++	????++	????+	????nt	????-	????++	????++	????++	????±	????nt
														TbRa12	????-	????-	????+	????+	????±	????++	????+	????±	????±	????-	????+	????-	????-
TbRa16	????nt	????nt	????nt	????nt	????-	????+	????nt	????nt	????nt	????nt	????nt	????nt	????nt
														TbRa24	????nt	????nt	????nt	????nt	????-	????-	????nt	????nt	????nt	????nt	????nt	????nt	????nt
TbRa26	????-	????+	????nt	????nt	????-	????-	????nt	????nt	????nt	????nt	????nt	????nt	????nt
														TbRa29	????nt	????nt	????nt	????nt	????-	????-	????nt	????nt	????nt	????nt	????nt	????nt	????nt
TbRa35	????++	????nt	????++	????++	????++	????++	????nt	????++	????++	????++	????++	????++	????nt
														TbRaB	????nt	????nt	????nt	????nt	????-	????-	????nt	????nt	????nt	????nt	????nt	????nt	????nt
TbRaC	????nt	????nt	????nt	????nt	????-	????-	????nt	????nt	????nt	????nt	????nt	????nt	????nt
														TbRaD	????nt	????nt	????nt	????nt	????-	????-	????nt	????nt	????nt	????nt	????nt	????nt	????nt
AAMK	????-	????-	????±	????-	????-	????-	????nt	????-	????-	????-	????nt	????±	????nt
														YY	????-	????-	????-	????-	????-	????-	????nt	????-	????-	????-	????nt	????+	????nt
DPEP	????-	????+	????-	????++	????-	????-	????nt	????++	????±	????+	????±	????±	????nt
														Contrast	????-	????-	????-	????-	????-	????-	????-	????-	????-	????-	????-	????-	????-

nt＝not?tested

Table 3

The result who produces for the OBMC interferon-of representative soluble antigen

Antigen	The patient
															????1	????2	????3	????4	????5	????6	????7	????8	????9	????10	????11	????12	????13
TbRa1	????+	????++	????-	????+++	????+	????-	????-	????±	????-	????-	????+	????±	????-
														TbRa3	????-	????±	????++	????-	????±	????-	????-	????++	????±	????-	????-	????-	????-
TbRa9	????++	????+	????nt	????nt	????++	????-	????nt	????nt	????nt	????nt	????nt	????nt	????nt
														TbRa10	????+	????+	????±	????±	????±	????+	????nt	????±	????-	????+	????±	????±	????-
TbRa11		????±	????+	????++	????++	????+	????nt	????-	????++	????++	????++	????±	????nt
														TbRa12	????-	????-	????+	????+	????±	????+++	????+	????±	????±	????-	????+	????-	????-
TbRa16	????nt	????nt	????nt	????nt	????+	????+	????nt	????nt	????nt	????nt	????nt	????nt	????nt
														TbRa24	????nt	????nt	????nt	????nt	????+	????-	????nt	????nt	????nt	????nt	????nt	????nt	????nt
TbRa26	????++	????++	????nt	????nt	????+	????+	????nt	????nt	????nt	????nt	????nt	????nt	????nt
														TbRa29	????nt	????nt	????nt	????nt	????+	????-	????nt	????nt	????nt	????nt	????nt	????nt	????nt
TbRa35	????++	????nt	????++	????++	????+++	????+++	????nt	????++	????++	????+++	????+++	????++	????nt
														TbRaB	????nt	????nt	????nt	????nt	????++	????+	????nt	????nt	????nt	????nt	????nt	????nt	????nt
TbRaC	????nt	????nt	????nt	????nt	????+	????+	????nt	????nt	????nt	????nt	????nt	????nt	????nt
														TbRaD	????nt	????nt	????nt	????nt	????+	????+	????nt	????nt	????nt	????nt	????nt	????nt	????nt
AAMK	????-	????-	????±	????-	????-	????-	????nt	????-	????-	????-	????nt	????±	????nt
														YY	????-	????-	????-	????-	????-	????-	????nt	????-	????-	????-	????nt	????+	????nt
DPEP	????+	????+	????+	????+++	????+	????-	????nt	????+++	????±	????+	????±	????±	????nt
														Contrast	????-	????-	????-	????-	????-	????-	????-	????-	????-	????-	????-	????-	????-

In table 2 and 3, provide 1.2 and 2 (with separately in substratum cultured cells compare) between stimulation index (SI) reply scoring for ±, the SI of 2-4 scoring for+, the SI of 4-8 or 2-4 scoring is when 1 μ g or littler concentration ++, greater than 8 SI scoring be +++.In addition, the influence of concentration to two kinds propagation in the above-mentioned antigen and interferon-generation has been described in the accompanying drawing.Produce both for propagation and interferon-, TbRa3 marks and is ++ with TbRa9 be+.

These results show that these soluble antigens can induce propagation and/or interferon-to produce in the T-cell from the individuality of mycobacterium tuberculosis immunity.B. use dna sequence dna from the serum identification code antigen of mycobacterium tuberculosis of suffering from lung or tuberculous pleuritis patient

Use set liquid screening said gene group DNA library and other H37Rv library from the serum of suffering from active patient lungy.Separate mycobacterium tuberculosis bacterial strain H37Rv genomic dna in order to prepare the H37Rv library, make part Sau3A digestion and be used for λ Zap expression vector system (Stratagene, La Jolla, Ca) construction expression library.Use three parts of different serum set liquid in the expression screening, every part contains the serum of suffering from the individuality acquisition of active lung or pleural diseases from three.Set liquid is denoted as TbL, and TbM and TbH refer in ELISA and immunoblotting formate the correlated response (being the TbL=low reactivity, reactive and TbH=hyperergy among the TbM=) with the H37Ra lysate.Also used from the 4th serum set liquid suffering from active phthisical 7 patients.All serum not with the reactivity of the raising of recombinant chou 38kD mycobacterium tuberculosis H37Ra Phosphoric acid esterase-conjugated protein.

All set liquid intestinal bacteria preadsorption, and be used for screening H37Ra and H37Rv expression library, as Sambrook etc., molecular cloning: laboratory manual. cold spring harbor laboratory, the cold spring port, NY, 1989 is described.Purifying phage plaque is expressed immunoreactivity antigen.Reclaim phasmid from plaque, and derive mycobacterium tuberculosis clone's nucleotide sequence.

32 clones of purifying, wherein 31 previous sequences of in the bacillus tuberculosis typus humanus, not identifying of representative.The representative series of the dna molecular of identifying provides in SEQ ID Nos:26-51 and 105.Wherein TbH-8-2 (SEQ ID No.105) is the second stage clone of TbH-8, and TbH-4 (SEQ ID No.43) is the not contiguous sequence from identical clone with TbH-4-FWD (SEQ ID No.44).Hereinafter be accredited as Tb38-1, TbH-4, TbH-8, the antigenic aminoacid sequence of TbH-9 and TbH-12 is seen SEQ ID Nos.88-92.Use the database of above identifying that these sequences are compared with the known sequences in the gene pool, show and TbH-4, TbH-8, TbH-9 and TbM-3 do not have tangible homology, but find with TbH-9 weak homology is arranged.Find that TbH-12 is that the 34kD antigen protein of before identifying at M.paratuberculosis (Acc.No.S28515) is a homologue.Find that Tb38-1 is arranged in before 34 base pair upstreams of the open reading-frame (ORF) of the antigen ESAT-6 (Sorensen etc., Infec.Immun.63:1710-1717,1995) that identifies at Mycobacterium bovis (Acc.No.U34848) and mycobacterium tuberculosis.

Using from the both is that the probe of isolating Tb38-1 and TbH-9 from the H37Ra library is identified the clone among the H37Rv.Tb38-1 and Tb38-1F2, Tb38-1F3, Tb38-1F5 and Tb38-1F6 (SEQ ID Nos:112,113,116,118 and 119) hybridization.Derive two open reading-frame (ORF)s among (SEQ IDNos:112 and 113 is the not contiguous sequence from clone Tb38-1F2) Tb38-1F2; One second, partial sequence may be the homologue of Tb38-1 corresponding to Tb37FL (SEQ ID No.114), and is called Tb38-IN (SEQ ID No.115).The Tb38-1F3 deduced amino acid provides at SEQ ID No.117.The TbH-9 probe is identified three clone: TbH-9-FL (SEQ ID No.106) in the H37Rv library, it may be the homologue (H37Ra) of TbH-9, TbH-9-1 (SEQ ID No.108), and TbH-9-4 (SEQ ID No.110), all is and the sequence of TbH-9 height correlation.These three clones' deduced amino acid is in that (SEQ ID Nos:107 provides in 109 and 111.

As mentioned above, further screen the mycobacterium tuberculosis genome dna library, found that 10 other reactivity clones, represent 7 different genes.One in these genes is accredited as 38kD antigen discussed above, measures one and is accredited as before shows the 14kD α-heat of crystallization shock protein that exists in mycobacterium tuberculosis, measures the third and is accredited as above-mentioned antigen TbH-8.5 the remaining clones' that measure dna sequence dna (hereinafter being referred to as TbH-29, TbH-30, TbH-32 and TbH-33) provides in SEQ ID NO:138-141 respectively, and the aminoacid sequence of corresponding indication provides in SEQ ID NO:142-145 respectively.Those of these antigenic DNA and aminoacid sequence and said gene storehouse are compared.Do not find homology for 5 of TbH-29 ' terminal (it comprises reactive open reading-frame (ORF)), but find that 3 of TbH-29 ' is terminal identical with mycobacterium tuberculosis clay Y227.Find TbH-32 and TbH-33 respectively with the mycobacterium tuberculosis insertion element IS110 of previous evaluation and identical with mycobacterium tuberculosis clay Y50.Finding does not have significant homology with TbH-30.

Sambrook is described as mentioned, uses the positive phagemid ehec infection XL-1BlueMRF ' from this additional screening.Carry out inducing of recombinant protein by adding IPTG.Make inductive and do not have flow through SDS-PAGE and transfer to the Nitrocellulose filter of inductive lysate with double.Filter and have reactive bacillus tuberculosis typus humanus's serum (1: 200 extent of dilution) and partly have reactive rabbit anteserum (1: 200 or 1: 250 extent of dilution) reaction with the terminal 4Kd of the N-of lacZ with TbH.Serum is incubation 2 hours at room temperature.By adding ¹²⁵The a-protein of I-mark and then to be exposed to the film scope be 16 hours to 11 days different time to measure bonded antibody.The result of immunoblotting is summarised in the table 4.

Table 4

People M.tb resists-lacZ

Antigenemia purifies the blood clearly

TbH-29????45Kb??????????45Kb

TbH-30 does not have reactive 29Kb

TbH-32????12Kb??????????12Kb

TbH-33????16Kb??????????16Kb

The positive reaction of recombinant human antigen of mycobacterium tuberculosis and bacillus tuberculosis typus humanus's serum and anti--lacZ serum shows the reactivity sensing fused protein of bacillus tuberculosis typus humanus's serum.It may be the result of bacillus tuberculosis typus humanus's serum identification conformational epitope that antigen does not have reactivity with anti--responding property of lacZ serum with bacillus tuberculosis typus humanus's serum, perhaps the Ag-Ab binding kinetics may be so, makes that it is not enough exposing 2 hours in immunoblotting.

Show 5A below, B and 6 provides respectively Tb38-1, the result of the T-cell tests that ESAT-6 and other representative recombinant antigen carry out:

Table 5A

The result of representative antigenic PBMC propagation

Antigen	Donor
													????1	????2	????3	??4	????5	??6	????7	????8	????9	????10	????11
Tb38.1	??+++	????+	????-	??-	????-	??++	????-	????+	????-	????++	????+++
												ESAT-6	??+++	????+	????+	??+	????-	??+	????-	????+	????+	????++	????+++
TbH-9	??++	????++	????-	??++	????±	??±	????++	????++	????++	????++	????++

Table 5B

The result that representative antigen PBMC interferon-produces

Antigen	Donor
													????1	????2	????3	????4	????5	????6	????7	??8	??9	????10	????11
Tb38.1	??+++	????+	????-	????+	????+	????+++	??-	??++	??-	??+++	??+++
												ESAT-6	??+++	????+	????+	????+	????+-	????+	??-	??+	??+	??+++	??+++
TbH-9	??++	????++	????-	????+++	????±	????±	??+++	??+++	??++	??+++	??++

Table 6

The summary of representative antigenic T-cell response

Antigen	Propagation			Interferon-			Amount to
								The patient 4	The patient 5	The patient 6	The patient 4	The patient 5	The patient 6
	TbH9	??++	??++	????++	????+++	??++								??++	????13
TbM7							??-	??+	????-	????++	??+	??-	????4
	TbH5	??-	??+	????+	????++	??++								??++	????8
TbL23							??-	??+	????±	????++	??++	??+	????7.5
	TbH4	??-	??++	????±	????++	??++								??±	????7
Contrast							??-	??-	????-	????-	??-	??-	????0

These results show that antigen of mycobacterium tuberculosis of the present invention and ESAT-6 both induce from propagation in the T-cell of the individuality of mycobacterium tuberculosis immunity and/or interferon-and produce.Known to the contriver, do not shown before that ESAT-6 stimulated human immune.

Make up a series of 6 overlapping peptides of the aminoacid sequence that covers antigen Tb38-1 with the method for embodiment 6 descriptions.The sequence of these peptides, hereinafter being referred to as pep-6 provides in SEQ IDNos.93-98 respectively.Use the result of the T-raji cell assay Raji of these peptides in table 7 and 8, to provide.These results confirm this existence, and help to determine to induce the position of T-cell epitope among the Tb38-1 that produces from the propagation in the T-cell of the individuality of mycobacterium tuberculosis immunity and/or interferon-.

Table 7

The result of the PBMC propagation of Tb38-1 peptide

Peptide	The patient
															????1	????2	????3	????4	????5	????6	????7	????8	????9	????10	????11	????12	????13
pep1	????-	????-	????-	????-	????±	????-	????-	????-	????-	????±	????-	????-	????+
														pep2	????±	????-	????-	????-	????±	????-	????-	????-	????±	????±	????-	????-	????+
pep3	????-	????-	????-	????-	????-	????-	????-	????-	????±	????-	????-	????-	????±
														pep4	????++	????-	????-	????-	????-	????-	????+	????-	????±	????±	????-	????-	????+
pep5	????++	????±	????-	????-	????-	????-	????+	????-	????±	????-	????-	????-	????+
														pep6	????-	????++	????-	????-	????-	????-	????±	????-	????±	????+	????-	????-	????+
Contrast	????-	????-	????-	????-	????-	????-	????-	????-	????-	????-	????-	????-	????-

Table 8

The result of the interferon-propagation of Tb38-1 peptide

Peptide	The patient
															????1	????2	????3	????4	????5	????6	??7	????8	????9	????10	????11	????12	????13
pep1	????+	????-	????-	????-	????±	????-	??-	????-	????-	????±	????-	????-	????+
														pep2		????-	????-	????-	????±	????-	??-	????-	????±	????±	????-	????-	????+
pep3	????-	????-	????-	????-	????-	????-	??-	????-	????±	????-	????-	????-	????±
														pep4	????++	????-	????-	????-	????-	????-	??+	????-	????±	????±	????-	????-	????+
pep5	????++	????±	????-	????-	????-	????-	??+	????-	????±	????-	????-	????-	????+
														pep6	????+	????++	????-	????-	????-	????-	??±	????-	????±	????+	????-	????-	????+
Contrast	????-	????-	????-	????-	????-	????-	??-	????-	????-	????-	????-	????-	????-

Study and measure antigen TbH-9 and Tb38-1 and whether represent cell protein or be secreted in the mycobacterium tuberculosis substratum.In first research, use identical with the method for embodiment 3A description basically method to produce the protein of anti-(A) mycobacterium tuberculosis secretory of rabbit anteserum, (B) known secretion reorganization antigen of mycobacterium tuberculosis 85b, (C) reorganization Tb38-1 and (D) reorganization TbH-9.On the denaturant gel that is fixed on the Nitrocellulose film, separate total mycobacterium tuberculosis lysate, mycobacterium tuberculosis substratum and recombinant antigen 85b, the concentrated supernatant of TbH-9 and Tb38-1 is surveyed the double trace with above-mentioned rabbit anteserum.

Use control serum (I series) and the antisecretary protein of antiserum(antisera) (II series), recombinant chou 85b, the result of this analysis of recombinant chou Tb38-1 and recombinant chou TbH-9 sees Fig. 3 A-D respectively, wherein swimming lane is denoted as: 1) molecular weight protein matter standard; 2) 5 μ g mycobacterium tuberculosis lysates; 3) 5 μ g excretory protein; 4) 50ng recombinant chou Tb38-1; 5) 50ng recombinant chou TbH-9; With 6) 50ng recombinant chou 85b.With 6 artificial reconstructed recombinant chou antigens of terminal histidine residues, therefore expection is to move larger about the mobility of 1kD than natural protein.In Fig. 3 D, recombinant chou TbH-9 lacks about 10kD of total length 42kD, so the size of the natural TbH-9 of immunoreactivity has significant difference (shown in the arrow) in the lysate swimming lane.These results prove that Tb38-1 and TbH-9 are intramolecularly antigen and are not the active excretory of mycobacterium tuberculosis.

By measuring TbH-9-specificity human T cell clone to recombinant chou TbH-9, the reactivity of secretion property mycobacterium tuberculosis protein matter and PPD proof TbH-9 is the antigenic discovery of intramolecularly.TbH-9-specific T-cells clone (being denoted as 131 TbH-9) produces from the PBMC of the positive donor of healthy PPD-.131 TbH-9 are to excretory albumen, recombinant chou TbH-9 and contrast antigen of mycobacterium tuberculosis, and the propagation of TbRa11 is replied by the absorption according to the tritiate thymidine of embodiment 1 described mensuration and is measured.Shown in Fig. 4 A, clone 131TbH-9 specificity responds to TbH-9, shows that TbH-9 is not the proteic main component of mycobacterium tuberculosis secretory.Secreted protein is then used in the generation that the 2nd TbH-9 specificity T that Fig. 4 B explanation prepares from the PBMC from the positive donor of healthy PPD-is cloned the IFN-γ of (being denoted as PPD800-10), and PPD or recombinant chou TbH-9 stimulate the T cell clone.These results confirm that further TbH-9 is not a mycobacterium tuberculosis secretory.C. use DNA series from the patient's who suffers from extrapulmonary tuberculosis serum identification code antigen of mycobacterium tuberculosis

From mycobacterium tuberculosis Erdman strains separation genomic dna, random shearing, and be used for λ ZAP expression system (Stratagene, La Jolla, CA) construction expression library.Embodiment 3B is described as mentioned, uses the independent library of serum set liquid screening that obtains from the individuality of suffering from extrapulmonary tuberculosis, and second antibody is and the anti-human IgG+A+M of alkaline phosphatase link coupled goat (H+L).

Be purified into 18 clones.Find that wherein 4 clones (hereinafter being referred to as XP14, XP24, XP31 and XP32) have certain similarity with known series.SEQ ID Nos:156-158 provide XP14 respectively, the dna sequence dna of the mensuration of XP24 and XP31, and 5 of XP32 ' and 3 ' dna sequence dna provide at SEQ ID Nos:159 and 160 respectively.The aminoacid sequence of XP14 indication provides in SEQ ID Nos:161.The aminoacid sequence that provides among the reverse complementary sequence coding SEQ IDNos:162 of discovery XP14.

Remaining 14 clones (hereinafter are referred to as XP1-XP6, XP17-XP19, XP22, XP25, XP27, XP30 and XP36) sequence compare with the sequence in the said gene storehouse, show except finding that having 3 of the XP2 of certain homology and XP6 ' with known mycobacterium tuberculosis clay does not all have homology terminal.SEQ ID Nos:163 and 164 provides the dna sequence dna of XP27 and XP34 respectively, XP4, XP5,5 ' sequence of XP17 and XP30 provides in SEQID Nos:165-168 respectively, XP2, XP3, XP6, XP18, XP19,5 of XP22 and XP25 ' and 3 ' sequence are respectively in SEQ ID Nos:169 and 170; 173 and 172; 173 and 174; 175 and 176; 177 and 178; 179 and 180; With 181 and 182 in provide.Above disclose and found that the dna sequence dna of XP1 and TbH4 is overlapping.SEQ ID No.183 provides the full length DNA sequence of TbH4-XP1.Find that this dna sequence dna comprises the open reading-frame (ORF) of aminoacid sequence shown in the coding SEQ ID No.184.Find that the reverse complementary sequence of TbH4-XP1 comprises the open reading-frame (ORF) of aminoacid sequence shown in the coding SEQ ID No.185.Find that the dna sequence dna of XP36 comprises two open reading-frame (ORF)s of aminoacid sequence shown in the coding SEQ ID Nos.186 and 187, reverse complementary sequence comprises the open reading-frame (ORF) of aminoacid sequence shown in the coding SEQ ID No.188.

According to the described preparation recombinant chou of embodiment 3B XP2 protein, use the metal ion affinity chromatography post during purifying.Describe in detail as Fig. 8 A-B and 9A-B, use mensuration as described herein, find that recombinant chou XP1 stimulates cell proliferation and IFN-γ generation from the isolating T cell of mycobacterium tuberculosis immunity donor.D. the proteinic rabbit with the Killing Mycobacterium Tuberculosis fractional separation resists-serum pref mycobacterium tuberculosis soluble antigen

According to embodiment 2 described preparation mycobacterium tuberculosis lysates above.By HPLC with the material fractional separation that obtains, and use from show minimum or not with other antigenic immunoreactive m tuberculosis infection patient's of the present invention serum set liquid serology activity by western blotting screening fraction.The method of describing with embodiment 3A produces the anti-rabbit-antiserum(antisera) that has reactive fraction most.Screen the mycobacterium tuberculosis Erdman strain gene group DNA expression library of preparation as mentioned above with anti--serum.Purifying is expressed the antigenic phage plaque of immunoreactivity.From plaque, reclaim phasmid, and measure mycobacterium tuberculosis clone's nucleotide sequence.

10 different clones of purifying.Wherein, finding one is aforesaid TbRa35, finds that one is the previous antigen of mycobacterium tuberculosis HSP60 that identifies.Among remaining 8 clones, find that 7 (hereinafter being referred to as RDIF2, RDIF5, RDIF8, RDIF10, RDIF11 and RDIF12) have and the previous certain similarity of identifying of mycobacterium tuberculosis sequence.SEQ ID Nos:189-193 provide RDIF2 respectively, RDIF5, and RDIF8, the dna sequence dna of the mensuration of RDIF10 and RDIF11, the aminoacid sequence of corresponding indication provides in SEQ ID Nos:194-198 respectively.5 of RDIF12 ' and 3 ' dna sequence dna provide in SEQ ID Nos:199 and 200 respectively.The dna sequence dna of the mensuration of RDIF7 and the aminoacid sequence of indication provide in SEQ ID Nos:201 and 202 respectively.Separated the another one clone, be referred to as RDIF6, but found identical with RDIF5.

Prepare recombinant chou RDIF6 as mentioned above, RDIF8, RDIF10 and RDIF11.Shown in Fig. 8 A-B and 9A-B, find these antigenic stimulation cell proliferation and IFN-γ generation from the isolating T cell of mycobacterium tuberculosis immunity donor.

Embodiment 4 is from the purifying and the sign of the polypeptide of the protein derivatives of tuberculin purifying

Following protein derivatives from the tuberculin purifying (PPD) separates mycobacterium tuberculosis polypeptides.

PPD (the Seibert that has some modifications according to disclosed preparation, F. etc., the protein derivatives of tuberculin purifying, the preparation and the analysis of a large amount of standard substances, U.S. tuberculosis summary (TheAmerican Review of Tuberculosis) 44:9-25,1941).

Mycobacterium tuberculosis Rv bacterial strain was grown for 6 weeks down at 37 ℃ in the synthetic medium in rolling bottle.The bottle that will contain bacterial growth then in water vapour is heated to 100 ℃ and keeps 3 hours with 0.22 μ filter sterile filtration substratum, and liquid phase concentrates 20 times with the 3kD mwco membrane.Make protein precipitation once with 50% ammoniumsulphate soln, with precipitating eight times with 25% ammoniumsulphate soln.The protein that obtains (PPD) passes through (Perseptive Biosystems, Framingham, MA) middle C18 post (7.8 * 300mM in Biocad HPLC system; Waters, Milford is MA) by reversed-phase liquid chromatography (RP-HPLC) fractional separation.Wash-out goes out fraction from pillar with linear gradient 0-100% damping fluid (0.1%TFA acetonitrile solution).Flow velocity is 10mL/ minute, at 214nm and 280nm monitoring elutriant.

Collect 6 fractions, drying, and be suspended in PBS, and test-induced delaying type hypersensitivity (DTH) reaction in the cavy of m tuberculosis infection respectively.Find that a fraction induces strong DTH reaction, then by the further fractional separation of RP-HPLC on the microbore Vydac C18 post (Cat.No.218TP5115) in Perkin Elmer/Applied Biosystems DivisionModel 172HPLC.Go out fraction with linear gradient 5-100% damping fluid (0.05%TFA acetonitrile solution) wash-out.Flow velocity is 80 μ L/ minutes, at 215nm monitoring elutriant.Collect 8 fractions, and the inducing action of the interior DTH of cavy of test m tuberculosis infection.Find that 1 fraction induces the strong DTH of about 16mm sclerosis.Other fraction is not induced the DTH that can monitor.Make positive fraction carry out the SDS-PAGE gel electrophoresis, find to comprise the single protein swimming band of about 12kD molecular weight.

Use aforesaid Perkin Elmer/Applied Biosystems Division Procise492 protein sequencer from N-terminal to hereinafter being referred to as this sequencing polypeptides of DPPD, find to have the N-end sequence shown in the SEQ ID No.129.This sequence compared with the known sequences in the said gene storehouse show there is not known homology.Isolate 4 cyanogen bromide fragments, find to have the sequence shown in the SEQ ID Nos.130-133.

Stimulate the ability of human PBMC's propagation and generation IFN-γ according to embodiment 1 described mensuration antigen DPPD.As shown in Figure 9, find the generation that DPPD stimulates proliferation and induces a large amount of IFN-γ; It is big to sell the PPD inductive than the merchant.

Table 9

To the propagation of DPPD and the result of interferon-mensuration

The PBMC donor	Stimulator	Propagation (CPM)	??IFN-γ(OD 450)
				????A	Substratum	????1,089	????0.17
	PPD (merchant sells)	????8,394	????1.29
					??DPPD	????13,451	????2.21
				????B	Substratum	????450	????0.09
	PPD (merchant sells)	????3,929	????1.26
					??DPPD	????6,184	????1.49
				????C	Substratum	????541	????0.11
	PPD (merchant sells)	????8,907	????0.76
					??DPPD	????23,024	????＞2.70

Embodiment 5

Representative diagnostic antigen purposes lungy

This embodiment describes the validity of several typical polypeptide diagnosis m tuberculosis infection in the skin test in detail.

The 100 μ LPBS or the PBS that individual intradermal injection are contained 0.1 μ g protein (for TbH-9 and TbRa35) or 0.1 μ g protein (for TbRa38-1) add Tween 20 ^TMScleroma was measured between 5-7 days in the injection back, and 5mm or bigger scleroma are replied and thought male.In 20 individualities of test, 2 is that PPD is negative, and 18 is the PPD positive.In the PPD positive individuals, suffer from active tuberculosis for 3,3 had before been infected tuberculosis, and 9 is healthy.In second test, with PBS or PBS add Tween 20 as mentioned above ^TMIn 0.1 μ g TbRa11 13 PPD positive individuals are tested.Two Journal of Sex Research the results are shown in Table 10.

Table 10

Result with the antigenic DTH test of representativeness

	The TbH-9 positive/total	The Tb38-1 positive/total	The TbRa35 positive/total	The accumulative total positive/total	The TbRa11 positive/total
						The PPD feminine gender	????0/2	????0/2	????0/2	????0/2	????0/2
						The PPD positive
Healthy	????5/9	????4/9	????4/9	????6/9	????1/4
						TB formerly	????3/5	????2/5	????2/5	????4/5	????3/5
Active	????3/4	????3/4	????0/4	????4/4	????1/4
						TOTAL	????11/18	????9/18	????6/18	????14/18	????5/13

Embodiment 6

Synthesizing of synthetic polypeptide

On the Millipore9050 peptide synthesizer, can synthesize polypeptide with HPTU (phosphofluoric acid O-benzotriazole-N, N, N ', N '-tetramethyl-uronium) activation with the FMOC chemistry.The Gly-Cys-Gly sequence can be connected with the N-terminal of peptide with the coupling that peptide is provided or the method for mark.Can carry out the cracking of peptide on solid phase carrier with following cleavage mixture: trifluoroacetic acid: dithioglycol: sulfo-phenylmethylether: water: phenol (40: 1: 2: 2: 3).After the cracking 2 hours, precipitation of peptides in cold methyl tertiary butyl ether.Then the peptide settling is dissolved in the water that contains 0.1% trifluoroacetic acid (TFA), and freeze-drying before passing through C18 reversed-phase HPLC purifying.Can use and (contain 0.1%TFA) in the gradient water 0%-60% acetonitrile (containing 0.1%TFA) comes the wash-out peptide.After the pure fraction of freeze-drying, can use the electrospray mass spectrum and characterize peptide by amino acid analysis.

Embodiment 7

The purifying of mycobacterium tuberculosis fusion protein matter and sign

Be prepared as follows and comprise TbRa3, the fusion rotein of 38kD and Tb38-1.

Modify each DNA by PCR and make up TbRa3,38kD and Tb38-1 are with the expression and the ensuing fusion rotein of the fusion that helps TbRa3-38kD-Tb38-1.Use primer PDM-64 and PDM-65 (SEQ ID NO:146 and 147) respectively, PDM-57 and PDM-58 (SEQ ID NO:148 and 149) and PDM-69 and PDM-60 (SEQ ID NO:150 and 151) use TbRa3, and 38kD and Tb38-1DNA carry out PCR.Use 10 μ L10X Pfu damping fluids in all cases, 2 μ L 10mMdNTPs, each PCR primer of 2 μ L, 10 μ M concentration, 81.5 μ L water, 1.5 μ L 10X PfuDNA polysaccharase (Stratagene, La Jola, CA) DNA with 1 μ L70ng/ μ L (TbRa3) or 50ng/ μ L (38kD and Tb38-1) carries out DNA cloning.For TbRa3, carried out 2 minutes 94 ℃ of sex change, then 96 ℃ of 40 cycles 15 seconds and 72 ℃ 1 minute and last 72 ℃ are 4 minutes.For 38kD, carried out 2 minutes 96 ℃ of sex change, then 96 ℃ of 40 cycles 30 seconds and 68 ℃ 15 seconds and 72 ℃ 3 minutes and last 72 ℃ are 4 minutes.For Tb38-1, carried out 2 minutes 94 ℃ of sex change, then 96 ℃ of 10 cycles 30 seconds, 68 ℃ of 15 seconds and 72 ℃ 1.5 minutes, 96 ℃ of 30 cycles 15 seconds, 64 ℃ of 15 seconds and 72 ℃ 1.5 minutes with last 72 ℃ 4 minutes.

The TbRa3PCR fragment digests with NdeI and EcoRI, and uses NdeI and EcoRI site directly to be cloned into pT 7 ∧ L2IL1 carriers.The 38kDPCR fragment digests with Sse8387I, with T4 archaeal dna polymerase Processing of Preparation flush end, and digests the pT 7 ∧ L2Ra3-1 carriers of directly being cloned into Stul and EcoRI digestion with EcoRI then.The 38-1PCR fragment with Eco47III and EcoRI digestion and directly subclone to pT 7 ∧ L2Ra3/38kD-17 with identical enzymic digestion.With NdeI and EcoRI site whole fusions are transferred to pET28b then.Confirm fusion construct by dna sequencing.

Express to make up be transformed into BLR pLys S E.coli (Novagen, Msdison, WI), and in LB meat soup with kantlex (30 μ g/mL) and paraxin (34 μ g/mL) grow overnight.500mL contains identical antibiotic 2XYT with this culture (12mL) inoculation, and is induced to the 1.2mM final concentration at 0.44OD560 with IPGT.Induced back 4 hours, the results bacterium, and in 20mM Tris (8.0), 100mM sodium-chlor, 0.1%DOC, 20 μ g/mL leupeptins, ultrasonic among the 20mMPMSF, centrifugal in 26000Xg afterwards.The pellet that obtains is suspended in the 8M urea again, 20mM Tris (8.0), in the 100mM sodium-chlor, and with the nickel resin that combines proline(Pro) (Invitrogen, Carlsbad, CA) combination.With above-mentioned damping fluid pillar is washed back imidazoles gradient (the 500mM imidazoles joins the 8M urea for 50mM, 100mM, and 20mMTris (8.0) is in the 100mM sodium-chlor) wash-out several times.Containing to some extent the elutriant of protein of interest matter then dialyses to 10mM Tris (8.0).

The DNA of the fusion rotein that obtains and aminoacid sequence provide in SEQ ID NO:152 and 153 respectively.

The fusion rotein that comprises two antigen TbH-9 and Tb38-1 (hereinafter being referred to as TbH-9-Tb38-1) that does not have hinge is with being similar to above-mentioned similarity method preparation.The dna sequence dna of TbH-9-Tb38-1 fusion rotein provides in SEQ ID NO:156.

Use the method for describing in the foregoing description 1 and measure the ability that fusion rotein TbH-9-Tb38-1 inducing T cell is bred and IFN-γ produces in the PBMC preparation.Use is from the PBMC of three donors: one shows in advance and replys TbH-9 and do not reply Tb38-1 (donor 131); One shows and replys Tb38-1 and do not reply TbH-9 (donor 184); One shows and replys two kinds of antigens (donor 201).(Fig. 5-7 proves two kinds of antigenic functionally activies in the fusion rotein to the result of these researchs separately).

Be prepared as follows and comprise TbRa3, antigen 38kD, the fusion rotein of Tb38-1 and DPEP.

Basically modify each DNA by PCR as mentioned above and make up TbRa3,38kD, Tb38-1, and be cloned in the carrier, the Tb38-1A fragment is used for increasing for primer PDM-69 (SEQ ID NO:150) and PDM-83 (SEQ ID NO:205).The different DraI sites that are to be in 3 of a coding region ' end of Tb38-1A and Tb38-1, described coding region keep last amino acid complete, produce the blunt restriction enzyme site in the frame simultaneously.With NdeI and EcoR1 site the TbRa3/38kD/Tb38-1A fusions is transferred to pET28b then.

With primer PDM-84 and PDM-85 (being respectively SEQ ID NO:206 and 207) and 1 μ L 50ng/ μ L DNA, carry out PCR with DPEP DNA.Carried out 2 minutes 94 ℃ of sex change, then 96 ℃ of 10 cycles 15 seconds, 68 ℃ of 15 seconds and 72 ℃ 1.5 minutes; 96 ℃ of 30 cycles 15 seconds, 64 ℃ of 15 seconds and 72 ℃ 1.5 minutes and last 72 ℃ 4 minutes.With EcoRI and Eco72I digestion DPEP PCR fragment, and the pET28Ra3/38kD/38-1A of directly being cloned into DraI and EcoRI digestion makes up.Prove that by dna sequencing this constructs is correct.Prepare recombinant protein as mentioned above.SEQ ID NO:208 and 209 kinds of DNA and aminoacid sequences that the fusion rotein (hereinafter being referred to as TbF-2) that obtains is provided respectively.

Measure fusion rotein TbF-2 and reactivity with aforesaid method by ELISA from the patient's of m tuberculosis infection serum.The result of these researchs (table 11) proves that all 4 kinds of antigen functions are independently in fusion rotein.

Table 11

TbF-2 merges the reactivity of recombinant chou and TB and normal serum

Serum I D	State	?TbF ?OD450	State	TbF-2 ?OD450	State	The ELISA reactivity
																38kD	?TbRa3	?Tb38-1	?DPEP
B931-40	?TB	?0.57	+	?0.321	+	-	+	-	+
										B931-41	?TB	?0.601	+	?0.396	+	+	+	+	-
B931-109	?TB	?0.494	+	?0.404	+	+	+	±	-
										B931-132	?TB	?1.502	+	?1.292	+	+	+	+	±
5004	?TB	?1.806	+	?1.666	+	±	±	+	-
										15004	?TB	?2.862	+	?2.468	+	+	+	+	-
39004	?TB	?2.443	+	?1.722	+	+	+	+	-
										68004	?TB	?2.871	+	?2.575	+	+	+	+	-
99004	?TB	?0.691	+	?0.971	+	-	±	+	-
										107004	?TB	?0.875	+	?0.732	+	-	±	+	-
92004	?TB	?1.632	+	?1.394	+	+	±	±	-
										97004	?TB	?1.491	+	?1.979	+	+	±	-	+
118004	?TB	?3.182	+	?3.045	+	+	±	-	-
										173004	?TB	?3.644	+	?3.578	+	+	+	+	-
175004	?TB	?3.332	+	?2.916	+	+	+	-	-
										274004	?TB	?3.696	+	?3.716	+	-	+	-	+
276004	?TB	?3.243	+	?2.56	+	-	-	+	-
										282004	?TB	?1.249	+	?1.234	+	+	-	-	-
289004	?TB	?1.373	+	?1.17	+	-	+	-	-
										308004	?TB	?3.708	+	?3.355	+	-	-	+	-
314004	?TB	?1.663	+	?1.399	+	-	-	+	-
										317004	?TB	?1.163	+	?0.92	+	+	-	-	-
312004	?TB	?1.709	+	?1.453	+	-	+	-	-
										380004	?TB	?0.238	-	?0.461	+	-	±	-	+
451004	?TB	?0.18	-	?0.2	-	-	-	-	±
										478004	?TB	?0.188	-	?0.469	+	-	-	-	±
410004	?TB	?0.384	+	?2.392	+	±	-	-	+
										411004	?TB	?0.306	+	?0.874	+	-	+	-	+
421004	?TB	?0.357	+	?1.456	+	-	+	-	+
										528004	?TB	?0.047	-	?0.196	-	-	-	-	+
A6-87	Normally	?0.094	-	?0.063	-	-	-	-	-
										A6-88	Normally	?0.214	-	?0.19	-	-	-	-	-
A6-89	Normally	?0.248	-	?0.125	-	-	-	-	-
										A6-90	Normally	?0.179	-	?0.206	-	-	-	-	-
A6-91	Normally	?0.135	-	?0.151	-	-	-	-	-
										A6-92	Normally	?0.064	-	?0.097	-	-	-	-	-
A6-93	Normally	?0.072	-	?0.098	-	-	-	-	-
										A6-94	Normally	?0.072	-	?0.064	-	-	-	-	-
A6-95	Normally	?0.125	-	?0.159	-	-	-	-	-
										A6-96	Normally	?0.121	-	?0.12	-	-	-	-	-
										Hold back		?0.284		?0.266

Those skilled in the art should understand that each antigenic order can change in the fused protein, and pre-in respect of suitable activity, as long as each epi-position function still exists.In addition, fused protein can use the proteinic clipped form that comprises active epi-position in making up.

Although described specific embodiments of the present invention for the purpose that describes in detail, do not break away from spirit and scope of the invention and can carry out various modifications by the above-mentioned the present invention of being appreciated that.

Sequence table (1) general information:

(i) applicant: Reed, Steven G.

Skeiky，Yasir?A.W.

Dillon，Davin?C.

Campos-Neto，Antonio

Houghton，Raymond

Vedvick，Thomas?S.

Twardzik，Daniel?R.

Lodes，Michael?J.

(ii) invention exercise question: the Compounds and methods for of immunotherapy and diagnosis of tuberculosis

(iii) sequence number: 214

(iv) contact address:

(A) address: SEED and BERRYLLP

(B) street: 6300 Columbia Center, 701 Fifth Avenue

(C) city: Seattle

(D) state: Washington

(E) country: the U.S.

(F) postcode (ZIP): 98104-7092

(v) computer-reader form:

(A) Floppy dish

(B) computer: IBM PC compatibility

(C) operating system: PC-DOS/MS-DOS

(D) floppy disk: Patent In Release#1.0, Version #1.30

(vi) current request for data:

(A) application number:

(B) applying date: 01-10-1997

(C) classification:

(viii) proxy/business quarters's information:

(A) title: Maki, David J.

(B) registration number: 31392

(C) reference/recording mechanism: 210121.411C7 (ix) telecommunication information: (A) phone: (206) 622-4900 (B) fax: the information of (206) 682-6031 (2) SEQ ID NO:1:

(i) sequence signature:

(A) length: 766 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:1:CGAGGCACCG, GTAGTTTGAA, CCAAACGCAC, AATCGACGGG, CAAACGAACG, GAAGAACACA, 60ACCATGAAGA, TGGTGAAATC, GATCGCCGCA, GGTCTGACCG, CCGCCGCTGC, AATCGGCGCC, 120GCTGCGGCCG, GTGTGACTTC, GATCATGGCT, GGCGGCCCGG, TCGTATACCA, GATGCAGCCG, 180GTCGTCTTCG, GCGCGCCACT, GCCGTTGGAC, CCGGCATCCG, CCCCTGACGT, CCCGACCGCC, 240GCCCAGTTGA, CCAGCCTGCT, CAACAGCCTC, GCCGATCCCA, ACGTGTCGTT, TGCGAACAAG, 300GGCAGTCTGG, TCGAGGGCGG, CATCGGGGGC, ACCGAGGCGC, GCATCGCCGA, CCACAAGCTG, 360AAGAAGGCCG, CCGAGCACGG, GGATCTGCCG, CTGTCGTTCA, GCGTGACGAA, CATCCAGCCG, 420GCGGCCGCCG, GTTCGGCCAC, CGCCGACGTT, TCCGTCTCGG, GTCCGAAGCT, CTCGTCGCCG, 480GTCACGCAGA, ACGTCACGTT, CGTGAATCAA, GGCGGCTGGA, TGCTGTCACG, CGCATCGGCG, 540ATGGAGTTGC, TGCAGGCCGC, AGGGNAACTG, ATTGGCGGGC, CGGNTTCAGC, CCGCTGTTCA, 600GCTACGCCGC, CCGCCTGGTG, ACGCGTCCAT, GTCGAACACT, CGCGCGTGTA, GCACGGTGCG, 660GTNTGCGCAG, GGNCGCACGC, ACCGCCCGGT, GCAAGCCGTC, CTCGAGATAG, GTGGTGNCTC, 720GNCACCAGNG, ANCACCCCCN, NNTCGNCNNT, TCTCGNTGNT, GNATGA, 766, (2) SEQ, ID, the information of NO:2:

(i) sequence signature:

(A) length: 752 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:2:ATGCATCACC, ATCACCATCA, CGATGAAGTC, ACGGTAGAGA, CGACCTCCGT, CTTCCGCGCA, 60GACTTCCTCA, GCGAGCTGGA, CGCTCCTGCG, CAAGCGGGTA, CGGAGAGCGC, GGTCTCCGGG, 120GTGGAAGGGC, TCCCGCCGGG, CTCGGCGTTG, CTGGTAGTCA, AACGAGGCCC, CAACGCCGGG, 180TCCCGGTTCC, TACTCGACCA, AGCCATCACG, TCGGCTGGTC, GGCATCCCGA, CAGCGACATA, 240TTTCTCGACG, ACGTGACCGT, GAGCCGTCGC, CATGCTGAAT, TCCGGTTGGA, AAACAACGAA, 300TTCAATGTCG, TCGATGTCGG, GAGTCTCAAC, GGCACCTACG, TCAACCGCGA, GCCCGTGGAT, 360TCGGCGGTGC, TGGCGAACGG, CGACGAGGTC, CAGATCGGCA, AGCTCCGGTT, GGTGTTCTTG, 420ACCGGACCCA, AGCAAGGCGA, GGATGACGGG, AGTACCGGGG, GCCCGTGAGC, GCACCCGATA, 480GCCCCGCGCT, GGCCGGGATG, TCGATCGGGG, CGGTCCTCCG, ACCTGCTACG, ACCGGATTTT, 540CCCTGATGTC, CACCATCTCC, AAGATTCGAT, TCTTGGGAGG, CTTGAGGGTC, NGGGTGACCC, 600CCCCGCGGGC, CTCATTCNGG, GGTNTCGGCN, GGTTTCACCC, CNTACCNACT, GCCNCCCGGN, 660TTGCNAATTC, NTTCTTCNCT, GCCCNNAAAG, GGACCNTTAN, CTTGCCGCTN, GAAANGGTNA, 720TCCNGGGCCC, NTCCTNGAAN, CCCCNTCCCC, CT, 752, (2) SEQ, ID, the information of NO:3:

(i) sequence signature:

(A) length: 813 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:3:CATATGCATC, ACCATCACCA, TCACACTTCT, AACCGCCCAG, CGCGTCGGGG, GCGTCGAGCA, 60CCACGCGACA, CCGGGCCCGA, TCGATCTGCT, AGCTTGAGTC, TGGTCAGGCA, TCGTCGTCAG, 120CAGCGCGATG, CCCTATGTTT, GTCGTCGACT, CAGATATCGC, GGCAATCCAA, TCTCCCGCCT, 180GCGGCCGGCG, GTGCTGCAAA, CTACTCCCGG, AGGAATTTCG, ACGTGCGCAT, CAAGATCTTC, 240ATGCTGGTCA, CGGCTGTCGT, TTTGCTCTGT, TGTTCGGGTG, TGGCCACGGC, CGCGCCCAAG, 300ACCTACTGCG, AGGAGTTGAA, AGGCACCGAT, ACCGGCCAGG, CGTGCCAGAT, TCAAATGTCC, 360GACCCGGCCT, ACAACATCAA, CATCAGCCTG, CCCAGTTACT, ACCCCGACCA, GAAGTCGCTG, 420GAAAATTACA, TCGCCCAGAC, GCGCGACAAG, TTCCTCAGCG, CGGCCACATC, GTCCACTCCA, 480CGCGAAGCCC, CCTACGAATT, GAATATCACC, TCGGCCACAT, ACCAGTCCGC, GATACCGCCG, 540CGTGGTACGC, AGGCCGTGGT, GCTCAMGGTC, TACCACAACG, CCGGCGGCAC, GCACCCAACG, 600ACCACGTACA, AGGCCTTCGA, TTGGGACCAG, GCCTATCGCA, AGCCAATCAC, CTATGACACG, 660CTGTGGCAGG, CTGACACCGA, TCCGCTGCCA, GTCGTCTTCC, CCATTGTTGC, AAGGTGAACT, 720GAGCAACGCA, GACCGGGACA, ACWGGTATCG, ATAGCCGCCN, AATGCCGGCT, TGGAACCCNG, 780TGAAATTATC, ACAACTTCGC, AGTCACNAAA, NAA, 813, (2) SEQ, ID, the information of NO:4:

(i) sequence signature:

(A) length: 447 base pairs

(B) type: nucleic acid

(C) chain number: strand

245 (210) 4 (211) 30 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC12447 (400) 4 atggggcacg cgactcagga ccaggccaga 30 (210) 5 (211) 19 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC695 (400) 5 gatttaggtg acactatag 19 (210) 6 (211) 20 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC694 (400) 6 taatacgact cactataggg 20 (210) 7 (211) 20 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC13210 (400) 7 aagcaccggg aagcagggag 20 (210) 8 (211) 20 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC13588 (400) 8 cgggcacgta gcagtagaac 20 (210) 9 (211) 20 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC13532 (400) 9 gagagggctg aagaacaaca 20 (210) 10 (211) 20 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC13641 (400) 10 aaggtggcga gaggaaagga 20 (210) 11 (211) 20 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC13586 (400) 11 tgttcaccgg caagttctac 20 (210) 12 (211) 20 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC13651 (400) 12 ctttgtcctc cacggtttac 20 (210) 13 (211) 20 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC13622 (400) 13 tttcctctcg ccaccttcca 20 (210) 14 (211) 21 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC13625 (400) 14 cttcggctgc ttctaaccaa c 21 (210) 15 (211) 20 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC13650 (400) 15 gtaaaccgtg gaggacaaag 20 (210) 16 (211) 21 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC13859 (400) 16 gctgccaacc aacacaacca c 21 (210) 17 (211) 18 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC13624 (400) 17 gcaggattag tcaaaacc 18 (210) 18 (211) 20 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC13531 (400) 18 aacatggggt gaggtggaga 20 (210) 19 (211) 20 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC13587 (400) 19 tcctcgtggg ctaagcatca 20 (210) 20 (211) 20 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC13623 (400) 20 atctccagga accccatagc 20 (210) 21 (211) 18 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC14444 (400) 21 tctccaggaa ccccatag 18 (210) 22 (211) 18 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC14445 (400) 22 gcaggattag tcaaaacc 18 (210) 23 (211) 843 (212) DNA (213) artificial sequence (220) (223) encoding zsig37 polypeptide degenerate nucleotide sequences (400) 23 atgggnwsnm gnggncargg nytnytnytn gcntaytgyy tnytnytngc nttygcnwsn 60 ggnytngtny tnwsnmgngt nccncaygtn carggngarc arcargartg ggarggnacn 120 gargarytnc cnwsnccncc ngaycaygcn garmgngcng argarcarca ygaraartay 180 mgnccnwsnc argaycargg nytnccngcn wsnmgntgyy tnmgntgytg ygayccnggn 240 acnwsnatgt ayccngcnac ngcngtnccn carathaaya thacnathyt naarggngar 300 aarggngaym gnggngaymg nggnytncar ggnaartayg gnaaracngg nwsngcnggn 360 gcnmgnggnc ayacnggncc naarggncar aarggnwsna tgggngcncc nggngarmgn 420 tgyaarwsnc aytaygcngc nttywsngtn ggnmgnaara arccnatgca ywsnaaycay 480 taytaycara cngtnathtt ygayacngar ttygtnaayy tntaygayca yttyaayatg 540 ttyacnggna arttytaytg ytaygtnccn ggnytntayt tyttywsnyt naaygtncay 600 acntggaayc araargarac ntayytncay athatgaara aygargarga rgtngtnath 660 ytnttygcnc argtnggnga ymgnwsnath atgcarwsnc arwsnytnat gytngarytn 720 mgngarcarg aycargtntg ggtnmgnytn tayaarggng armgngaraa ygcnathtty 780 wsngargary tngayacnta yathacntty wsnggntayy tngtnaarca ygcnacngar 840 ccn 843 (210) 24 (211) 24 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC15040 (400) 24 actcattcta gactagggct cggt 24 (210) 25 (211) 24 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC15033 (400) 25 atgaatggat ccctggtcct gagt 24 (210) 26 (211) 7 (212) PRT (213) artificial sequence (220) (223) Glu-Glu affinity tag peptide (400) 26 Glu Glu Tyr Met Pro Met Glu 15 (210) 27 (211) 24 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC15721 (400) 27 ctgtaggaat tcatgggctc ccgt 24 (210) 28 (211) 24 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC15035 (400) 28 attcatggat ccgggctcgg tggc 24 (210) 29 (211) 20 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC13006 (400) 29 ggctgtcctc taagcgtcac 20 (210) 30 (211) 19 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC13007 (400) 30 aggggtcaca gggatgcca 19 (210) 31 (211) 6 (212) PRT (213) artificial sequence (220) (223) Glu-Glu peptide (400) 31 Gly Tyr Met Pro Val Asp 15 (210) 32 (211) 25 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC6768 (400) 32 gcaattaacc ctcactaaag ggaac 25 (210) 33 (211) 21 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC18297 (400) 33 tcctgaaagg cgagaaaggt g 21 (210) 34 (211) 20 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC18298 (400) 34 ttccctgagt ctgagctagg 20 (210) 35 (211) 21 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC18402 (400) 35 tccagagtga ctggggaagt g 21 (210) 36 (211) 21 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC18403 (400) 36 agtgacgagt tcgacaccta c 21 (210) 37 (211) 21 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC18456 (400) 37 tgtgttccca ttcctggaca c 21 (210) 38 (211) 21 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC18457 (400) 38 tccttccagc tggctggaaa g 21 (210) 39 (211) 20 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC18560 (400) 39 agaatgcagg gataggtcag 20 (210) 40 (211) 20 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC18561 (400) 40 tcagaggatc ctgacagcag 20 (210) 41 (211) 21 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC18687 (400) 41 tggacacgtg agagggactt c 21 (210) 42 (211) 20 (212) DNA (213) artificial sequence (220) (223) oligonucleotides ZC18688 (400) 42 agcagtagaa cttcccagtg 20 (210) 43 (211) 2559 (212) DNA (213) Mus musculus (220) (221) CDS (222) (70) ... (912) (223) murine homologue (400) 43 gaattcggat cctggaagag atgggattgt tataggcgga aagagagaaa cccagagaag 60 tccaggaag atg ggc tcc tgt gca cag gga ttc atg ctg gga tgc tgc ctg 111 ...

(i) sequence signature:

(A) length: 604 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:5:GTCCCACTGC, GGTCGCCGAG, TATGTCGCCC, AGCAAATGTC, TGGCAGCCGC, CCAACGGAAT, 60CCGGTGATCC, GACGTCGCAG, GTTGTCGAAC, CCGCCGCCGC, GGAAGTATCG, GTCCATGCCT, 120AGCCCGGCGA, CGGCGAGCGC, CGGAATGGCG, CGAGTGAGGA, GGCGGGCAAT, TTGGCGGGGC, 180CCGGCGACGG, NGAGCGCCGG, AATGGCGCGA, GTGAGGAGGT, GGNCAGTCAT, GCCCAGNGTG, 240ATCCAATCAA, CCTGNATTCG, GNCTGNGGGN, CCATTTGACA, ATCGAGGTAG, TGAGCGCAAA, 300TGAATGATGG, AAAACGGGNG, GNGACGTCCG, NTGTTCTGGT, GGTGNTAGGT, GNCTGNCTGG, 360NGTNGNGGNT, ATCAGGATGT, TCTTCGNCGA, AANCTGATGN, CGAGGAACAG, GGTGTNCCCG, 420NNANNCCNAN, GGNGTCCNAN, CCCNNNNTCC, TCGNCGANAT, CANANAGNCG, NTTGATGNGA, 480NAAAAGGGTG, GANCAGNNNN, AANTNGNGGN, CCNAANAANC, NNNANNGNNG, NNAGNTNGNT, 540NNNTNTTNNC, ANNNNNNNTG, NNGNNGNNCN, NNNCAANCNN, NTNNNNGNAA, NNGGNTTNTT, 600NAAT, 604, (2) SEQ, ID, the information of NO:6:

(i) sequence signature:

(A) length: 633 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:6:TTGCANGTCG, AACCACCTCA, CTAAAGGGAA, CAAAAGCTNG, AGCTCCACCG, CGGTGGCGGC, 60CGCTCTAGAA, CTAGTGKATM, YYYCKGGCTG, CAGSAATYCG, GYACGAGCAT, TAGGACAGTC, 120TAACGGTCCT, GTTACGGTGA, TCGAATGACC, GACGACATCC, TGCTGATCGA, CACCGACGAA, 180CGGGTGCGAA, CCCTCACCCT, CAACCGGCCG, CAGTCCCGYA, ACGCGCTCTC, GGCGGCGCTA, 240CGGGATCGGT, TTTTCGCGGY, GTTGGYCGAC, GCCGAGGYCG, ACGACGACAT, CGACGTCGTC, 300ATCCTCACCG, GYGCCGATCC, GGTGTTCTGC, GCCGGACTGG, ACCTCAAGGT, AGCTGGCCGG, 360GCAGACCGCG, CTGCCGGACA, TCTCACCGCG, GTGGGCGGCC, ATGACCAAGC, CGGTGATCGG, 420CGCGATCAAC, GGCGCCGCGG, TCACCGGCGG, GCTCGAACTG, GCGCTGTACT, GCGACATCCT, 480GATCGCCTCC, GAGCACGCCC, GCTTCGNCGA, CACCCACGCC, CGGGTGGGGC, TGCTGCCCAC, 540CTGGGGACTC, AGTGTGTGCT, TGCCGCAAAA, GGTCGGCATC, GGNCTGGGCC, GGTGGATGAG, 600CCTGACCGGC, GACTACCTCT, CCGTGACCGA, CGC, 633, (2) SEQ, ID, the information of NO:7:

(i) sequence signature:

(A) length: 1362 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:7:CGACGACGAC, GGCGCCGGAG, AGCGGGCGCG, AACGGCGATC, GACGCGGCCC, TGGCCAGAGT, 60CGGCACCACC, CAGGAGGGAG, TCGAATCATG, AAATTTGTCA, ACCATATTGA, GCCCGTCGCG, 120CCCCGCCGAG, CCGGCGGCGC, GGTCGCCGAG, GTCTATGCCG, AGGCCCGCCG, CGAGTTCGGC, 180CGGCTGCCCG, AGCCGCTCGC, CATGCTGTCC, CCGGACGAGG, GACTGCTCAC, CGCCGGCTGG, 240GCGACGTTGC, GCGAGACACT, GCTGGTGGGC, CAGGTGCCGC, GTGGCCGCAA, GGAAGCCGTC, 300GCCGCCGCCG, TCGCGGCCAG, CCTGCGCTGC, CCCTGGTGCG, TCGACGCACA, CACCACCATG, 360CTGTACGCGG, CAGGCCAAAC, CGACACCGCC, GCGGCGATCT, TGGCCGGCAC, AGCACCTGCC, 420GCCGGTGACC, CGAACGCGCC, GTATGTGGCG, TGGGCGGCAG, GAACCGGGAC, ACCGGCGGGA, 480CCGCCGGCAC, CGTTCGGCCC, GGATGTCGCC, GCCGAATACC, TGGGCACCGC, GGTGCAATTC, 540CACTTCATCG, CACGCCTGGT, CCTGGTGCTG, CTGGACGAAA, CCTTCCTGCC, GGGGGGCCCG, 600CGCGCCCAAC, AGCTCATGCG, CCGCGCCGGT, GGACTGGTGT, TCGCCCGCAA, GGTGCGCGCG, 660GAGCATCGGC, CGGGCCGCTC, CACCCGCCGG, CTCGAGCCGC, GAACGCTGCC, CGACGATCTG, 720GCATGGGCAA, CACCGTCCGA, GCCCATAGCA, ACCGCGTTCG, CCGCGCTCAG, CCACCACCTG, 780GACACCGCGC, CGCACCTGCC, GCCACCGACT, CGTCAGGTGG, TCAGGCGGGT, CGTGGGGTCG, 840TGGCACGGCG, AGCCAATGCC, GATGAGCAGT, CGCTGGACGA, ACGAGCACAC, CGCCGAGCTG, 900CCCGCCGACC, TGCACGCGCC, CACCCGTCTT, GCCCTGCTGA, CCGGCCTGGC, CCCGCATCAG, 960GTGACCGACG, ACGACGTCGC, CGCGGCCCGA, TCCCTGCTCG, ACACCGATGC, GGCGCTGGTT, 1020GGCGCCCTGG, CCTGGGCCGC, CTTCACCGCC, GCGCGGCGCA, TCGGCACCTG, GATCGGCGCC, 1080GCCGCCGAGG, GCCAGGTGTC, GCGGCAAAAC, CCGACTGGGT, GAGTGTGCGC, GCCCTGTCGG, 1140TAGGGTGTCA, TCGCTGGCCC, GAGGGATCTC, GCGGCGGCGA, ACGGAGGTGG, CGACACAGGT, 1200GGAAGCTGCG, CCCACTGGCT, TGCGCCCCAA, CGCCGTCGTG, GGCGTTCGGT, TGGCCGCACT, 1260GGCCGATCAG, GTCGGCGCCG, GCCCTTGGCC, GAAGGTCCAG, CTCAACGTGC, CGTCACCGAA, 1320GGACCGGACG, GTCACCGGGG, GTCACCCTGC, GCGCCCAAGG, AA, 1362, (2) SEQ, ID, the information of NO:8:

(i) sequence signature:

(A) length: 1458 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:8:GCGACGACCC, CGATATGCCG, GGCACCGTAG, CGAAAGCCGT, CGCCGACGCA, CTCGGGCGCG, 60GTATCGCTCC, CGTTGAGGAC, ATTCAGGACT, GCGTGGAGGC, CCGGCTGGGG, GAAGCCGGTC, 120TGGATGACGT, GGCCCGTGTT, TACATCATCT, ACCGGCAGCG, GCGCGCCGAG, CTGCGGACGG, 180CTAAGGCCTT, GCTCGGCGTG, CGGGACGAGT, TAAAGCTGAG, CTTGGCGGCC, GTGACGGTAC, 240TGCGCGAGCG, CTATCTGCTG, CACGACGAGC, AGGGCCGGCC, GGCCGAGTCG, ACCGGCGAGC, 300TGATGGACCG, ATCGGCGCGC, TGTGTCGCGG, CGGCCGAGGA, CCAGTATGAG, CCGGGCTCGT, 360CGAGGCGGTG, GGCCGAGCGG, TTCGCCACGC, TATTACGCAA, CCTGGAATTC, CTGCCGAATT, 420CGCCCACGTT, GATGAACTCT, GGCACCGACC, TGGGACTGCT, CGCCGGCTGT, TTTGTTCTGC, 480CGATTGAGGA, TTCGCTGCAA, TCGATCTTTG, CGACGCTGGG, ACAGGCCGCC, GAGCTGCAGC, 540GGGCTGGAGG, CGGCACCGGA, TATGCGTTCA, GCCACCTGCG, ACCCGCCGGG, GATCGGGTGG, 600CCTCCACGGG, CGGCACGGCC, AGCGGACCGG, TGTCGTTTCT, ACGGCTGTAT, GACAGTGCCG, 660CGGGTGTGGT, CTCCATGGGC, GGTCGCCGGC, GTGGCGCCTG, TATGGCTGTG, CTTGATGTGT, 720CGCACCCGGA, TATCTGTGAT, TTCGTCACCG, CCAAGGCCGA, ATCCCCCAGC, GAGCTCCCGC, 780ATTTCAACCT, ATCGGTTGGT, GTGACCGACG, CGTTCCTGCG, GGCCGTCGAA, CGCAACGGCC, 840TACACCGGCT, GGTCAATCCG, CGAACCGGCA, AGATCGTCGC, GCGGATGCCC, GCCGCCGAGC, 900TGTTCGACGC, CATCTGCAAA, GCCGCGCACG, CCGGTGGCGA, TCCCGGGCTG, GTGTTTCTCG, 960ACACGATCAA, TAGGGCAAAC, CCGGTGCCGG, GGAGAGGCCG, CATCGAGGCG, ACCAACCCGT, 1020GCGGGGAGGT, CCCACTGCTG, CCTTACGAGT, CATGTAATCT, CGGCTCGATC, AACCTCGCCC, 1080GGATGCTCGC, CGACGGTCGC, GTCGACTGGG, ACCGGCTCGA, GGAGGTCGCC, GGTGTGGCGG, 1140TGCGGTTCCT, TGATGACGTC, ATCGATGTCA, GCCGCTACCC, CTTCCCCGAA, CTGGGTGAGG, 1200CGGCCCGCGC, CACCCGCAAG, ATCGGGCTGG, GAGTCATGGG, TTTGGCGGAA, CTGCTTGCCG, 1260CACTGGGTAT, TCCGTACGAC, AGTGAAGAAG, CCGTGCGGTT, AGCCACCCGG, CTCATGCGTC, 1320GCATACAGCA, GGCGGCGCAC, ACGGCATCGC, GGAGGCTGGC, CGAAGAGCGG, GGCGCATTCC, 1380CGGCGTTCAC, CGATAGCCGG, TTCGCGCGGT, CGGGCCCGAG, GCGCAACGCA, CAGGTCACCT, 1440CCGTCGCTCC, GACGGGCA, 1458, (2) SEQ, ID, the information of NO:9:

(i) sequence signature:

(A) length: 862 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:9:ACGGTGTAAT, CGTGCTGGAT, CTGGAACCGC, GTGGCCCGCT, ACCTACCGAG, ATCTACTGGC, 60GGCGCAGGGG, GCTGGCCCTG, GGCATCGCGG, TCGTCGTAGT, CGGGATCGCG, GTGGCCATCG, 120TCATCGCCTT, CGTCGACAGC, AGCGCCGGTG, CCAAACCGGT, CAGCGCCGAC, AAGCCGGCCT, 180CCGCCCAGAG, CCATCCGGGC, TCGCCGGCAC, CCCAAGCACC, CCAGCCGGCC, GGGCAAACCG, 240AAGGTAACGC, CGCCGCGGCC, CCGCCGCAGG, GCCAAAACCC, CGAGACACCC, ACGCCCACCG, 300CCGCGGTGCA, GCCGCCGCCG, GTGCTCAAGG, AAGGGGACGA, TTGCCCCGAT, TCGACGCTGG, 360CCGTCAAAGG, TTTGACCAAC, GCGCCGCAGT, ACTACGTCGG, CGACCAGCCG, AAGTTCACCA, 420TGGTGGTCAC, CAACATCGGC, CTGGTGTCCT, GTAAACGCGA, CGTTGGGGCC, GCGGTGTTGG, 480CCGCCTACGT, TTACTCGCTG, GACAACAAGC, GGTTGTGGTC, CAACCTGGAC, TGCGCGCCCT, 540CGAATGAGAC, GCTGGTCAAG, ACGTTTTCCC, CCGGTGAGCA, GGTAACGACC, GCGGTGACCT, 600GGACCGGGAT, GGGATCGGCG, CCGCGCTGCC, CATTGCCGCG, GCCGGCGATC, GGGCCGGGCA, 660CCTACAATCT, CGTGGTACAA, CTGGGCAATC, TGCGCTCGCT, GCCGGTTCCG, TTCATCCTGA, 720ATCAGCCGCC, GCCGCCGCCC, GGGCCGGTAC, CCGCTCCGGG, TCCAGCGCAG, GCGCCTCCGC, 780CGGAGTCTCC, CGCGCAAGGC, GGATAATTAT, TGATCGCTGA, TGGTCGATTC, CGCCAGCTGT, 840GACAACCCCT, CGCCTCGTGC, CG, 862, (2) SEQ, ID, the information of NO:10:

(i) sequence signature:

(A) length: 622 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:10:TTGATCAGCA, CCGGCAAGGC, GTCACATGCC, TCCCTGGGTG, TGCAGGTGAC, CAATGACAAA, 60GACACCCCGG, GCGCCAAGAT, CGTCGAACTA, GTGGCCGGTG, GTGCTGCCGC, GAACGCTGGA, 120GTGCCGAAGG, GCGTCGTTGT, CACCAAGGTC, GACGACCGCC, CGATCAACAG, CGCGGACGCG, 180TTGGTTGCCG, CCGTGCGGTC, CAAAGCGCCG, GGCGCCACGG, TGGCGCTAAC, CTTTCAGGAT, 240CCCTCGGGCG, GTAGCCGCAC, AGTGCAAGTC, ACCCTCGGCA, AGGCGGAGCA, GTGATGAAGG, 300TCGCCGCGCA, GTGTTCAAAG, CTCGGATATA, CGGTGGCACC, CATGGAACAG, CGTGCGGAGT, 360TGGTGGTTGG, CCGGGCACTT, GTCGTCGTCG, TTGACGATCG, CACGGCGCAC, GGCGATGAAG, 420ACCACAGCGG, GCCGCTTGTC, ACCGAGCTGC, TCACCGAGGC, CGGGTTTGTT, GTCGACGGCG, 480TGGTGGCGGT, GTCGGCCGAC, GAGGTCGAGA, TCCGAAATGC, GCTGAACACA, GCGGTGATCG, 540GCGGGGTGGA, CCTGGTGGTG, TCGGTCGGCG, GGACCGGNGT, GACGNCTCGC, GATGTCACCC, 600CGGAAGCCAC, CCGNGACATT, CT, 622, (2) SEQ, ID, the information of NO:11:

(i) sequence signature:

(A) length: 1200 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:11:GGCGCAGCGG, TAAGCCTGTT, GGCCGCCGGC, ACACTGGTGT, TGACAGCATG, CGGCGGTGGC, 60ACCAACAGCT, CGTCGTCAGG, CGCAGGCGGA, ACGTCTGGGT, CGGTGCACTG, CGGCGGCAAG, 120AAGGAGCTCC, ACTCCAGCGG, CTCGACCGCA, CAAGAAAATG, CCATGGAGCA, GTTCGTCTAT, 180GCCTACGTGC, GATCGTGCCC, GGGCTACACG, TTGGACTACA, ACGCCAACGG, GTCCGGTGCC, 240GGGGTGACCC, AGTTTCTCAA, CAACGAAACC, GATTTCGCCG, GCTCGGATGT, CCCGTTGAAT, 300CCGTCGACCG, GTCAACCTGA, CCGGTCGGCG, GAGCGGTGCG, GTTCCCCGGC, ATGGGACCTG, 360CCGACGGTGT, TCGGCCCGAT, CGCGATCACC, TACAATATCA, AGGGCGTGAG, CACGCTGAAT, 420CTTGACGGAC, CCACTACCGC, CAAGATTTTC, AACGGCACCA, TCACCGTGTG, GAATGATCCA, 480CAGATCCAAG, CCCTCAACTC, CGGCACCGAC, CTGCCGCCAA, CACCGATTAG, CGTTATCTTC, 540CGCAGCGACA, AGTCCGGTAC, GTCGGACAAC, TTCCAGAAAT, ACCTCGACGG, TGTATCCAAC, 600GGGGCGTGGG, GCAAAGGCGC, CAGCGAAACG, TTCAGCGGGG, GCGTCGGCGT, CGGCGCCAGC, 660GGGAACAACG, GAACGTCGGC, CCTACTGCAG, ACGACCGACG, GGTCGATCAC, CTACAACGAG, 720TGGTCGTTTG, CGGTGGGTAA, GCAGTTGAAC, ATGGCCCAGA, TCATCACGTC, GGCGGGTCCG, 780GATCCAGTGG, CGATCACCAC, CGAGTCGGTC, GGTAAGACAA, TCGCCGGGGC, CAAGATCATG, 840GGACAAGGCA, ACGACCTGGT, ATTGGACACG, TCGTCGTTCT, ACAGACCCAC, CCAGCCTGGC, 900TCTTACCCGA, TCGTGCTGGC, GACCTATGAG, ATCGTCTGCT, CGAAATACCC, GGATGCGACG, 960ACCGGTACTG, CGGTAAGGGC, GTTTATGCAA, GCCGCGATTG, GTCCAGGCCA, AGAAGGCCTG, 1020GACCAATACG, GCTCCATTCC, GTTGCCCAAA, TCGTTCCAAG, CAAAATTGGC, GGCCGCGGTG, 1080AATGCTATTT, CTTGACCTAG, TGAAGGGAAT, TCGACGGTGA, GCGATGCCGT, TCCGCAGGTA, 1140GGGTCGCAAT, TTGGGCCGTA, TCAGCTATTG, CGGCTGCTGG, GCCGAGGCGG, GATGGGCGAG, 1200, (2) SEQ, ID, the information of NO:12:

(i) sequence signature:

(A) length: 1155 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:12:GCAAGCAGCT, GCAGGTCGTG, CTGTTCGACG, AACTGGGCAT, GCCGAAGACC, AAACGCACCA, 60AGACCGGCTA, CACCACGGAT, GCCGACGCGC, TGCAGTCGTT, GTTCGACAAG, ACCGGGCATC, 120CGTTTCTGCA, ACATCTGCTC, GCCCACCGCG, ACGTCACCCG, GCTCAAGGTC, ACCGTCGACG, 180GGTTGCTCCA, AGCGGTGGCC, GCCGACGGCC, GCATCCACAC, CACGTTCAAC, CAGACGATCG, 240CCGCGACCGG, CCGGCTCTCC, TCGACCGAAC, CCAACCTGCA, GAACATCCCG, ATCCGCACCG, 300ACGCGGGCCG, GCGGATCCGG, GACGCGTTCG, TGGTCGGGGA, CGGTTACGCC, GAGTTGATGA, 360CGGCCGACTA, CAGCCAGATC, GAGATGCGGA, TCATGGGGCA, CCTGTCCGGG, GACGAGGGCC, 420TCATCGAGGC, GTTCAACACC, GGGGAGGACC, TGTATTCGTT, CGTCGCGTCC, CGGGTGTTCG, 480GTGTGCCCAT, CGACGAGGTC, ACCGGCGAGT, TGCGGCGCCG, GGTCAAGGCG, ATGTCCTACG, 540GGCTGGTTTA, CGGGTTGAGC, GCCTACGGCC, TGTCGCAGCA, GTTGAAAATC, TCCACCGAGG, 600AAGCCAACGA, GCAGATGGAC, GCGTATTTCG, CCCGATTCGG, CGGGGTGCGC, GACTACCTGC, 660GCGCCGTAGT, CGAGCGGGCC, CGCAAGGACG, GCTACACCTC, GACGGTGCTG, GGCCGTCGCC, 720GCTACCTGCC, CGAGCTGGAC, AGCAGCAACC, GTCAAGTGCG, GGAGGCCGCC, GAGCGGGCGG, 780CGCTGAACGC, GCCGATCCAG, GGCAGCGCGG, CCGACATCAT, CAAGGTGGCC, ATGATCCAGG, 840TCGACAAGGC, GCTCAACGAG, GCACAGCTGG, CGTCGCGCAT, GCTGCTGCAG, GTCCACGACG, 900AGCTGCTGTT, CGAAATCGCC, CCCGGTGAAC, GCGAGCGGGT, CGAGGCCCTG, GTGCGCGACA, 960AGATGGGCGG, CGCTTACCCG, CTCGACGTCC, CGCTGGAGGT, GTCGGTGGGC, TACGGCCGCA, 1020GCTGGGACGC, GGCGGCGCAC, TGAGTGCCGA, GCGTGCATCT, GGGGCGGGAA, TTCGGCGATT, 1080TTTCCGCCCT, GAGTTCACGC, TCGGCGCAAT, CGGGACCGAG, TTTGTCCAGC, GTGTACCCGT, 1140CGAGTAGCCT, CGTCA, 1155, (2) SEQ, ID, the information of NO:13:

(i) sequence signature:

(A) length: 1771 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:13:GAGCGCCGTC, TGGTGTTTGA, ACGGTTTTAC, CGGTCGGCAT, CGGCACGGGC, GTTGCCGGGT, 60TCGGGCCTCG, GGTTGGCGAT, CGTCAAACAG, GTGGTGCTCA, ACCACGGCGG, ATTGCTGCGC, 120ATCGAAGACA, CCGACCCAGG, CGGCCAGCCC, CCTGGAACGT, CGATTTACGT, GCTGCTCCCC, 180GGCCGTCGGA, TGCCGATTCC, GCAGCTTCCC, GGTGCGACGG, CTGGCGCTCC, GAGCACGGAC, 240ATCGAGAACT, CTCGGGGTTC, GGCGAACGTT, ATCTCAGTGG, AATCTCAGTC, CACGCGCGCA, 300ACCTAGTTGT, GCAGTTACTG, TTGAAAGCCA, CACCCATGCC, AGTCCACGCA, TGGCCAAGTT, 360GGCCCGAGTA, GTGGGCCTAG, TACAGGAAGA, GCAACCTAGC, GACATGACGA, ATCACCCACG, 420GTATTCGCCA, CCGCCGCAGC, AGCCGGGAAC, CCCAGGTTAT, GCTCAGGGGC, AGCAGCAAAC, 480GTACAGCCAG, CAGTTCGACT, GGCGTTACCC, ACCGTCCCCG, CCCCCGCAGC, CAACCCAGTA, 540CCGTCAACCC, TACGAGGCGT, TGGGTGGTAC, CCGGCCGGGT, CTGATACCTG, GCGTGATTCC, 600GACCATGACG, CCCCCTCCTG, GGATGGTTCG, CCAACGCCCT, CGTGCAGGCA, TGTTGGCCAT, 660CGGCGCGGTG, ACGATAGCGG, TGGTGTCCGC, CGGCATCGGC, GGCGCGGCCG, CATCCCTGGT, 720CGGGTTCAAC, CGGGCACCCG, CCGGCCCCAG, CGGCGGCCCA, GTGGCTGCCA, GCGCGGCGCC, 780AAGCATCCCC, GCAGCAAACA, TGCCGCCGGG, GTCGGTCGAA, CAGGTGGCGG, CCAAGGTGGT, 840GCCCAGTGTC, GTCATGTTGG, AAACCGATCT, GGGCCGCCAG, TCGGAGGAGG, GCTCCGGCAT, 900CATTCTGTCT, GCCGAGGGGC, TGATCTTGAC, CAACAACCAC, GTGATCGCGG, CGGCCGCCAA, 960GCCTCCCCTG, GGCAGTCCGC, CGCCGAAAAC, GACGGTAACC, TTCTCTGACG, GGCGGACCGC, 1020ACCCTTCACG, GTGGTGGGGG, CTGACCCCAC, CAGTGATATC, GCCGTCGTCC, GTGTTCAGGG, 1080CGTCTCCGGG, CTCACCCCGA, TCTCCCTGGG, TTCCTCCTCG, GACCTGAGGG, TCGGTCAGCC, 1140GGTGCTGGCG, ATCGGGTCGC, CGCTCGGTTT, GGAGGGCACC, GTGACCACGG, GGATCGTCAG, 1200CGCTCTCAAC, CGTCCAGTGT, CGACGACCGG, CGAGGCCGGC, AACCAGAACA, CCGTGCTGGA, 1260CGCCATTCAG, ACCGACGCCG, CGATCAACCC, CGGTAACTCC, GGGGGCGCGC, TGGTGAACAT, 1320GAACGCTCAA, CTCGTCGGAG, TCAACTCGGC, CATTGCCACG, CTGGGCGCGG, ACTCAGCCGA, 1380TGCGCAGAGC, GGCTCGATCG, GTCTCGGTTT, TGCGATTCCA, GTCGACCAGG, CCAAGCGCAT, 1440CGCCGACGAG, TTGATCAGCA, CCGGCAAGGC, GTCACATGCC, TCCCTGGGTG, TGCAGGTGAC, 1500CAATGACAAA, GACACCCCGG, GCGCCAAGAT, CGTCGAAGTA, GTGGCCGGTG, GTGCTGCCGC, 1560GAACGCTGGA, GTGCCGAAGG, GCGTCGTTGT, CACCAAGGTC, GACGACCGCC, CGATCAACAG, 1620CGCGGACGCG, TTGGTTGCCG, CCGTGCGGTC, CAAAGCGCCG, GGCGCCACGG, TGGCGCTAAC, 1680CTTTCAGGAT, CCCTCGGGCG, GTAGCCGCAC, AGTGCAAGTC, ACCCTCGGCA, AGGCGGAGCA, 1740GTGATGAAGG, TCGCCGCGCA, GTGTTCAAAG, C, 1771, (2) SEQ, ID, the information of NO:14:

(i) sequence signature:

(A) length: 1058 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:14:CTCCACCGCG, GTGGCGGCCG, CTCTAGAACT, AGTGGATCCC, CCGGGCTGCA, GGAATTCGGC, 60ACGAGGATCC, GACGTCGCAG, GTTGTCGAAC, CCGCCGCCGC, GGAAGTATCG, GTCCATGCCT, 120AGCCCGGCGA, CGGCGAGCGC, CGGAATGGCG, CGAGTGAGGA, GGCGGGCAAT, TTGGCGGGGC, 180CCGGCGACGG, CGAGCGCCGG, AATGGCGCGA, GTGAGGAGGC, GGGCAGTCAT, GCCCAGCGTG, 240ATCCAATCAA, CCTGCATTCG, GCCTGCGGGC, CCATTTGACA, ATCGAGGTAG, TGAGCGCAAA, 300TGAATGATGG, AAAACGGGCG, GTGACGTCCG, CTGTTCTGGT, GGTGCTAGGT, GCCTGCCTGG, 360CGTTGTGGCT, ATCAGGATGT, TCTTCGCCGA, AACCTGATGC, CGAGGAACAG, GGTGTTCCCG, 420TGAGCCCGAC, GGCGTCCGAC, CCCGCGCTCC, TCGCCGAGAT, CAGGCAGTCG, CTTGATGCGA, 480CAAAAGGGTT, GACCAGCGTG, CACGTAGCGG, TCCGAACAAC, CGGGAAAGTC, GACAGCTTGC, 540TGGGTATTAC, CAGTGCCGAT, GTCGACGTCC, GGGCCAATCC, GCTCGCGGCA, AAGGGCGTAT, 600GCACCTACAA, CGACGAGCAC, GGTGTCCCGT, TTCGGGTACA, AGGCGACAAC, ATCTCGGTGA, 660AACTGTTCGA, CGACTGGAGC, AATCTCGGCT, CGATTTCTGA, ACTGTCAACT, TCACGCGTGC, 720TCGATCCTGC, CGCTGGGGTG, ACGCAGCTGC, TGTCCGGTGT, CACGAACCTC, CAAGCGCAAG, 780GTACCGAAGT, GATAGACGGA, ATTTCGACCA, CCAAAATCAC, CGGGACCATC, CCCGCGAGCT, 840CTGTCAAGAT, GCTTGATCCT, GGCGCCAAGA, GTGCAAGGCC, GGCGACCGTG, TGGATTGCCC, 900AGGACGGCTC, GCACCACCTC, GTCCGAGCGA, GCATCGACCT, CGGATCCGGG, TCGATTCAGC, 960TCACGCAGTC, GAAATGGAAC, GAACCCGTCA, ACGTCGACTA, GGCCGAAGTT, GCGTCGACGC, 1020GTTGNTCGAA, ACGCCCTTGT, GAACGGTGTC, AACGGNAC, 1058, (2) SEQ, ID, the information of NO:15:

(i) sequence signature:

(A) length: 542 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:15:GAATTCGGCA, CGAGAGGTGA, TCGACATCAT, CGGGACCAGC, CCCACATCCT, GGGAACAGGC, 60GGCGGCGGAG, GCGGTCCAGC, GGGCGCGGGA, TAGCGTCGAT, GACATCCGCG, TCGCTCGGGT, 120CATTGAGCAG, GACATGGCCG, TGGACAGCGC, CGGCAAGATC, ACCTACCGCA, TCAAGCTCGA, 180AGTGTCGTTC, AAGATGAGGC, CGGCGCAACC, GCGCTAGCAC, GGGCCGGCGA, GCAAGACGCA, 240AAATCGCACG, GTTTGCGGTT, GATTCGTGCG, ATTTTGTGTC, TGCTCGCCGA, GGCCTACCAG, 300GCGCGGCCCA, GGTCCGCGTG, CTGCCGTATC, CAGGCGTGCA, TCGCGATTCC, GGCGGCCACG, 360CCGGAGTTAA, TGCTTCGCGT, CGACCCGAAC, TGGGCGATCC, GCCGGNGAGC, TGATCGATGA, 420CCGTGGCCAG, CCCGTCGATG, CCCGAGTTGC, CCGAGGAAAC, GTGCTGCCAG, GCCGGTAGGA, 480AGCGTCCGTA, GGCGGCGGTG, CTGACCGGCT, CTGCCTGCGC, CCTCAGTGCG, GCCAGCGAGC, 540GG, 542, (2) SEQ, ID, the information of NO:16:

(i) sequence signature:

(A) length: 913 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:16:CGGTGCCGCC, CGCGCCTCCG, TTGCCCCCAT, TGCCGCCGTC, GCCGATCAGC, TGCGCATCGC, 60CACCATCACC, GCCTTTGCCG, CCGGCACCGC, CGGTGGCGCC, GGGGCCGCCG, ATGCCACCGC, 120TTGACCCTGG, CCGCCGGCGC, CGCCATTGCC, ATACAGCACC, CCGCCGGGGG, CACCGTTACC, 180GCCGTCGCCA, CCGTCGCCGC, CGCTGCCGTT, TCAGGCCGGG, GAGGCCGAAT, GAACCGCCGC, 240CAAGCCCGCC, GCCGGCACCG, TTGCCGCCTT, TTCCGCCCGC, CCCGCCGGCG, CCGCCAATTG, 300CCGAACAGCC, AMGCACCGTT, GCCGCCAGCC, CCGCCGCCGT, TAACGGCGCT, GCCGGGCGCC, 360GCCGCCGGAC, CCGCCATTAC, CGCCGTTCCC, GTTCGGTGCC, CCGCCGTTAC, CGGCGCCGCC, 420GTTTGCCGCC, AATATTCGGC, GGGCACCGCC, AGACCCGCCG, GGGCCACCAT, TGCCGCCGGG, 480CACCGAAACA, ACAGCCCAAC, GGTGCCGCCG, GCCCCGCCGT, TTGCCGCCAT, CACCGGCCAT, 540TCACCGCCAG, CAGCGCCGTT, AATGTTTATG, AACCCGGTAC, CGCCAGCGCG, GCCCCTATTG, 600CCGGGCGCCG, GAGNGCGTGC, CCGCCGGCGC, CGCCAACGCC, CAAAAGCCCG, GGGTTGCCAC, 660CGGCCCCGCC, GGACCCACCG, GTCCCGCCGA, TCCCCCCGTT, GCCGCCGGTG, CCGCCGCCAT, 720TGGTGCTGCT, GAAGCCGTTA, GCGCCGGTTC, CGCSGGTTCC, GGCGGTGGCG, CCNTGGCCGC, 780CGGCCCCGCC, GTTGCCGTAC, AGCCACCCCC, CGGTGGCGCC, CTTGCCGCCA, TTGCCGCCAT, 840TGCCGCCGTT, GCCGCCATTG, CCGCCGTTCC, CGCCGCCACC, GCCGGNTTGG, CCGCCGGCGC, 900CGCCGGCGGC, CGC, 913, (2) SEQ, ID, the information of NO:17:

(i) sequence signature:

(A) length: 1872 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:17:GACTACGTTG, GTGTAGAAAA, ATCCTGCCGC, CCGGACCCTT, AAGGCTGGGA, CAATTTCTGA, 60TAGCTACCCC, GACACAGGAG, GTTACGGGAT, GAGCAATTCG, CGCCGCCGCT, CACTCAGGTG, 120GTCATGGTTG, CTGAGCGTGC, TGGCTGCCGT, CGGGCTGGGC, CTGGCCACGG, CGCCGGCCCA, 180GGCGGCCCCG, CCGGCCTTGT, CGCAGGACCG, GTTCGCCGAC, TTCCCCGCGC, TGCCCCTCGA, 240CCCGTCCGCG, ATGGTCGCCC, AAGTGGCGCC, ACAGGTGGTC, AACATCAACA, CCAAACTGGG, 300CTACAACAAC, GCCGTGGGCG, CCGGGACCGG, CATCGTCATC, GATCCCAACG, GTGTCGTGCT, 360CACCAACAAC, CACGTGATCG, CGGGCGCCAC, CGACATCAAT, GCGTTCAGCG, TCGGCTCCGG, 420CCAAACCTAC, GGCGTCGATG, TGGTCGGGTA, TGACCGCACC, CAGGATGTCG, CGGTGCTGCA, 480GCTGCGCGGT, GCCGGTGGCC, TGCCGTCGGC, GGCGATCGGT, GGCGGCGTCG, CGGTTGGTGA, 540GCCCGTCGTC, GCGATGGGCA, ACAGCGGTGG, GCAGGGCGGA, ACGCCCCGTG, CGGTGCCTGG, 600CAGGGTGGTC, GCGCTCGGCC, AAACCGTGCA, GGCGTCGGAT, TCGCTGACCG, GTGCCGAAGA, 660GACATTGAAC, GGGTTGATCC, AGTTCGATGC, CGCAATCCAG, CCCGGTGATT, CGGGCGGGCC, 720CGTCGTCAAC, GGCCTAGGAC, AGGTGGTCGG, TATGAACACG, GCCGCGTCCG, ATAACTTCCA, 780GCTGTCCCAG, GGTGGGCAGG, GATTCGCCAT, TCCGATCGGG, CAGGCGATGG, CGATCGCGGG, 840CCAAATCCGA, TCGGGTGGGG, GGTCACCCAC, CGTTCATATC, GGGCCTACCG, CCTTCCTCGG, 900CTTGGGTGTT, GTCGACAACA, ACGGCAACGG, CGCACGAGTC, CAACGCGTGG, TCGGAAGCGC, 960TCCGGCGGCA, AGTCTCGGCA, TCTCCACCGG, CGACGTGATC, ACCGCGGTCG, ACGGCGCTCC, 1020GATCAACTCG, GCCACCGCGA, TGGCGGACGC, GCTTAACGGG, CATCATCCCG, GTGACGTCAT, 1080CTCGGTGAAC, TGGCAAACCA, AGTCGGGCGG, CACGCGTACA, GGGAACGTGA, CATTGGCCGA, 1140GGGACCCCCG, GCCTGATTTG, TCGCGGATAC, CACCCGCCGG, CCGGCCAATT, GGATTGGCGC, 1200CAGCCGTGAT, TGCCGCGTGA, GCCCCCGAGT, TCCGTCTCCC, GTGCGCGTGG, CATTGTGGAA, 1260GCAATGAACG, AGGCAGAACA, CAGCGTTGAG, CACCCTCCCG, TGCAGGGCAG, TTACGTCGAA, 1320GGCGGTGTGG, TCGAGCATCC, GGATGCCAAG, GACTTCGGCA, GCGCCGCCGC, CCTGCCCGCC, 1380GATCCGACCT, GGTTTAAGCA, CGCCGTCTTC, TACGAGGTGC, TGGTCCGGGC, GTTCTTCGAC, 1440GCCAGCGCGG, ACGGTTCCGN, CGATCTGCGT, GGACTCATCG, ATCGCCTCGA, CTACCTGCAG, 1500TGGCTTGGCA, TCGACTGCAT, CTGTTGCCGC, CGTTCCTACG, ACTCACCGCT, GCGCGACGGC, 1560GGTTACGACA, TTCGCGACTT, CTACAAGGTG, CTGCCCGAAT, TCGGCACCGT, CGACGATTTC, 1620GTCGCCCTGG, TCGACACCGC, TCACCGGCGA, GGTATCCGCA, TCATCACCGA, CCTGGTGATG, 1680AATCACACCT, CGGAGTCGCA, CCCCTGGTTT, CAGGAGTCCC, GCCGCGACCC, AGACGGACCG, 1740TACGGTGACT, ATTACGTGTG, GAGCGACACC, AGCGAGCGCT, ACACCGACGC, CCGGATCATC, 1800TTCGTCGACA, CCGAAGAGTC, GAACTGGTCA, TTCGATCCTG, TCCGCCGACA, GTTNCTACTG, 1860GCACCGATTC, TT, 1872, (2) SEQ, ID, the information of NO:18:

(i) sequence signature:

(A) length: 1482 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:18:CTTCGCCGAA, ACCTGATGCC, GAGGAACAGG, GTGTTCCCGT, GAGCCCGACG, GCGTCCGACC, 60CCGCGCTCCT, CGCCGAGATC, AGGCAGTCGC, TTGATGCGAC, AAAAGGGTTG, ACCAGCGTGC, 120ACGTAGCGGT, CCGAACAACC, GGGAAAGTCG, ACAGCTTGCT, GGGTATTACC, AGTGCCGATG, 180TCGACGTCCG, GGCCAATCCG, CTCGCGGCAA, AGGGCGTATG, CACCTACAAC, GACGAGCAGG, 240GTGTCCCGTT, TCGGGTACAA, GGCGACAACA, TCTCGGTGAA, ACTGTTCGAC, GACTGGAGCA, 300ATCTCGGCTC, GATTTCTGAA, CTGTCAACTT, CACGCGTGCT, CGATCCTGCC, GCTGGGGTGA, 360CGCAGCTGCT, GTCCGGTGTC, ACGAACCTCC, AAGCGCAAGG, TACCGAAGTG, ATAGACGGAA, 420TTTCGACCAC, CAAAATCACC, GGGACCATCC, CCGCGAGCTC, TGTCAAGATG, CTTGATCCTG, 480GCGCCAAGAG, TGCAAGGCCG, GCGACCGTGT, GGATTGCCCA, GGACGGCTCG, CACCACCTCG, 540TCCGAGCGAG, CATCGACCTC, GGATCCGGGT, CGATTCAGCT, CACGCAGTCG, AAATGGAACG, 600AACCCGTCAA, CGTCGACTAG, GCCGAAGTTG, CGTCGACGCG, TTGCTCGAAA, CGCCCTTGTG, 660AACGGTGTCA, ACGGCACCCG, AAAACTGACC, CCCTGACGGC, ATCTGAAAAT, TGACCCCCTA, 720GACCGGGCGG, TTGGTGGTTA, TTCTTCGGTG, GTTCCGGCTG, GTGGGACGCG, GCCGAGGTCG, 780CGGTCTTTGA, GCCGGTAGCT, GTCGCCTTTG, AGGGCGACGA, CTTCAGCATG, GTGGACGAGG, 840CGGTCGATCA, TGGCGGCAGC, AACGACGTCG, TCGCCGCCGA, AAACCTCGCC, CCACCGGCCG, 900AAGGCCTTAT, TGGACGTGAC, GATCAAGCTG, GCCCGCTCAT, ACCGGGAGGA, CACCAGCTGG, 960AAGAAGAGGT, TGGCGGCCTC, GGGCTCAAAC, GGAATGTAAC, CGACTTCGTC, AACCACCAGG, 1020AGCGGATAGC, GGCCAAACCG, GGTGAGTTCG, GCGTAGATGC, GCCCGGCGTG, GTGAGCCTCG, 1080GCGAACCGTG, CTACCCATTC, GGCGGCGGTG, GCGAACAGCA, CCCGATGACC, GGCCTGACAC, 1140GCGCGTATCG, CCAGGCCGAC, CGCAAGATGA, GTCTTCCCGG, TGCCAGGCGG, GGCCCAAAAA, 1200CACGACGTTA, TCGCGGGCGG, TGATGAAATC, CAGGGTGCCC, AGATGTGCGA, TGGTGTCGCG, 1260TTTGAGGCCA, CGAGCATGCT, CAAAGTCGAA, CTCTTCCAAC, GACTTCCGAA, CCGGGAAGCG, 1320GGCGGCGCGG, ATGCGGCCCT, CACCACCATG, GGACTCCCGG, GCTGACACTT, CCCGCTGCAG, 1380GCAGGCGGCC, AGGTATTCTT, CGTGGCTCCA, GTTCTCGGCG, CGGGCGCGAT, CGGCCAGCCG, 1440GGACACTGAC, TCACGCAGGG, TGGGAGCTTT, CAATGCTCTT, GT, 1482, (2) SEQ, ID, the information of NO:19:

(i) sequence signature:

(A) length: 876 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:19:GAATTCGGCA, CGAGCCGGCG, ATAGCTTCTG, GGCCGCGGCC, GACCAGATGG, CTCGAGGGTT, 60CGTGCTCGGG, GCCACCGCCG, GGCGCACCAC, CCTGACCGGT, GAGGGCCTGC, AACACGCCGA, 120CGGTCACTCG, TTGCTGCTGG, ACGCCACCAA, CCCGGCGGTG, GTTGCCTACG, ACCCGGCCTT, 180CGCCTACGAA, ATCGGCTACA, TCGNGGAAAG, CGGACTGGCC, AGGATGTGCG, GGGAGAACCC, 240GGAGAACATC, TTCTTCTACA, TCACCGTCTA, CAACGAGCCG, TACGTGCAGC, CGCCGGAGCC, 300GGAGAACTTC, GATCCCGAGG, GCGTGCTGGG, GGGTATCTAC, CGNTATCACG, CGGCCACCGA, 360GCAACGCACC, AACAAGGNGC, AGATCCTGGC, CTCCGGGGTA, GCGATGCCCG, CGGCGCTGCG, 420GGCAGCACAG, ATGCTGGCCG, CCGAGTGGGA, TGTCGCCGCC, GACGTGTGGT, CGGTGACCAG, 480TTGGGGCGAG, CTAAACCGCG, ACGGGGTGGT, CATCGAGACC, GAGAAGCTCC, GCCACCCCGA, 540TCGGCCGGCG, GGCGTGCCCT, ACGTGACGAG, AGCGCTGGAG, AATGCTCGGG, GCCCGGTGAT, 600CGCGGTGTCG, GACTGGATGC, GCGCGGTCCC, CGAGCAGATC, CGACCGTGGG, TGCCGGGCAC, 660ATACCTCACG, TTGGGCACCG, ACGGGTTCGG, TTTTTCCGAC, ACTCGGCCCG, CCGGTCGTCG, 720TTACTTCAAC, ACCCACGCCG, AATCCCAGGT, TGGTCGCGGT, TTTGGGAGGG, GTTGGCCGGG, 780TCGACGGGTG, AATATCCACC, CATTCGGTGC, CGGTCGTGGG, CCGCCCGCCC, AGTTACCCGG, 840ATTCGACGAA, GGTGGGGGGT, TGCGCCCGAN, TAAGTT, 876, (2) SEQ, ID, the information of NO:20:

(i) sequence signature:

(A) length: 1021 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:20:ATCCCCCCGG, GCTGCAGGAA, TTCGGCACGA, GAGACAAAAT, TCCACGCGTT, AATGCAGGAA, 60CAGATTCATA, ACGAATTCAC, AGCGGCACAA, CAATATGTCG, CGATCGCGGT, TTATTTCGAC, 120AGCGAAGACC, TGCCGCAGTT, GGCGAAGCAT, TTTTACAGCC, AAGCGGTCGA, GGAACGAAAC, 180CATGCAATGA, TGCTCGTGCA, ACACCTGCTC, GACCGCGACC, TTCGTGTCGA, AATTCCCGGC, 240GTAGACACGG, TGCGAAACCA, GTTCGACAGA, CCCCGCGAGG, CACTGGCGCT, GGCGCTCGAT, 300CAGGAACGCA, CAGTCACCGA, CCAGGTCGGT, CGGCTGACAG, CGGTGGCCCG, CGACGAGGGC, 360GATTTCCTCG, GCGAGCAGTT, CATGCAGTGG, TTCTTGCAGG, AACAGATCGA, AGAGGTGGCC, 420TTGATGGCAA, CCCTGGTGCG, GGTTGCCGAT, CGGGCCGGGG, CCAACCTGTT, CGAGCTAGAG, 480AACTTCGTCG, CACGTGAAGT, GGATGTGGCG, CCGGCCGCAT, CAGGCGCCCC, GCACGCTGCC, 540GGGGGCCGCC, TCTAGATCCC, TGGGGGGGAT, CAGCGAGTGG, TCCCGTTCGC, CCGCCCGTCT, 600TCCAGCCAGG, CCTTGGTGCG, GCCGGGGTGG, TGAGTACCAA, TCCAGGCCAC, CCCGACCTCC, 660CGGNAAAAGT, CGATGTCCTC, GTACTCATCG, ACGTTCCAGG, AGTACACCGC, CCGGCCCTGA, 720GCTGCCGAGC, GGTCAACGAG, TTGCGGATAT, TCCTTTAACG, CAGGCAGTGA, GGGTCCCACG, 780GCGGTTGGCC, CGACCGCCGT, GGCCGCACTG, CTGGTCAGGT, ATCGGGGGGT, CTTGGCGAGC, 840AACAACGTCG, GCAGGAGGGG, TGGAGCCCGC, CGGATCCGCA, GACCGGGGGG, GCGAAAACGA, 900CATCAACACC, GCACGGGATC, GATCTGCGGA, GGGGGGTGCG, GGAATACCGA, ACCGGTGTAG, 960GAGCGCCAGC, AGTTGTTTTT, CCACCAGCGA, AGCGTTTTCG, GGTCATCGGN, GGCNNTTAAG, 1020T, 1021, (2) SEQ, ID, the information of NO:21:

(i) sequence signature:

(A) length: 321 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) Topology: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 21: CGTGCCGACG AACGGAAGAA CACAACCATG AAGATGGTGA AATCGATCGC CGCAGGTCTG 60ACCGCCGCGG CTGCAATCGG CGCCGCTGCG GCCGGTGTGA CTTCGATCAT GGCTGGCGGN 120CCGGTCGTAT ACCAGATGCA GCCGGTCGTC TTCGGCGCGC CACTGCCGTT GGACCCGGNA 180TCCGCCCCTG ANGTCCCGAC CGCCGCCCAG TGGACCAGNC TGCTCAACAC NCTCGNCGAT 240CCCAACGTGT CGTTTGNGAA CAAGGGNAGT CTGGTCGAGG GNGGNATCGG NGGNANCGAG 300GGNGNGNATC GNCGANCACA A 321 (2) SEQ ID NO: 22 information about:

(i) sequence signature:

(A) length: 373 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) Topology: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 22: TCTTATCGGT TCCGGTTGGC GACGGGTTTT GGGNGCGGGT GGTTAACCCG CTCGGCCAGC 60CGATCGACGG GCGCGGAGAC GTCGACTCCG ATACTCGGCG CGCGCTGGAG CTCCAGGCGC 120CCTCGGTGGT GNACCGGCAA GGCGTGAAGG AGCCGTTGNA GACCGGGATC AAGGCGATTG 180ACGCGATGAC CCCGATCGGC CGCGGGCAGC GCCAGCTGAT CATCGGGGAC CGCAAGACCG 240GCAAAAACCG CCGTCTGTGT CGGACACCAT CCTCAAACCA GCGGGAAGAA CTGGGAGTCC 300GGTGGATCCC AAGAAGCAGG TGCGCTTGTG TATACGTTGG CCATCGGGCA AGAAGGGGAA 360CTTACCATCG CCG 373 (2) SEQ ID NO: 23 information:

(i) sequence signature:

(A) length: 352 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) Topology: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 23: GTGACGCCGT GATGGGATTC CTGGGCGGGG CCGGTCCGCT GGCGGTGGTG GATCAGCAAC 60TGGTTACCCG GGTGCCGCAA GGCTGGTCGT TTGCTCAGGC AGCCGCTGTG CCGGTGGTGT 120TCTTGACGGC CTGGTACGGG TTGGCCGATT TAGCCGAGAT CAAGGCGGGC GAATCGGTGC 180TGATCCATGC CGGTACCGGC GGTGTGGGCA TGGCGGCTGT GCAGCTGGCT CGCCAGTGGG 240GCGTGGAGGT TTTCGTCACC GCCAGCCGTG GNAAGTGGGA CACGCTGCGC GCCATNGNGT 300TTGACGACGA NCCATATCGG NGATTCCCNC ACATNCGAAG TTCCGANGGA GA 352 (2) SEQ ID NO: 24 information:

(i) sequence signature:

(A) length: 726 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:24:GAAATCCGCG, TTCATTCCGT, TCGACCAGCG, GCTGGCGATA, ATCGACGAAG, TGATCAAGCC, 60GCGGTTCGCG, GCGCTCATGG, GTCACAGCGA, GTAATCAGCA, AGTTCTCTGG, TATATCGCAC, 120CTAGCGTCCA, GTTGCTTGCC, AGATCGCTTT, CGTACCGTCA, TCGCATGTAC, CGGTTCGCGT, 180GCCGCACGCT, CATGCTGGCG, GCGTGCATCC, TGGCCACGGG, TGTGGCGGGT, CTCGGGGTCG, 240GCGCGCAGTC, CGCAGCCCAA, ACCGCGCCGG, TGCCCGACTA, CTACTGGTGC, CCGGGGCAGC, 300CTTTCGACCC, CGCATGGGGG, CCCAACTGGG, ATCCCTACAC, CTGCCATGAC, GACTTCCACC, 360GCGACAGCGA, CGGCCCCGAC, CACAGCCGCG, ACTACCCCGG, ACCCATCCTC, GAAGGTCCCG, 420TGCTTGACGA, TCCCGGTGCT, GCGCCGCCGC, CCCCGGCTGC, CGGTGGCGGC, GCATAGCGCT, 480CGTTGACCGG, GCCGCATCAG, CGAATACGCG, TATAAACCCG, GGCGTGCCCC, CGGCAAGCTA, 540CGACCCCCGG, CGGGCCAGAT, TTACGCTCCC, GTGCCGATGG, ATCGCGCCGT, CCGATGACAG, 600AAAATAGGCG, ACGGTTTTGG, CAACCGCTTG, GAGGACGCTT, GAAGGGAACC, TGTGATGAAC, 660GGCGACAGCG, CCTCCACCAT, CGACATCGAC, AAGGTTGTTA, CCCGCACACC, CGTTCGCCGG, 720ATCGTG, 726, (2) SEQ, ID, the information of NO:25:

(i) sequence signature:

(A) length: 580 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:25:CGCGACGACG, ACGAACGTCG, GGCCCACCAC, CGCCTATGCG, TTGATGCAGG, CGACCGGGAT, 60GGTCGCCGAC, CATATCCAAG, CATGCTGGGT, GCCCACTGAG, CGACCTTTTG, ACCAGCCGGG, 120CTGCCCGATG, GCGGCCCGGT, GAAGTCATTG, CGCCGGGGCT, TGTGCACCTG, ATGAACCCGA, 180ATAGGGAACA, ATAGGGGGGT, GATTTGGCAG, TTCAATGTCG, GGTATGGCTG, GAAATCCAAT, 240GGCGGGGCAT, GCTCGGCGCC, GACCAGGCTC, GCGCAGGCGG, GCCAGCCCGA, ATCTGGAGGG, 300AGCACTCAAT, GGCGGCGATG, AAGCCCCGGA, CCGGCGACGG, TCCTTTGGAA, GCAACTAAGG, 360AGGGGCGCGG, CATTGTGATG, CGAGTACCAC, TTGAGGGTGG, CGGTCGCCTG, GTCGTCGAGC, 420TGACACCCGA, CGAAGCCGCC, GCACTGGGTG, ACGAACTCAA, AGGCGTTACT, AGCTAAGACC, 480AGCCCAACGG, CGAATGGTCG, GCGTTACGCG, CACACCTTCC, GGTAGATGTC, CAGTGTCTGC, 540TCGGCGATGT, ATGCCCAGGA, GAACTCTTGG, ATACAGCGCT, 580, (2) SEQ, ID, the information of NO:26:

(i) sequence signature:

(A) length: 160 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:26:AACGGAGGCG CCGGGGGTTT TGGCGGGGCC GGGGCGGTCG GCGGCAACGG CGGGGCCGGC 60GGTACCGCCG GGTTGTTCGG TGTCGGCGGG GCCGGTGGGG CCGGAGGCAA CGGCATCGCC 120GGTGTCACGG GTACGTCGGC CAGCACACCG GGTGGATCCG 160 (2) SEQ ID NO:27:

(i) sequence signature:

(A) length: 272 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:27:GACACCGATA CGATGGTGAT GTACGCCAAC GTTGTCGACA CGCTCGAGGC GTTCACGATC 60CAGCGCACAC CCGACGGCGT GACCATCGGC GATGCGGCCC CGTTCGCGGA GGCGGCTGCC 120AAGGCGATGG GAATCGACAA GCTGCGGGTA ATTCATACCG GAATGGACCC CGTCGTCGCT 180GAACGCGAAC AGTGGGACGA CGGCAACAAC ACGTTGGCGT TGGCGCCCGG TGTCGTTGTC 240GCCTACGAGC GCAACGTACA GACCAACGCC CG 272 (2) SEQ ID NO:28:

(i) sequence signature:

(A) length: 317 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) Topology: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 28: GCAGCCGGTG GTTCTCGGAC TATCTGCGCA CGGTGACGCA GCGCGACGTG CGCGAGCTGA 60AGCGGATCGA GCAGACGGAT CGCCTGCCGC GGTTCATGCG CTACCTGGCC GCTATCACCG 120CGCAGGAGCT GAACGTGGCC GAAGCGGCGC GGGTCATCGG GGTCGACGCG GGGACGATCC 180GTTCGGATCT GGCGTGGTTC GAGACGGTCT ATCTGGTACA TCGCCTGCCC GCCTGGTCGC 240GGAATCTGAC CGCGAAGATC AAGAAGCGGT CAAAGATCCA CGTCGTCGAC AGTGGCTTCG 300CGGCCTGGTT GCGCGGG 317 (2) SEQ ID NO: 29 information about:

(i) sequence signature:

(A) length: 182 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:29:GATCGTGGAG CTGTCGATGA ACAGCGTTGC CGGACGCGCG GCGGCCAGCA CGTCGGTGTA 60GCAGCGCCGG ACCACCTCGC CGGTGGGCAG CATGGTGATG ACCACGTCGG CCTCGGCCAC 120CGCTTCGGGC GCGCTACGAA ACACCGCGAC ACCGTGCGCG GCGGCGCCGG ACGCCGCCGT 180GG 182 (2) SEQ ID NO:30:

(i) sequence signature:

(A) length: 308 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) Topology: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 30: GATCGCGAAG TTTGGTGAGC AGGTGGTCGA CGCGAAAGTC TGGGCGCCTG CGAAGCGGGT 60CGGCGTTCAC GAGGCGAAGA CACGCCTGTC CGAGCTGCTG CGGCTCGTCT ACGGCGGGCA 120GAGGTTGAGA TTGCCCGCCG CGGCGAGCCG GTAGCAAAGC TTGTGCCGCT GCATCCTCAT 180GAGACTCGGC GGTTAGGCAT TGACCATGGC GTGTACCGCG TGCCCGACGA TTTGGACGCT 240CCGTTGTCAG ACGACGTGCT CGAACGCTTT CACCGGTGAA GCGCTACCTC ATCGACACCC 300ACGTTTGG 308 (2) SEQ ID NO: 31 information about:

(i) sequence signature:

(A) length: 267 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:31:CCGACGACGA GCAACTCACG TGGATGATGG TCGGCAGCGG CATTGAGGAC GGAGAGAATC 60CGGCCGAAGC TGCCGCGCGG CAAGTGCTCA TAGTGACCGG CCGTAGAGGG CTCCCCCGAT 120GGCACCGGAC TATTCTGGTG TGCCGCTGGC CGGTAAGAGC GGGTAAAAGA ATGTGAGGGG 180ACACGATGAG CAATCACACC TACCGAGTGA TCGAGATCGT CGGGACCTCG CCCGACGGCG 240TCGACGCGGC AATCCAGGGC GGTCTGG 267 (2) SEQ ID NO:32:

(i) sequence signature:

(A) length: 1539 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:32:CTCGTGCCGA, AAGAATGTGA, GGGGACACGA, TGAGCAATCA, CACCTACCGA, GTGATCGAGA, 60TCGTCGGGAC, CTCGCCCGAC, GGCGTCGACG, CGGCAATCCA, GGGCGGTCTG, GCCCGAGCTG, 120CGCAGACCAT, GCGCGCGCTG, GACTGGTTCG, AAGTACAGTC, AATTCGAGGC, CACCTGGTCG, 180ACGGAGCGGT, CGCGCACTTC, CAGGTGACTA, TGAAAGTCGG, CTTCCGCTGG, AGGATTCCTG, 240AACCTTCAAG, CGCGGCCGAT, AACTGAGGTG, CATCATTAAG, CGACTTTTCC, AGAACATCCT, 300GACGCGCTCG, AAACGCGGTT, CAGCCGACGG, TGGCTCCGCC, GAGGCGCTGC, CTCCAAAATC, 360CCTGCGACAA, TTCGTCGGCG, GCGCCTACAA, GGAAGTCGGT, GCTGAATTCG, TCGGGTATCT, 420GGTCGACCTG, TGTGGGCTGC, AGCCGGACGA, AGCGGTGCTC, GACGTCGGCT, GCGGCTCGGG, 480GCGGATGGCG, TTGCCGCTCA, CCGGCTATCT, GAACAGCGAG, GGACGCTACG, CCGGCTTCGA, 540TATCTCGCAG, AAAGCCATCG, CGTGGTGCCA, GGAGCACATC, ACCTCGGCGC, ACCCCAACTT, 600CCAGTTCGAG, GTCTCCGACA, TCTACAACTC, GCTGTACAAC, CCGAAAGGGA, AATACCAGTC, 660ACTAGACTTT, CGCTTTCCAT, ATCCGGATGC, GTCGTTCGAT, GTGGTGTTTC, TTACCTCGGT, 720GTTCACCCAC, ATGTTTCCGC, CGGACGTGGA, GCACTATCTG, GACGAGATCT, CCCGCGTGCT, 780GAAGCCCGGC, GGACGATGCC, TGTGCACGTA, CTTCTTGCTC, AATGACGAGT, CGTTAGCCCA, 840CATCGCGGAA, GGAAAGAGTG, CGCACAACTT, CCAGCATGAG, GGACCGGGTT, ATCGGACAAT, 900CCACAAGAAG, CGGCCCGAAG, AAGCAATCGG, CTTGCCGGAG, ACCTTCGTCA, GGGATGTCTA, 960TGGCAAGTTC, GGCCTCGCCG, TGCACGAACC, ATTGCACTAC, GGCTCATGCA, GTGGCCGGGA, 1020ACCACGCCTA, AGCTTCCAGG, ACATCGTCAT, CGCGACCAAA, ACCGCGAGCT, AGGTCGGCAT, 1080CCGGGAAGCA, TCGCGACACC, GTGGCGCCGA, GCGCCGCTGC, CGGCAGGCCG, ATTAGGCGGG, 1140CAGATTAGCC, CGCCGCGGCT, CCCGGCTCCG, AGTACGGCGC, CCCGAATGGC, GTCACCGGCT, 1200GGTAACCACG, CTTGCGCGCC, TGGGCGGCGG, CCTGCCGGAT, CAGGTGGTAG, ATGCCGACAA, 1260AGCCTGCGTG, ATCGGTCATC, ACCAACGGTG, ACAGCAGCCG, GTTGTGCACC, AGCGCGAACG, 1320CCACCCCGGT, CTCCGGGTCT, GTCCAGCCGA, TCGAGCCGCC, CAAGCCCACA, TGACCAAACC, 1380CCGGCATCAC, GTTGCCGATC, GGCATACCGT, GATAGCCAAG, ATGAAAATTT, AAGGGCACCA, 1440ATAGATTTCG, ATCCGGCAGA, ACTTGCCGTC, GGTTGCGGGT, CAGGCCCGTG, ACCAGCTCCC, 1500GCGACAAGAA, CCGTATGCCG, TCGATCTCGC, CTCGTGCCG, 1539, (2) SEQ, ID, the information of NO:33:

(i) sequence signature:

(A) length: 851 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:33:CTGCAGGGTG, GCGTGGATGA, GCGTCACCGC, GGGGCAGGCC, GAGCTGACCG, CCGCCCAGGT, 60CCGGGTTGCT, GCGGCGGCCT, ACGAGACGGC, GTATGGGCTG, ACGGTGCCCC, CGCCGGTGAT, 120CGCCGAGAAC, CGTGCTGAAC, TGATGATTCT, GATAGCGACC, AACCTCTTGG, GGCAAAACAC, 180CCCGGCGATC, GCGGTCAACG, AGGCCGAATA, CGGCGAGATG, TGGGCCCAAG, ACGCCGCCGC, 240GATGTTTGGC, TACGCCGCGG, CGACGGCGAC, GGCGACGGCG, ACGTTGCTGC, CGTTCGAGGA, 300GGCGCCGGAG, ATGACCAGCG, CGGGTGGGCT, CCTCGAGCAG, GCCGCCGCGG, TCGAGGAGGC, 360CTCCCACACC, GCCGCGGCGA, ACCAGTTGAT, GAACAATGTG, CCCCAGGCGC, TGAAACAGTT, 420GGCCCAGCCC, ACGCAGGGCA, CCACGCCTTC, TTCCAAGCTG, GGTGGCCTGT, GGAAGACGGT, 480CTCGCCGCAT, CGGTCGCCGA, TCAGCAACAT, GGTGTCGATG, GCCAACAACC, ACATGTCGAT, 540GACCAACTCG, GGTGTGTCGA, TGACCAACAC, CTTGAGCTCG, ATGTTGAAGG, GCTTTGCTCC, 600GGCGGCGGCC, GCCCAGGCCG, TGCAAACCGC, GGCGCAAAAC, GGGGTCCGGG, CGATGAGCTC, 660GCTGGGCAGC, TCGCTGGGTT, CTTCGGGTCT, GGGCGGTGGG, GTGGCCGCCA, ACTTGGGTCG, 720GGCGGCCTCG, GTACGGTATG, GTCACCGGGA, TGGCGGAAAA, TATGCANAGT, CTGGTCGGCG, 780GAACGGTGGT, CCGGCGTAAG, GTTTACCCCC, GTTTTCTGGA, TGCGGTGAAC, TTCGTCAACG, 840GAAACAGTTA, C, 851, (2) SEQ, ID, the information of NO:34:

(i) sequence signature:

(A) length: 254 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:34:GATCGATCGG GCGGAAATTT GGACCAGATT CGCCTCCGGC GATAACCCAA TCAATCGAAC 60CTAGATTTAT TCCGTCCAGG GGCCCGAGTA ATGGCTCGCA GGAGAGGAAC CTTACTGCTG 120CGGGCACCTG TCGTAGGTCC TCGATACGGC GGAAGGCGTC GACATTTTCC ACCGACACCC 180CCATCCAAAC GTTCGAGGGC CACTCCAGCT TGTGAGCGAG GCGACGCAGT CGCAGGCTGC 240GCTTGGTCAA GATC 254 (2) SEQ ID NO:35:

(i) sequence signature:

(A) length: 1227 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:35:GATCCTGACC, GAAGCGGCCG, CCGCCAAGGC, GAAGTCGCTG, TTGGACCAGG, AGGGACGGGA, 60CGATCTGGCG, CTGCGGATCG, CGGTTCAGCC, GGGGGGGTGC, GCTGGATTGC, GCTATAACCT, 120TTTCTTCGAC, GACCGGACGC, TGGATGGTGA, CCAAACCGCG, GAGTTCGGTG, GTGTCAGGTT, 180GATCGTGGAC, CGGATGAGCG, CGCCGTATGT, GGAAGGCGCG, TCGATCGATT, TCGTCGACAC, 240TATTGAGAAG, CAAGGTTCAC, CATCGACAAT, CCCAACGCCA, CCGGCTCCTG, CGCGTGCGGG, 300GATTCGTTCA, ACTGATAAAA, CGCTAGTACG, ACCCCGCGGT, GCCCAACACG, TACGAGCACA, 360CCAAGACCTG, ACCGCGCTGG, AAAAGCAACT, GAGCGATGCC, TTGCACCTGA, CCGCGTGGCG, 420GGCCGCCGGC, GGCAGGTGTC, ACCTGCATGG, TGAACAGCAC, CTGGGCCTGA, TATTGCGACC, 480AGTACACGAT, TTTGTCGATC, GAGGTCACTT, CGACCTGGGA, GAACTGCTTG, CGGAACGCGT, 540CGCTGCTCAG, CTTGGCCAAG, GCCTGATCGG, AGCGCTTGTC, GCGCACGCCG, TCGTGGATAC, 600CGCACAGCGC, ATTGCGAACG, ATGGTGTCCA, CATCGCGGTT, CTCCAGCGCG, TTGAGGTATC, 660CCTGAATCGC, GGTTTTGGCC, GGTCCCTCCG, AGAATGTGCC, TGCCGTGTTG, GCTCCGTTGG, 720TGCGGACCCC, GTATATGATC, GCCGCCGTCA, TAGCCGACAC, CAGCGCGAGG, GCTACCACAA, 780TGCCGATCAG, CAGCCGCTTG, TGCCGTCGCT, TCGGGTAGGA, CACCTGCGGC, GGCACGCCGG, 840GATATGCGGC, GGGCGGCAGC, GCCGCGTCGT, CTGCCGGTCC, CGGGGCGAAG, GCCGGTTCGG, 900CGGCGCCGAG, GTCGTGGGGG, TAGTCCAGGG, CTTGGGGTTC, GTGGGATGAG, GGCTCGGGGT, 960ACGGCGCCGG, TCCGTTGGTG, CCGACACCGG, GGTTCGGCGA, GTGGGGACCG, GGCATTGTGG, 1020TTCTCCTAGG, GTGGTGGACG, GGACCAGCTG, CTAGGGCGAC, AACCGCCCGT, CGCGTCAGCC, 1080GGCAGCATCG, GCAATCAGGT, GAGCTCCCTA, GGCAGGCTAG, CGCAACAGCT, GCCGTCAGCT, 1140CTCAACGCGA, CGGGGCGGGC, CGCGGCGCCG, ATAATGTTGA, AAGACTAGGC, AACCTTAGGA, 1200ACGAAGGACG, GAGATTTTGT, GACGATC, 1227, (2) SEQ, ID, the information of NO:36:

(i) sequence signature:

(A) length: 181 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:36:GCGGTGTCGG CGGATCCGGC GGGTGGTTGA ACGGCAACGG CGGGGCCGGC GGGGCCGGCG 60GGACCGGCGC TAACGGTGGT GCCGGCGGCA ACGCCTGGTT GTTCGGGGCC GGCGGGTCCG 120GCGGNGCCGG CACCAATGGT GGNGTCGGCG GGTCCGGCGG ATTTGTCTAC GGCAACGGCG 180G 181 (2) SEQ ID NO:37:

(i) sequence signature:

(A) length: 290 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) Topology: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 37: GCGGTGTCGG CGGATCCGGC GGGTGGTTGA ACGGCAACGG CGGTGTCGGC GGCCGGGGCG 60GCGACGGCGT CTTTGCCGGT GCCGGCGGCC AGGGCGGCCT CGGTGGGCAG GGCGGCAATG 120GCGGCGGCTC CACCGGCGGC AACGGCGGTC TTGGCGGCGC GGGCGGTGGC GGAGGCAACG 180CCCCGGAGGG CGGCTTCGGT GGCAACGGCG GTAAGGGTGG CCAGGGCGGN ATTGGCGGCG 240GCACTCAGAG CGCGACCGGC CTCGGNGGTG ACGGCGGTGA CGGCGGTGAC 290 (2) SEQ ID NO: 38 information about:

(i) sequence signature:

(A) length: 34 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:38:GATCCAGTGG CATGGNGGGT GTCAGTGGAA GCAT 34 (2) SEQ ID NO:39:

(i) sequence signature:

(A) length: 155 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:39:GATCGCTGCT CGTCCCCCCC TTGCCGCCGA CGCCACCGGT CCCACCGTTA CCGAACAAGC 60TGGCGTGGTC GCCAGCACCC CCGGCACCGC CGACGCCGGA GTCGAACAAT GGCACCGTCG 120TATCCCCACC ATTGCCGCCG GNCCCACCGG CACCG 155 (2) SEQ ID NO:40:

(i) sequence signature:

(A) length: 53 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:40:ATGGCGTTCA CGGGGCGCCG GGGACCGGGC AGCCCGGNGG GGCCGGGGGG TGG 53 (2) SEQ ID NO:41:

(i) sequence signature:

(A) length: 132 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:41:GATCCACCGC GGGTGCAGAC GGTGCCCGCG GCGCCACCCC GACCAGCGGC GGCAACGGCG 60GCACCGGCGG CAACGGCGCG AACGCCACCG TCGTCGGNGG GGCCGGCGGG GCCGGCGGCA 120AGGGCGGCAA CG 132 (2) SEQ ID NO:42:

(i) sequence signature:

(A) length: 132 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:42:GATCGGCGGC CGGNACGGNC GGGGACGGCG GCAAGGGCGG NAACGGGGGC GCCGNAGCCA 60CCNGCCAAGA ATCCTCCGNG TCCNCCAATG GCGCGAATGG CGGACAGGGC GGCAACGGCG 120GCANCGGCGG CA 132 (2) SEQ ID NO:43:

(i) sequence signature:

(A) length: 702 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:43:CGGCACGAGG, ATCGGTACCC, CGCGGCATCG, GCAGCTGCCG, ATTCGCCGGG, TTTCCCCACC, 60CGAGGAAAGC, CGCTACCAGA, TGGCGCTGCC, GAAGTAGGGC, GATCCGTTCG, CGATGCCGGC, 120ATGAACGGGC, GGCATCAAAT, TAGTGCAGGA, ACCTTTCAGT, TTAGCGACGA, TAATGGCTAT, 180AGCACTAAGG, AGGATGATCC, GATATGACGC, AGTCGCAGAC, CGTGACGGTG, GATCAGCAAG, 240AGATTTTGAA, CAGGGCCAAC, GAGGTGGAGG, CCCCGATGGC, GGACCCACCG, ACTGATGTCC, 300CCATCACACC, GTGCGAACTC, ACGGNGGNTA, AAAACGCCGC, CCAACAGNTG, GTNTTGTCCG, 360CCGACAACAT, GCGGGAATAC, CTGGCGGCCG, GTGCCAAAGA, GCGGCAGCGT, CTGGCGACCT, 420CGCTGCGCAA, CGCGGCCAAG, GNGTATGGCG, AGGTTGATGA, GGAGGCTGCG, ACCGCGCTGG, 480ACAACGACGG, CGAAGGAACT, GTGCAGGCAG, AATCGGCCGG, GGCCGTCGGA, GGGGACAGTT, 540CGGCCGAACT, AACCGATACG, CCGAGGGTGG, CCACGGCCGG, TGAACCCAAC, TTCATGGATC, 600TCAAAGAAGC, GGCAAGGAAG, CTCGAAACGG, GCGACCAAGG, CGCATCGCTC, GCGCACTGNG, 660GGGATGGGTG, GAACACTTNC, ACCCTGACGC, TGCAAGGCGA, CG, 702, (2) SEQ, ID, the information of NO:44:

(i) sequence signature:

(A) length: 298 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) Topology: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 44: GAAGCCGCAG CGCTGTCGGG CGACGTGGCG CTCAAAGCGG CATCGCTCGG TGGCGGTGGA 60GGCGGCGGGG TGCCGTCGGC GCCGTTGGGA TCCGCGATCG GGGGCGCCGA ATCGGTGCGG 120CCCGCTGGCG CTGGTGACAT TGCCGGCTTA GGCCAGGGAA GGGCCGGCGG CGGCGCCGCG 180CTGGGCGGCG GTGGCATGGG AATGCCGATG GGTGCCGCGC ATCAGGGACA AGGGGGCGCC 240AAGTCCAAGG GTTCTCAGCA GGAAGACGAG GCGCTCTACA CCGAGGATCC TCGTGCCG 298 (2) SEQ ID NO: 45 information about:

(i) sequence signature:

(A) length: 1058 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:45:CGGCACGAGG, ATCGAATCGC, GTCGCCGGGA, GCACAGCGTC, GCACTGCACC, AGTGGAGGAG, 60CCATGACCTA, CTCGCCGGGT, AACCCCGGAT, ACCCGCAAGC, GCAGCCCGCA, GGCTCCTACG, 120GAGGCGTCAC, ACCCTCGTTC, GCCCACGCCG, ATGAGGGTGC, GAGCAAGCTA, CCGATGTACC, 180TGAACATCGC, GGTGGCAGTG, CTCGGTCTGG, CTGCGTACTT, CGCCAGCTTC, GGCCCAATGT, 240TCACCCTCAG, TACCGAACTC, GGGGGGGGTG, ATGGCGCAGT, GTCCGGTGAC, ACTGGGCTGC, 300CGGTCGGGGT, GGCTCTGCTG, GCTGCGCTGC, TTGCCGGGGT, GGTTCTGGTG, CCTAAGGCCA, 360AGAGCCATGT, GACGGTAGTT, GCGGTGCTCG, GGGTACTCGG, CGTATTTCTG, ATGGTCTCGG, 420CGACGTTTAA, CAAGCCCAGC, GCCTATTCGA, CCGGTTGGGC, ATTGTGGGTT, GTGTTGGCTT, 480TCATCGTGTT, CCAGGCGGTT, GCGGCAGTCC, TGGCGCTCTT, GGTGGAGACC, GGCGCTATCA, 540CCGCGCCGGC, GCCGCGGCCC, AAGTTCGACC, CGTATGGACA, GTACGGGCGG, TACGGGCAGT, 600ACGGGCAGTA, CGGGGTGCAG, CCGGGTGGGT, ACTACGGTCA, GCAGGGTGCT, CAGCAGGCCG, 660CGGGACTGCA, GTCGCCCGGC, CCGCAGCAGT, CTCCGCAGCC, TCCCGGATAT, GGGTCGCAGT, 720ACGGCGGCTA, TTCGTCCAGT, CCGAGCCAAT, CGGGCAGTGG, ATACACTGCT, CAGCCCCCGG, 780CCCAGCCGCC, GGCGCAGTCC, GGGTCGCAAC, AATCGCACCA, GGGCCCATCC, ACGCCACCTA, 840CCGGCTTTCC, GAGCTTCAGC, CCACCACCAC, CGGTCAGTGC, CGGGACGGGG, TCGCAGGCTG, 900GTTCGGCTCC, AGTCAACTAT, TCAAACCCCA, GCGGGGGCGA, GCAGTCGTCG, TCCCCCGGGG, 960GGGCGCCGGT, CTAACCGGGC, GTTCCCGCGT, CCGGTCGCGC, GTGTGCGCGA, AGAGTGAACA, 1020GGGTGTCAGC, AAGCGCGGAC, GATCCTCGTG, CCGAATTC, 1058, (2) SEQ, ID, the information of NO:46:

(i) sequence signature:

(A) length: 327 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) Topology: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 46: CGGCACGAGA GACCGATGCC GCTACCCTCG CGCAGGAGGC AGGTAATTTC GAGCGGATCT 60CCGGCGACCT GAAAACCCAG ATCGACCAGG TGGAGTCGAC GGCAGGTTCG TTGCAGGGCC 120AGTGGCGCGG CGCGGCGGGG ACGGCGGCCC AGGCCGCGGT GGTGCGCTTC CAAGAAGCAG 180CCAATAAGCA GAAGCAGGAA CTCGACGAGA TCTCGACGAA TATTCGTCAG GCCGGCGTCC 240AATACTCGAG GGCCGACGAG GAGCAGCAGC AGGCGCTGTC CTCGCAAATG GGCTTCTGAC 300CCGCTAATAC GAAAAGAAAC GGAGCAA 327 (2) SEQ ID NO: 47 information about:

(i) sequence signature:

(A) length: 170 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:47:CGGTCGCGAT GATGGCGTTG TCGAACGTGA CCGATTCTGT ACCGCCGTCG TTGAGATCAA 60CCAACAACGT GTTGGCGTCG GCAAATGTGC CGNACCCGTG GATCTCGGTG ATCTTGTTCT 120TCTTCATCAG GAAGTGCACA CCGGCCACCC TGCCCTCGGN TACCTTTCGG 170 (2) SEQ ID NO:48:

(i) sequence signature:

(A) length: 127 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:48:GATCCGGCGG CACGGGGGGT GCCGGCGGCA GCACCGCTGG CGCTGGCGGC AACGGCGGGG 60CCGGGGGTGG CGGCGGAACC GGTGGGTTGC TCTTCGGCAA CGGCGGTGCC GGCGGGCACG 120GGGCCGT 127 (2) SEQ ID NO:49:

(i) sequence signature:

(A) length: 81 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:49:CGGCGGCAAG GGCGGCACCG CCGGCAACGG GAGCGGCGCG GCCGGCGGCA ACGGCGGCAA 60CGGCGGCTCC GGCCTCAACG G 81 (2) SEQ ID NO:50:

(i) sequence signature:

(A) length: 149 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:50:GATCAGGGCT GGCCGGCTCC GGCCAGAAGG GCGGTAACGG AGGAGCTGCC GGATTGTTTG 60GCAACGGCGG GGCCGGNGGT GCCGGCGCGT CCAACCAAGC CGGTAACGGC GGNGCCGGCG 120GAAACGGTGG TGCCGGTGGG CTGATCTGG 149 (2) SEQ ID NO:51:

(i) sequence signature:

(A) length: 355 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) Topology: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 51: CGGCACGAGA TCACACCTAC CGAGTGATCG AGATCGTCGG GACCTCGCCC GACGGTGTCG 60ACGCGGNAAT CCAGGGCGGT CTGCCCCGAG CTGCGCAGAC CATGCGCGCG CTGGACTGGT 120TCGAAGTACA GTCAATTCGA GGCCACCTGG TCGACGGAGC GGTCGCGCAC TTCCAGGTGA 180CTATGAAAGT CGGCTTCCGC CTGGAGGATT CCTGAACCTT CAAGCGCGGC CGATAACTGA 240GGTGCATCAT TAAGCGACTT TTCCAGAACA TCCTGACGCG CTCGAAACGC GGTTCAGCCG 300ACGGTGGCTC CGCCGAGGCG CTGCCTCCAA AATCCCTGCG ACAATTCGTC GGCGG 355 (2) SEQ ID NO: 52 information about:

(i) sequence signature:

(A) length: 999 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:52:ATGCATCACC, ATCACCATCA, CATGCATCAG, GTGGACCCCA, ACTTGACACG, TCGCAAGGGA, 60CGATTGGCGG, CACTGGCTAT, CGCGGCGATG, GCCAGCGCCA, GCCTGGTGAC, CGTTGCGGTG, 120CCCGCGACCG, CCAACGCCGA, TCCGGAGCCA, GCGCCCCCGG, TACCCACAAC, GGCCGCCTCG, 180CCGCCGTCGA, CCGCTGCAGC, GCCACCCGCA, CCGGCGACAC, CTGTTGCCCC, CCCACCACCG, 240GCCGCCGCCA, ACACGCCGAA, TGCCCAGCCG, GGCGATCCCA, ACGCAGCACC, TCCGCCGGCC, 300GACCCGAACG, CACCGCCGCC, ACCTGTCATT, GCCCCAAACG, CACCCCAACC, TGTCCGGATC, 360GACAACCCGG, TTGGAGGATT, CAGCTTCGCG, CTGCCTGCTG, GCTGGGTGGA, GTCTGACGCC, 420GCCCACTTCG, ACTACGGTTC, AGCACTCCTC, AGCAAAACCA, CCGGGGACCC, GCCATTTCCC, 480GGACAGCCGC, CGCCGGTGGC, CAATGACACC, CGTATCGTGC, TCGGCCGGCT, AGACCAAAAG, 540CTTTACGCCA, GCGCCGAAGC, CACCGACTCC, AAGGCCGCGG, CCCGGTTGGG, CTCGGACATG, 600GGTGAGTTCT, ATATGCCCTA, CCCGGGCACC, CGGATCAACC, AGGAAACCGT, CTCGCTCGAC, 660GCCAACGGGG, TGTCTGGAAG, CGCGTCGTAT, TACGAAGTCA, AGTTCAGCGA, TCCGAGTAAG, 720CCGAACGGCC, AGATCTGGAC, GGGCGTAATC, GGCTCGCCCG, CGGCGAACGC, ACCGGACGCC, 780GGGCCCCCTC, AGCGCTGGTT, TGTGGTATGG, CTCGGGACCG, CCAACAACCC, GGTGGACAAG, 840GGCGCGGCCA, ACGCGCTGGC, CGAATCGATC, CGGCCTTTGG, TCGCCCCGCC, GCCGGCGCCG, 900GCACCGGCTC, CTGCAGAGCC, CGCTCCGGCG, CCGGCGCCGG, CCGGGGAAGT, CGCTCCTACC, 960CCGACGACAC, CGACACCGCA, GCGGACCTTA, CCGGCCTGA, 999, (2) SEQ, ID, the information of NO:53:

(i) sequence signature:

(A) length: 332 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:53:Met His His His His His His Met His Gln Val Asp Pro Asn Leu Thr1 5 10 15Arg Arg Lys Gly Arg Leu Ala Ala Leu Ala Ile Ala Ala Met Ala Ser

20??????????????????25??????????????????30Ala?Ser?Leu?Val?Thr?Val?Ala?Val?Pro?Ala?Thr?Ala?Asn?Ala?Asp?Pro

35??????????????????40??????????????????45Glu?Pro?Ala?Pro?Pro?Val?Pro?Thr?Thr?Ala?Ala?Ser?Pro?Pro?Ser?Thr

50??????????????????55??????????????????60Ala?Ala?Ala?Pro?Pro?Ala?Pro?Ala?Thr?Pro?Val?Ala?Pro?Pro?Pro?Pro65??????????????????70??????????????????75??????????????????80Ala?Ala?Ala?Asn?Thr?Pro?Asn?Ala?Gln?Pro?Gly?Asp?Pro?Asn?Ala?Ala

85??????????????????90??????????????????95Pro?Pro?Pro?Ala?Asp?Pro?Asn?Ala?Pro?Pro?Pro?Pro?Val?Ile?Ala?Pro

100?????????????????105?????????????????110Asn?Ala?Pro?Gln?Pro?Val?Arg?Ile?Asp?Asn?Pro?Val?Gly?Gly?Phe?Ser

115?????????????????120?????????????????125Phe?Ala?Leu?Pro?Ala?Gly?Trp?Val?Glu?Ser?Asp?Ala?Ala?His?Phe?Asp

130?????????????????135?????????????????140Tyr?Gly?Ser?Ala?Leu?Leu?Ser?Lys?Thr?Thr?Gly?Asp?Pro?Pro?Phe?Pro145?????????????????150?????????????????155?????????????????160Gly?Gln?Pro?Pro?Pro?Val?Ala?Asn?Asp?Thr?Arg?Ile?Vel?Leu?Gly?Arg

165?????????????????170?????????????????175Leu?Asp?Gln?Lys?Leu?Tyr?Ala?Ser?Ala?Glu?Ala?Thr?Asp?Ser?Lys?Ala

180?????????????????185?????????????????190Ala?Ala?Arg?Leu?Gly?Ser?Asp?Met?Gly?Glu?Phe?Tyr?Met?Pro?Tyr?Pro

195?????????????????200?????????????????205Gly?Thr?Arg?Ile?Asn?Gln?Glu?Thr?Val?Ser?Leu?Asp?Ala?Asn?Gly?Val

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

245?????????????????250?????????????????255Ala?Pro?Asp?Ala?Gly?Pro?Pro?Gln?Arg?Trp?Phe?Val?Val?Trp?Leu?Gly

260?????????????????265?????????????????270Thr?Ala?Asn?Asn?Pro?Val?Asp?Lys?Gly?Ala?Ala?Lys?Ala?Leu?Ala?Glu

275?????????????????280?????????????????285Ser?Ile?Arg?Pro?Leu?Val?Ala?Pro?Pro?Pro?Ala?Pro?Ala?Pro?Ala?Pro

290?????????????????295?????????????????300Ala?Glu?Pro?Ala?Pro?Ala?Pro?Ala?Pro?Ala?Gly?Glu?Val?Ala?Pro?Thr305?????????????????310?????????????????315?????????????????320Pro?Thr?Thr?Pro?Thr?Pro?Gln?Arg?Thr?Leu?Pro?Ala

The information of 325 330 (2) SEQ ID NO:54:

(i) sequence signature:

(A) length: 20 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: SEQ ID NO:54:Asp Pro Val Asp Ala Val Ile Asn Thr Thr Xaa Asn Tyr Gly Gln Val1 5 10 15Val Ala Ala Leu

The information of 20 (2) SEQ ID NO:55:

(i) sequence signature:

(A) length: 15 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:55:Ala Val Glu Ser Gly Met Leu Ala Leu Gly Thr Pro Ala Pro Ser1 5 10 15 (2) SEQ ID NO:56:

(i) sequence signature:

(A) length: 19 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:56:Ala Ala Met Lys Pro Arg Thr Gly Asp Gly Pro Leu Glu Ala Ala Lys1 5 10 15Glu Gly Arg (2) SEQ ID NO:57:

(i) sequence signature:

(A) length: 15 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:57:Tyr Tyr Trp Cys Pro Gly Gln Pro Phe Asp Pro Ala Trp Gly Pro1 5 10 15 (2) SEQ ID NO:58:

(i) sequence signature:

(A) length: 14 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:58:Asp Ile Gly Ser Glu Ser Thr Glu Asp Gln Gln Xaa Ala Val1 5 10 (2) SEQ ID NO:59:

(i) sequence signature:

(A) length: 13 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:59:Ala Glu Glu Ser Ile Ser Thr Xaa Glu Xaa Ile Val Pro1 5 10 (2) SEQ ID NO:60:

(i) sequence signature:

(A) length: 17 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:60:Asp Pro Glu Pro Ala Pro Pro Val Pro Thr Ala Ala Ala Ala Pro Pro1 5 10 15Ala (2) SEQ ID NO:61:

(i) sequence signature:

(A) length: 15 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:61:Ala Pro Lys Thr Tyr Xaa Glu Glu Leu Lys Gly Thr Asp Thr Gly1 5 10 15 (2) SEQ ID NO:62:

(i) sequence signature:

(A) length: 30 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: SEQ ID NO:62:Asp Pro Ala Ser Ala Pro Asp Val Pro Thr Ala Ala Gln Gln Thr Ser1 5 10 15Leu Leu Asn Asn Leu Ala Asp Pro Asp Val Ser Phe Ala Asp

The information of 20 25 30 (2) SEQ ID NO:63:

(i) sequence signature:

(A) length: 187 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:63:Thr Gly Ser Leu Asn Gln Thr His Asn Arg Arg Ala Asn Glu Arg Lys1 5 10 15Asn Thr Thr Met Lys Met Val Lys Ser Ile Ala Ala Gly Leu Thr Ala

20??????????????????25??????????????????30Ala?Ala?Ala?Ile?Gly?Ala?Ala?Ala?Ala?Gly?Val?Thr?Ser?Ile?Met?Ala

35??????????????????40??????????????????45Gly?Gly?Pro?Val?Val?Tyr?Gln?Met?Gln?Pro?Val?Val?Phe?Gly?Ala?Pro

50??????????????????55??????????????????60Leu?Pro?Leu?Asp?Pro?Ala?Ser?Ala?Pro?Asp?Val?Pro?Thr?Ala?Ala?Gln65???????????????????70??????????????????75?????????????????80Leu?Thr?Ser?Leu?Leu?Asn?Ser?Leu?Ala?Asp?Pro?Asn?Val?Ser?Phe?Ala

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

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

115?????????????????120?????????????????125Leu?Ser?Phe?Ser?Val?Thr?Asn?Ile?Gln?Pro?Ala?Ala?Ala?Gly?Ser?Ala

130?????????????????135?????????????????140Thr?Ala?Asp?Val?Ser?Val?Ser?Gly?Pro?Lys?Leu?Ser?Ser?Pro?Val?Thr145?????????????????150?????????????????155?????????????????160Gln?Asn?Val?Thr?Phe?Val?Asn?Gln?Gly?Gly?Trp?Met?Leu?Ser?Arg?Ala

165?????????????????170?????????????????175Ser?Ala?Met?Glu?Leu?Leu?Gln?Ala?Ala?Gly?Xaa

The information of 180 185 (2) SEQ ID NO:64:

(i) sequence signature:

(A) length: 148 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:64:Asp Glu Val Thr Val Glu Thr Thr Ser Val Phe Arg Ala Asp Phe Leu1 5 10 15Ser Glu Leu Asp Ala Pro Ala Gln Ala Gly Thr Glu Ser Ala Val Ser

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

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

50??????????????????55??????????????????60Ala?Gly?Arg?His?Pro?Asp?Ser?Asp?Ile?Phe?Leu?Asp?Asp?Val?Thr?Val65??????????????????70??????????????????75??????????????????80Ser?Arg?Arg?His?Ala?Glu?Phe?Arg?Leu?Glu?Asn?Asn?Glu?Phe?Asn?Val

85??????????????????90??????????????????95Val?Asp?Val?Gly?Ser?Leu?Asn?Gly?Thr?Tyr?Val?Asn?Arg?Glu?Pro?Val

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

115?????????????????120?????????????????125Arg?Leu?Val?Phe?Leu?Thr?Gly?Pro?Lys?Gln?Gly?Glu?Asp?Asp?Gly?Ser

The information of 130 135 140Thr Gly Gly Pro145 (2) SEQ ID NO:65:

(i) sequence signature:

(A) length: 230 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:65:Thr Ser Asn Arg Pro Ala Arg Arg Gly Arg Arg Ala Pro Arg Asp Thr1 5 10 15Gly Pro Asp Arg Ser Ala Ser Leu Ser Leu Val Arg His Arg Arg Gln

20??????????????????25??????????????????30Gln?Arg?Asp?Ala?Leu?Cys?Leu?Ser?Ser?Thr?Gln?Ile?Ser?Arg?Gln?Ser

35??????????????????40??????????????????45Asn?Leu?Pro?Pro?Ala?Ala?Gly?Gly?Ala?Ala?Asn?Tyr?Ser?Arg?Arg?Asn

50??????????????????55??????????????????60Phe?Asp?Val?Arg?Ile?Lys?Ile?Phe?Met?Leu?Val?Thr?Ala?Val?Val?Leu65??????????????????70??????????????????75??????????????????80Leu?Cys?Cys?Ser?Gly?Val?Ala?Thr?Ala?Ala?Pro?Lys?Thr?Tyr?Cys?Glu

85??????????????????90??????????????????95Glu?Leu?Lys?Gly?Thr?Asp?Thr?Gly?Gln?Ala?Cys?Gln?Ile?Gln?Met?Ser

100?????????????????105?????????????????110Asp?Pro?Ala?Tyr?Asn?Ile?Asn?Ile?Ser?Leu?Pro?Ser?Tyr?Tyr?Pro?Asp

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

130?????????????????135?????????????????140Ser?Ala?Ala?Thr?Ser?Ser?Thr?Pro?Arg?Glu?Ala?Pro?Tyr?Glu?Leu?Asn145?????????????????150?????????????????155?????????????????160Ile?Thr?Ser?Ala?Thr?Tyr?Gln?Ser?Ala?Ile?Pro?Pro?Arg?Gly?Thr?Gln

165?????????????????170?????????????????175Ala?Val?Val?Leu?Xaa?Val?Tyr?His?Asn?Ala?Gly?Gly?Thr?His?Pro?Thr

180?????????????????185?????????????????190Thr?Thr?Tyr?Lys?Ala?Phe?Asp?Trp?Asp?Gln?Ala?Tyr?Arg?Lys?Pro?Ile

195?????????????????200?????????????????205Thr?Tyr?Asp?Thr?Leu?Trp?Gln?Ala?Asp?Thr?Asp?Pro?Leu?Pro?Val?Val

The information of 210 215 220Phe Pro Ile Val Ala Arg225,230 (2) SEQ ID NO:66:

(i) sequence signature:

(A) length: 132 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:66:Thr Ala Ala Ser Asp Asn Phe Gln Leu Ser Gln Gly Gly Gln Gly Phe1 5 10 15Ala Ile Pro Ile Gly Gln Ala Met Ala Ile Ala Gly Gln Ile Arg Ser

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

35??????????????????40??????????????????45Leu?Gly?Val?Val?Asp?Asn?Asn?Gly?Asn?Gly?Ala?Arg?Val?Gln?Arg?Val

50??????????????????55??????????????????60Val?Gly?Ser?Ala?Pro?Ala?Ala?Ser?Leu?Gly?Ile?Ser?Thr?Gly?Asp?Val65???????????????????70??????????????????75??????????????????80Ile?Thr?Ala?Val?Asp?Gly?Ala?Pro?Ile?Asn?Ser?Ala?Thr?Ala?Met?Ala

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

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

115?????????????????120?????????????????125Gly?Pro?Pro?Ala

The information of 130 (2) SEQ ID NO:67:

(i) sequence signature:

(A) length: 100 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:67:Val Pro Leu Arg Ser Pro Ser Met Ser Pro Ser Lys Cys Leu Ala Ala1 5 10 15Ale Gln Arg Asn Pro Val Ile Arg Arg Arg Arg Leu Ser Asn Pro Pro

20??????????????????25??????????????????30Pro?Arg?Lys?Tyr?Arg?Ser?Met?Pro?Ser?Pro?Ala?Thr?Ala?Ser?Ala?Gly

35??????????????????40??????????????????45Met?Ala?Arg?Val?Arg?Arg?Arg?Ala?Ile?Trp?Arg?Gly?Pro?Ala?Thr?Xaa

50??????????????????55??????????????????60Ser?Ala?Gly?Met?Ala?Arg?Val?Arg?Arg?Trp?Xaa?Val?Met?Pro?Xaa?Val65??????????????????70??????????????????75??????????????????80Ile?Gln?Ser?Thr?Xaa?Ile?Arg?Xaa?Xaa?Gly?Pro?Phe?Asp?Asn?Arg?Gly

85??????????????????90??????????????????95Ser?Glu?Arg?Lys

The information of 100 (2) SEQ ID NO:68:

(i) sequence signature:

(A) length: 163 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:68:Met Thr Asp Asp Ile Leu Leu Ile Asp Thr Asp Glu Arg Val Arg Thr1 5 10 15Leu Thr Leu Asn Arg Pro Gln Ser Arg Asn Ala Leu Ser Ala Ala Leu

20??????????????????25??????????????????30Arg?Asp?Arg?Phe?Phe?Ala?Xaa?Leu?Xaa?Asp?Ala?Glu?Xaa?Asp?Asp?Asp

35??????????????????40??????????????????45Ile?Asp?Val?Val?Ile?Leu?Thr?Gly?Ala?Asp?Pro?Val?Phe?Cys?Ala?Gly

50??????????????????55??????????????????60Leu?Asp?Leu?Lys?Val?Ala?Gly?Arg?Ala?Asp?Arg?Ala?Ala?Gly?His?Leu65??????????????????70??????????????????75??????????????????80Thr?Ala?Val?Gly?Gly?His?Asp?Gln?Ala?Gly?Asp?Arg?Arg?Asp?Gln?Arg

85??????????????????90??????????????????95Arg?Arg?Gly?His?Arg?Arg?Ala?Arg?Thr?Gly?Ala?Val?Leu?Arg?His?Pro

100?????????????????105?????????????????110Asp?Arg?Leu?Arg?Ala?Arg?Pro?Leu?Arg?Arg?His?Pro?Arg?Pro?Gly?Gly

115?????????????????120?????????????????125Ala?Ala?Ala?His?Leu?Gly?Thr?Gln?Cys?Val?Leu?Ala?Ala?Lys?Gly?Arg

The information of 130 135 140His Arg Xaa Gly Pro Val Asp Glu Pro Asp Arg Arg Leu Pro Val Arg145,150 155 160Asp Arg Arg (2) SEQ ID NO:69:

(i) sequence signature:

(A) length: 344 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:69:Met Lys Phe Val Asn His Ile Glu Pro Val Ala Pro Arg Arg Ala Gly1 5 10 15Gly Ala Val Ala Glu Val Tyr Ala Glu Ala Arg Arg Glu Phe Gly Arg

20??????????????????25??????????????????30Leu?Pro?Glu?Pro?Leu?Ala?Met?Leu?Ser?Pro?Asp?Glu?Gly?Leu?Leu?Thr

35??????????????????40??????????????????45Ala?Gly?Trp?Ala?Thr?Leu?Arg?Glu?Thr?Leu?Leu?Val?Gly?Gln?Val?Pro

50??????????????????55??????????????????60Arg?Gly?Arg?Lys?Glu?Ala?Val?Ala?Ala?Ala?Val?Ala?Ala?Ser?Leu?Arg65??????????????????70??????????????????75??????????????????80Cys?Pro?Trp?Cys?Va1?Asp?Ala?His?Thr?Thr?Met?Leu?Tyr?Ala?Ala?Gly

85??????????????????90??????????????????95Gln?Thr?Asp?Thr?Ala?Ala?Ala?Ile?Leu?Ala?Gly?Thr?Ala?Pro?Ala?Ala

100?????????????????105?????????????????110Gly?Asp?Pro?Asn?Ala?Pro?Tyr?Val?Ala?Trp?Ala?Ala?Gly?Thr?Gly?Thr

115?????????????????120?????????????????125Pro?Ala?Gly?Pro?Pro?Ala?Pro?Phe?Gly?Pro?Asp?Val?Ala?Ala?Glu?Tyr

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

165?????????????????170?????????????????175Met?Arg?Arg?Ala?Gly?Gly?Leu?Val?Phe?Ala?Arg?Lys?Val?Arg?Ala?Glu

180?????????????????185?????????????????190His?Arg?Pro?Gly?Arg?Ser?Thr?Arg?Arg?Leu?Glu?Pro?Arg?Thr?Leu?Pro

195?????????????????200?????????????????205Asp?Asp?Leu?Ala?Trp?Ala?Thr?Pro?Ser?Glu?Pro?Ile?Ala?Thr?Ala?Phe

210?????????????????215?????????????????220Ala?Ala?Leu?Ser?His?His?Leu?Asp?Thr?Ala?Pro?His?Leu?Pro?Pro?Pro225?????????????????230?????????????????235?????????????????240?Thr?Arg?Gln?Val?Val?Arg?Arg?Val?Val?Gly?Ser?Trp?His?Gly?Glu?Pro

245?????????????????250?????????????????255Met?Pro?Met?Ser?Ser?Arg?Trp?Thr?Asn?Glu?His?Thr?Ala?Glu?Leu?Pro

260?????????????????265?????????????????270Ala?Asp?Leu?His?Ala?Pro?Thr?Arg?Leu?Ala?Leu?Leu?Thr?Gly?Leu?Ala

275?????????????????280?????????????????285Pro?His?Gln?Val?Thr?Asp?Asp?Asp?Val?Ala?Ala?Ala?Arg?Ser?Leu?Leu

290?????????????????295?????????????????300Asp?Thr?Asp?Ala?Ala?Leu?Val?Gly?Ala?Leu?Ala?Trp?Ala?Ala?Phe?Thr305?????????????????310?????????????????315?????????????????320Ala?Ala?Arg?Arg?Ile?Gly?Thr?Trp?Ile?Gly?Ala?Ala?Ala?Glu?Gly?Gln

325?????????????????330?????????????????335Val?Ser?Arg?Gln?Asn?Pro?Thr?Gly

The information of 340 (2) SEQ ID NO:70:

(i) sequence signature:

(A) length: 485 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:70:Asp Asp Pro Asp Met Pro Gly Thr Val Ala Lys Ala Val Ala Asp Ala1 5 10 15Leu Gly Arg Gly Ile Ala Pro Val Glu Asp Ile Gln Asp Cys Val Glu

20??????????????????25??????????????????30Ala?Arg?Leu?Gly?Glu?Ala?Gly?Leu?Asp?Asp?Val?Ala?Arg?Val?Tyr?Ile

35??????????????????40??????????????????45Ile?Tyr?Arg?Gln?Arg?Arg?Ala?Glu?Leu?Arg?Thr?Ala?Lys?Ala?Leu?Leu

50??????????????????55??????????????????60Gly?Val?Arg?Asp?Glu?Leu?Lys?Leu?Ser?Leu?Ala?Ala?Val?Thr?Val?Leu65??????????????????70??????????????????75??????????????????80Arg?Glu?Arg?Tyr?Leu?Leu?His?Asp?Glu?Gln?Gly?Arg?Pro?Ala?Glu?Ser

85??????????????????90??????????????????95Thr?Gly?Glu?Leu?Met?Asp?Arg?Ser?Ala?Arg?Cys?Val?Ala?Ala?Ala?Glu

100?????????????????105?????????????????110Asp?Gln?Tyr?Glu?Pro?Gly?Ser?Ser?Arg?Arg?Trp?Ala?Glu?Arg?Phe?Ala

115?????????????????120?????????????????125Thr?Leu?Leu?Arg?Asn?Leu?Glu?Phe?Leu?Pro?Asn?Ser?Pro?Thr?Leu?Met

130?????????????????135?????????????????140Asn?Ser?Gly?Thr?Asp?Leu?Gly?Leu?Leu?Ala?Gly?Cys?Phe?Val?Leu?Pro145?????????????????150?????????????????155?????????????????160Ile?Glu?Asp?Ser?Leu?Gln?Ser?Ile?Phe?Ala?Thr?Leu?Gly?Gln?Ala?Ala

165?????????????????170?????????????????175Glu?Leu?Gln?Arg?Ala?Gly?Gly?Gly?Thr?Gly?Tyr?Ala?Phe?Ser?His?Leu

180?????????????????185?????????????????190Arg?Pro?Ala?Gly?Asp?Arg?Val?Ala?Ser?Thr?Gly?Gly?Thr?Ala?Ser?Gly

195?????????????????200?????????????????205Pro?Val?Ser?Phe?Leu?Arg?Leu?Tyr?Asp?Ser?Ala?Ala?Gly?Val?Val?Ser

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

245?????????????????250?????????????????255Glu?Leu?Pro?His?Phe?Asn?Leu?Ser?Val?Gly?Val?Thr?Asp?Ala?Phe?Leu

260?????????????????265?????????????????270Arg?Ala?Val?Glu?Arg?Asn?Gly?Leu?His?Arg?Leu?Val?Asn?Pro?Arg?Thr

275?????????????????280?????????????????285Gly?Lys?Ile?Val?Ala?Arg?Met?Pro?Ala?Ala?Glu?Leu?Phe?Asp?Ala?Ile

290?????????????????295?????????????????300Cys?Lys?Ala?Ala?His?Ala?Gly?Gly?Asp?Pro?Gly?Leu?Val?Phe?Leu?Asp305?????????????????310?????????????????315?????????????????320Thr?Ile?Asn?Arg?Ala?Asn?Pro?Val?Pro?Gly?Arg?Gly?Arg?Ile?Glu?Ala

325?????????????????330?????????????????335Thr?Asn?Pro?Cys?Gly?Glu?Val?Pro?Leu?Leu?Pro?Tyr?Glu?Ser?Cys?Asn

340?????????????????345?????????????????350Leu?Gly?Ser?Ile?Asn?Leu?Ala?Arg?Met?Leu?Ala?Asp?Gly?Arg?Val?Asp

355?????????????????360?????????????????365Trp?Asp?Arg?Leu?Glu?Glu?Val?Ala?Gly?Val?Ala?Val?Arg?Phe?Leu?Asp

370?????????????????375?????????????????380Asp?Val?Ile?Asp?Val?Ser?Arg?Tyr?Pro?Phe?Pro?Glu?Leu?Gly?Glu?Ala385?????????????????390?????????????????395?????????????????400Ala?Arg?Ala?Thr?Arg?Lys?Ile?Gly?Leu?Gly?Val?Met?Gly?Leu?Ala?Glu

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

420?????????????????425?????????????????430Leu?Ala?Thr?Arg?Leu?Met?Arg?Arg?Ile?Gln?Gln?Ala?Ala?His?Thr?Ala

435?????????????????440?????????????????445Ser?Arg?Arg?Leu?Ala?Glu?Glu?Arg?Gly?Ala?Phe?Pro?Ala?Phe?Thr?Asp

450?????????????????455?????????????????460Ser?Arg?Phe?Ala?Arg?Ser?Gly?Pro?Arg?Arg?Asn?Ala?Gln?Val?Thr?Ser465?????????????????470?????????????????475?????????????????480Val?Ala?Pro?Thr?Gly

The information of 485 (2) SEQ ID NO:71:

(i) sequence signature:

(A) length: 267 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:71:Gly Val Ile Val Leu Asp Leu Glu Pro Arg Gly Pro Leu Pro Thr Glu1 5 10 15Ile Tyr Trp Arg Arg Arg Gly Leu Ala Leu Gly Ile Ala Val Val Val

20??????????????????25??????????????????30Val?Gly?Ile?Ala?Val?Ala?Ile?Val?Ile?Ala?Phe?Val?Asp?Ser?Ser?Ala

35??????????????????40??????????????????45Gly?Ala?Lys?Pro?Val?Ser?Ala?Asp?Lys?Pro?Ala?Ser?Ala?Gln?Ser?His

50??????????????????55??????????????????60Pro?Gly?Ser?Pro?Ala?Pro?Gln?Ala?Pro?Gln?Pro?Ala?Gly?Gln?Thr?Glu65??????????????????70??????????????????75??????????????????80Gly?Asn?Ala?Ala?Ala?Ala?Pro?Pro?Gln?Gly?Gln?Asn?Pro?Glu?Thr?Pro

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

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

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

130?????????????????135?????????????????140Ile?Gly?Leu?Val?Ser?Cys?Lys?Arg?Asp?Val?Gly?Ala?Ala?Val?Leu?Ala145?????????????????150?????????????????155?????????????????160Ala?Tyr?Val?Tyr?Ser?Leu?Asp?Asn?Lys?Arg?Leu?Trp?Ser?Asn?Leu?Asp

165?????????????????170?????????????????175Cys?Ala?Pro?Ser?Asn?Glu?Thr?Leu?Val?Lys?Thr?Phe?Ser?Pro?Gly?Glu

180?????????????????185?????????????????190Gln?Val?Thr?Thr?Ala?Val?Thr?Trp?Thr?Gly?Met?Gly?Ser?Ala?Pro?Arg

195?????????????????200?????????????????205Cys?Pro?Leu?Pro?Arg?Pro?Ala?Ile?Gly?Pro?Gly?Thr?Tyr?Asn?Leu?Val

210?????????????????215?????????????????220Val?Gln?Leu?Gly?Asn?Leu?Arg?Ser?Leu?Pro?Val?Pro?Phe?Ile?Leu?Asn225?????????????????230?????????????????235?????????????????240Gln?Pro?Pro?Pro?Pro?Pro?Gly?Pro?Val?Pro?Ala?Pro?Gly?Pro?Ala?Gln

245?????????????????250?????????????????255Ala?Pro?Pro?Pro?Glu?Ser?Pro?Ala?Gln?Gly?Gly

The information of 260 265 (2) SEQ ID NO:72:

(i) sequence signature:

(A) length: 97 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:72:Leu Ile Ser Thr Gly Lys Ala Ser His Ala Ser Leu Gly Val Gln Val1 5 10 15Thr Asn Asp Lys Asp Thr Pro Gly Ala Lys Ile Val Glu Val Val Ala

20??????????????????25??????????????????30Gly?Gly?Ala?Ala?Ala?Asn?Ala?Gly?Val?Pro?Lys?Gly?Val?Val?Val?Thr

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

50??????????????????55??????????????????60Val?Arg?Ser?Lys?Ala?Pro?Gly?Ala?Thr?Val?Ala?Leu?Thr?Phe?Gln?Asp65??????????????????70??????????????????75??????????????????80Pro?Ser?Gly?Gly?Ser?Arg?Thr?Val?Gln?Val?Thr?Leu?Gly?Lys?Ala?Glu

The information of 85 90 95Gln (2) SEQ ID NO:73:

(i) sequence signature:

(A) length: 364 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:73:Gly Ala Ala Val Ser Leu Leu Ala Ala Gly Thr Leu Val Leu Thr Ala1 5 10 15Cys Gly Gly Gly Thr Asn Ser Ser Ser Ser Gly Ala Gly Gly Thr Ser

20??????????????????25??????????????????30Gly?Ser?Val?His?Cys?Gly?Gly?Lys?Lys?Glu?Leu?His?Ser?Ser?Gly?Ser

35??????????????????40??????????????????45Thr?Ala?Gln?Glu?Asn?Ala?Met?Glu?Gln?Phe?Val?Tyr?Ala?Tyr?Val?Arg

50??????????????????55??????????????????60Ser?Cys?Pro?Gly?Tyr?Thr?Leu?Asp?Tyr?Asn?Ala?Asn?Gly?Ser?Gly?Ala65??????????????????70??????????????????75??????????????????80Gly?Val?Thr?Gln?Phe?Leu?Asn?Asn?Glu?Thr?Asp?Phe?Ala?Gly?Ser?Asp

85??????????????????90??????????????????95Val?Pro?Leu?Asn?Pro?Ser?Thr?Gly?Gln?Pro?Asp?Arg?Ser?Ala?Glu?Arg

100?????????????????105?????????????????110Cys?Gly?Ser?Pro?Ala?Trp?Asp?Leu?Pro?Thr?Val?Phe?Gly?Pro?Ile?Ala

115?????????????????120?????????????????125Ile?Thr?Tyr?Asn?Ile?Lys?Gly?Val?Ser?Thr?Leu?Asn?Leu?Asp?Gly?Pro

130?????????????????135?????????????????140Thr?Thr?Ala?Lys?Ile?Phe?Asn?Gly?Thr?Ile?Thr?Val?Trp?Asn?Asp?Pro145?????????????????150?????????????????155?????????????????160Gln?Ile?Gln?Ala?Leu?Asn?Ser?Gly?Thr?Asp?Leu?Pro?Pro?Thr?Pro?Ile

165?????????????????170?????????????????175Ser?Val?Ile?Phe?Arg?Ser?Asp?Lys?Ser?Gly?Thr?Ser?Asp?Asn?Phe?Gln

180?????????????????185?????????????????190Lys?Tyr?Leu?Asp?Gly?Val?Ser?Asn?Gly?Ala?Trp?Gly?Lys?Gly?Ala?Ser

195?????????????????200?????????????????205Glu?Thr?Phe?Ser?Gly?Gly?Val?Gly?Val?Gly?Ala?Ser?Gly?Asn?Asn?Gly

210?????????????????215?????????????????220Thr?Ser?Ala?Leu?Leu?Gln?Thr?Thr?Asp?Gly?Ser?Ile?Thr?Tyr?Asn?Glu225?????????????????230?????????????????235?????????????????240Trp?Ser?Phe?Ala?Val?Gly?Lys?Gln?Leu?Asn?Met?Ala?Gln?Ile?Ile?Thr

245?????????????????250?????????????????255Ser?Ala?Gly?Pro?Asp?Pro?Val?Ala?Ile?Thr?Thr?Glu?Ser?Val?Gly?Lys

260?????????????????265?????????????????270Thr?Ile?Ala?Gly?Ala?Lys?Ile?Met?Gly?Gln?Gly?Asn?Asp?Leu?Val?Leu

275?????????????????280?????????????????285Asp?Thr?Ser?Ser?Phe?Tyr?Arg?Pro?Thr?Gln?Pro?Gly?Ser?Tyr?Pro?Ile

290?????????????????295?????????????????300Val?Leu?Ala?Thr?Tyr?Glu?Ile?Val?Cys?Ser?Lys?Tyr?Pro?Asp?Ala?Thr305?????????????????310?????????????????315?????????????????320Thr?Gly?Thr?Ala?Val?Arg?Ala?Phs?Met?Gln?Ala?Ala?Ile?Gly?Pro?Gly

325?????????????????330?????????????????335Gln?Glu?Gly?Leu?Asp?Gln?Tyr?Gly?Ser?Ile?Pro?Leu?Pro?Lys?Ser?Phe

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

The information of 355 360 (2) SEQ ID NO:74:

(i) sequence signature:

(A) length: 309 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:74:Gln Ala Ala Ala Gly Arg Ala Val Arg Arg Thr Gly His Ala Glu Asp1 5 10 15Gln Thr His Gln Asp Arg Leu His His Gly Cys Arg Arg Ala Ala Val

20??????????????????25??????????????????30Val?Val?Arg?Gln?Asp?Arg?Ala?Ser?Val?Ser?Ala?Thr?Ser?Ala?Arg?Pro

35??????????????????40??????????????????45Pro?Arg?Arg?His?Pro?Ala?Gln?Gly?His?Arg?Arg?Arg?Val?Ala?Pro?Ser

50??????????????????55??????????????????60Gly?Gly?Arg?Arg?Arg?Pro?His?Pro?His?His?Val?Gln?Pro?Asp?Asp?Arg65??????????????????70??????????????????75??????????????????80Arg?Asp?Arg?Pro?Ala?Leu?Leu?Asp?Arg?Thr?Gln?Pro?Ala?Glu?His?Pro

85??????????????????90??????????????????95Asp?Pro?His?Arg?Arg?Gly?Pro?Ala?Asp?Pro?Gly?Arg?Val?Arg?Gly?Arg

100?????????????????105?????????????????110Gly?Arg?Leu?Arg?Arg?Val?Asp?Asp?Gly?Arg?Leu?Gln?Pro?Asp?Arg?Asp

115?????????????????120?????????????????125Ala?Asp?His?Gly?Ala?Pro?Val?Arg?Gly?Arg?Gly?Pro?His?Arg?Gly?Val

130?????????????????135?????????????????140Gln?His?Arg?Gly?Gly?Pro?Val?Phe?Val?Arg?Arg?Val?Pro?Gly?Val?Arg145?????????????????150?????????????????155?????????????????160Cys?Ala?His?Arg?Arg?Gly?His?Arg?Arg?Val?Ala?Ala?Pro?Gly?Gln?Gly

165?????????????????170?????????????????175Asp?Val?Leu?Arg?Ala?Gly?Leu?Arg?Val?Glu?Arg?Leu?Arg?Pro?Val?Ala

180?????????????????185?????????????????190Ala?Val?Glu?Asn?Leu?His?Arg?Gly?Ser?Gln?Arg?Ala?Asp?Gly?Arg?Val

195?????????????????200?????????????????205Phe?Arg?Pro?Iie?Arg?Arg?Gly?Ala?Arg?Leu?Pro?Ala?Arg?Arg?Ser?Arg

210?????????????????215?????????????????220Ala?Gly?Pro?Gln?Gly?Arg?Leu?His?Leu?Asp?Gly?Ala?Gly?Pro?Ser?Pro225?????????????????230?????????????????235?????????????????240Leu?Pro?Ala?Arg?Ala?Gly?Gln?Gln?Gln?Pro?Ser?Ser?Ala?Gly?Gly?Arg

245?????????????????250?????????????????255Arg?Ala?Gly?Gly?Ala?Glu?Arg?Ala?Asp?Pro?Gly?Gln?Arg?Gly?Arg?His

260?????????????????265?????????????????270His?Gln?Gly?Gly?His?Asp?Pro?Gly?Arg?Gln?Gly?Ala?Gln?Arg?Gly?Thr

275?????????????????280?????????????????285Ala?Gly?Val?Ala?His?Ala?Ala?Ala?Gly?Pro?Arg?Arg?Ala?Ala?Val?Arg

The information of 290 295 300Asn Arg Pro Arg Arg305 (2) SEQ ID NO:75:

(i) sequence signature:

(A) length: 580 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: SEQ ID NO:75:Ser Ala Val Trp Cys Leu Asn Gly Phe Thr Gly Arg His Arg His Gly1 5 10 15Arg Cys Arg Val Arg Ala Ser Gly Trp Arg Ser Ser Asn Arg Trp Cys

20??????????????????25??????????????????30Ser?Thr?Thr?Ala?Asp?Cys?Cys?Ala?Ser?Lys?Thr?Pro?Thr?Gln?Ala?Ala

35??????????????????40??????????????????45Ser?Pro?Leu?Glu?Arg?Arg?Phe?Thr?Cys?Cys?Ser?Pro?Ala?Val?Gly?Cys

50??????????????????55??????????????????60Arg?Phe?Arg?Ser?Phe?Pro?Val?Arg?Arg?Leu?Ala?Leu?Gly?Ala?Arg?Thr65??????????????????70??????????????????75??????????????????80Ser?Arg?Thr?Leu?Gly?Val?Arg?Arg?Thr?Leu?Ser?Gln?Trp?Asn?Leu?Ser

85??????????????????90??????????????????95Pro?Arg?Ala?Gln?Pro?Ser?Cys?Ala?Val?Thr?Val?Glu?Ser?His?Thr?His

100?????????????????105?????????????????110Ala?Ser?Pro?Arg?Mer?Ala?Lys?Leu?Ala?Arg?Val?Val?Gly?Leu?Val?Gln

115?????????????????120?????????????????125Glu?Glu?Gln?Pro?Ser?Asp?Met?Thr?Asn?His?Pro?Arg?Tyr?Ser?Pro?Pro

130?????????????????135?????????????????140Pro?Gln?Gln?Pro?Gly?Thr?Pro?Gly?Tyr?Ala?Gln?Gly?Gln?Gln?Gln?Thr145?????????????????150?????????????????155?????????????????160Tyr?Ser?Gln?Gln?Phe?Asp?Trp?Arg?Tyr?Pro?Pro?Ser?Pro?Pro?Pro?Gln

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

180?????????????????185?????????????????190Gly?Leu?Ile?Pro?Gly?Val?Ile?Pro?Thr?Met?Thr?Pro?Pro?Pro?Gly?Met

195?????????????????200?????????????????205Val?Arg?Gln?Arg?Pro?Arg?Ala?Gly?Met?Leu?Ala?Ile?Gly?Ala?Val?Thr

210?????????????????215?????????????????220Ile?Ala?Val?Val?Ser?Ala?Gly?Ile?Gly?Gly?Ala?Ala?Ala?Ser?Leu?Val225?????????????????230?????????????????235?????????????????240Gly?Phe?Asn?Arg?Ala?Pro?Ala?Gly?Pro?Ser?Gly?Gly?Pro?Val?Ala?Ala

245?????????????????250?????????????????255Ser?Ala?Ala?Pro?Ser?Ile?Pro?Ala?Ala?Asn?Met?Pro?Pro?Gly?Ser?Val

260?????????????????265?????????????????270Glu?Gln?Val?Ala?Ala?Lys?Val?Val?Pro?Ser?Val?Val?Met?Leu?Glu?Thr

275?????????????????280?????????????????285Asp?Leu?Gly?Arg?Gln?Ser?Glu?Glu?Gly?Ser?Gly?Ile?Ile?Leu?Ser?Ala

290?????????????????295?????????????????300Glu?Gly?Leu?Ile?Leu?Thr?Asn?Asn?His?Val?Ile?Ala?Ala?Ala?Ala?Lys305?????????????????310?????????????????315?????????????????320Pro?Pro?Leu?Gly?Ser?Pro?Pro?Pro?Lys?Thr?Thr?Val?Thr?Phe?Ser?Asp

325?????????????????330?????????????????335Gly?Arg?Thr?Ala?Pro?Phe?Thr?Val?Val?Gly?Ala?Asp?Pro?Thr?Ser?Asp

340?????????????????345?????????????????350Ile?Ala?Val?Val?Arg?Val?Gln?Gly?Val?Ser?Gly?Leu?Thr?Pro?Ile?Ser

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

370?????????????????375?????????????????380Gly?Ser?Pro?Leu?Gly?Leu?Glu?Gly?Thr?Val?Thr?Thr?Gly?Ile?Val?Ser385?????????????????390?????????????????395?????????????????400Ala?Leu?Asn?Arg?Pro?Val?Ser?Thr?Thr?Gly?Glu?Ala?Gly?Asn?Gln?Asn

405?????????????????410?????????????????415Thr?Val?Leu?Asp?Ala?Ile?Gln?Thr?Asp?Ala?Ala?Ile?Asn?Pro?Gly?Asn

420?????????????????425?????????????????430Ser?Gly?Gly?Ala?Leu?Val?Asn?Met?Asn?Ala?Gln?Leu?Val?Gly?Val?Asn

435?????????????????440?????????????????445Ser?Ala?Ile?Ala?Thr?Leu?Gly?Ala?Asp?Ser?Ala?Asp?Ala?Gln?Ser?Gly

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

485?????????????????490?????????????????495Val?Gln?Val?Thr?Asn?Asp?Lys?Asp?Thr?Pro?Gly?Ala?Lys?Ile?Val?Glu

500?????????????????505?????????????????510Val?Val?Ala?Gly?Gly?Ala?Ala?Ala?Asn?Ala?Gly?Val?Pro?Lys?Gly?Val

515?????????????????520?????????????????525Val?Val?Thr?Lys?Val?Asp?Asp?Arg?Pro?Ile?Asn?Ser?Ala?Asp?Ala?Leu

530?????????????????535?????????????????540Val?Ala?Ala?Val?Arg?Ser?Lys?Ala?Pro?Gly?Ala?Thr?Val?Ala?Leu?Thr545?????????????????550?????????????????555?????????????????560Phe?Gln?Asp?Pro?Ser?Gly?Gly?Ser?Arg?Thr?Val?Gln?Val?Thr?Leu?Gly

565?????????????????570?????????????????575Lys?Ala?Glu?Gln

The information of 580 (2) SEQ ID NO:76:

(i) sequence signature:

(A) length: 233 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:76:Met Asn Asp Gly Lys Arg Ala Val Thr Ser Ala Val Leu Val Val Leu1 5 10 15Gly Ala Cys Leu Ala Leu Trp Leu Ser Gly Cys Ser Ser Pro Lys Pro

20??????????????????25??????????????????30Asp?Ala?Glu?Glu?Gln?Gly?Val?Pro?Val?Ser?Pro?Thr?Ala?Ser?Asp?Pro

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

50??????????????????55??????????????????60Thr?Ser?Val?His?Val?Ala?Val?Arg?Thr?Thr?Gly?Lys?Val?Asp?Ser?Leu65??????????????????70??????????????????75??????????????????80Leu?Gly?Ile?Thr?Ser?Ala?Asp?Val?Asp?Val?Arg?Ala?Asn?Pro?Leu?Ala

85??????????????????90??????????????????95Ala?Lys?Gly?Val?Cys?Thr?Tyr?Asn?Asp?Glu?Gln?Gly?Val?Pro?Phe?Arg

100?????????????????105?????????????????110Val?Gln?Gly?Asp?Asn?Ile?Ser?Val?Lys?Leu?Phe?Asp?Asp?Trp?Ser?Asn

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

130?????????????????135?????????????????140Ala?Gly?Val?Thr?Gln?Leu?Leu?Ser?Gly?Val?Thr?Asn?Leu?Gln?Ala?Gln145?????????????????150?????????????????155?????????????????160Gly?Thr?Glu?Val?Ile?Asp?Gly?Ile?Ser?Thr?Thr?Lys?Ile?Thr?Gly?Thr

165?????????????????170?????????????????175Ile?Pro?Ala?Ser?Ser?Val?Lys?Met?Leu?Asp?Pro?Gly?Ala?Lys?Ser?Ala

180?????????????????185?????????????????190Arg?Pro?Ala?Thr?Val?Trp?Ile?Ala?Gln?Asp?Gly?Ser?His?His?Leu?Val

195?????????????????200?????????????????205Arg?Ala?Ser?Ile?Asp?Leu?Gly?Ser?Gly?Ser?Ile?Gln?Leu?Thr?Gln?Ser

The information of 210 215 220Lys Trp Asn Glu Pro Val Asn Val Asp225,230 (2) SEQ ID NO:77:

(i) sequence signature:

(A) length: 66 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:77:Val Ile Asp Ile Ile Gly Thr Ser Pro Thr Ser Trp Glu Gln Ala Ala1 5 10 15Ala Glu Ala Val Gln Arg Ala Arg Asp Ser Val Asp Asp Ile Arg Val

20?????????????????25??????????????????30Ala?Arg?Val?Ile?Glu?Cln?Asp?Met?Ala?Val?Asp?Ser?Ala?Gly?Lys?Ile

35??????????????????40??????????????????45Thr?Tyr?Arg?Ile?Lys?Leu?Glu?Val?Ser?Phe?Lys?Met?Arg?Pro?Ala?Gln

The information of 50 55 60Pro Arg65 (2) SEQ ID NO:78:

(i) sequence signature:

(A) length: 69 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:78:Val Pro Pro Ala Pro Pro Leu Pro Pro Leu Pro Pro Ser Pro Ile Ser1 5 10 15Cys Ala Ser Pro Pro Ser Pro Pro Leu Pro Pro Ala Pro Pro Val Ala

20??????????????????25??????????????????30Pro?Gly?Pro?Pro?Met?Pro?Pro?Leu?Asp?Pro?Trp?Pro?Pro?Ala?Pro?Pro

35??????????????????40??????????????????45Leu?Pro?Tyr?Ser?Thr?Pro?Pro?Gly?Ala?Pro?Leu?Pro?Pro?Ser?Pro?Pro

The information of 50 55 60Ser Pro Pro Leu Pro, 65 (2) SEQ ID NO:79:

(i) sequence signature:

(A) length: 355 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:79:Met Ser Asn Ser Arg Arg Arg Ser Leu Arg Trp Ser Trp Leu Leu Ser1 5 10 15Val Leu Ala Ala Val Gly Leu Gly Leu Ala Thr Ala Pro Ala Gln Ala

20??????????????????25??????????????????30Ala?Pro?Pro?Ala?Leu?Ser?Gln?Asp?Arg?Phe?Ala?Asp?Phe?Pro?Ala?Leu

35??????????????????40??????????????????45Pro?Leu?Asp?Pro?Ser?Ala?Met?Val?Ala?Gln?Val?Ala?Pro?Gln?Val?Val

50??????????????????55??????????????????60Asn?Ile?Asn?Thr?Lys?Leu?Gly?Tyr?Asn?Asn?Ala?Val?Gly?Ala?Gly?Thr65??????????????????70??????????????????75??????????????????80Gly?Ile?Val?Ile?Asp?Pro?Asn?Gly?Val?Val?Leu?Thr?Asn?Asn?His?Val

85??????????????????90??????????????????95Ile?Ala?Gly?Ala?Thr?Asp?Ile?Asn?Ala?Phe?Ser?Val?Gly?Ser?Gly?Gln

100?????????????????105?????????????????110Thr?Tyr?Gly?Val?Asp?Val?Val?Gly?Tyr?Asp?Arg?Thr?Gln?Asp?Val?Ala

115?????????????????120?????????????????125Val?Leu?Gln?Leu?Arg?Gly?Ala?Gly?Gly?Leu?Pro?Ser?Ala?Ala?Ile?Gly

130?????????????????135?????????????????140Gly?Gly?Val?Ala?Val?Gly?Glu?Pro?Val?Val?Ala?Met?Gly?Asn?Ser?Gly145?????????????????150?????????????????155?????????????????160Gly?Gln?Gly?Gly?Thr?Pro?Arg?Ala?Val?Pro?Gly?Arg?Val?Val?Ala?Leu

165?????????????????170?????????????????175Gly?Gln?Thr?Val?Gln?Ala?Ser?Asp?Ser?Leu?Thr?Gly?Ala?Glu?Glu?Thr

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

195?????????????????200?????????????????205Gly?Gly?Pro?Val?Val?Asn?Gly?Leu?Gly?Gln?Val?Val?Gly?Met?Asn?Thr

210?????????????????215?????????????????220Ala?Ala?Ser?Asp?Asn?Phe?Gln?Leu?Ser?Gln?Gly?Gly?Gln?Gly?Phe?Ala225?????????????????230?????????????????235?????????????????240Ile?Pro?Ile?Gly?Gln?Ala?Met?Ala?Ile?Ala?Gly?Gln?Ile?Arg?Ser?Gly

245?????????????????250?????????????????255Gly?Gly?Ser?Pro?Thr?Val?His?Ile?Gly?Pro?Thr?Ala?Phe?Leu?Gly?Leu

260?????????????????265?????????????????270Gly?Val?Val?Asp?Asn?Asn?Gly?Asn?Gly?Ala?Arg?Val?Gln?Arg?Val?Val

275?????????????????280?????????????????285Gly?Ser?Ala?Pro?Ala?Ala?Ser?Leu?Gly?Ile?Ser?Thr?Gly?Asp?Val?Ile

290?????????????????295?????????????????300Thr?Ala?Val?Asp?Gly?Ala?Pro?Ile?Asn?Ser?Ala?Thr?Ala?Met?Ala?Asp305?????????????????310?????????????????315?????????????????320Ala?Leu?Asn?Gly?His?His?Pro?Gly?Asp?Val?Ile?Ser?Val?Asn?Trp?Gln

325?????????????????330?????????????????335Thr?Lys?Ser?Gly?Gly?Thr?Arg?Thr?Gly?Asn?Val?Thr?Leu?Ala?Glu?Gly

The information of 340 345 350Pro Pro Ala (2) SEQ ID NO:80:

(i) sequence signature:

(A) length: 205 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:80:Ser Pro Lys Pro Asp Ala Glu Glu Gln Gly Val Pro Val Ser Pro Thr1 5 10 15Ala Ser Asp Pro Ala Leu Leu Ala Glu Ile Arg Gln Ser Leu Asp Ala

20??????????????????25??????????????????30Thr?Lys?Gly?Leu?Thr?Ser?Val?His?Val?Ala?Val?Arg?Thr?Thr?Gly?Lys

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

50??????????????????55??????????????????60Asn?Pro?Leu?Ala?Ala?Lys?Gly?Val?Cys?Thr?Tyr?Asn?Asp?Glu?Gln?Gly65??????????????????70??????????????????75??????????????????80Val?Pro?Phe?Arg?Val?Gln?Gly?Asp?Asn?Ile?Ser?Val?Lys?Leu?Phe?Asp

85??????????????????90??????????????????95Asp?Trp?Ser?Asn?Leu?Gly?Ser?Ile?Ser?Glu?Leu?Ser?Thr?Ser?Arg?Val

100?????????????????105?????????????????110Leu?Asp?Pro?Ala?Ala?Gly?Val?Thr?Gln?Leu?Leu?Ser?Gly?Val?Thr?Asn

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

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

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

180?????????????????185?????????????????190Leu?Thr?Gln?Ser?Lys?Trp?Asn?Glu?Pro?Val?Asn?Val?Asp

The information of 195 200 205 (2) SEQ ID NO:81:

(i) sequence signature:

(A) length: 286 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:81:Gly Asp Ser Phe Trp Ala Ala Ala Asp Gln Met Ala Arg Gly Phe Val1 5 10 15Leu Gly Ala Thr Ala Gly Arg Thr Thr Ieu Thr Gly Glu Gly Leu Gln

20??????????????????25??????????????????30His?Ala?Asp?Gly?His?Ser?Leu?Leu?Leu?Asp?Ala?Thr?Asn?Pro?Ala?Val

35??????????????????40??????????????????45Val?Ala?Tyr?Asp?Pro?Ala?Phe?Ala?Tyr?Glu?Ile?Gly?Tyr?Ile?Xaa?Glu

50??????????????????55??????????????????60Ser?Gly?Leu?Ala?Arg?Met?Cys?Gly?Glu?Asn?Pro?Glu?Asn?Ile?Phe?Phe65??????????????????70??????????????????75??????????????????80Tyr?Ile?Thr?Val?Tyr?Asn?Glu?Pro?Tyr?Val?Gln?Pro?Pro?Glu?Pro?Glu

85??????????????????90??????????????????95Asn?Phe?Asp?Pro?Glu?Gly?Val?Leu?Gly?Gly?Ile?Tyr?Arg?Tyr?His?Ala

100?????????????????105?????????????????110Ala?Thr?Glu?Gln?Arg?Thr?Asn?Lys?Xaa?Gln?Ile?Leu?Ala?Ser?Gly?Val

115?????????????????120?????????????????125Ala?Met?Pro?Ala?Ala?Leu?Arg?Ala?Ala?Gln?Met?Leu?Ala?Ala?Glu?Trp

130?????????????????135?????????????????140Asp?Val?Ala?Ala?Asp?Val?Trp?Ser?Val?Thr?Ser?Trp?Gly?Glu?Leu?Asn145?????????????????150?????????????????155?????????????????160Arg?Asp?Gly?Val?Val?Ile?Glu?Thr?Glu?Lys?Leu?Arg?His?Pro?Asp?Arg

165?????????????????170?????????????????175Pro?Ala?Gly?Val?Pro?Tyr?Val?Thr?Arg?Ala?Leu?Glu?Asn?Ala?Arg?Gly

180?????????????????185?????????????????190Pro?Val?Ile?Ala?Val?Ser?Asp?Trp?Met?Arg?Ala?Val?Pro?Glu?Gln?Ile

195?????????????????200?????????????????205Arg?Pro?Trp?Val?Pro?Gly?Thr?Tyr?Leu?Thr?Leu?Gly?Thr?Asp?Gly?Phe

210?????????????????215?????????????????220Gly?Phe?Ser?Asp?Thr?Arg?Pro?Ala?Gly?Arg?Arg?Tyr?Phe?Asn?Thr?Asp225?????????????????230?????????????????235?????????????????240Ala?Glu?Ser?Gln?Val?Gly?Arg?Gly?Phe?Gly?Arg?Gly?Trp?Pro?Gly?Arg

245?????????????????250?????????????????255Arg?Val?Asn?Ile?Asp?Pro?Phe?Gly?Ala?Gly?Arg?Gly?Pro?Pro?Ala?Gln

260?????????????????265?????????????????270Leu?Pro?Gly?Phe?Asp?Glu?Gly?Gly?Gly?Leu?Arg?Pro?Xaa?Lys

The information of 275 280 285 (2) SEQ ID NO:82:

(i) sequence signature:

(A) length: 173 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:82:Thr Lys Phe His Ala Leu Met Gln Glu Gln Ile His Asn Glu Phe Thr1 5 10 15Ala Ala Gln Gln Tyr Val Ala Ile Ala Val Tyr Phe Asp Ser Glu Asp

20??????????????????25??????????????????30Leu?Pro?Gln?Leu?Ala?Lys?His?Phe?Tyr?Ser?Gln?Ala?Val?Glu?Glu?Arg

35??????????????????40??????????????????45Asn?His?Ala?Met?Met?Leu?Val?Gln?His?Leu?Leu?Asp?Arg?Asp?Leu?Arg

50??????????????????55??????????????????60Val?Glu?Ile?Pro?Gly?Val?Asp?Thr?Val?Arg?Asn?Gln?Phe?Asp?Arg?Pro65??????????????????70??????????????????75??????????????????80Arg?Glu?Ala?Leu?Ala?Leu?Ala?Leu?Asp?Gln?Glu?Arg?Thr?Val?Thr?Asp

85??????????????????90??????????????????95Gln?Val?Gly?Arg?Leu?Thr?Ala?Val?Ala?Arg?Asp?Glu?Gly?Asp?Phe?Leu

100?????????????????105?????????????????110Gly?Glu?Gln?Phe?Met?Gln?Trp?Phe?Leu?Gln?Glu?Gln?Ile?Glu?Glu?Val

115?????????????????120?????????????????125Ala?Leu?Met?Ala?Thr?Leu?Val?Arg?Val?Ala?Asp?Arg?Ala?Gly?Ala?Asn

130?????????????????135?????????????????140Leu?Phe?Glu?Leu?Glu?Asn?Phe?Val?Ala?Arg?Glu?Val?Asp?Val?Ala?Pro145?????????????????150?????????????????155?????????????????160Ala?Ala?Ser?Gly?Ala?Pro?His?Ala?Ala?Gly?Gly?Arg?Leu

The information of 165 170 (2) SEQ ID NO:83:

(i) sequence signature:

(A) length: 107 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:83:Arg Ala Asp Glu Arg Lys Asn Thr Thr Met Lys Met Val Lys Ser Ile1 5 10 15Ala Ala Gly Leu Thr Ala Ala Ala Ala Ile Gly Ala Ala Ala Ala Gly

20??????????????????25?????????????????30Val?Thr?Ser?Ile?Met?Ala?Gly?Gly?Pro?Val?Val?Tyr?Gln?Met?Gln?Pro

35??????????????????40??????????????????45Val?Val?Phe?Gly?Ala?Pro?Leu?Pro?Leu?Asp?Pro?Xaa?Ser?Ala?Pro?Xaa

50??????????????????55??????????????????60Val?Pro?Thr?Ala?Ala?Gln?Trp?Thr?Xaa?Leu?Leu?Asn?Xaa?Leu?Xaa?Asp65??????????????????70??????????????????75??????????????????80Pro?Asn?Val?Ser?Phe?Xaa?Asn?Lys?Gly?Ser?Leu?Val?Clu?Gly?Gly?Ile

85??????????????????90??????????????????95Gly?Gly?Xaa?Glu?Gly?Xaa?Xaa?Arg?Arg?Xaa?Gln

The information of 100 105 (2) SEQ ID NO:84:

(i) sequence signature:

(A) length: 125 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:84:Val Leu Ser Val Pro Val Gly Asp Gly Phe Trp Xaa Arg Val Val Asn1 5 10 15Pro Leu Gly Gln Pro Ile Asp Gly Arg Gly Asp Val Asp Ser Asp Thr

20??????????????????25??????????????????30Arg?Arg?Ala?Leu?Glu?Leu?Gln?Ala?Pro?Ser?Val?Val?Xaa?Arg?Gln?Gly

35??????????????????40??????????????????45Val?Lys?Glu?Pro?Leu?Xaa?Thr?Gly?Ile?Lys?Ala?Ile?Asp?Ala?Met?Thr

50??????????????????55??????????????????60Pro?Ile?Gly?Arg?Gly?Gln?Arg?Gln?Leu?Ile?Ile?Gly?Asp?Arg?Lys?Thr65??????????????????70??????????????????75??????????????????80Gly?Lys?Asn?Arg?Arg?Leu?Cys?Arg?Thr?Pro?Ser?Ser?Asn?Gln?Arg?Glu

85??????????????????90??????????????????95Glu?Leu?Gly?Val?Arg?Trp?Ile?Pro?Arg?Ser?Arg?Cys?Ala?Cys?Val?Tyr

100?????????????????105?????????????????110Val?Gly?His?Arg?Ala?Arg?Arg?Gly?Thr?Tyr?His?Arg?Arg

The information of 115 120 125 (2) SEQ ID NO:85:

(i) sequence signature:

(A) length: 117 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:85:Cys Asp Ala Val Met Gly Phe Leu Gly Gly Ala Gly Pro Leu Ala Val1 5 10 15Val Asp Gln Gln Leu Val Thr Arg Val Pro Gln Gly Trp Ser Phe Ala

20??????????????????25??????????????????30Gln?Ala?Ala?Ala?Val?Pro?Val?Val?Phe?Leu?Thr?Ala?Trp?Tyr?Gly?Leu

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

50??????????????????55??????????????????60Gly?Thr?Gly?Gly?Val?Gly?Met?Ala?Ala?Val?Gln?Leu?Ala?Arg?Gln?Trp65??????????????????70??????????????????75??????????????????80Gly?Val?Glu?Val?Phe?Val?Thr?Ala?Ser?Arg?Gly?Lys?Trp?Asp?Thr?Leu

85??????????????????90??????????????????95Arg?Ala?Xaa?Xaa?Phe?Asp?Asp?Xaa?Pro?Tyr?Arg?Xaa?Phe?Pro?His?Xaa

100?????????????????105?????????????????110Arg?Ser?Ser?Xaa?Gly

The information of 115 (2) SEQ ID NO:86:

(i) sequence signature:

(A) length: 103 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:86:Met Tyr Arg Phe Ala Cys Arg Thr Leu Met Leu Ala Ala Cys Ile Leu1 5 10 15Ala Thr Gly Val Ala Gly Leu Gly Val Gly Ala Gln Ser Ala Ala Gln

20??????????????????25??????????????????30Thr?Ala?Pro?Val?Pro?Asp?Tyr?Tyr?Trp?Cys?Pro?Gly?Gln?Pro?Phe?Asp

35??????????????????40??????????????????45Pro?Ala?Trp?Gly?Pro?Asn?Trp?Asp?Pro?Tyr?Thr?Cys?His?Asp?Asp?Phe

50??????????????????55??????????????????60lis?Arg?Asp?Ser?Asp?Gly?Pro?Asp?His?Ser?Arg?Asp?Tyr?Pro?Gly?Pro65??????????????????70??????????????????75??????????????????80Ile?Leu?Glu?Gly?Pro?Val?Leu?Asp?Asp?Pro?Gly?Ala?Ala?Pro?Pro?Pro

85??????????????????90??????????????????95Pro?Ala?Ala?Gly?Gly?Gly?Ala

The information of 100 (2) SEQ ID NO:87:

(i) sequence signature:

(A) length: 88 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:87:Val Gln Cys Arg Val Trp Leu Glu Ile Gln Trp Arg Gly Met Leu Gly1 5 10 15Ala Asp Gln Ala Arg Ala Gly Gly Pro Ala Arg Ile Trp Arg Glu His

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

35??????????????????40??????????????????45Thr?Lys?Glu?Gly?Arg?Gly?Ile?Val?Met?Arg?Val?Pro?Leu?Glu?Gly?Gly

50??????????????????55??????????????????60Gly?Arg?Leu?Val?Val?Glu?Leu?Thr?Pro?Asp?Glu?Ala?Ala?Ala?Leu?Gly65??????????????????70??????????????????75??????????????????80Asp?Glu?Leu?Lys?Gly?Val?Thr?Ser

The information of 85 (2) SEQ ID NO:88:

(i) sequence signature:

(A) length: 95 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:88:Thr Asp Ala Ala Thr Leu Ala Gln Glu Ala Gly Asn Phe Glu Arg Ile1 5 10 15Ser Gly Asp Leu Lys Thr Gln Ile Asp Gln Val Glu Ser Thr Ala Gly

20??????????????????25??????????????????30Ser?Leu?Gln?Gly?Gln?Trp?Arg?Gly?Ala?Ala?Gly?Thr?Ala?Ala?Gln?Ala

35??????????????????40??????????????????45Ala?Val?Val?Arg?Phe?Gln?Glu?Ala?Ala?Asn?Lys?Gln?Lys?Gln?Glu?Leu

50??????????????????55??????????????????60Asp?Glu?Ile?Ser?Thr?Asn?Ile?Arg?Gln?Ala?Gly?Val?Gln?Tyr?Ser?Arg65??????????????????70??????????????????75??????????????????80Ala?Asp?Glu?Glu?Gln?Gln?Gln?Ala?Leu?Ser?Ser?Gln?Met?Gly?Phe

The information of 85 90 95 (2) SEQ ID NO:89:

(i) sequence signature:

(A) length: 166 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:89:Met Thr Gln Ser Gln Thr Val Thr Val Asp Gln Gln Glu Ile Leu Asn1 5 10 15Arg Ala Asn Glu Val Glu Ala Pro Met Ala Asp Pro Pro Thr Asp Val

20??????????????????25??????????????????30Pro?Ile?Thr?Pro?Cys?Glu?Leu?Thr?Xaa?Xaa?Lys?Asn?Ala?Ala?Gln?Gln

35??????????????????40??????????????????45Xaa?Val?Leu?Ser?Ala?Asp?Asn?Met?Arg?Glu?Tyr?Leu?Ala?Ala?Gly?Ala

50??????????????????55??????????????????60Lys?Glu?Arg?Gln?Arg?Leu?Ala?Thr?Ser?Leu?Arg?Asn?Ala?Ala?Lys?Xaa65??????????????????70??????????????????75??????????????????80Tyr?Gly?Glu?Val?Asp?Glu?Glu?Ala?Ala?Thr?Ala?Leu?Asp?Asn?Asp?Gly

85??????????????????90??????????????????95Glu?Gly?Thr?Val?Gln?Ala?Glu?Ser?Ala?Gly?Ala?Val?Gly?Gly?Asp?Ser

100?????????????????105?????????????????110Ser?Ala?Glu?Leu?Thr?Asp?Thr?Pro?Arg?Val?Ala?Thr?Ala?Cly?Glu?Pro

115?????????????????120?????????????????125Asn?Phe?Met?Asp?Leu?Lys?Glu?Ala?Ala?Arg?Lys?Leu?Glu?Thr?Gly?Asp

130?????????????????135?????????????????140G1n?Gly?Ala?Ser?Leu?Ala?His?Xaa?Gly?Asp?Gly?Trp?Asn?Thr?Xaa?Thr145?????????????????150?????????????????155?????????????????160Leu?Thr?Leu?Gln?Gly?Asp

The information of 165 (2) SEQ ID NO:90:

(i) sequence signature:

(A) length: 5 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:90:Arg Ala Glu Arg Met1 5 (2) SEQ ID NO:91:

(i) sequence signature:

(A) length: 263 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:91:Val Ala Trp Met Ser Val Thr Ala Gly Gln Ala Glu Leu Thr Ala Ala1 5 10 15Gln Val Arg Val Ala Ala Ala Ala Tyr Glu Thr Ala Tyr Gly Leu Thr

20??????????????????25??????????????????30Val?Pro?Pro?Pro?Val?Ile?Ala?Glu?Asn?Arg?Ala?Clu?Leu?Met?Ile?Leu

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

50??????????????????55??????????????????60Glu?Ala?Glu?Tyr?Gly?Glu?Met?Trp?Ala?Gln?Asp?Ala?Ala?Ala?Met?Phe65??????????????????70??????????????????75??????????????????80Gly?Tyr?Ala?Ala?Ala?Thr?Ala?Thr?Ala?Thr?Ala?Thr?Leu?Leu?Pro?Phe

85??????????????????90??????????????????95Glu?Glu?Ala?Pro?Glu?Met?Thr?Ser?Ala?Gly?Gly?Leu?Leu?Glu?Gln?Ala

100?????????????????105?????????????????110Ala?Ala?Val?Glu?Glu?Ala?Ser?Asp?Thr?Ala?Ala?Ala?Asn?Gln?Leu?Met

115?????????????????120?????????????????125Asn?Asn?Val?Pro?Gln?Ala?Leu?Lys?Gln?Leu?Ala?Gln?Pro?Thr?Gln?Gly

130?????????????????135?????????????????140Thr?Thr?Pro?Ser?Ser?Lys?Leu?Gly?Gly?Leu?Trp?Lys?Thr?Val?Ser?Pro145?????????????????150?????????????????155?????????????????160His?Arg?Ser?Pro?Ile?Ser?Asn?Met?Val?Ser?Met?Ala?Asn?Asn?His?Met

165?????????????????170?????????????????175Ser?Met?Thr?Asn?Ser?Gly?Val?Ser?Met?Thr?Asn?Thr?Leu?Ser?Ser?Met

180?????????????????185?????????????????190Leu?Lys?Gly?Phe?Ala?Pro?Ala?Ala?Ala?Ala?Gln?Ala?Val?Gln?Thr?Ala

195?????????????????200?????????????????205Ala?Gln?Asn?Gly?Val?Arg?Ala?Met?Ser?Ser?Leu?Gly?Ser?Ser?Leu?Gly

210?????????????????215?????????????????220Ser?Ser?Gly?Leu?Gly?Gly?Gly?Val?Ala?Ala?Asn?Leu?Gly?Arg?Ala?Ala225?????????????????230?????????????????235?????????????????240Ser?Val?Arg?Tyr?Gly?His?Arg?Asp?Gly?Gly?Lys?Tyr?Ala?Xaa?Ser?Gly

245?????????????????250?????????????????255Arg?Arg?Asn?Gly?Gly?Pro?Ala

The information of 260 (2) SEQ ID NO:92:

(i) sequence signature:

(A) length: 303 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:92:Met Thr Tyr Ser Pro Gly Asn Pro Gly Tyr Pro Gln Ala Gln Pro Ala1 5 10 15Gly Ser Tyr Gly Gly Val Thr Pro Ser Phe Ala His Ala Asp Glu Gly

20??????????????????25??????????????????30Ala?Ser?Lys?Leu?Pro?Met?Tyr?Leu?Asn?Ile?Ala?Val?Ala?Val?Leu?Gly

35??????????????????40??????????????????45Leu?Ala?Ala?Tyr?Phe?Ala?Ser?Phe?Gly?Pro?Met?Phe?Thr?Leu?Ser?Thr

50??????????????????55??????????????????60Glu?Leu?Gly?Gly?Gly?Asp?Gly?Ala?Val?Ser?Gly?Asp?Thr?Gly?Leu?Pro65??????????????????70??????????????????75??????????????????80Val?Gly?Val?Ala?Leu?Leu?Ala?Ala?Leu?Leu?Ala?Gly?Val?Val?Leu?Val

85??????????????????90??????????????????95Pro?Lys?Ala?Lys?Ser?His?Val?Thr?Val?Val?Ala?Val?Leu?Gly?Val?Leu

100?????????????????105?????????????????110Gly?Val?Phe?Leu?Met?Val?Ser?Ala?Thr?Phe?Asn?Lys?Pro?Ser?Ala?Tyr

115?????????????????120?????????????????125Ser?Thr?Gly?Trp?Ala?Leu?Trp?Val?Val?Leu?Ala?Phe?Ile?Val?Phe?Gln

130?????????????????135?????????????????140Ala?Val?Ala?Ala?Val?Leu?Ala?Leu?Leu?Val?Glu?Thr?Gly?Ala?Ile?Thr145?????????????????150?????????????????155?????????????????160Ala?Pro?Ala?Pro?Arg?Pro?Lys?Phe?Asp?Pro?Tyr?Gly?Gln?Tyr?Gly?Arg

165?????????????????170?????????????????175Tyr?Gly?Gln?Tyr?Gly?Gln?Tyr?Gly?Val?Gln?Pro?Gly?Gly?Tyr?Tyr?Gly

180?????????????????185?????????????????190Gln?Gln?Gly?Ala?Gln?Gln?Ala?Ala?Gly?Leu?Gln?Ser?Pro?Gly?Pro?Gln

195?????????????????200?????????????????205Gln?Ser?Pro?Gln?Pro?Pro?Gly?Tyr?Gly?Ser?Gln?Tyr?Gly?Gly?Tyr?Ser

210?????????????????215?????????????????220Ser?Ser?Pro?Ser?Gln?Ser?Gly?Ser?Gly?Tyr?Thr?Ala?Gln?Pro?Pro?Ala225?????????????????230?????????????????235?????????????????240Gln?Pro?Pro?Ala?Gln?Ser?Gly?Ser?Gln?Gln?Ser?His?Gln?Gly?Pro?Ser

245?????????????????250?????????????????255Thr?Pro?Pro?Thr?Gly?Phe?Pro?Ser?Phe?Ser?Pro?Pro?Pro?Pro?Val?Ser

260?????????????????265?????????????????270Ala?Gly?Thr?Gly?Ser?Gln?Ala?Gly?Ser?Ala?Pro?Val?Asn?Tyr?Ser?Asn

275?????????????????280?????????????????285Pro?Ser?Gly?Gly?Glu?Gln?Ser?Ser?Ser?Pro?Gly?Gly?Ala?Pro?Val

The information of 290 295 300 (2) SEQ ID NO:93:

(i) sequence signature:

(A) length: 28 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:93:Gly Cys Gly Glu Thr Asp Ala Ala Thr Leu Ala Gln Glu Ala Gly Asn1 5 10 15Phe Glu Arg Ile Ser Gly Asp Leu Lys Thr Gln Ile

The information of 20 25 (2) SEQ ID NO:94:

(i) sequence signature:

(A) length: 16 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:94:Asp Gln Val Glu Ser Thr Ala Gly Ser Leu Gln Gly Gln Trp Arg Gly1 5 10 15 (2) SEQ ID NO:95:

(i) sequence signature:

(A) length: 27 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:95:Gly Cys Gly Ser Thr Ala Gly Ser Leu Gln Gly Gln Trp Arg Gly Ala1 5 10 15ALa Gly Thr Ala Ala Gln Ala Ala Val Val Arg

The information of 20 25 (2) SEQ ID NO:96:

(i) sequence signature:

(A) length: 27 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:96:Gly Cys Gly Gly Thr Ala Ala Gln Ala Ala Val Val Arg Phe Gln Glu1 5 10 15Ala Ala Ash Lys Gln Lys Gln Glu Leu Asp Glu

The information of 20 25 (2) SEQ ID NO:97:

(i) sequence signature:

(A) length: 27 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:97:Gly Cys Gly Ala Asn Lys Gln Lys Gln Glu Leu Asp Glu Ile Ser Thr1 5 10 15Asn Ile Arg Gln Ala Gly Val Gln Tyr Ser Arg

The information of 20 25 (2) SEQ ID NO:98:

(i) sequence signature:

(A) length: 28 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:98:Gly Cys Gly Ile Arg Gln Ala Gly Val Gln Tyr Ser Arg Ala Asp Glu1 5 10 15Glu Gln Gln Gln Ala Leu Ser Ser Gln Met Gly Phe

The information of 20 25 (2) SEQ ID NO:99:

(i) sequence signature:

(A) length: 507 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:99:ATGAAGATGG, TGAAATCGAT, CGCCGCAGGT, CTGACCGCCG, CGGCTGCAAT, CGGCGCCGCT, 60GCGGCCGGTG, TGACTTCGAT, CATGGCTGGC, GGCCCGGTCG, TATACCAGAT, GCAGCCGGTC, 120GTCTTCGGCG, CGCCACTGCC, GTTGGACCCG, GCATCCGCCC, CTGACGTCCC, GACCGCCGCC, 180CAGTTGACCA, GCCTGCTCAA, CAGCCTCGCC, GATCCCAACG, TGTCGTTTGC, GAACAAGGGC, 240AGTCTGGTCG, AGGGCGGCAT, CGGGGGCACC, GAGGCGCGCA, TCGCCGACCA, CAAGCTGAAG, 300AAGGCCGCCG, AGCACGGGGA, TCTGCCGCTG, TCGTTCAGCG, TGACGAACAT, CCAGCCGGCG, 360GCCGCCGGTT, CGGCCACCGC, CGACGTTTCC, GTCTCGGGTC, CGAAGCTCTC, GTCGCCGGTC, 420ACGCAGAACG, TCACGTTCGT, GAATCAAGGC, GGCTGGATGC, TGTCACGCGC, ATCGGCGATG, 480GAGTTGCTGC, AGGCCGCAGG, GAACTGA, 507, (2) SEQ, ID, the information of NO:100:

(i) sequence signature:

(A) length: 168 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:100:Met Lys Met Val Lys Ser Ile Ala Ala Gly Leu Thr Ala Ala Ala Ala1 5 10 15Ile Gly Ala Ala Ala Ala Gly Val Thr Ser Ile Met Ala Gly Gly Pro

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

35??????????????????40??????????????????45Asp?Pro?Ala?Ser?Ala?Pro?Asp?Val?Pro?Thr?Ala?Ala?Gln?Leu?Thr?Ser

50??????????????????55??????????????????60Leu?Leu?Asn?Ser?Leu?Ala?Asp?Pro?Asn?Val?Ser?Phe?Ala?Asn?Lys?Gly65??????????????????70??????????????????75??????????????????80Ser?Leu?Val?Glu?Gly?Gly?Ile?Gly?Gly?Thr?Glu?Ala?Arg?Ile?Ala?Asp

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

100?????????????????105?????????????????110Ser?Val?Thr?Asn?Ile?Gln?Pro?Ala?Ala?Ala?Gly?Ser?Ala?Thr?Ala?Asp

115?????????????????120?????????????????125Val?Ser?Val?Ser?Gly?Pro?Lys?Leu?Ser?Ser?Pro?Val?Thr?Gln?Asn?Val

130?????????????????135?????????????????140Thr?Phe?Val?Asn?Gln?Gly?Gly?Trp?Met?Leu?Ser?Arg?Ala?Ser?Ala?Met145?????????????????150?????????????????155?????????????????160Glu?Leu?Leu?Gln?Ala?Ala?Gly?Asn

The information of 165 (2) SEQ ID NO:101:

(i) sequence signature:

(A) length: 500 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:101:CGTGGCAATG, TCGTTGACCG, TCGGGGCCGG, GGTCGCCTCC, GCAGATCCCG, TGGACGCGGT, 60CATTAACACC, ACCTGCAATT, ACGGGCAGGT, AGTAGCTGCG, CTCAACGCGA, CGGATCCGGG, 120GGCTGCCGCA, CAGTTCAACG, CCTCACCGGT, GGCGCAGTCC, TATTTGCGCA, ATTTCCTCGC, 180CGCACCGCCA, CCTCAGCGCG, CTGCCATGGC, CGCGCAATTG, CAAGCTGTGC, CGGGGGCGGC, 240ACAGTACATC, GGCCTTGTCG, AGTCGGTTGC, CGGCTCCTGC, AACAACTATT, AAGCCCATGC, 300GGGCCCCATC, CCGCGACCCG, GCATCGTCGC, CGGGGCTAGG, CCAGATTGCC, CCGCTCCTCA, 360ACGGGCCGCA, TCCCGCGACC, CGGCATCGTC, GCCGGGGCTA, GGCCAGATTG, CCCCGCTCCT, 420CAACGGGCCG, CATCTCGTGC, CGAATTCCTG, CAGCCCGGGG, GATCCACTAG, TTCTAGAGCG, 480GCCGCCACCG, CGGTGGAGCT, 500, (2) SEQ, ID, the information of NO:102:

(i) sequence signature:

(A) length: 96 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:102:Val Ala Met Ser Leu Thr Val Gly Ala Gly Val Ala Ser Ala Asp Pro1 5 10 15Val Asp Ala Val Ile Asn Thr Thr Cys Asn Tyr Gly Gln Val Val Ala

20??????????????????25??????????????????30Ala?Leu?Asn?Ala?Thr?Asp?Pro?Gly?Ala?Ala?Ala?Gln?Phe?Asn?Ala?Ser

35??????????????????40??????????????????45Pro?Val?Ala?Gln?Ser?Tyr?Leu?Arg?Asn?Phe?Leu?Ala?Ala?Pro?Pro?Pro

50??????????????????55??????????????????60Gln?Arg?Ala?Ala?Met?Ala?Ala?Gln?Leu?Gln?Ala?Val?Pro?Gly?Ala?Ala65??????????????????70??????????????????75??????????????????80Gln?Tyr?Ile?Gly?Leu?Val?Glu?Ser?Val?Ala?Gly?Ser?Cys?Asn?Asn?Tyr

The information of 85 90 95 (2) SEQ ID NO:103:

(i) sequence signature:

(A) length: 154 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ ID NO:103:ATGACAGAGC AGCAGTGGAA TTTCGCGGGT ATCGAGGCCG CGGCAAGCGC AATCCAGGGA 60AATGTCACGT CCATTCATTC CCTCCTTGAC GAGGGGAAGC AGTCCCTGAC CAAGCTCGCA 120GCGGCCTGGG GCGGTAGCGG TTCGGAAGCG TACC 154, (2) information of SEQ ID NO:104:

(i) sequence signature:

(A) length: 51 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID N0:104:Met Thr Glu Gln Gln Trp Asn Phe Ala Gly Ile Glu Ala Ala Ala Ser1 5 10 15Ala Ile Gln Gly Asn Val Thr Ser Ile His Ser Leu Leu Asp Glu Gly

20??????????????????25??????????????????30Lys?Gln?Ser?Leu?Thr?Lys?Leu?Ala?Ala?Ala?Trp?Gly?Gly?Ser?Gly?Ser

35??????????????????40??????????????????45Glu?Ala?Tyr

The information of 50 (2) SEQ ID NO:105:

(i) sequence signature:

(A) length: 282 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) Topology: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 105: CGGTCGCGCA CTTCCAGGTG ACTATGAAAG TCGGCTTCCG NCTGGAGGAT TCCTGAACCT 60TCAAGCGCGG CCGATAACTG AGGTGCATCA TTAAGCGACT TTTCCAGAAC ATCCTGACGC 120GCTCGAAACG CGGCACAGCC GACGGTGGCT CCGNCGAGGC GCTGNCTCCA AAATCCCTGA 180GACAATTCGN CGGGGGCGCC TACAAGGAAG TCGGTGCTGA ATTCGNCGNG TATCTGGTCG 240ACCTGTGTGG TCTGNAGCCG GACGAAGCGG TGCTCGACGT CG 282 (2) SEQ ID NO: 106 information:

(i) sequence signature:

(A) length: 3058 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:106:GATCGTACCC, GTGCGAGTGC, TCGGGCCGTT, TGAGGATGGA, GTGCACGTGT, CTTTCGTGAT, 60GGCATACCCA, GAGATGTTGG, CGGCGGCGGC, TGACACCCTG, CAGAGCATCG, GTGCTACCAC, 120TGTGGCTAGC, AATGCCGCTG, CGGCGGCCCC, GACGACTGGG, GTGGTGCCCC, CCGCTGCCGA, 180TGAGGTGTCG, GCGCTGACTG, CGGCGCACTT, CGCCGCACAT, GCGGCGATGT, ATCAGTCCGT, 240GAGCGCTCGG, GCTGCTGCGA, TTCATGACCA, GTTCGTGGCC, ACCCTTGCCA, GCAGCGCCAG, 300CTCGTATGCG, GCCACTGAAG, TCGCCAATGC, GGCGGCGGCC, AGCTAAGCCA, GGAACAGTCG, 360GCACGAGAAA, CCACGAGAAA, TAGGGACACG, TAATGGTGGA, TTTCGGGGCG, TTACCACCGG, 420AGATCAACTC, CGCGAGGATG, TACGCCGGCC, CGGGTTCGGC, CTCGCTGGTG, GCCGCGGCTC, 480AGATGTGGGA, CAGCGTGGCG, AGTGACCTGT, TTTCGGCCGC, GTCGGCGTTT, CAGTCGGTGG, 540TCTGGGGTCT, GACGGTGGGG, TCGTGGATAG, GTTCGTCGGC, GGGTCTGATG, GTGGCGGCGG, 600CCTCGCCGTA, TGTGGCGTGG, ATGAGCGTCA, CCGCGGGGCA, GGCCGAGCTG, ACCGCCGCCC, 660AGGTCCGGGT, TGCTGCGGCG, GCCTACGAGA, CGGCGTATGG, GCTGACGGTG, CCCCCGCCGG, 720TGATCGCCGA, GAACCGTGCT, GAACTGATGA, TTCTGATAGC, GACCAACCTC, TTGGGGCAAA, 780ACACCCCGGC, GATCGCGGTC, AACGAGGCCG, AATACGGCGA, GATGTGGGCC, CAAGACGCCG, 840CCGCGATGTT, TGGCTACGCC, GCGGCGACGG, CGACGGCGAC, GGCGACGTTG, CTGCCGTTCG, 900AGGAGGCGCC, GGAGATGACC, AGCGCGGGTG, GGCTCCTCGA, GCAGGCCGCC, GCGGTCGAGG, 960AGGCCTCCGA, CACCGCCGCG, GCGAACCAGT, TGATGAACAA, TGTGCCCCAG, GCGCTGCAAC, 1020AGCTGGCCCA, GCCCACGCAG, GGCACCACGC, CTTCTTCCAA, GCTGGGTGGC, CTGTGGAAGA, 1080CGGTCTCGCC, GCATCGGTCG, CCGATCAGCA, ACATGGTGTC, GATGGCCAAC, AACCACATGT, 1140CGATGACCAA, CTCGGGTGTG, TCGATGACCA, ACACCTTGAG, CTCGATGTTG, AAGGGCTTTG, 1200CTCCGGCGGC, GGCCGCCCAG, GCCGTGCAAA, CCGCGGCGCA, AAACGGGGTC, CGGGCGATGA, 1260GCTCGCTGGG, CAGCTCGCTG, GGTTCTTCGG, GTCTGGGCGG, TGGGGTGGCC, GCCAACTTGG, 1320GTCGGGCGGC, CTCGGTCGGT, TCGTTGTCGG, TGCCGCAGGC, CTGGGCCGCG, GCCAACCAGG, 1380CAGTCACCCC, GGCGGCGCGG, GCGCTGCCGC, TGACCAGCCT, GACCAGCGCC, GCGGAAAGAG, 1440GGCCCGGGCA, GATGCTGGGC, GGGCTGCCGG, TGGGGCAGAT, GGGCGCCAGG, GCCGGTGGTG, 1500GGCTCAGTGG, TGTGCTGCGT, GTTCCGCCGC, GACCCTATGT, GATGCCGCAT, TCTCCGGCGG, 1560CCGGCTAGGA, GAGGGGGCGC, AGACTGTCGT, TATTTGACCA, GTGATCGGCG, GTCTCGGTGT, 1620TTCCGCGGCC, GGCTATGACA, ACAGTCAATG, TGCATGACAA, GTTACAGGTA, TTAGGTCCAG, 1680GTTCAACAAG, GAGACAGGCA, ACATGGCCTC, ACGTTTTATG, ACGGATCCGC, ACGCGATGCG, 1740GGACATGGCG, GGCCGTTTTG, AGGTGCACGC, CCAGACGGTG, GAGGACGAGG, CTCGCCGGAT, 1800GTGGGCGTCC, GCGCAAAACA, TTTCCGGTGC, GGGCTGGAGT, GGCATGGCCG, AGGCGACCTC, 1860GCTAGACACC, ATGGCCCAGA, TGAATCAGGC, GTTTCGCAAC, ATCGTGAACA, TGCTGCACGG, 1920GGTGCGTGAC, GGGCTGGTTC, GCGACGCCAA, CAACTACGAG, CAGCAAGAGC, AGGCCTCCCA, 1980GCAGATCCTC, AGCAGCTAAC, GTCAGCCGCT, GCAGCACAAT, ACTTTTACAA, GCGAAGGAGA, 2040ACAGGTTCGA, TGACCATCAA, CTATCAATTC, GGGGATGTCG, ACGCTCACGG, CGCCATGATC, 2100CGCGCTCAGG, CCGGGTTGCT, GGAGGCCGAG, CATCAGGCCA, TCATTCGTGA, TGTGTTGACC, 2160GCGAGTGACT, TTTGGGGCGG, CGCCGGTTCG, GCGGCCTGCC, AGGGGTTCAT, TACCCAGTTG, 2220GGCCGTAACT, TCCAGGTGAT, CTACGAGCAG, GCCAACGCCC, ACGGGCAGAA, GGTGCAGGCT, 2280GCCGGCAACA, ACATGGCGCA, AACCGACAGC, GCCGTCGGCT, CCAGCTGGGC, CTGACACCAG, 2340GCCAAGGCCA, GGGACGTGGT, GTACGAGTGA, AGTTCCTCGC, GTGATCCTTC, GGGTGGCAGT, 2400CTAAGTGGTC, AGTGCTGGGG, TGTTGGTGGT, TTGCTGCTTG, GCGGGTTCTT, CGGTGCTGGT, 2460CAGTGCTGCT, CGGGCTCGGG, TGAGGACCTC, GAGGCCCAGG, TAGCGCCGTC, CTTCGATCCA, 2520TTCGTCGTGT, TGTTCGGCGA, GGACGGCTCC, GACGAGGCGG, ATGATCGAGG, CGCGGTCGGG, 2580GAAGATGCCC, ACGACGTCGG, TTCGGCGTCG, TACCTCTCGG, TTGAGGCGTT, CCTGGGGGTT, 2640GTTGGACCAG, ATTTGGCGCC, AGATCTGCTT, GGGGAAGGCG, GTGAACGCCA, GCAGGTCGGT, 2700GCGGGCGGTG, TCGAGGTGCT, CGGCCACCGC, GGGGAGTTTG, TCGGTCAGAG, CGTCGAGTAC, 2760CCGATCATAT, TGGGCAACAA, CTGATTCGGC, GTCGGGCTGG, TCGTAGATGG, AGTGCAGCAG, 2820GGTGCGCACC, CACGGCCAGG, AGGGCTTCGG, GGTGGCTGCC, ATCAGATTGG, CTGCGTAGTG, 2880GGTTCTGCAG, CGCTGCCAGG, CCGCTGCGGG, CAGGGTGGCG, CCGATCGCGG, CCACCAGGCC, 2940GGCGTGGGCG, TCGCTGGTGA, CCAGCGCGAC, CCCGGACAGG, CCGCGGGCGA, CCAGGTCGCG, 3000GAAGAACGCC, AGCCAGCCGG, CCCCGTCCTC, GGCGGAGGTG, ACCTGGATGC, CCAGGATC, 3058, (2) SEQ, ID, the information of NO:107:

(i) sequence signature:

(A) length: 391 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:107:Met Val Asp Phe Gly Ala Leu Pro Pro Glu Ile Asn Ser Ala Arg Met1 5 10 15Tyr Ala Gly Pro Gly Ser Ala Ser Leu Val Ala Ala Ala Gln Met Trp

20??????????????????25??????????????????30Asp?Ser?Val?Ala?Ser?Asp?Leu?Phe?Ser?Ala?Ala?Ser?Ala?Phe?Gln?Ser

35??????????????????40??????????????????45Val?Val?Trp?Gly?Leu?Thr?Val?Gly?Ser?Trp?Ile?Gly?Ser?Ser?Ala?Gly

50??????????????????55??????????????????60Leu?Met?Val?Ala?Ala?Ala?Ser?Pro?Tyr?Val?Ala?Trp?Met?Ser?Val?Thr65??????????????????70??????????????????75??????????????????80Ala?Gly?Gln?Ala?Glu?Leu?Thr?Ala?Ala?Gln?Val?Arg?Val?Ala?Ala?Ala

85??????????????????90??????????????????95Ala?Tyr?Glu?Thr?Ala?Tyr?Gly?Leu?Thr?Val?Pro?Pro?Pro?Val?Ile?Ala

100?????????????????105?????????????????1l0Glu?Asn?Arg?Ala?Glu?Leu?Met?Ile?Leu?Ile?Ala?Thr?Asn?Leu?Leu?Gly

115?????????????????120?????????????????125Gln?Asn?Thr?Pro?Ala?Ile?Ala?Val?Asn?Glu?Ala?Glu?Tyr?Gly?Glu?Met

130?????????????????135?????????????????140Trp?Ala?Gln?Asp?Ala?Ala?Ala?Met?Phe?Gly?Tyr?Ala?Ala?Ala?Thr?Ala145?????????????????150?????????????????155?????????????????160Thr?Ala?Thr?Ala?Thr?Leu?Leu?Pro?Phe?Glu?Glu?Ala?Pro?Glu?Met?Thr

165?????????????????170?????????????????175Ser?Ala?Gly?Gly?Leu?Leu?Glu?Gln?Ala?Ala?Ala?Val?Glu?Glu?Ala?Ser

180?????????????????185?????????????????190Asp?Thr?Ala?Ala?Ala?Asn?Gln?Leu?Met?Asn?Asn?Val?Pro?Gln?Ala?Leu

195?????????????????200?????????????????205Gln?Gln?Leu?Ala?Gln?Pro?Thr?Gln?Gly?Thr?Thr?Pro?Ser?Ser?Lys?Leu

210?????????????????215?????????????????220Gly?Gly?Leu?Trp?Lys?Thr?Val?Ser?Pro?His?Arg?Ser?Pro?Ile?Ser?Asn225?????????????????230?????????????????235?????????????????240Met?Val?Ser?Met?Ala?Asn?Asn?His?Met?Ser?Met?Thr?Asn?Ser?Gly?Val

245?????????????????250?????????????????255Ser?Met?Thr?Asn?Thr?Leu?Ser?Ser?Met?Leu?Lys?Gly?Phe?Ala?Pro?Ala

260?????????????????265?????????????????270Ala?Ala?Ala?Gln?Ala?Val?Gln?Thr?Ala?Ala?Gln?Asn?Gly?Val?Arg?Ala

275?????????????????280?????????????????285Met?Ser?Ser?Leu?Gly?Ser?Ser?Leu?Gly?Ser?Ser?Gly?Leu?Gly?Gly?Gly

290?????????????????295?????????????????300Val?Ala?Ala?Asn?Leu?Gly?Arg?Ala?Ala?Ser?Val?Gly?Ser?Leu?Ser?Val305?????????????????310?????????????????315?????????????????320Pro?Gln?Ala?Trp?Ala?Ala?Ala?Asn?Gln?Ala?Val?Thr?Pro?Ala?Ala?Arg

325?????????????????330?????????????????335Ala?Leu?Pro?Leu?Thr?Ser?Leu?Thr?Ser?Ala?Ala?Glu?Arg?Gly?Pro?Gly

340?????????????????345?????????????????350Gln?Met?Leu?Gly?Gly?Leu?Pro?Val?Gly?Gln?Met?Gly?Ala?Arg?Ala?Gly

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

The information of 370 375 380Pro His Ser Pro Ala Ala Gly385,390 (2) SEQ ID NO:108:

(i) sequence signature:

(A) length: a l725 base pair

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:108:GACGTCAGCA, CCCGCCGTGC, AGGGCTGGAG, CGTGGTCGGT, TTTGATCTGC, GGTCAAGGTG, 60ACGTCCCTCG, GCGTGTCGCC, GGCGTGGATG, CAGACTCGAT, GCCGCTCTTT, AGTGCAACTA, 120ATTTCGTTGA, AGTGCCTGCG, AGGTATAGGA, CTTCACGATT, GGTTAATGTA, GCGTTCACCC, 180CGTGTTGGGG, TCGATTTGGC, CGGACCAGTC, GTCACCAACG, CTTGGCGTGC, GCGCCAGGCG, 240GGCGATCAGA, TCGCTTGACT, ACCAATCAAT, CTTGAGCTCC, CGGGCCGATG, CTCGGGCTAA, 300ATGAGGAGGA, GCACGCGTGT, CTTTCACTGC, GCAACCGGAG, ATGTTGGCGG, CCGCGGCTGG, 360CGAACTTCGT, TCCCTGGGGG, CAACGCTGAA, GGCTAGCAAT, GCCGCCGCAG, CCGTGCCGAC, 420GACTGGGGTG, GTGCCCCCGG, CTGCCGACGA, GGTGTCGCTG, CTGCTTGCCA, CACAATTCCG, 480TACGCATGCG, GCGACGTATC, AGACGGCCAG, CGCCAAGGCC, GCGGTGATCC, ATGAGCAGTT, 540TGTGACCACG, CTGGCCACCA, GCGCTAGTTC, ATATGCGGAC, ACCGAGGCCG, CCAACGCTGT, 600GGTCACCGGC, TAGCTGACCT, GACGGTATTC, GAGCGGAAGG, ATTATCGAAG, TGGTGGATTT, 660CGGGGCGTTA, CCACCGGAGA, TCAACTCCGC, GAGGATGTAC, GCCGGCCCGG, GTTCGGCCTC, 720GCTGGTGGCC, GCCGCGAAGA, TGTGGGACAG, CGTGGCGAGT, GACCTGTTTT, CGGCCGCGTC, 780GGCGTTTCAG, TCGGTGGTCT, GGGGTCTGAC, GGTGGGGTCG, TGGATAGGTT, CGTCGGCGGG, 840TCTGATGGCG, GCGGCGGCCT, CGCCGTATGT, GGCGTGGATG, AGCGTCACCG, CGGGGCAGGC, 900CCAGCTGACC, GCCGCCCAGG, TCCGGGTTGC, TGCGGCGGCC, TACGAGACAG, CGTATAGGCT, 960GACGGTGCCC, CCGCCGGTGA, TCGCCGAGAA, CCGTACCGAA, CTGATGACGC, TGACCGCGAC, 1020CAACCTCTTG, GGGCAAAACA, CGCCGGCGAT, CGAGGCCAAT, CAGGCCGCAT, ACAGCCAGAT, 1080GTGGGGCCAA, GACGCGGAGG, CGATGTATGG, CTACGCCGCC, ACGGCGGCGA, CGGCGACCGA, 1140GGCGTTGCTG, CCGTTCGAGG, ACGCCCCACT, GATCACCAAC, CCCGGCGGGC, TCCTTGAGCA, 1200GGCCGTCGCG, GTCGAGGAGG, CCATCGACAC, CGCCGCGGCG, AACCAGTTGA, TGAACAATGT, 1260GCCCCAAGCG, CTGCAACAGC, TGGCCCAGCC, AGCGCAGGGC, GTCGTACCTT, CTTCCAAGCT, 1320GGGTGGGCTG, TGGACGGCGG, TCTCGCCGCA, TCTGTCGCCG, CTCAGCAACG, TCAGTTCGAT, 1380AGCCAACAAC, CACATGTCGA, TGATGGGCAC, GGGTGTGTCG, ATGACCAACA, CCTTGCACTC, 1440GATGTTGAAG, GGCTTAGCTC, CGGCGGCGGC, TCAGGCCGTG, GAAACCGCGG, CGGAAAACGG, 1500GGTCTGGGCG, ATGAGCTCGC, TGGGCAGCCA, GCTGGGTTCG, TCGCTGGGTT, CTTCGGGTCT, 1560GGGCGCTGGG, GTGGCCGCCA, ACTTGGGTCG, GGCGGCCTCG, GTCGGTTCGT, TGTCGGTGCC, 1620GCCAGCATGG, GCCGCGGCCA, ACCAGGCGGT, CACCCCGGCG, GCGCGGGCGC, TGCCGCTGAC, 1680CAGCCTGACC, AGCGCCGCCC, AAACCGCCCC, CGGACACATG, CTGGG, 1725, (2) SEQ, ID, the information of NO:109:

(i) sequence signature:

(A) length: 359 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: SEQ ID NO:109:Val Val Asp Phe Gly Ala Leu Pro Pro Glu Ile Asn Ser Ala Arg Met1 5 10 15Tyr Ala Gly Pro Gly Ser Ala Ser Leu Val Ala Ala Ala Lys Met Trp

20??????????????????25??????????????????30Asp?Ser?Val?Ala?Ser?Asp?Leu?Phe?Ser?Ala?Ala?Ser?Ala?Phe?Gln?Ser

35??????????????????40??????????????????45Val?Val?Trp?Gly?Leu?Thr?Val?Gly?Ser?Trp?Ile?Gly?Ser?Ser?Ala?Gly

50??????????????????55??????????????????60Leu?Met?Ala?Ala?Ala?Ala?Ser?Pro?Tyr?Val?Ala?Trp?Met?Ser?Val?Thr65??????????????????70??????????????????75??????????????????80Ala?Gly?Gln?Ala?Gln?Leu?Thr?Ala?Ala?Gln?Val?Arg?Val?Ala?Ala?Ala

85??????????????????90??????????????????95Ala?Tyr?Glu?Thr?Ala?Tyr?Arg?Leu?Thr?Val?Pro?Pro?Pro?Val?Ile?Ala

100?????????????????105?????????????????110Glu?Asn?Arg?Thr?Glu?Leu?Met?Thr?Leu?Thr?Ala?Thr?Asn?Leu?Leu?Gly

115?????????????????120?????????????????125Gln?Asn?Thr?Pro?Ala?Ile?Glu?Ala?Asn?Gln?Ala?Ala?Tyr?Ser?Gln?Met

130?????????????????135?????????????????140Trp?Gly?Gln?Asp?Ala?Glu?Ala?Met?Tyr?Gly?Tyr?Ala?Ala?Thr?Ala?Ala145?????????????????150?????????????????155?????????????????160Thr?Ala?Thr?Glu?Ala?Leu?Leu?Pro?Phe?Glu?Asp?Ala?Pro?Leu?Ile?Thr

165?????????????????170?????????????????175Asn?Pro?Gly?Gly?Leu?Leu?Glu?Gln?Ala?Val?Ala?Val?Glu?Glu?Ala?Ile

180?????????????????185?????????????????190Asp?Thr?Ala?Ala?Ala?Asn?Gln?Leu?Met?Asn?Asn?Val?Pro?Gln?Ala?Leu

195?????????????????200?????????????????205Gln?Gln?Leu?Ala?Gln?Pro?Ala?Gln?Gly?Val?Val?Pro?Ser?Ser?Lys?Leu

210?????????????????215?????????????????220Gly?Gly?Leu?Trp?Thr?Ala?Val?Ser?Pro?His?Leu?Ser?Pro?Leu?Ser?Asn225?????????????????230?????????????????235?????????????????240Val?Ser?Ser?Ile?Ala?Asn?Asn?His?Met?Ser?Met?Met?Gly?Thr?Gly?Val

245?????????????????250?????????????????255Ser?Met?Thr?Asn?Thr?Leu?His?Ser?Met?Leu?Lys?Gly?Leu?Ala?Pro?Ala

260?????????????????265?????????????????270Ala?Ala?Gln?Ala?Val?Glu?Thr?Ala?Ala?Glu?Asn?Gly?Val?Trp?Ala?Met

275?????????????????280?????????????????285Ser?Ser?Leu?Gly?Ser?Gln?Leu?Gly?Ser?Ser?Leu?Gly?Ser?Ser?Gly?Leu

290?????????????????295?????????????????300Gly?Ala?Gly?Val?Ala?Ala?Asn?Leu?Gly?Arg?Ala?Ala?Ser?Val?Gly?Ser305?????????????????310?????????????????315?????????????????320Leu?Ser?Val?Pro?Pro?Ala?Trp?Ala?Ala?Ala?Asn?Gln?Ala?Val?Thr?Pro

325?????????????????330?????????????????335Ala?Ala?Arg?Ala?Leu?Pro?Leu?Thr?Ser?Leu?Thr?Ser?Ala?Ala?Gln?Thr

340?????????????????345?????????????????350Ala?Pro?Gly?His?Met?Leu?Gly

The information of 355 (2) SEQ ID NO:110:

(i) sequence signature:

(A) length: 3027 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:110:AGTTCAGTCG, AGAATGATAC, TGACGGGCTG, TATCCACGAT, GGCTGAGACA, ACCGAACCAC, 60CGTCGGACGC, GGGGACATCG, CAAGCCGACG, CGATGGCGTT, GGCCGCCGAA, GCCGAAGCCG, 120CCGAAGCCGA, AGCGCTGGCC, GCCGCGGCGC, GGGCCCGTGC, CCGTGCCGCC, CGGTTGAAGC, 180GTGAGGCGCT, GGCGATGGCC, CCAGCCGAGG, ACGAGAACGT, CCCCGAGGAT, ATGCAGACTG, 240GGAAGACGCC, GAAGACTATG, ACGACTATGA, CGACTATGAG, GCCGCAGACC, AGGAGGCCGC, 300ACGGTCGGCA, TCCTGGCGAC, GGCGGTTGCG, GGTGCGGTTA, CCAAGACTGT, CCACGATTGC, 360CATGGCGGCC, GCAGTCGTCA, TCATCTGCGG, CTTCACCGGG, CTCAGCGGAT, ACATTGTGTG, 420GCAACACCAT, GAGGCCACCG, AACGCCAGCA, GCGCGCCGCG, GCGTTCGCCG, CCGGAGCCAA, 480GCAAGGTGTC, ATCAACATGA, CCTCGCTGGA, CTTCAACAAG, GCCAAAGAAG, ACGTCGCGCG, 540TGTGATCGAC, AGCTCCACCG, GCGAATTCAG, GGATGACTTC, CAGCAGCGGG, CAGCCGATTT, 600CACCAAGGTT, GTCGAACAGT, CCAAAGTGGT, CACCGAAGGC, ACGGTGAACG, CGACAGCCGT, 660CGAATCCATG, AACGAGCATT, CCGCCGTGGT, GCTCGTCGCG, GCGACTTCAC, GGGTCACCAA, 720TTCCGCTGGG, GCGAAAGACG, AACCACGTGC, GTGGCGGCTC, AAAGTGACCG, TGACCGAAGA, 780GGGGGGACAG, TACAAGATGT, CGAAAGTTGA, GTTCGTACCG, TGACCGATGA, CGTACGCGAC, 840GTCAACACCG, AAACCACTGA, CGCCACCGAA, GTCGCTGAGA, TCGACTCAGC, CGCAGGCGAA, 900GCCGGTGATT, CGGCGACCGA, GGCATTTGAC, ACCGACTCTG, CAACGGAATC, TACCGCGCAG, 960AAGGGTCAGC, GGCACCGTGA, CCTGTGGCGA, ATGCAGGTTA, CCTTGAAACC, CGTTCCGGTG, 1020ATTCTCATCC, TGCTCATGTT, GATCTCTGGG, GGCGCGACGG, GATGGCTATA, CCTTGAGCAA, 1080TACGACCCGA, TCAGCAGACG, GACTCCGGCG, CCGCCCGTGC, TGCCGTCGCC, GCGGCGTCTG, 1140ACGGGACAAT, CGCGCTGTTG, TGTATTCACC, CGACACGTCG, ACCAAGACTT, CGCTACCGCC, 1200AGGTCGCACC, TCGCCGGCGA, TTTCCTGTCC, TATACGACCA, GTTCACGCAG, CAGATCGTGG, 1260CTCCGGCGGC, CAAACAGAAG, TCACTGAAAA, CCACCGCCAA, GGTGGTGCGC, GCGGCCGTGT, 1320CGGAGCTACA, TCCGGATTCG, GCCGTCGTTC, TGGTTTTTGT, CGACCAGAGC, ACTACCAGTA, 1380AGGACAGCCC, CAATCCGTCG, ATGGCGGCCA, GCAGCGTGAT, GGTGACCCTA, GCCAAGGTCG, 1440ACGGCAATTG, GCTGATCACC, AAGTTCACCC, CGGTTTAGGT, TGCCGTAGGC, GGTCGCCAAG, 1500TCTGACGGGG, GCGCGGGTGG, CTGCTCGTGC, GAGATACCGG, CCGTTCTCCG, GACAATCACG, 1560GCCCGACCTC, AAACAGATCT, CGGCCGCTGT, CTAATCGGCC, GGGTTATTTA, AGATTAGTTG, 1620CCACTGTATT, TACCTGATGT, TCAGATTGTT, CAGCTGGATT, TAGCTTCGCG, GCAGGGCGGC, 1680TGGTGCACTT, TGCATCTGGG, GTTGTGACTA, CTTGAGAGAA, TTTGACCTGT, TGCCGACGTT, 1740GTTTGCTGTC, CATCATTGGT, GCTAGTTATG, GCCGAGCGGA, AGGATTATCG, AAGTGGTGGA, 1800CTTCGGGGCG, TTACCACCGG, AGATCAACTC, CGCGAGGATG, TACGCCGGCC, CGGGTTCGGC, 1860CTCGCTGGTG, GCCGCCGCGA, AGATGTGGGA, CAGCGTGGCG, AGTGACCTGT, TTTCGGCCGC, 1920GTCGGCGTTT, CAGTCGGTGG, TCTGGGGTCT, GACGACGGGA, TCGTGGATAG, GTTCGTCGGC, 1980GGGTCTGATG, GTGGCGGCGG, CCTCGCCGTA, TGTGGCGTGG, ATGAGCGTCA, CCGCGGGGCA, 2040GGCCGAGCTG, ACCGCCGCCC, AGGTCCGGGT, TGCTGCGGCG, GCCTACGAGA, CGGCGTATGG, 2100GCTGACGGTG, CCCCCGCCGG, TGATCGCCGA, GAACCGTGCT, GAACTGATGA, TTCTGATAGC, 2160GACCAACCTC, TTGGGGCAAA, ACACCCCGGC, GATCGCGGTC, AACGAGGCCG, AATACGGGGA, 2220GATGTGGGCC, CAAGACGCCG, CCGCGATGTT, TGGCTACGCC, GCCACGGCGG, CGACGGCGAC, 2280CGAGGCGTTG, CTGCCGTTCG, AGGACGCCCC, ACTGATCACC, AACCCCGGCG, GGCTCCTTGA, 2340GCAGGCCGTC, GCGGTCGAGG, AGGCCATCGA, CACCGCCGCG, GCGAACCAGT, TGATGAACAA, 2400TGTGCCCCAA, GCGCTGCAAC, AACTGGCCCA, GCCCACGAAA, AGCATCTGGC, CGTTCGACCA, 2460ACTGAGTGAA, CTCTGGAAAG, CCATCTCGCC, GCATCTGTCG, CCGCTCAGCA, ACATCGTGTC, 2520GATGCTCAAC, AACCACGTGT, CGATGACCAA, CTCGGGTGTG, TCGATGGCCA, GCACCTTGCA, 2580CTCAATGTTG, AAGGGCTTTG, CTCCGGCGGC, GGCTCAGGCC, GTGGAAACCG, CGGCGCAAAA, 2640CGGGGTCCAG, GCGATGAGCT, CGCTGGGCAG, CCAGCTGGGT, TCGTCGCTGG, GTTCTTCGGG, 2700TCTGGGCGCT, GGGGTGGCCG, CCAACTTGGG, TCGGGCGGCC, TCGGTCGGTT, CGTTGTCGGT, 2760GCCGCAGGCC, TGGGCCGCGG, CCAACCAGGC, GGTCACCCCG, GCGGCGCGGG, CGCTGCCGCT, 2820GACCAGCCTG, ACCAGCGCCG, CCCAAACCGC, CCCCGGACAC, ATGCTGGGCG, GGCTACCGCT, 2880GGGGCAACTG, ACCAATAGCG, GCGGCGGGTT, CGGCGGGGTT, AGCAATGCGT, TGCGGATGCC, 2940GCCGCGGGCG, TACGTAATGC, CCCGTGTGCC, CGCCGCCGGG, TAACGCCGAT, CCGCACGCAA, 3000TGCGGGCCCT, CTATGCGGGC, AGCGATC, 3027, (2) SEQ, ID, the information of NO:111:

(i) sequence signature:

(A) length: 396 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: SEQ ID NO:111:Val Val Asp Phe Gly Ala Leu Pro Pro Glu Ile Asn Ser Ala Arg Met1 5 10 15Tyr Ala Gly Pro Gly Ser Ala Ser Leu Val Ala Ala Ala Lys Met Trp

20??????????????????25??????????????????30Asp?Ser?Val?Ala?Ser?Asp?Leu?Phe?Ser?Ala?Ala?Ser?Ala?Phe?Gln?Ser

35??????????????????40??????????????????45Val?Val?Trp?Gly?Leu?Thr?Thr?Gly?Ser?Trp?Ile?Gly?Ser?Ser?Ala?Gly

50??????????????????55??????????????????60Leu?Met?Val?Ala?Ala?Ala?Ser?Pro?Tyr?Val?Ala?Trp?Met?Ser?Val?Thr65??????????????????70??????????????????75??????????????????80Ala?Gly?Gln?Ala?Glu?Leu?Thr?Ala?Ala?Gln?Val?Arg?Val?Ala?Ala?Ala

85??????????????????90??????????????????95Ala?Tyr?Glu?Thr?Ala?Tyr?Gly?Leu?Thr?Val?Pro?Pro?Pro?Val?Ile?Ala

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

115?????????????????120?????????????????125Gln?Asn?Thr?Pro?Ala?Ile?Ala?Val?Asn?Glu?Ala?Glu?Tyr?Gly?Glu?Met

130?????????????????135?????????????????140Trp?Ala?Gln?Asp?Ala?Ala?Ala?Met?Phe?Gly?Tyr?Ala?Ala?Thr?Ala?Ala145?????????????????150?????????????????155?????????????????160Thr?Ala?Thr?Glu?Ala?Leu?Leu?Pro?Phe?Glu?Asp?Ala?Pro?Leu?Ile?Thr

165?????????????????170?????????????????175Asn?Pro?Gly?Gly?Leu?Leu?Glu?Gln?Ala?Val?Ala?Val?Glu?Glu?Ala?Ile

180?????????????????185?????????????????190Asp?Thr?Ala?Ala?Ala?Asn?Gln?Leu?Met?Asn?Asn?Val?Pro?Gln?Ala?Leu

195?????????????????200?????????????????205Gln?Gln?Leu?Ala?Gln?Pro?Thr?Lys?Ser?Ile?Trp?Pro?Phe?Asp?Gln?Leu

210?????????????????215?????????????????220Ser?Glu?Leu?Trp?Lys?Ala?Ile?Ser?Pro?His?Leu?Ser?Pro?Leu?Ser?Asn225?????????????????230?????????????????235?????????????????240Ile?Val?Ser?Met?Leu?Asn?Asn?His?Val?Ser?Met?Thr?Asn?Ser?Gly?Val

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

260?????????????????265?????????????????270Ala?Ala?Gln?Ala?Val?Glu?Thr?Ala?Ala?Gln?Asn?Gly?Val?Gln?Ala?Met

275?????????????????280?????????????????285Ser?Ser?Leu?Gly?Ser?Gln?Leu?Gly?Ser?Ser?Leu?Gly?Ser?Ser?Gly?Leu

290?????????????????295?????????????????300Gly?Ala?Gly?Val?Ala?Ala?Asn?Leu?Gly?Arg?Ala?Ala?Ser?Val?Gly?Ser305?????????????????310?????????????????315?????????????????320Leu?Ser?Val?Pro?Gln?Ala?Trp?Ala?Ala?Ala?Asn?Gln?Ala?Val?Thr?Pro

325?????????????????330?????????????????335Ala?Ala?Arg?Ala?Leu?Pro?Leu?Thr?Ser?Leu?Thr?Ser?Ala?Ala?Gln?Thr

340?????????????????345?????????????????350Ala?Pro?Gly?His?Met?Leu?Gly?Gly?Leu?Pro?Leu?Gly?Gln?Leu?Thr?Asn

355?????????????????360?????????????????365Ser?Gly?Gly?Gly?Phe?Gly?Gly?Val?Ser?Asn?Ala?Leu?Arg?Met?Pro?Pro

The information of 370 375 380Arg Ala Tyr Val Met Pro Arg Val Pro Ala Ala Gly385,390 395 (2) SEQ ID NO:112:

(i) sequence signature:

(A) length: 1616 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:112:CATCGGAGGG, AGTGATCACC, ATGCTGTGGC, ACGCAATGCC, ACCGGAGTAA, ATACCGCACG, 60GCTGATGGCC, GGCGCGGGTC, CGGCTCCAAT, GCTTGCGGCG, GCCGCGGGAT, GGCAGACGCT, 120TTCGGCGGCT, CTGGACGCTC, AGGCCGTCGA, GTTGACCGCG, CGCCTGAACT, CTCTGGGAGA, 180AGCCTGGACT, GGAGGTGGCA, GCGACAAGGC, GCTTGCGGCT, GCAACGCCGA, TGGTGGTCTG, 240GCTACAAACC, GCGTCAACAC, AGGCCAAGAC, CCGTGCGATG, CAGGCGACGG, CGCAAGCCGC, 300GGCATACACC, CAGGCCATGG, CCACGACGCC, GTCGCTGCCG, GAGATCGCCG, CCAACCACAT, 360CACCCAGGCC, GTCCTTACGG, CCACCAACTT, CTTCGGTATC, AACACGATCC, CGATCGCGTT, 420GACCGAGATG, GATTATTTCA, TCCGTATGTG, GAACCAGGCA, GCCCTGGCAA, TGGAGGTCTA, 480CCAGGCCGAG, ACCGCGGTTA, ACACGCTTTT, CGAGAAGCTC, GAGCCGATGG, CGTCGATCCT, 540TGATCCCGGC, GCGAGCCAGA, GCACGACGAA, CCCGATCTTC, GGAATGCCCT, CCCCTGGCAG, 600CTCAACACCG, GTTGGCCAGT, TGCCGCCGGC, GGCTACCCAG, ACCCTCGGCC, AACTGGGTGA, 660GATGAGCGGC, CCGATGCAGC, AGCTGACCCA, GCCGCTGCAG, CAGGTGACGT, CGTTGTTCAG, 720CCAGGTGGGC, GGCACCGGCG, GCGGCAACCC, AGCCGACGAG, GAAGCCGCGC, AGATGGGCCT, 780GCTCGGCACC, AGTCCGCTGT, CGAACCATCC, GCTGGCTGGT, GGATCAGGCC, CCAGCGCGGG, 840CGCGGGCCTG, CTGCGCGCGG, AGTCGCTACC, TGGCGCAGGT, GGGTCGTTGA, CCCGCACGCC, 900GCTGATGTCT, CAGCTGATCG, AAAAGCCGGT, TGCCCCCTCG, GTGATGCCGG, CGGCTGCTGC, 960CGGATCGTCG, GCGACGGGTG, GCGCCGCTCC, GGTGGGTGCG, GGAGCGATGG, GCCAGGGTGC, 1020GCAATCCGGC, GGCTCCACCA, GGCCGGGTCT, GGTCGCGCCG, GCACCGCTCG, CGCAGGAGCG, 1080TGAAGAAGAC, GACGAGGACG, ACTGGGACGA, AGAGGACGAC, TGGTGAGCTC, CCGTAATGAC, 1140AACAGACTTC, CCGGCCACCC, GGGCCGGAAG, ACTTGCCAAC, ATTTTGGCGA, GGAAGGTAAA, 1200GAGAGAAAGT, AGTCCAGCAT, GGCAGAGATG, AAGACCGATG, CCGCTACCCT, CGCGCAGGAG, 1260GCAGGTAATT, TCGAGCGGAT, CTCCGGCGAC, CTGAAAACCC, AGATCGACCA, GGTGGAGTCG, 1320ACGGCAGGTT, CGTTGCAGGG, CCAGTGGCGC, GGCGCGGCGG, GGACGGCCGC, CCAGGCCGCG, 1380GTGGTGCGCT, TCCAAGAAGC, AGCCAATAAG, CAGAAGCAGG, AACTCGACGA, GATCTCGACG, 1440AATATTCGTC, AGGCCGGCGT, CCAATACTCG, AGGGCCGACG, AGGAGCAGCA, GCAGGCGCTG, 1500TCCTCGCAAA, TGGGCTTCTG, ACCCGCTAAT, ACGAAAAGAA, ACGGAGCAAA, AACATGACAG, 1560AGCAGCAGTG, GAATTTCGCG, GGTATCGAGG, CCGCGGCAAG, CGCAATCCAG, GGAAAT, 1616, (2) SEQ, ID, the information of NO:113:

(i) sequence signature:

(A) length: 432 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) Topology: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 113: CTAGTGGATG GGACCATGGC CATTTTCTGC AGTCTCACTG CCTTCTGTGT TGACATTTTG 60GCACGCCGGC GGAAACGAAG CACTGGGGTC GAAGAACGGC TGCGCTGCCA TATCGTCCGG 120AGCTTCCATA CCTTCGTGCG GCCGGAAGAG CTTGTCGTAG TCGGCCGCCA TGACAACCTC 180TCAGAGTGCG CTCAAACGTA TAAACACGAG AAAGGGCGAG ACCGACGGAA GGTCGAACTC 240GCCCGATCCC GTGTTTCGCT ATTCTACGCG AACTCGGCGT TGCCCTATGC GAACATCCCA 300GTGACGTTGC CTTCGGTCGA AGCCATTGCC TGACCGGCTT CGCTGATCGT CCGCGCCAGG 360TTCTGCAGCG CGTTGTTCAG CTCGGTAGCC GTGGCGTCCC ATTTTTGCTG GACACCCTGG 420TACGCCTCCG AA 432 (2) SEQ ID NO: 114 information:

(i) sequence signature:

(A) length: 368 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:114:Met Leu Trp His Ala Met Pro Pro Glu Xaa Asn Thr Ala Arg Leu Met1 5 10 15Ala Gly Ala Gly Pro Ala Pro Met Leu Ala Ala Ala Ala Gly Trp Gln

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

35??????????????????40??????????????????45Leu?Asn?Ser?Leu?Gly?Glu?Ala?Trp?Thr?Gly?Gly?Gly?Ser?Asp?Lys?Ala

50??????????????????55??????????????????60Leu?Ala?Ala?Ala?Thr?Pro?Met?Val?Val?Trp?Leu?Gln?Thr?Ala?Ser?Thr65??????????????????70??????????????????75??????????????????80Gln?Ala?Lys?Thr?Arg?Ala?Met?Gln?Ala?Thr?Ala?Gln?Ala?Ala?Ala?Tyr

85??????????????????90??????????????????95Thr?Gln?Ala?Met?Ala?Thr?Thr?Pro?Ser?Leu?Pro?Glu?Ile?Ala?Ala?Asn

100?????????????????105?????????????????110His?Ile?Thr?Gln?Ala?Val?Leu?Thr?Ala?Thr?Asn?Phe?Phe?Gly?Ile?Asn

115?????????????????120?????????????????125Thr?Ile?Pro?Ile?Ala?Leu?Thr?Glu?Met?Asp?Tyr?Phe?Ile?Arg?Met?Trp

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

165?????????????????170?????????????????175Gly?Ala?Ser?Gln?Ser?Thr?Thr?Asn?Pro?Ile?Phe?Gly?Met?Pro?Ser?Pro

180?????????????????185?????????????????190Gly?Ser?Ser?Thr?Pro?Val?Gly?Gln?Leu?Pro?Pro?Ala?Ala?Thr?Gln?Thr

195?????????????????200?????????????????205Leu?Gly?Gln?Leu?Gly?Glu?Met?Ser?Gly?Pro?Met?Gln?Gln?Leu?Thr?Gln

210?????????????????215?????????????????220Pro?Leu?Gln?Gln?Val?Thr?Ser?Leu?Phe?Ser?Gln?Val?Gly?Gly?Thr?Gly225?????????????????230?????????????????235?????????????????240Gly?Gly?Asn?Pro?Ala?Asp?Glu?Glu?Ala?Ala?Gln?Met?Gly?Leu?Leu?Gly

245?????????????????250?????????????????255Thr?Ser?Pro?Leu?Ser?Asn?His?Pro?Leu?Ala?Gly?Gly?Ser?Gly?Pro?Ser

260?????????????????265?????????????????270Ala?Gly?Ala?Gly?Leu?Leu?Arg?Ala?Glu?Ser?Leu?Pro?Gly?Ala?Gly?Gly

275?????????????????280?????????????????285Ser?Leu?Thr?Arg?Thr?Pro?Leu?Met?Ser?Gln?Leu?Ile?Glu?Lys?Pro?Val

290?????????????????295?????????????????300Ala?Pro?Ser?Val?Met?Pro?Ala?Ala?Ala?Ala?Gly?Ser?Ser?Ala?Thr?Gly305?????????????????310?????????????????315?????????????????320Gly?Ala?Ala?Pro?Val?Gly?Ala?Gly?Ala?Met?Gly?Gln?Gly?Ala?Gln?Ser

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

340?????????????????345?????????????????350Glu?Arg?Glu?Glu?Asp?Asp?Glu?Asp?Asp?Trp?Asp?Glu?Glu?Asp?Asp?Trp

The information of 355 360 365 (2) SEQ ID NO:115:

(i) sequence signature:

(A) length: 100 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: SEQ ID NO:115:Met Ala Glu Met Lys Thr Asp Ala Ala Thr Leu Ala Gln Glu Ala Gly1 5 10 15Asn Phe Glu Arg Ile Ser Gly Asp Leu Lys Thr Gln Ile Asp Gln Val

20??????????????????25??????????????????30Glu?Ser?Thr?Ala?Gly?Ser?Leu?Gln?Gly?Gln?Trp?Arg?Gly?Ala?Ala?Gly

35??????????????????40??????????????????45Thr?Ala?Ala?Gln?Ala?Ala?Val?Val?Arg?Phe?Gln?Glu?Ala?Ala?Asn?Lys

50??????????????????55??????????????????60Gln?Lys?Gln?Glu?Leu?Asp?Glu?Ile?Ser?Thr?Asn?Ile?Arg?Gln?Ala?Gly65??????????????????70??????????????????75??????????????????80Val?Gln?Tyr?Ser?Arg?Ala?Asp?Glu?Glu?Gln?Gln?Gln?Ala?Leu?Ser?Ser

85??????????????????90??????????????????95Gln?Met?Gly?Phe

The information of 100 (2) SEQ ID NO:116:

(i) sequence signature:

(A) length: 396 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) Topology: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 116: GATCTCCGGC GACCTGAAAA CCCAGATCGA CCAGGTGGAG TCGACGGCAG GTTCGTTGCA 60GGGCCAGTGG CGCGGCGCGG CGGGGACGGC CGCCCAGGCC GCGGTGGTGC GCTTCCAAGA 120AGCAGCCAAT AAGCAGAAGC AGGAACTCGA CGAGATCTCG ACGAATATTC GTCAGGCCGG 180CGTCCAATAC TCGAGGGCCG ACGAGGAGCA GCAGCAGGCG CTGTCCTCGC AAATGGGCTT 240CTGACCCGCT AATACGAAAA GAAACGGAGC AAAAACATGA CAGAGCAGCA GTGGAATTTC 300GCGGGTATCG AGGCCGCGGC AAGCGCAATC CAGGGAAATG TCACGTCCAT TCATTCCCTC 360CTTGACGAGG GGAAGCAGTC CCTGACCAAG CTCGCA 396 (2) SEQ ID NO: 117 information:

(i) sequence signature:

(A) length: 80 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: SEQ ID NO:117:Ile Ser Gly Asp Leu Lys Thr Gln Ile Asp Gln Val Glu Ser Thr Ala1 5 10 15Gly Ser Leu Gln Gly Gln Trp Arg Gly Ala Ala Gly Thr Ala Ala Gln

20??????????????????25??????????????????30Ala?Ala?Val?Val?Arg?Phe?Gln?Glu?Ala?Ala?Asn?Lys?Gln?Lys?Gln?Glu

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

The information of 50 55 60Arg Ala Asp Glu Glu Gln Gln Gln Ala Leu Ser Ser Gln Met Gly Phe65,70 75 80 (2) SEQ ID NO:118:

(i) sequence signature:

(A) length: 387 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) Topology: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 118: GTGGATCCCG ATCCCGTGTT TCGCTATTCT ACGCGAACTC GGCGTTGCCC TATGCGAACA 60TCCCAGTGAC GTTGCCTTCG GTCGAAGCCA TTGCCTGACC GGCTTCGCTG ATCGTCCGCG 120CCAGGTTCTG CAGCGCGTTG TTCAGCTCGG TAGCCGTGGC GTCCCATTTT TGCTGGACAC 180CCTGGTACGC CTCCGAACCG CTACCGCCCC AGGCCGCTGC GAGCTTGGTC AGGGACTGCT 240TCCCCTCGTC AAGGAGGGAA TGAATGGACG TGACATTTCC CTGGATTGCG CTTGCCGCGG 300CCTCGATACC CGCGAAATTC CACTGCTGCT CTGTCATGTT TTTGCTCCGT TTCTTTTCGT 360ATTAGCGGGT CAGAAGCCCA TTTGCGA 387 (2) SEQ ID NO: 119 information:

(i) sequence signature:

(A) length: 272 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:119:CGGCACGAGG ATCTCGGTTG GCCCAACGGC GCTGGCGAGG GCTCCGTTCC GGGGGCGAGC 60TGCGCGCCGG ATGCTTCCTC TGCCCGCAGC CGCGCCTGGA TGGATGGACC AGTTGCTACC 120TTCCCGACGT TTCGTTCGGT GTCTGTGCGA TAGCGGTGAC CCCGGCGCGC ACGTCGGGAG 180TGTTGGGGGG CAGGCCGGGT CGGTGGTTCG GCCGGGGACG CAGACGGTCT GGACGGAACG 240GGCGGGGGTT CGCCGATTGG CATCTTTGCC CA 272 (2) SEQ ID NO:120:

(i) sequence signature:

(A) length: 20 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: SEQ ID NO:120Asp Pro Val Asp Ala Val Ile Asn Thr Thr Cys Asn Tyr Gly Gln Val1 5 10 15Val Ala Ala Leu

The information of 20 (2) SEQ ID NO:121:

(i) sequence signature:

(A) length: 15 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:121:Ala Val Glu Ser Gly Met Leu Ala Leu Gly Thr Pro Ala Pro Ser1 5 10 15 (2) SEQ ID NO:122:

(i) sequence signature:

(A) length: 19 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:122:Ala Ala Met Lys Pro Arg Thr Gly Asp Gly Pro Leu Glu Ala Ala Lys1 5 10 15Glu Gly Arg (2) SEQ ID NO:123:

(i) sequence signature:

(A) length: 15 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:123:Tyr Tyr Tro Cys Pro Gly Gln Pro Phe Asp Pro Ala Trp Gly Pro1 5 10 15 (2) SEQ ID NO:124:

(i) sequence signature:

(A) length: 14 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:124:Asp Ile Gly Ser Glu Ser Thr Glu Asp Gln Gln Xaa Ala Val1 5 10 (2) SEQ ID NO:125:

(i) sequence signature:

(A) length: 13 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:125:Ala Glu Glu Ser Ile Ser Thr Xaa Glu Xaa Ile Val Pro1 5 10 (2) SEQ ID NO:126:

(i) sequence signature:

(A) length: 17 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:126:Aso Pro Glu Pro Ala Pro Pro Val Pro Thr Thr Ala Ala Ser pro Pro1 5 10 15Ser (2) SEQ ID NO:127:

(i) sequence signature:

(A) length: 15 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:127:Ala Pro Lys Thr Tyr Xaa Glu Glu Leu Lys Gly Thr Asp Thr Gly1 5 10 15 (2) SEQ ID NO:128:

(i) sequence signature:

(A) length: 30 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: SEQ ID NO:128:Asp Pro Ala Ser Ala Pro Asp Val Pro Thr Ala Ala Gln Leu Thr Ser1 5 10 15 Leu Leu Asn Ser Leu Ala Asp Pro Asn Val Ser Phe Ala Asn

The information of 20 25 30 (2) SEQ ID NO:129:

(i) sequence signature:

(A) length: 22 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: SEQ ID NO:129:Asp Pro Pro Asp Pro His Gln Xaa Asp Met Thr Lys Gly Tyr Tyr Pro1 5 10 15Gly Gly Arg Arg Xaa Phe

The information of 20 (2) SEQ ID NO:130:

(i) sequence signature:

(A) length: 7 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:130:Asp Pro Gly Tyr Thr Pro Gly 15 (2) SEQ ID NO:131:

(i) sequence signature:

(A) length: 10 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linearity

(ix) feature:

(D) out of Memory: second residue of/notes=＂ can be Pro or Thr ＂ (xi) sequence description: the information of SEQ ID NO:131:Xaa Xaa Gly Phe Thr Gly Pro Gln Phe Tyr1 5 10 (2) SEQ ID NO:132:

(i) sequence signature:

(A) length: 9 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linearity

(ix) feature:

(D) out of Memory: second residue of/notes=＂ can be Gln or Leu ＂ (xi) sequence description: the information of SEQ ID NO:132:Xaa Pro Xaa Val Thr Ala Tyr Ala Gly1 5 (2) SEQ ID NO:133:

(i) sequence signature:

(A) length: 9 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:133:Xaa Xaa Xaa Glu Lys Pro Phe Leu Arg1 5 (2) SEQ ID NO:134:

(i) sequence signature:

(A) length: 15 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:134:Xaa Asp Ser Glu Lys Ser Ala Thr Ile Lys Val Thr Asp Ala Ser1 5 10 15 (2) SEQ ID NO:135:

(i) sequence signature:

(A) length: 15 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:135:Ala Gly Asp Thr Xaa Ile Tyr Ile Val Gly Asn Leu Thr Ala Asp1 5 10 15 (2) SEQ ID NO:136:

(i) sequence signature:

(A) length: 15 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: the information of SEQ ID NO:136:Ala Pro Glu Ser Gly Ala Gly Leu Gly Gly Thr Val Gln Ala Gly1 5 10 15 (2) SEQ ID NO:137:

(i) sequence signature:

(A) length: 21 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: SEQ ID NO:137:Xaa Tyr Ile Ala Tyr Xaa Thr Thr Ala Gly Ile Val Pro Gly Lys Ile1 5 10 15 Asn Val His Leu Val

The information of 20 (2) SEQ ID NO:138:

(i) sequence signature:

(A) length: 882 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(ii) molecule type: DNA, (genome), (xi) sequence description: SEQ, ID, NO:138:GCAACGCTGT, CGTGGCCTTT, GCGGTGATCG, GTTTCGCCTC, GCTGGCGGTG, GCGGTGGCGG, 60TCACCATCCG, ACCGACCGCG, GCCTCAAAAC, CGGTAGAGGG, ACACCAAAAC, GCCCAGCCAG, 120GGAAGTTCAT, GCCGTTGTTG, CCGACGCAAC, AGCAGGCGCC, GGTCCCGCCG, CCTCCGCCCG, 180ATGATCCCAC, CGCTGGATTC, CAGGGCGGCA, CCATTCCGGC, TGTACAGAAC, GTGGTGCCGC, 240GGCCGGGTAC, CTCACCCGGG, GTGGGTGGGA, CGCCGGCTTC, GCCTGCGCCG, GAAGCGCCGG, 300CCGTGCCCGG, TGTTGTGCCT, GCCCCGGTGC, CAATCCCGGT, CCCGATCATC, ATTCCCCCGT, 360TCCCGGGTTG, GCAGCCTGGA, ATGCCGACCA, TCCCCACCGC, ACCGCCGACG, ACGCCGGTGA, 420CCACGTCGGC, GACGACGCCG, CCGACCACGC, CGCCGACCAC, GCCGGTGACC, ACGCCGCCAA, 480CGACGCCGCC, GACCACGCCG, GTGACCACGC, CGCCAACGAC, GCCGCCGACC, ACGCCGGTGA, 540CCACGCCACC, AACGACCGTC, GCCCCGACGA, CCGTCGCCCC, GACGACGGTC, GCTCCGACCA, 600CCGTCGCCCC, GACCACGGTC, GCTCCAGCCA, CCGCCACGCC, GACGACCGTC, GCTCCGCAGC, 660CGACGCAGCA, GCCCACGCAA, CAACCAACCC, AACAGATGCC, AACCCAGCAG, CAGACCGTGG, 720CCCCGCAGAC, GGTGGCGCCG, GCTCCGCAGC, CGCCGTCCGG, TGGCCGCAAC, GGCAGCGGCG, 780GGGGCGACTT, ATTCGGCGGG, TTCTGATCAC, GGTCGCGGCT, TCACTACGGT, CGGAGGACAT, 840GGCCGGTGAT, GCGGTGACGG, TGGTGCTGCC, CTGTCTCAAC, GA, 882, (2) SEQ, ID, the information of NO:139:

(i) sequence signature:

(A) length: 815 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(ii) molecule type: DNA, (genome), (xi) sequence description: SEQ, ID, NO:139:CCATCAACCA, ACCGCTCGCG, CCGCCCGCGC, CGCCGGATCC, GCCGTCGCCG, CCACGCCCGC, 60CGGTGCCTCC, GGTGCCCCCG, TTGCCGCCGT, CGCCGCCGTC, GCCGCCGACC, GGCTGGGTGC, 120CTAGGGCGCT, GTTACCGCCC, TGGTTGGCGG, GGACGCCGCC, GGCACCACCG, GTACCGCCGA, 180TGGCGCCGTT, GCCGCCGGCG, GCACCGTTGC, CACCGTTGCC, ACCGTTGCCA, CCGTTGCCGA, 240CCAGCCACCC, GCCGCGACCA, CCGGCACCGC, CGGCGCCGCC, CGCACCGCCG, GCGTGCCCGT, 300TCGTGCCCGT, ACCGCCGGCA, CCGCCGTTGC, CGCCGTCACC, GCCGACGGAA, CTACCGGCGG, 360ACGCGGCCTG, CCCGCCGGCG, CCGCCCGCAC, CGCCATTGGC, ACCGCCGTCA, CCGCCGGCTG, 420GGAGTGCCGC, GATTAGGGCA, CTGACCGGCG, CAACCAGCGC, AAGTACTCTC, GGTCACCGAG, 480CACTTCCAGA, CGACACCACA, GCACGGGGTT, GTCGGCGGAC, TGGGTGAAAT, GGCAGCCGAT, 540AGCGGCTAGC, TGTCGGCTGC, GGTCAACCTC, GATCATGATG, TCGAGGTGAC, CGTGACCGCG, 600CCCCCCGAAG, GAGGCGCTGA, ACTCGGCGTT, GAGCCGATCG, GCGATCGGTT, GGGGCAGTGC, 660CCAGGCCAAT, ACGGGGATAC, CGGGTGTCNA, AGCCGCCGCG, AGCGCAGCTT, CGGTTGCGCG, 720ACNGTGGTCG, GGGTGGCCTG, TTACGCCGTT, GTCNTCGAAC, ACGAGTAGCA, GGTCTGCTCC, 780GGCGAGGGCA, TCCACCACGC, GTTGCGTCAG, CTCGT, 815, (2) SEQ, ID, the information of NO:140:

(i) sequence signature:

(A) length: 1152 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(ii) molecule type: DNA, (genome), (xi) sequence description: SEQ, ID, NO:140:ACCAGCCGCC, GGCTGAGGTC, TCAGATCAGA, GAGTCTCCGG, ACTCACCGGG, GCGGTTCAGC, 60CTTCTCCCAG, AACAACTGCT, GAAGATCCTC, GCCCGCGAAA, CAGGCGCTGA, TTTGACGCTC, 120TATGACCGGT, TGAACGACGA, GATCATCCGG, CAGATTGATA, TGGCACCGCT, GGGCTAACAG, 180GTGCGCAAGA, TGGTGCAGCT, GTATGTCTCG, GACTCCGTGT, CGCGGATCAG, CTTTGCCGAC, 240GGCCGGGTGA, TCGTGTGGAG, CGAGGAGCTC, GGCGAGAGCC, AGTATCCGAT, CGAGACGCTG, 300GACGGCATCA, CGCTGTTTGG, GCGGCCGACG, ATGACAACGC, CCTTCATCGT, TGAGATGCTC, 360AAGCGTGAGC, GCGACATCCA, GCTCTTCACG, ACCGACGGCC, ACTACCAGGG, CCGGATCTCA, 420ACACCCGACG, TGTCATACGC, GCCGCGGCTC, CGTCAGCAAG, TTCACCGCAC, CGACGATCCT, 480GCGTTCTGCC, TGTCGTTAAG, CAAGCGGATC, GTGTCGAGGA, AGATCCTGAA, TCAGCAGGCC, 540TTGATTCGGG, CACACACGTC, GGGGCAAGAC, GTTGCTGAGA, GCATCCGCAC, GATGAAGCAC, 600TCGCTGGCCT, GGGTCGATCG, ATCGGGCTCC, CTGGCGGAGT, TGAACGGGTT, CGAGGGAAAT, 660GCCGCAAAGG, CATACTTCAC, CGCGCTGGGG, CATCTCGTCC, CGCAGGAGTT, CGCATTCCAG, 720GGCCGCTCGA, CTCGGCCGCC, GTTGGACGCC, TTCAACTCGA, TGGTCAGCCT, CGGCTATTCG, 780CTGCTGTACA, AGAACATCAT, AGGGGCGATC, GAGCGTCACA, GCCTGAACGC, GTATATCGGT, 840TTCCTACACC, AGGATTCACG, AGGGCACGCA, ACGTCTCGTG, CCGAATTCGG, CACGAGCTCC, 900GCTGAAACCG, CTGGCCGGCT, GCTCAGTGCC, CGTACGTAAT, CCGCTGCGCC, CAGGCCGGCC, 960CGCCGGCCGA, ATACCAGCAG, ATCGGACAGC, GAATTGCCGC, CCAGCCGGTT, GGAGCCGTGC, 1020ATACCGCCGG, CACACTCACC, GGCAGCGAAC, AGGCCTGGCA, CCGTGGCGGC, GCCGGTGTCC, 1080GCGTCTACTT, CGACACCGCC, CATCACGTAG, TGACACGTCG, GCCCGACTTC, CATTGCCTGC, 1140GTTCGGCACG, AG, 1152, (2) SEQ, ID, the information of NO:141:

(i) sequence signature:

(A) length: 655 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(ii) molecule type: DNA, (genome), (xi) sequence description: SEQ, ID, NO:141:CTCGTGCCGA, TTCGGCAGGG, TGTACTTGCC, GGTGGTGTAN, GCCGCATGAG, TGCCGACGAC, 60CAGCAATGCG, GCAACAGCAC, GGATCCCGGT, CAACGACGCC, ACCCGGTCCA, CGTGGGCGAT, 120CCGCTCGAGT, CCGCCCTGGG, CGGCTCTTTC, CTTGGGCAGG, GTCATCCGAC, GTGTTTCCGC, 180CGTGGTTTGC, CGCCATTATG, CCGGCGCGCC, GCGTCGGGCG, GCCGGTATGG, CCGAANGTCG, 240ATCAGCACAC, CCGAGATACG, GGTCTGTGCA, AGCTTTTTGA, GCGTCGCGCG, GGGCAGCTTC, 300GCCGGCAATT, CTACTAGCGA, GAAGTCTGGC, CCGATACGGA, TCTGACCGAA, GTCGCTGCGG, 360TGCAGCCCAC, CCTCATTGGC, GATGGCGCCG, ACGATGGCGC, CTGGACCGAT, CTTGTGCCGC, 420TTGCCGACGG, CGACGCGGTA, GGTGGTCAAG, TCCGGTCTAC, GCTTGGGCCT, TTGCGGACGG, 480TCCCGACGCT, GGTCGCGGTT, GCGCCGCGAA, AGCGGCGGGT, CGGGTGCCAT, CAGGAATGCC, 540TCACCGCCGC, GGCACTGCAC, GGCCAGTGCC, GCGGCGATGT, CAGCCATCGG, GACATCATGC, 600TCGCGTTCAT, ACTCCTCGAC, CAGTCGGCGG, AACAGCTCGA, TTCCCGGACC, GCCCA, 655, (2) SEQ, ID, the information of NO:142:

(i) sequence signature:

(A) length: 267 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linearity

(ii) molecule type: peptide (xi) sequence description: SEQ ID NO:142:Asn Ala Val Val Ala Phe Ala Val Ile Gly Phe Ala Ser Leu Ala Val1 5 10 15Ala Val Ala Val Thr Ile Arg Pro Thr Ala Ala Ser Lys Pro Val Glu

20??????????????????25??????????????????30Gly?His?Gln?Asn?Ala?Gln?Pro?Gly?Lys?Phe?Met?Pro?Leu?Leu?Pro?Thr

35??????????????????40??????????????????45Gln?Gln?Gln?Ala?Pro?Val?Pro?Pro?Pro?Pro?Pro?Asp?Asp?Pro?Thr?Ala

50??????????????????55??????????????????60Gly?Phe?Gln?Gly?Gly?Thr?Ile?Pro?Ala?Val?Gln?Asn?Val?Val?Pro?Arg65??????????????????70??????????????????75??????????????????80Pro?Gly?Thr?Ser?Pro?Gly?Val?Gly?Gly?Thr?Pro?Ala?Ser?Pro?Ala?Pro

85??????????????????90??????????????????95Glu?Ala?Pro?Ala?Val?Pro?Gly?Val?Val?Pro?Ala?Pro?Val?Pro?Ile?Pro

100?????????????????105?????????????????110Val?Pro?Ile?Ile?Ile?Pro?Pro?Phe?Pro?Gly?Trp?Gln?Pro?Gly?Met?Pro

115?????????????????120?????????????????125Thr?Ile?Pro?Thr?Ala?Pro?Pro?Thr?Thr?Pro?Val?Thr?Thr?Ser?Ala?Thr

130?????????????????135?????????????????140Thr?Pro?Pro?Thr?Thr?Pro?Pro?Thr?Thr?Pro?Val?Thr?Thr?Pro?Pro?Thr145?????????????????150?????????????????155?????????????????160Thr?Pro?Pro?Thr?Thr?Pro?Val?Thr?Thr?Pro?Pro?Thr?Thr?Pro?Pro?Thr

165?????????????????170?????????????????175Thr?Pro?Val?Thr?Thr?Pro?Pro?Thr?Thr?Val?Ala?Pro?Thr?Thr?Val?Ala

180?????????????????185?????????????????190Pro?Thr?Thr?Val?Ala?Pro?Thr?Thr?Val?Ala?Pro?Thr?Thr?Val?Ala?Pro

195?????????????????200?????????????????205Ala?Thr?Ala?Thr?Pro?Thr?Thr?Val?Ala?Pro?Gln?Pro?Thr?Gln?Gln?Pro

210?????????????????215?????????????????220Thr?Gln?Gln?Pro?Thr?Gln?Gln?Met?Pro?Thr?Gln?Gln?Gln?Thr?Val?Ala225?????????????????230?????????????????235?????????????????240Pro?Gln?Thr?Val?Ala?Pro?Ala?Pro?Gln?Pro?Pro?Ser?Gly?Gly?Arg?Asn

245?????????????????250?????????????????255Gly?Ser?Gly?Gly?Gly?Asp?Leu?Phe?Gly?Gly?Phe

The information of 260 265 (2) SEQ ID NO:143:

(i) sequence signature:

(A) length: 174 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linearity

(ii) molecule type: peptide (xi) sequence description: SEQ ID NO:143:Ile Asn Gln Pro Leu Ala Pro Pro Ala Pro Pro Asp Pro Pro Ser Pro1 5 10 15Pro Arg Pro Pro Val Pro Pro Val Pro Pro Leu Pro Pro Ser Pro Pro

20??????????????????25??????????????????30Ser?Pro?Pro?Thr?Gly?Trp?Val?Pro?Arg?Ala?Leu?Leu?Pro?Pro?Trp?Leu

35??????????????????40??????????????????45Ala?Gly?Thr?Pro?Pro?Ala?Pro?Pro?Val?Pro?Pro?Met?Ala?Pro?Leu?Pro

50??????????????????55??????????????????60Pro?Ala?Ala?Pro?Leu?Pro?Pro?Leu?Pro?Pro?Leu?Pro?Pro?Leu?Pro?Thr65??????????????????70??????????????????75??????????????????80Ser?His?Pro?Pro?Arg?Pro?Pro?Ala?Pro?Pro?Ala?Pro?Pro?Ala?Pro?Pro

85??????????????????90??????????????????95Ala?Cys?Pro?Phe?Val?Pro?Val?Pro?Pro?Ala?Pro?Pro?Leu?Pro?Pro?Ser

100?????????????????105?????????????????110Pro?Pro?Thr?Glu?Leu?Pro?Ala?Asp?Ala?Ala?Cys?Pro?Pro?Ala?Pro?Pro

115?????????????????120?????????????????125Ala?Pro?Pro?Leu?Ala?Pro?Pro?Ser?Pro?Pro?Ala?Gly?Ser?Ala?Ala?Ile

130?????????????????135?????????????????140Arg?Ala?Leu?Thr?Gly?Ala?Thr?Ser?Ala?Ser?Thr?Leu?Gly?His?Arg?Ala145?????????????????150?????????????????155?????????????????160Leu?Pro?Asp?Asp?Thr?Thr?Ala?Arg?Gly?Cys?Arg?Arg?Thr?Gly

The information of 165 170 (2) SEQ ID NO:144:

(i) sequence signature:

(A) length: 35 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linearity

(ii) molecule type: peptide (xi) sequence description: SEQ ID NO:144:Gln Pro Pro Ala Glu Val Ser Asp Gln Arg Val Ser Gly Leu Thr Gly1 5 10 15Ala Val Gln Pro Ser Pro Arg Thr Thr Ala Glu Asp Pro Arg Pro Arg

20??????????????????25??????????????????30Asn?Arg?Arg

The information of 35 (2) SEQ ID NO:145:

(i) sequence signature:

(A) length: 104 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linearity

(ii) molecule type: peptide (xi) sequence description: SEQ ID NO:145:Arg Ala Asp Ser Ala Gly Cys Thr Cys Arg Trp Cys Xaa Pro His Glu1 5 10 15Cys Arg Arg Pro Ala Met Arg Gln Gln His Gly Ser Arg Ser Thr Thr

20??????????????????25??????????????????30Pro?Pro?Gly?Pro?Arg?Gly?Arg?Ser?Ala?Arg?Val?Arg?Pro?Gly?Arg?Leu

35??????????????????40??????????????????45Phe?Pro?Trp?Ala?Gly?Ser?Ser?Asp?Val?Phe?Pro?Pro?Trp?Phe?Ala?Ala

50??????????????????55??????????????????60Ile?Met?Pro?Ala?Arg?Arg?Val?Gly?Arg?Pro?Val?Trp?Pro?Xaa?Val?Asp65??????????????????70??????????????????75??????????????????80Gln?His?Thr?Arg?Asp?Thr?Gly?Leu?Cys?Lys?Leu?Phe?Glu?Arg?Arg?Ala

85??????????????????90??????????????????95Gly?Gln?Leu?Arg?Arg?Gln?Phe?Tyr

The information of 100 (2) SEQ ID NO:146:

(i) sequence signature:

(A) length: 53 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(ii) molecule type: other nucleic acid

(A) illustrate :/desc=＂ PCR primer ＂

(vi) originate: (A) microorganism: mycobacterium tuberculosis (xi) sequence description: the information of SEQ ID NO:146:GGATCCATAT GGGCCATCAT CATCATCATC ACGTGATCGA CATCATCGGG ACC 53 (2) SEQ ID NO:147:

(i) sequence signature:

(A) length: 42 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(ii) molecule type: other nucleic acid

(A) illustrate :/desc=＂ PCR primer ＂

(vi) originate: (A) microorganism: mycobacterium tuberculosis (xi) sequence description: the information of SEQ ID NO:147:CCTGAATTCA GGCCTCGGTT GCGCCGGCCT CATCTTGAAC GA 42 (2) SEQ ID NO:148:

(i) sequence signature:

(A) length: 31 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(ii) molecule type: other nucleic acid

(A) illustrate :/desc=＂ PCR primer ＂

(vi) originate: (A) microorganism: mycobacterium tuberculosis (xi) sequence description: the information of SEQ ID NO:148:GGATCCTGCA GGCTCGAAAC CACCGAGCGG T 31 (2) SEQ ID NO:149:

(i) sequence signature:

(A) length: 31 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(ii) molecule type: other nucleic acid

(A) illustrate :/desc=＂ PCR primer ＂

(vi) originate: (A) microorganism: mycobacterium tuberculosis (xi) sequence description: the information of SEQ ID NO:149:CTCTGAATTC AGCGCTGGAA ATCGTCGCGA T 31 (2) SEQ ID NO:150:

(i) sequence signature:

(A) length: 33 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(ii) molecule type: other nucleic acid

(A) illustrate :/desc=＂ PCR primer ＂

(vi) originate: (A) microorganism: mycobacterium tuberculosis (xi) sequence description: the information of SEQ ID NO:150:GGATCCAGCG CTGAGATGAA GACCGATGCC GCT 33 (2) SEQ ID NO:151:

(i) sequence signature:

(A) length: 33 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(ii) molecule type: other nucleic acid

(A) illustrate :/desc=＂ PCR primer ＂

(vi) originate: (A) microorganism: mycobacterium tuberculosis (xi) sequence description: the information of SEQ ID NO:151:GAGAGAATTC TCAGAAGCCC ATTTGCGAGG ACA 33 (2) SEQ ID NO:152:

(i) sequence signature:

(A) length: 1993 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(ii) molecule type: DNA (genome)

(A) illustrate :/desc=＂ PCR primer ＂

(vi) originate:

(A) microorganism: mycobacterium tuberculosis

(ix) feature:

(A) title/keyword: CDS

(B) position: 152..1273 (xi) sequence description: SEQ ID NO:152:TGTTCTTCGA CGGCAGGCTG GTGGAGGAAG GGCCCACCGA ACAGCTGTTC TCCTCGCCGA 60AGCATGCGGA AACCGCCCGA TACGTCGCCG GACTGTCGGG GGACGTCAAG GACGCCAAGC 120GCGGAAATTG AAGAGCACAG AAAGGTATGG C GTG AAA ATT CGT TTG CAT ACG 172

Val?Lys?Ile?Arg?Leu?His?Thr

1???????????????5CTG?TTG?GCC?GTG?TTG?ACC?GCT?GCG?CCG?CTG?CTG?CTA?GCA?GCG?GCG?GGC?????????220Leu?Leu?Ala?Val?Leu?Thr?Ala?Ala?Pro?Leu?Leu?Leu?Ala?Ala?Ala?Gly

10??????????????????15??????????????????20TGT?GGC?TCG?AAA?CCA?CCG?AGC?GGT?TCG?CCT?GAA?ACG?GGC?GCC?GGC?GCC?????????268Cys?Gly?Ser?Lys?Pro?Pro?Ser?Gly?Ser?Pro?Glu?Thr?Gly?Ala?Gly?Ala

25??????????????????30??????????????????35GGT?ACT?GTC?GCG?ACT?ACC?CCC?GCG?TCG?TCG?CCG?GTG?ACG?TTG?GCG?GAG?????????316Gly?Thr?Val?Ala?Thr?Thr?Pro?Ala?Ser?Ser?Pro?Val?Thr?Leu?Ala?Glu?40??????????????????45??????????????????50??????????????????55ACC?GGT?AGC?ACG?CTG?CTC?TAC?CCG?CTG?TTC?AAC?CTG?TGG?GGT?CCG?GCC?????????364Thr?Gly?Ser?Thr?Leu?Leu?Tyr?Pro?Leu?Phe?Asn?Leu?Trp?Gly?Pro?Ala

60??????????????????65??????????????????70TTT?CAC?GAG?AGG?TAT?CCG?AAC?GTC?ACG?ATC?ACC?GCT?CAG?GGC?ACC?GGT?????????412Phe?His?Glu?Arg?Tyr?Pro?Asn?Val?Thr?Ile?Thr?Ala?Gln?Gly?Thr?Gly

75??????????????????80??????????????????85TCT?GGT?GCC?GGG?ATC?GCG?CAG?GCC?GCC?GCC?GGG?ACG?GTC?AAC?ATT?GGG?????????460Ser?Gly?Ala?Gly?Ile?Ala?Gln?Ala?Ala?Ala?Gly?Thr?Val?Asn?Ile?Gly

90??????????????????95?????????????????100GCC?TCC?GAC?GCC?TAT?CTG?TCG?GAA?GGT?GAT?ATG?GCC?GCG?CAC?AAG?GGG?????????508Ala?Ser?Asp?Ala?Tyr?Leu?Ser?Glu?Gly?Asp?Met?Ala?Ala?His?Lys?Gly

105?????????????????110?????????????????115CTG?ATG?AAC?ATC?GCG?CTA?GCC?ATC?TCC?GCT?CAG?CAG?GTC?AAC?TAC?AAC?????????556Leu?Met?Asn?Ile?Ala?Leu?Ala?Ile?Ser?Ala?Gln?Gln?Val?Asn?Tyr?Asn120?????????????????125?????????????????130?????????????????135CTG?CCC?GGA?GTG?AGC?GAG?CAC?CTC?AAG?CTG?AAC?GGA?AAA?GTC?CTG?GCG?????????604Leu?Pro?Gly?Val?Ser?Glu?His?Leu?Lys?Leu?Asn?Gly?Lys?Val?Leu?Ala

140?????????????????145?????????????????150GCC?ATG?TAC?CAG?GGC?ACC?ATC?AAA?ACC?TGG?GAC?GAC?CCG?CAG?ATC?GCT?????????652Ala?Met?Tyr?Gln?Gly?Thr?Ile?Lys?Thr?Trp?Asp?Asp?Pro?Gln?Ile?Ala

155?????????????????160?????????????????165GCG?CTC?AAC?CCC?GGC?GTG?AAC?CTG?CCC?GGC?ACC?GCG?GTA?GTT?CCG?CTG?????????700Ala?Leu?Asn?Pro?Gly?Val?Asn?Leu?Pro?Gly?Thr?Ala?Val?Val?Pro?Leu

170?????????????????175?????????????????180CAC?CGC?TCC?GAC?GGG?TCC?GGT?GAC?ACC?TTC?TTG?TTC?ACC?CAG?TAC?CTG?????????748His?Arg?Ser?Asp?Gly?Ser?Gly?Asp?Thr?Phe?Leu?Phe?Thr?Gln?Tyr?Leu

185?????????????????190?????????????????195TCC?AAG?CAA?GAT?CCC?GAG?GGC?TGG?GGC?AAG?TCG?CCC?GGC?TTC?GGC?ACC?????????796Ser?Lys?Gln?Asp?Pro?Glu?Gly?Trp?Gly?Lys?Ser?Pro?Gly?Phe?Gly?Thr200?????????????????205?????????????????210?????????????????215ACC?GTC?GAC?TTC?CCG?GCG?GTG?CCG?GGT?GCG?CTG?GGT?GAG?AAC?GGC?AAC?????????844Thr?Val?Asp?Phe?Pro?Ala?Val?Pro?Gly?Ala?Leu?Gly?Glu?Asn?Gly?Asn

220?????????????????225?????????????????230GGC?GGC?ATG?GTG?ACC?GGT?TGC?GCC?GAG?ACA?CCG?GGC?TGC?GTG?GCC?TAT?????????892Gly?Gly?Met?Val?Thr?Gly?Cys?Ala?Glu?Thr?Pro?Gly?Cys?Val?Ala?Tyr

235?????????????????240?????????????????245ATC?GGC?ATC?AGC?TTC?CTC?GAC?CAG?GCC?AGT?CAA?CGG?GGA?CTC?GGC?GAG????????940Ile?Gly?Ile?Ser?Phe?Leu?Asp?Gln?Ala?Ser?Gln?Arg?Gly?Leu?Gly?Glu

250?????????????????255?????????????????260GCC?CAA?CTA?GGC?AAT?AGC?TCT?GGC?AAT?TTC?TTG?TTG?CCC?GAC?GCG?CAA????????988Ala?Gln?Leu?Gly?Asn?Ser?Ser?Gly?Asn?Phe?Leu?Leu?Pro?Asp?Ala?Gln

265?????????????????270?????????????????275AGC?ATT?CAG?GCC?GCG?GCG?GCT?GGC?TTC?GCA?TCG?AAA?ACC?CCG?GCG?AAC???????1036Ser?Ile?Gln?Ala?Ala?Ala?Ala?Gly?Phe?Ala?Ser?Lys?Thr?Pro?Ala?Asn280?????????????????285?????????????????290?????????????????295CAG?GCG?ATT?TCG?ATG?ATC?GAC?GGG?CCC?GCC?CCG?GAC?GGC?TAC?CCG?ATC???????1084Gln?Ala?Ile?Ser?Met?Ile?Asp?Gly?Pro?Ala?Pro?Asp?Gly?Tyr?Pro?Ile

300?????????????????305?????????????????310ATC?AAC?TAC?GAG?TAC?GCC?ATC?GTC?AAC?AAC?CGG?CAA?AAG?GAC?GCC?GCC???????1132Ile?Asn?Tyr?Glu?Tyr?Ala?Ile?Val?Asn?Asn?Arg?Gln?Lys?Asp?Ala?Ala

315?????????????????320?????????????????325ACC?GCG?CAG?ACC?TTG?CAG?GCA?TTT?CTG?CAC?TGG?GCG?ATC?ACC?GAC?GGC???????1180Thr?Ala?Gln?Thr?Leu?Gln?Ala?Phe?Leu?His?Trp?Ala?Ile?Thr?Asp?Gly

330?????????????????335?????????????????340AAC?AAG?GCC?TCG?TTC?CTC?GAC?CAG?GTT?CAT?TTC?CAG?CCG?CTG?CCG?CCC???????1228Asn?Lys?Ala?Ser?Phe?Leu?Asp?Gln?Val?His?Phe?Gln?Pro?Leu?Pro?Pro

345, 350, 355GCG, GTG, GTG, AAG, TTG, TCT, GAC, GCG, TTG, ATC, GCG, ACG, ATT, TCC, AGC, 1273Ala, Val, Val, Lys, Leu, Ser, Asp, Ala, Leu, Ile, Ala, Thr, Ile, Ser, Ser360, 365, 370TAGCCTCGTT, GACCACCACG, CGACAGCAAC, CTCCGTCGGG, CCATCGGGCT, GCTTTGCGGA, 1333GCATGCTGGC, CCGTGCCGGT, GAAGTCGGCC, GCGCTGGCCC, GGCCATCCGG, TGGTTGGGTG, 1393GGATAGGTGC, GGTGATCCCG, CTGCTTGCGC, TGGTCTTGGT, GCTGGTGGTG, CTGGTCATCG, 1453AGGCGATGGG, TGCGATCAGG, CTCAACGGGT, TGCATTTCTT, CACCGCCACC, GAATGGAATC, 1513CAGGCAACAC, CTACGGCGAA, ACCGTTGTCA, CCGACGCGTC, GCCCATCCGG, TCGGCGCCTA, 1573CTACGGGGCG, TTGCCGCTGA, TCGTCGGGAC, GCTGGCGACC, TCGGCAATCG, CCCTGATCAT, 1633CGCGGTGCCG, GTCTCTGTAG, GAGCGGCGCT, GGTGATCGTG, GAACGGCTGC, CGAAACGGTT, 1693GGCCGAGGCT, GTGGGAATAG, TCCTGGAATT, GCTCGCCGGA, ATCCCCAGCG, TGGTCGTCGG, 1753TTTGTGGGGG, GCAATGACGT, TCGGGCCGTT, CATCGCTCAT, CACATCGCTC, CGGTGATCGC, 1813TCACAACGCT, CCCGATGTGC, CGGTGCTGAA, CTACTTGCGC, GGCGACCCGG, GCAACGGGGA, 1873GGGCATGTTG, GTGTCCGGTC, TGGTGTTGGC, GGTGATGGTC, GTTCCCATTA, TCGCCACCAC, 1933CACTCATGAC, CTGTTCCGGC, AGGTGCCGGT, GTTGCCCCGG, GAGGGCGCGA, TCGGGAATTC, 1993, (2) SEQ, ID, the information of NO:153:

(i) sequence signature:

(A) length: 374 amino acid

(B) type: amino acid

(D) topology: linearity

(ii) molecule type: protein (xi) sequence description: SEQ ID NO:153:Val Lys Ile Arg Leu His Thr Leu Leu Ala Val Leu Thr Ala Ala Pro 15 10 15Leu Leu Leu Ala Ala Ala Gly Cys Gly Ser Lys Pro Pro Ser Gly Ser

20??????????????????25??????????????????30Pro?Glu?Thr?Gly?Ala?Gly?Ala?Gly?Thr?Val?Ala?Thr?Thr?Pro?Ala?Ser

35??????????????????40??????????????????45Ser?Pro?Val?Thr?Leu?Ala?Glu?Thr?Gly?Ser?Thr?Leu?Leu?Tyr?Pro?Leu

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

85??????????????????90??????????????????95Ala?Gly?Thr?Val?Asn?Ile?Gly?Ala?Ser?Asp?Ala?Tyr?Leu?Ser?Glu?Gly

100?????????????????105?????????????????110Asp?Met?Ala?Ala?His?Lys?Gly?Leu?Met?Asn?Ile?Ala?Leu?Ala?Ile?Ser

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

130?????????????????135?????????????????140Leu?Asn?Gly?Lys?Val?Leu?Ala?Ala?Met?Tyr?Gln?Gly?Thr?Ile?Lys?Thr145?????????????????150?????????????????155?????????????????160Trp?Asp?Asp?Pro?Gln?Ile?Ala?Ala?Leu?Asn?Pro?Gly?Val?Asn?Leu?Pro

165?????????????????170?????????????????175Gly?Thr?Ala?Val?Val?Pro?Leu?His?Arg?Ser?Asp?Gly?Ser?Gly?Asp?Thr

180?????????????????185?????????????????190Phe?Leu?Phe?Thr?Gln?Tyr?Leu?Ser?Lys?Gln?Asp?Pro?Glu?Gly?Trp?Gly

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

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

245?????????????????250?????????????????255Ser?Gln?Arg?Gly?Leu?Gly?Glu?Ala?Gln?Leu?Gly?Asn?Ser?Ser?Gly?Asn

260?????????????????265?????????????????270Phe?Leu?Leu?Pro?Asp?Ala?Gln?Ser?Ile?Gln?Ala?Ala?Ala?Ala?Gly?Phe

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

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

325?????????????????330?????????????????335His?Trp?Ala?Ile?Thr?Asp?Gly?Asn?Lys?Ala?Ser?Phe?Leu?Asp?Gln?Val

340?????????????????345?????????????????350His?Phe?Gln?Pro?Leu?Pro?Pro?Ala?Val?Val?Lys?Leu?Ser?Asp?Ala?Leu

355?????????????????360?????????????????365Ile?Ala?Thr?Ile?Ser?Ser

The information of 370 (2) SEQ ID NO:154:

(i) sequence signature:

(A) length: 1993 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ, ID, NO:154:TGTTCTTCGA, CGGCAGGCTG, GTGGAGGAAG, GGCCCACCGA, ACAGCTGTTC, TCCTCGCCGA, 60AGCATGCGGA, AACCGCCCGA, TACGTCGCCG, GACTGTCGGG, GGACGTCAAG, GACGCCAAGC, 120GCGGAAATTG, AAGAGCACAG, AAAGGTATGG, CGTGAAAATT, CGTTTGCATA, CGCTGTTGGC, 180CGTGTTGACC, GCTGCGCCGC, TGCTGCTAGC, AGCGGCGGGC, TGTGGCTCGA, AACCACCGAG, 240CGGTTCGCCT, GAAACGGGCG, CCGGCGCCGG, TACTGTCGCG, ACTACCCCCG, CGTCGTCGCC, 300GGTGACGTTG, GCGGAGACCG, GTAGCACGCT, GCTCTACCCG, CTGTTCAACC, TGTGGGGTCC, 360GGCCTTTCAC, GAGAGGTATC, CGAACGTCAC, GATCACCGCT, CAGGGCACCG, GTTCTGGTGC, 420CGGGATCGCG, CAGGCCGCCG, CCGGGACGGT, CAACATTGGG, GCCTCCGACG, CCTATCTGTC, 480GGAAGGTGAT, ATGGCCGCGC, ACAAGGGGCT, GATGAACATC, GCGCTAGCCA, TCTCCGCTCA, 540GCAGGTCAAC, TACAACCTGC, CCGGAGTGAG, CGAGCACCTC, AAGCTGAACG, GAAAAGTCCT, 600GGCGGCCATG, TACCAGGGCA, CCATCAAAAC, CTGGGACGAC, CCGCAGATCG, CTGCGCTCAA, 660CCCCGGCGTG, AACCTGCCCG, GCACCGCGGT, AGTTCCGCTG, CACCGCTCCG, ACGGGTCCGG, 720TGACACCTTC, TTGTTCACCC, AGTACCTGTC, CAAGCAAGAT, CCCGAGGGCT, GGGGCAAGTC, 780GCCCGGCTTC, GGCACCACCG, TCGACTTCCC, GGCGGTGCCG, GGTGCGCTGG, GTGAGAACGG, 840CAACGGCGGC, ATGGTGACCG, GTTGCGCCGA, GACACCGGGC, TGCGTGGCCT, ATATCGGCAT, 900CAGCTTCCTC, GACCAGGCCA, GTCAACGGGG, ACTCGGCGAG, GCCCAACTAG, GCAATAGCTC, 960TGGCAATTTC, TTGTTGCCCG, ACGCGCAAAG, CATTCAGGCC, GCGGCGGCTG, GCTTCGCATC, 1020GAAAACCCCG, GCGAACCAGG, CGATTTCGAT, GATCGACGGG, CCCGCCCCGG, ACGGCTACCC, 1080GATCATCAAC, TACGAGTACG, CCATCGTCAA, CAACCGGCAA, AAGGACGCCG, CCACCGCGCA, 1140GACCTTGCAG, GCATTTCTGC, ACTGGGCGAT, CACCGACGGC, AACAAGGCCT, CGTTCCTCGA, 1200CCAGGTTCAT, TTCCAGCCGC, TGCCGCCCGC, GGTGGTGAAG, TTGTCTGACG, CGTTGATCGC, 1260GACGATTTCC, AGCTAGCCTC, GTTGACCACC, ACGCGACAGC, AACCTCCGTC, GGGCCATCGG, 1320GCTGCTTTGC, GGAGCATGCT, GGCCCGTGCC, GGTGAAGTCG, GCCGCGCTGG, CCCGGCCATC, 1380CGGTGGTTGG, GTGGGATAGG, TGCGGTGATC, CCGCTGCTTG, CGCTGGTCTT, GGTGCTGGTG, 1440GTGCTGGTCA, TCGAGGCGAT, GGGTGCGATC, AGGCTCAACG, GGTTGCATTT, CTTCACCGCC, 1500ACCGAATGGA, ATCCAGGCAA, CACCTACGGC, GAAACCGTTG, TCACCGACGC, GTCGCCCATC, 1560CGGTCGGCGC, CTACTACGGG, GCGTTGCCGC, TGATCGTCGG, GACGCTGGCG, ACCTCGGCAA, 1620TCGCCCTGAT, CATCGCGGTG, CCGGTCTCTG, TAGGAGCGGC, GCTGGTGATC, GTGGAACGGC, 1680TGCCGAAACG, GTTGGCCGAG, GCTGTGGGAA, TAGTCCTGGA, ATTGCTCGCC, GGAATCCCCA, 1740GCGTGGTCGT, CGGTTTGTGG, GGGGCAATGA, CGTTCGGGCC, GTTCATCGCT, CATCACATCG, 1800CTCCGGTGAT, CGCTCACAAC, GCTCCCGATG, TGCCGGTGCT, GAACTACTTG, CGCGGCGACC, 1860CGGGCAACGG, GGAGGGCATG, TTGGTGTCCG, GTCTGGTGTT, GGCGGTGATG, GTCGTTCCCA, 1920TTATCGCCAC, CACCACTCAT, GACCTGTTCC, GGCAGGTGCC, GGTGTTGCCC, CGGGAGGGCG, 1980CGATCGGGAA, TTC, 1993, (2) SEQ, ID, the information of NO:155:

(i) sequence signature:

(A) length: 374 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: SEQ ID NO:155:Met Lys Ile Arg Leu His Thr Leu Leu Ala Val Leu Thr Ala Ala Pro1 5 10 15Leu Leu Leu Ala Ala Ala Gly Cys Gly Ser Lys Pro Pro Ser Gly Ser

20??????????????????25??????????????????30Pro?Glu?Thr?Gly?Ala?Gly?Ala?Gly?Thr?Val?Ala?Thr?Thr?Pro?Ala?Ser

35??????????????????40??????????????????45Ser?Pro?Val?Thr?Leu?Ala?Glu?Thr?Gly?Ser?Thr?Leu?Leu?Tyr?Pro?Leu

50??????????????????55??????????????????60Phe?Asn?Leu?Trp?Gly?Pro?Ala?Phe?His?Glu?Arg?Tyr?Pro?Asn?Val?Thr65??????????????????70??????????????????75??????????????????80Ile?Thr?Ala?Gln?Gly?Thr?Gly?Ser?Gly?Ala?Gly?Ile?Ala?Gln?Ala?Ala

85??????????????????90??????????????????95Ala?Gly?Thr?Val?Asn?Ile?Gly?Ala?Ser?Asp?Ala?Tyr?Leu?Ser?Glu?Gly

100?????????????????105?????????????????110Asp?Met?Ala?Ala?His?Lys?Gly?Leu?Met?Asn?Ile?Ala?Leu?Ala?Ile?Ser

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

130?????????????????135?????????????????140Leu?Asn?Gly?Lys?Val?Leu?Ala?Ala?Met?Tyr?Gln?Gly?Thr?Ile?Lys?Thr145?????????????????150?????????????????155?????????????????160Trp?Asp?Asp?Pro?Gln?Ile?Ala?Ala?Leu?Asn?Pro?Gly?Val?Asn?Leu?Pro

165?????????????????170?????????????????175Gly?Thr?Ala?Val?Val?Pro?Leu?His?Arg?Ser?Asp?Gly?Ser?Gly?Asp?Thr

180?????????????????185?????????????????190Phe?Leu?Phe?Thr?Gln?Tyr?Leu?Ser?Lys?Gln?Asp?Pro?Glu?Gly?Trp?Gly

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

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

245?????????????????250?????????????????255Ser?Gln?Arg?Gly?Leu?Gly?Glu?Ala?Gln?Leu?Gly?Asn?Ser?Ser?Gly?Asn

260?????????????????265?????????????????270Phe?Leu?Leu?Pro?Asp?Ala?Gln?Ser?Ile?Gln?Ala?Ala?Ala?Ala?Gly?Phe

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

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

325?????????????????330?????????????????335His?Trp?Ala?Ile?Thr?Asp?Gly?Asn?Lys?Ala?Ser?Phe?Leu?Asp?Gln?Val

340?????????????????345?????????????????350His?Phe?Gln?Pro?Leu?Pro?Pro?Ala?Val?Val?Lys?Leu?Ser?Asp?Ala?Leu

355?????????????????360?????????????????365Ile?Ala?Thr?Ile?Ser?Ser

The information of 370 (2) SEQ ID NO:156:

(i) sequence signature:

(A) length: 1777 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ, ID, NO:156:GGTCTTGACC, ACCACCTGGG, TGTCGAAGTC, GGTGCCCGGA, TTGAAGTCCA, GGTACTCGTG, 60GGTGGGGCGG, GCGAAACAAT, AGCGACAAGC, ATGCGAGCAG, CCGCGGTAGC, CGTTGACGGT, 120GTAGCGAAAC, GGCAACGCGG, CCGCGTTGGG, CACCTTGTTC, AGCGCTGATT, TGCACAACAC, 180CTCGTGGAAG, GTGATGCCGT, CGAATTGTGG, CGCGCGAACG, CTGCGGACCA, GGCCGATCCG, 240CTGCAACCCG, GCAGCGCCCG, TCGTCAACGG, GCATCCCGTT, CACCGCGACG, GCTTGCCGGG, 300CCCAACGCAT, ACCATTATTC, GAACAACCGT, TCTATACTTT, GTCAACGCTG, GCCGCTACCG, 360AGCGCCGCAC, AGGATGTGAT, ATGCCATCTC, TGCCCGCACA, GACAGGAGCC, AGGCCTTATG, 420ACAGCATTCG, GCGTCGAGCC, CTACGGGCAG, CCGAAGTACC, TAGAAATCGC, CGGGAAGCGC, 480ATGGCGTATA, TCGACGAAGG, CAAGGGTGAC, GCCATCGTCT, TTCAGCACGG, CAACCCCACG, 540TCGTCTTACT, TGTGGCGCAA, CATCATGCCG, CACTTGGAAG, GGCTGGGCCG, GCTGGTGGCC, 600TGCGATCTGA, TCGGGATGGG, CGCGTCGGAC, AAGCTCAGCC, CATCGGGACC, CGACCGCTAT, 660AGCTATGGCG, AGCAACGAGA, CTTTTTGTTC, GCGCTCTGGG, ATGCGCTCGA, CCTCGGCGAC, 720CACGTGGTAC, TGGTGCTGCA, CGACTGGGGC, TCGGCGCTCG, GCTTCGACTG, GGCTAACCAG, 780CATCGCGACC, GAGTGCAGGG, GATCGCGTTC, ATGGAAGCGA, TCGTCACCCC, GATGACGTGG, 840GCGGACTGGC, CGCCGGCCGT, GCGGGGTGTG, TTCCAGGGTT, TCCGATCGCC, TCAAGGCGAG, 900CCAATGGCGT, TGGAGCACAA, CATCTTTGTC, GAACGGGTGC, TGCCCGGGGC, GATCCTGCGA, 960CAGCTCAGCG, ACGAGGAAAT, GAACCACTAT, CGGCGGCCAT, TCGTGAACGG, CGGCGAGGAC, 1020CGTCGCCCCA, CGTTGTCGTG, GCCACGAAAC, CTTCCAATCG, ACGGTGAGCC, CGCCGAGGTC, 1080GTCGCGTTGG, TCAACGAGTA, CCGGAGCTGG, CTCGAGGAAA, CCGACATGCC, GAAACTGTTC, 1140ATCAACGCCG, AGCCCGGCGC, GATCATCACC, GGCCGCATCC, GTGACTATGT, CAGGAGCTGG, 1200CCCAACCAGA, CCGAAATCAC, AGTGCCCGGC, GTGCATTTCG, TTCAGGAGGA, CAGCGATGGC, 1260GTCGTATCGT, GGGCGGGCGC, TCGGCAGCAT, CGGCGACCTG, GGAGCGCTCT, CATTTCACGA, 1320GACCAAGAAT, GTGATTTCCG, GCGAAGGCGG, CGCCCTGCTT, GTCAACTCAT, AAGACTTCCT, 1380GCTCCGGGCA, GAGATTCTCA, GGGAAAAGGG, CACCAATCGC, AGCCGCTTCC, TTCGCAACGA, 1440GGTCGACAAA, TATACGTGGC, AGGACAAAGG, TCTTCCTATT, TGCCCAGCGA, ATTAGTCGCT, 1500GCCTTTCTAT, GGGCTCAGTT, CGAGGAAGCC, GAGCGGATCA, CGCGTATCCG, ATTGGACCTA, 1560TGGAACCGGT, ATCATGAAAG, CTTCGAATCA, TTGGAACAGC, GGGGGCTCCT, GCGCCGTCCG, 1620ATCATCCCAC, AGGGCTGCTC, TCACAACGCC, CACATGTACT, ACGTGTTACT, AGCGCCCAGC, 1680GCCGATCGGG, AGGAGGTGCT, GGCGCGTCTG, ACGAGCGAAG, GTATAGGCGC, GGTCTTTCAT, 1740TACGTGCCGC, TTCACGATTC, GCCGGCCGGG, CGTCGCT, 1777, (2) SEQ, ID, the information of NO:157:

(i) sequence signature:

(A) length: 324 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 157: GAGATTGAAT CGTACCGGTC TCCTTAGCGG CTCCGTCCCG TGAATGCCCA TATCACGCAC 60GGCCATGTTC TGGCTGTCGA CCTTCGCCCC ATGCCCGGAC GTTGGTAAAC CCAGGGTTTG 120ATCAGTAATT CCGGGGGACG GTTGCGGGAA GGCGGCCAGG ATGTGCGTGA GCCGCGGCGC 180CGCCGTCGCC CAGGCGACCG CTGGATGCTC AGCCCCGGTG CGGCGACGTA GCCAGCGTTT 240GGCGCGTGTC GTCCACAGTG GTACTCCGGT GACGACGCGG CGCGGTGCCT GGGTGAAGAC 300CGTGACCGAC GCCGCCGATT CAGA 324 (2) SEQ ID NO: 158 information:

(i) sequence signature:

(A) length: 1338 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ, ID, NO:158:GCGGTACCGC, CGCGTTGCGC, TGGCACGGGA, CCTGTACGAC, CTGAACCACT, TCGCCTCGCG, 60AACGATTGAC, GAACCGCTCG, TGCGGCGGCT, GTGGGTGCTC, AAGGTGTGGG, GTGATGTCGT, 120CGATGACCGG, CGCGGCACCC, GGCCACTACG, CGTCGAAGAC, GTCCTCGCCG, CCCGCAGCGA, 180GCACGACTTC, CAGCCCGACT, CGATCGGCGT, GCTGACCCGT, CCTGTCGCTA, TGGCTGCCTG, 240GGAAGCTCGC, GTTCGGAAGC, GATTTGCGTT, CCTCACTGAC, CTCGACGCCG, ACGAGCAGCG, 300GTGGGCCGCC, TGCGACGAAC, GGCACCGCCG, CGAAGTGGAG, AACGCGCTGG, CGGTGCTGCG, 360GTCCTGATCA, ACCTGCCGGC, GATCGTGCCG, TTCCGCTGGC, ACGGTTGCGG, CTGGACGCGG, 420CTGAATCGAC, TAGATGAGAG, CAGTTGGGCA, CGAATCCGGC, TGTGGTGGTG, AGCAAGACAC, 480GAGTACTGTC, ATCACTATTG, GATGCACTGG, ATGACCGGCC, TGATTCAGCA, GGACCAATGG, 540AACTGCCCGG, GGCAAAACGT, CTCGGAGATG, ATCGGCGTCC, CCTCGGAACC, CTGCGGTGCT, 600GGCGTCATTC, GGACATCGGT, CCGGCTCGCG, GGATCGTGGT, GACGCCAGCG, CTGAAGGAGT, 660GGAGCGCGGC, GGTGCACGCG, CTGCTGGACG, GCCGGCAGAC, GGTGCTGCTG, CGTAAGGGCG, 720GGATCGGCGA, GAAGCGCTTC, GAGGTGGCGG, CCCACGAGTT, CTTGTTGTTC, CCGACGGTCG, 780CGCACAGCCA, CGCCGAGCGG, GTTCGCCCCG, AGCACCGCGA, CCTGCTGGGC, CCGGCGGCCG, 840CCGACAGCAC, CGACGAGTGT, GTGCTACTGC, GGGCCGCAGC, GAAAGTTGTT, GCCGCACTGC, 900CGGTTAACCG, GCCAGAGGGT, CTGGACGCCA, TCGAGGATCT, GCACATCTGG, ACCGCCGAGT, 960CGGTGCGCGC, CGACCGGCTC, GACTTTCGGC, CCAAGCACAA, ACTGGCCGTC, TTGGTGGTCT, 1020CGGCGATCCC, GCTGGCCGAG, CCGGTCCGGC, TGGCGCGTAG, GCCCGAGTAC, GGCGGTTGCA, 1080CCAGCTGGGT, GCAGCTGCCG, GTGACGCCGA, CGTTGGCGGC, GCCGGTGCAC, GACGAGGCCG, 1140CGCTGGCCGA, GGTCGCCGCC, CGGGTCCGCG, AGGCCGTGGG, TTGACTGGGC, GGCATCGCTT, 1200GGGTCTGAGC, TGTACGCCCA, GTCGGCGCTG, CGAGTGATCT, GCTGTCGGTT, CGGTCCCTGC, 1260TGGCGTCAAT, TGACGGCGCG, GGCAACAGCA, GCATTGGCGG, CGCCATCCTC, CGCGCGGCCG, 1320GGGCCCACCG, CTACAACC, 1338, (2) SEQ, ID, the information of NO:159:

(i) sequence signature:

(A) length: 321 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 159: CCGGCGGCAC CGGCGGCACC GGCGGTACCG GCGGCAACGG CGCTGACGCC GCTGCTGTGG 60TGGGCTTCGG CGCGAACGGC GACCCTGGCT TCGCTGGCGG CAAAGGCGGT AACGGCGGAA 120TAGGTGGGGC CGCGGTGACA GGCGGGGTCG CCGGCGACGG CGGCACCGGC GGCAAAGGTG 180GCACCGGCGG TGCCGGCGGC GCCGGCAACG ACGCCGGCAG CACCGGCAAT CCCGGCGGTA 240AGGGCGGCGA CGGCGGGATC GGCGGTGCCG GCGGGGCCGG CGGCGCGGCC GGCACCGGCA 300ACGGCGGCCA TGCCGGCAAC C 321 (2) SEQ ID NO: 160 information:

(i) sequence signature:

(A) length: 492 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ, ID, NO:160:GAAGACCCGG, CCCCGCCATA, TCGATCGGCT, CGCCGACTAC, TTTCGCCGAA, CGTGCACGCG, 60GCGGCGTCGG, GCTGATCATC, ACCGGTGGCT, ACGCGCCCAA, CCGCACCGGA, TGGCTGCTGC, 120CGTTCGCCTC, CGAACTCGTC, ACTTCGGCGC, AAGCCCGACG, GCACCGCCGA, ATCACCAGGG, 180CGGTCCACGA, TTCGGGTGCA, AAGATCCTGC, TGCAAATCCT, GCACGCCGGA, CGCTACGCCT, 240ACCACCCACT, TGCGGTCAGC, GCCTCGCCGA, TCAAGGCGCC, GATCACCCCG, TTTCGTCCGC, 300GAGCACTATC, GGCTCGCGGG, GTCGAAGCGA, CCATCGCGGA, TTTCGCCCGC, TGCGCGCAGT, 360TGGCCCGCGA, TGCCGGCTAC, GACGGCGTCG, AAATCATGGG, CAGCGAAGGG, TATCTGCTCA, 420ATCAGTTCCT, GGCGCCGCGC, ACCAACAAGC, GCACCGACTC, GTGGGGCGGC, ACACCGGCCA, 480ACCGTCGCCG, GT, 492, (2) SEQ, ID, the information of NO:161:

(i) sequence signature:

(A) length: 536 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: SEQ ID NO:161:Phe Ala Gln His Leu Val Glu Gly Asp Ala Val Glu Leu Trp Arg Ala1 5 10 15Asn Ala Ala Asp Gln Ala Asp Pro Leu Gln Pro Gly Ser Ala Arg Arg

20??????????????????25??????????????????30Gln?Arg?Ala?Sar?Arg?Ser?Pro?Arg?Arg?Leu?Ala?Gly?Pro?Asn?Ala?Tyr

35??????????????????40??????????????????45His?Tyr?Ser?Asn?Asn?Arg?Ser?Ile?Leu?Cys?Gln?Arg?Trp?Pro?Leu?Pro

50??????????????????55??????????????????60Ser?Ala?Ala?Gln?Asp?Val?Ile?Cys?His?Leu?Cys?Pro?His?Arg?Gln?Glu65??????????????????70??????????????????75??????????????????80Pro?Gly?Leu?Met?Thr?Ala?Phe?Gly?Val?Glu?Pro?Tyr?Gly?Gln?Pro?Lys

85??????????????????90??????????????????95Tyr?Leu?Glu?Ile?Ala?Gly?Lys?Arg?Met?Ala?Tyr?Ile?Asp?Glu?Gly?Lys

100?????????????????105?????????????????110Gly?Asp?Ala?Ile?Val?Phe?Gln?His?Gly?Asn?Pro?Thr?Ser?Ser?Tyr?Leu

115?????????????????120?????????????????125Trp?Arg?Asn?Ile?Met?Pro?His?Leu?Glu?Gly?Leu?Gly?Arg?Leu?Val?Ala

130?????????????????135?????????????????140Cys?Asp?Leu?Ile?Gly?Met?Gly?Ala?Ser?Asp?Lys?Leu?Ser?Pro?Ser?Gly145?????????????????150?????????????????155?????????????????160Pro?Asp?Arg?Tyr?Ser?Tyr?Gly?Glu?Gln?Arg?Asp?Phe?Leu?Phe?Ala?Leu

165?????????????????170?????????????????175Trp?Asp?Ala?Leu?Asp?Leu?Gly?Asp?His?Val?Val?Leu?Val?Leu?His?Asp

180?????????????????185?????????????????190Trp?Gly?Ser?Ala?Leu?Gly?Phe?Asp?Trp?Ala?Asn?Gln?His?Arg?Asp?Arg

195?????????????????200?????????????????205Val?Gln?Gly?Ile?Ala?Phe?Met?Glu?Ala?Ile?Val?Thr?Pro?Met?Thr?Trp

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

245?????????????????250?????????????????255Val?Leu?Pro?Gly?Ala?Ile?Leu?Arg?Gln?Leu?Ser?Asp?Glu?Glu?Met?Asn

260?????????????????265?????????????????270His?Tyr?Arg?Arg?Pro?Phe?Val?Asn?Gly?Gly?Glu?Asp?Arg?Arg?Pro?Thr

275?????????????????280?????????????????285Leu?Ser?Trp?Pro?Arg?Asn?Leu?Pro?Ile?Asp?Gly?Glu?Pro?Ala?Glu?Val

290?????????????????295?????????????????300Val?Ala?Leu?Val?Asn?Glu?Tyr?Arg?Ser?Trp?Leu?Glu?Glu?Thr?Asp?Met305?????????????????310?????????????????315?????????????????320Pro?Lys?Leu?Phe?Ile?Asn?Ala?Glu?Pro?Gly?Ala?Ile?Ile?Thr?Gly?Arg

325?????????????????330?????????????????335Ile?Arg?Asp?Tyr?Val?Arg?Ser?Trp?Pro?Asn?Gln?Thr?Glu?Ile?Thr?Val

340?????????????????345?????????????????350Pro?Gly?Val?His?Phe?Val?Gln?Glu?Asp?Ser?Asp?Gly?Val?Val?Ser?Trp

355?????????????????360?????????????????365Ala?Gly?Ala?Arg?Gln?His?Arg?Arg?Pro?Gly?Ser?Ala?Leu?Ile?Ser?Arg

370?????????????????375?????????????????380Asp?Gln?Glu?Cys?Asp?Phe?Arg?Arg?Arg?Arg?Arg?Pro?Ala?Cys?Gln?Leu385?????????????????390?????????????????395?????????????????400Ile?Arg?Leu?Pro?Ala?Pro?Gly?Arg?Asp?Ser?Gln?Gly?Lys?Gly?His?Gln

405?????????????????410?????????????????415Ser?Gln?Pro?Leu?Pro?Ser?Gln?Arg?Gly?Arg?Gln?Ile?Tyr?Val?Ala?Gly

420?????????????????425?????????????????430Gln?Arg?Ser?Ser?Tyr?Leu?Pro?Ser?Glu?Leu?Val?Ala?Ala?Phe?Leu?Trp

435?????????????????440?????????????????445Ala?Gln?Phe?Glu?Glu?Ala?Glu?Arg?Ile?Thr?Arg?Ile?Arg?Leu?Asp?Leu

450?????????????????455?????????????????460Trp?Asn?Arg?Tyr?His?Glu?Ser?Phe?Glu?Ser?Leu?Glu?Gln?Arg?Gly?Leu465?????????????????470?????????????????475?????????????????480Leu?Arg?Arg?Pro?Ile?Ile?Pro?Gln?Gly?Cys?Ser?His?Asn?Ala?His?Met

485?????????????????490?????????????????495Tyr?Tyr?Val?Leu?Leu?Ala?Pro?Ser?Ala?Asp?Arg?Glu?Glu?Val?Leu?Ala

500?????????????????505?????????????????510Arg?Leu?Thr?Ser?Glu?Gly?Ile?Gly?Ala?Val?Phe?His?Tyr?Val?Pro?Leu

515?????????????????520?????????????????525His?Asp?Ser?Pro?Ala?Gly?Arg?Arg

The information of 530 535 (2) SEQ ID NO:162:

(i) sequence signature:

(A) length: 284 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: SEQ ID NO:162:Asn Glu Ser Ala Pro Arg Ser Pro Met Leu Pro Ser Ala Arg Pro Arg1 5 10 15Tyr Asp Ala Ile Ala Val Leu Leu Asn Glu Met His Ala Gly His Cys

20??????????????????25??????????????????30Asp?Phe?Gly?Leu?Val?Gly?Pro?Ala?Pro?Asp?Ile?Val?Thr?Asp?Ala?Ala

35??????????????????40??????????????????45Gly?Asp?Asp?Arg?Ala?Gly?Leu?Gly?Val?Asp?Glu?Gln?Phe?Arg?His?Val

50??????????????????55??????????????????60Gly?Phe?Leu?Glu?Pro?Ala?Pro?Val?Leu?Val?Asp?Gln?Arg?Asp?Asp?Leu65??????????????????70??????????????????75??????????????????80Gly?Gly?Leu?Thr?Val?Asp?Trp?Lys?Val?Ser?Trp?Pro?Arg?Gln?Arg?Gly

85??????????????????90??????????????????95Ala?Thr?Val?Leu?Ala?Ala?Val?His?Glu?Trp?Pro?Pro?Ile?Val?Val?His

100?????????????????105?????????????????110Phe?Leu?Val?Ala?Glu?Leu?Ser?Gln?Asp?Arg?Pro?Gly?Gln?His?Pro?Phe

115?????????????????120?????????????????125Asp?Lys?Asp?Val?Val?Leu?Gln?Arg?His?Trp?Leu?Ala?Leu?Arg?Arg?Ser

130?????????????????135?????????????????140Glu?Thr?Leu?Glu?His?Thr?Pro?His?Gly?Arg?Arg?Pro?Val?Arg?Pro?Arg145?????????????????150?????????????????155?????????????????160His?Arg?Gly?Asp?Asp?Arg?Phe?His?Glu?Arg?Asp?Pro?Leu?His?Ser?Val

165?????????????????170?????????????????175Ala?Met?Leu?Val?Ser?Pro?Val?Glu?Ala?Glu?Arg?Arg?Ala?Pro?Val?Val

180?????????????????185?????????????????190Gln?His?Gln?Tyr?His?Val?Val?Ala?Glu?Val?Glu?Arg?Ile?Pro?Glu?Arg

195?????????????????200?????????????????205Glu?Gln?Lys?Val?Ser?Leu?Leu?Ala?Ile?Ala?Ile?Ala?Val?Gly?Ser?Arg

210?????????????????215?????????????????220Trp?Ala?Glu?Leu?Val?Arg?Arg?Ala?His?Pro?Asp?Gln?Ile?Ala?Gly?His225?????????????????230?????????????????235?????????????????240Gln?Pro?Ala?Gln?Pro?Phe?Gln?Val?Arg?His?Asp?Val?Ala?Pro?Gln?Val

245?????????????????250?????????????????255Arg?Arg?Arg?Gly?Val?Ala?Val?Leu?Lys?Asp?Asp?Gly?Val?Thr?Leu?Ala

260?????????????????265?????????????????270Phe?Val?Asp?Ile?Arg?His?Ala?Leu?Pro?Gly?Asp?Phe

The information of 275 280 (2) SEQ ID NO:163:

(i) sequence signature:

(A) length: 264 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: the information of SEQ ID NO:163:ATGAACATGT CGTCGGTGGT GGGTCGCAAG GCCTTTGCGC GATTCGCCGG CTACTCCTCC 60GCCATGCACG CGATCGCCGG TTTCTCCGAT GCGTTGCGCC AAGACCTGCG GGGTAGCGGA 120ATCGCCGTCT CGGTGATCCA CCCGGCGCTG ACCCAGACAC CGCTGTTGGC CAACGTCGAC 180CCCGCCGACA TGCCGCCGCC GTTTCGCAGC CTCACGCCCA TTCCCGTTCA CTGGGTCGCG 240GCAGCGGTGC TTGACGGTGT GGCG 264 (2) SEQ ID NO:164:

(i) sequence signature:

(A) length: 1171 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ, ID, NO:164:TAGTCGGCGA, CGATGACGTC, GCGGTCCAGG, CCGACCGCTT, CAAGCACCAG, CGCGACCACG, 60AAGCCGGTGC, GATCCTTACC, CGCGAAGCAG, TGGGTGAGCA, CCGGGCGTCC, GGCGGCAAGC, 120AGTGTGACGA, CACGATGTAG, CGCGCGCTGT, GCTCCATTGC, GCGTTGGGAA, TTGGCGATAC, 180TCGTCGGTCA, TGTAGCGGGT, GGCCGCGTCA, TTTATCGACT, GGCTGGATTC, GCCGGACTCG, 240CCGTTGGACC, CGTCATTGGT, TAGCAGCCTC, TTGAATGCGG, TTTCGTGCGG, CGCTGAGTCG, 300TCGGCGTCAT, CATCGGCGAG, GTCGGGGAAC, GGCAGCAGGT, GGACGTCGAT, GCCGTCCGGA, 360ACCCGTCCTG, GACCGCGGCG, GGCAACCTCC, CGGGACGACC, GCAGGTCGGC, AACGTCGGTG, 420ATCCCCAGCC, GGCGCAGCGT, TGCCCCTCGT, GCCGAATTCG, GCACGAGGCT, GGCGAGCCAC, 480CGGGCATCAC, CAAGCAACGC, TTGCCCAGTA, CGGATCGTCA, CTTCCGCATC, CGGCAGACCA, 540ATCTCCTCGC, CGCCCATCGT, CAGATCCCGC, TCGTGCGTTG, ACAAGAACGG, CCGCAGATGT, 600GCCAGCGGGT, ATCGGAGATT, GAACCGCGCA, CGCAGTTCTT, CAATCGCTGC, GCGCTGCCGC, 660ACTATTGGCA, CTTTCCGGCG, GTCGCGGTAT, TCAGCAAGCA, TGCGAGTCTC, GACGAACTCG, 720CCCCACGTAA, CCCACGGCGT, AGCTCCCGGC, GTGACGCGGA, GGATCGGCGG, GTGATCTTTG, 780CCGCCACGCT, CGTAGCCGTT, GATCCACCGC, TTCGCGGTGC, CGGCGGGGAG, GCCGATCAGC, 840TTATCGACCT, CGGCGTATGC, CGACGGCAAG, CTGGGCGCGT, TCGTCGAGGT, CAAGAACTCC, 900ACCATCGGCA, CCGGCACCAA, GGTGCCGCAC, CTGACCTACG, TCGGCGACGC, CGACATCGGC, 960GAGTACAGCA, ACATCGGCGC, CTCCAGCGTG, TTCGTCAACT, ACGACGGTAC, GTCCAAACGG, 1020CGCACCACCG, TCGGTTCGCA, CGTACGGACC, GGGTCCGACA, CCATGTTCGT, GGCCCCAGTA, 1080ACCATCGGCG, ACGGCGCGTA, TACCGGGGCC, GGCACAGTGG, TGCGGGAGGA, TGTCCCGCCG, 1140GGGGCGCTGG, CAGTGTCGGC, GGGTCCGCAA, C, 1171, (2) SEQ, ID, the information of NO:165:

(i) sequence signature:

(A) length: 227 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

, (xi) sequence description: SEQ ID NO:165:GCAAAGGCGG CACCGGCGGG GCCGGCATGA ACAGCCTCGA CCCGCTGCTA GCCGCCCAAG 60ACGGCGGCCA AGGCGGCACC GGCGGCACCG GCGGCAACGC CGGCGCCGGC GGCACCAGCT 120TCACCCAAGG CGCCGACGGC AACGCCGGCA ACGGCGGTGA CGGCGGGGTC GGCGGCAACG 180GCGGAAACGG CGGAAACGGC GCAGACAACA CCACCACCGC CGCCGCC 227, (2) information of SEQ ID NO:166:

(i) sequence signature:

(A) length: 304 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 166: CCTCGCCACC ATGGGCGGGC AGGGCGGTAG CGGTGGCGCC GGCTCTACCC CAGGCGCCAA 60GGGCGCCCAC GGCTTCACTC CAACCAGCGG CGGCGACGGC GGCGACGGCG GCAACGGCGG 120CAACTCCCAA GTGGTCGGCG GCAACGGCGG CGACGGCGGC AATGGCGGCA ACGGCGGCAG 180CGCCGGCACG GGCGGCAACG GCGGCCGCGG CGGCGACGGC GCGTTTGGTG GCATGAGTGC 240CAACGCCACC AACCCTGGTG AAAACGGGCC AAACGGTAAC CCCGGCGGCA ACGGTGGCGC 300CGGC 304 (2) SEQ ID NO : 167 information:

(i) sequence signature:

(A) length: 1439 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity, (xi) sequence description: SEQ, ID, NO:167:GTGGGACGCT, GCCGAGGCTG, TATAACAAGG, ACAACATCGA, CCAGCGCCGG, CTCGGTGAGC, 60TGATCGACCT, ATTTAACAGT, GCGCGCTTCA, GCCGGCAGGG, CGAGCACCGC, GCCCGGGATC, 120TGATGGGTGA, GGTCTACGAA, TACTTCCTCG, GCAATTTCGC, TCGCGCGGAA, GGGAAGCGGG, 180GTGGCGAGTT, CTTTACCCCG, CCCAGCGTGG, TCAAGGTGAT, CGTGGAGGTG, CTGGAGCCGT, 240CGAGTGGGCG, GGTGTATGAC, CCGTGCTGCG, GTTCCGGAGG, CATGTTTGTG, CAGACCGAGA, 300AGTTCATCTA, CGAACACGAC, GGCGATCCGA, AGGATGTCTC, GATCTATGGC, CAGGAAAGCA, 360TTGAGGAGAC, CTGGCGGATG, GCGAAGATGA, ACCTCGCCAT, CCACGGCATC, GACAACAAGG, 420GGCTCGGCGC, CCGATGGAGT, GATACCTTCG, CCCGCGACCA, GCACCCGGAC, GTGCAGATGG, 480ACTACGTGAT, GGCCAATCCG, CCGTTCAACA, TCAAAGACTG, GGCCCGCAAC, GAGGAAGACC, 540CACGCTGGCG, CTTCGGTGTT, CCGCCCGCCA, ATAACGCCAA, CTACGCATGG, ATTCAGCACA, 600TCCTGTACAA, CTTGGCGCCG, GGAGGTCGGG, CGGGCGTGGT, GATGGCCAAC, GGGTCGATGT, 660CGTCGAACTC, CAACGGCAAG, GGGGATATTC, GCGCGCAAAT, CGTGGAGGCG, GATTTGGTTT, 720CCTGCATGGT, CGCGTTACCC, ACCCAGCTGT, TCCGCAGCAC, CGGAATCCCG, GTGTGCCTGT, 780GGTTTTTCGC, CAAAAACAAG, GCGGCAGGTA, AGCAAGGGTC, TATCAACCGG, TGCGGGCAGG, 840TGCTGTTCAT, CGACGCTCGT, GAACTGGGCG, ACCTAGTGGA, CCGGGCCGAG, CGGGCGCTGA, 900CCAACGAGGA, GATCGTCCGC, ATCGGGGATA, CCTTCCACGC, GAGCACGACC, ACCGGCAACG, 960CCGGCTCCGG, TGGTGCCGGC, GGTAATGGGG, GCACTGGCCT, CAACGGCGCG, GGCGGTGCTG, 1020GCGGGGCCGG, CGGCAACGCG, GGTGTCGCCG, GCGTGTCCTT, CGGCAACGCT, GTGGGCGGCG, 1080ACGGCGGCAA, CGGCGGCAAC, GGCGGCCACG, GCGGCGACGG, CACGACGGGC, GGCGCCGGCG, 1140GCAAGGGCGG, CAACGGCAGC, AGCGGTGCCG, CCAGCGGCTC, AGGCGTCGTC, AACGTCACCG, 1200CCGGCCACGG, CGGCAACGGC, GGCAATGGCG, GCAACGGCGG, CAACGGCTCC, GCGGGCGCCG, 1260GCGGCCAGGG, CGGTGCCGGC, GGCAGCGCCG, GCAACGGCGG, CCACGGCGGC, GGTGCCACCG, 1320GCGGCGCCAG, CGGCAAGGGC, GGCAACGGCA, CCAGCGGTGC, CGCCAGCGGC, TCAGGCGTCA, 1380TCAACGTCAC, CGCCGGCCAC, GGCGGCAACG, GCGGCAATGG, CCGCAACGGC, GGCAACGGC, 1439, (2) SEQ, ID, the information of NO:168:

(i) sequence signature:

(A) length: 329 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 168: GGGCCGGCGG GGCCGGATTT TCTCGTGCCT TGATTGTCGC TGGGGATAAC GGCGGTGATG 60GTGGTAACGG CGGGATGGGC GGGGCTGGCG GGGCTGGCGG CCCCGGCGGG GCCGGCGGCC 120TGATCAGCCT GCTGGGCGGC CAAGGCGCCG GCGGGGCCGG CGGGACCGGC GGGGCCGGCG 180GTGTTGGCGG TGACGGCGGG GCCGGCGGCC CCGGCAACCA GGCCTTCAAC GCAGGTGCCG 240GCGGGGCCGG CGGCCTGATC AGCCTGCTGG GCGGCCAAGG CGCCGGCGGG GCCGGCGGGA 300CCGGCGGGGC CGGCGGTGTT GGCGGTGAC 329 (2) SEQ ID NO: 169 information:

(i) sequence signature:

(A) length: 80 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: the information of SEQ ID NO:169:GCAACGGTGG CAACGGCGGC ACCAGCACGA CCGTGGGGAT GGCCGGAGGT AACTGTGGTG 60CCGCCGGGCT GATCGGCAAC 80 (2) SEQ ID NO:170:

(i) sequence signature:

(A) length: 392 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 170: GGGCTGTGTC GCACTCACAC CGCCGCATTC GGCGACGTTG GCCGCCCAAT ATCCAGCTCA 60AGGCCTACTA CTTACCGTCG GAGGACCGCC GCATCAAGGT GCGGGTCAGC GCCCAAGGAA 120TCAAGGTCAT CGACCGCGAC GGGCATCGAG GCCGTCGTCG CGCGGCTCGG GCAGGATCCG 180CCCCGGCGCA CTTCGCGCGC CAAGCGGGCT CATCGCTCCG AACGGCGGCG ATCCTGTGAG 240CACAACTGAT GGCGCGCAAC GAGATTCGTC CAATTGTCAA GCCGTGTTCG ACCGCAGGGA 300CCGGTTATAC GTATGTCAAC CTATGTCACT CGCAAGAACC GGCATAACGA TCCCGTGATC 360CGCCGACAGC CCACGAGTGC AAGACCGTTA CA 392 (2) SEQ ID NO: 171 information:

(i) sequence signature:

(A) length: 535 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ, ID, NO:171:ACCGGCGCCA, CCGGCGGCAC, CGGGTTCGCC, GGTGGCGCCG, GCGGGGCCGG, CGGGCAGGGC, 60GGTATCAGCG, GTGCCGGCGG, CACCAACGGC, TCTGGTGGCG, CTGGCGGCAC, CGGCGGACAA, 120GGCGGCGCCG, GGGGCGCTGG, CGGGGCCGGC, GCCGATAACC, CCACCGGCAT, CGGCGGCGCC, 180GGCGGCACCG, GCGGCACCGG, CGGAGCGGCC, GGAGCCGGCG, GGGCCGGTGG, CGCCATCGGT, 240ACCGGCGGCA, CCGGCGGCGC, GGTGGGCAGC, GTCGGTAACG, CCGGGATCGG, CGGTACCGGC, 300GGTACGGGTG, GTGTCGGTGG, TGCTGGTGGT, GCAGGTGCGG, CTGCGGCCGC, TGGCAGCAGC, 360GCTACCGGTG, GCGCCGGGTT, CGCCGGCGGC, GCCGGCGGAG, AAGGCGGACC, GGGCGGCAAC, 420AGCGGTGTGG, GCGGCACCAA, CGGCTCCGGC, GGCGCCGGCG, GTGCAGGCGG, CAAGGGCGGC, 480ACCGGAGGTG, CCGGCGGGTC, CGGCGCGGAC, AACCCCACCG, GTGCTGGTTT, CGCCG, 535, (2) SEQ, ID, the information of NO:172:

(i) sequence signature:

(A) length: 690 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ, ID, NO:172:CCGACGTCGC, CGGGGCGATA, CGGGGGTCAC, CGACTACTAC, ATCATCCGCA, CCGAGAATCG, 60GCCGCTGCTG, CAACCGCTGC, GGGCGGTGCC, GGTCATCGGA, GATCCGCTGG, CCGACCTGAT, 120CCAGCCGAAC, CTGAAGGTGA, TCGTCAACCT, GGGCTACGGC, GACCCGAACT, ACGGCTACTC, 180GACGAGCTAC, GCCGATGTGC, GAACGCCGTT, CGGGCTGTGG, CCGAACGTGC, CGCCTCAGGT, 240CATCGCCGAT, GCCCTGGCCG, CCGGAACACA, AGAAGGCATC, CTTGACTTCA, CGGCCGACCT, 300GCAGGCGCTG, TCCGCGCAAC, CGCTCACGCT, CCCGCAGATC, CAGCTGCCGC, AACCCGCCGA, 360TCTGGTGGCC, GCGGTGGCCG, CCGCACCGAC, GCCGGCCGAG, GTGGTGAACA, CGCTCGCCAG, 420GATCATCTCA, ACCAACTACG, CCGTCCTGCT, GCCCACCGTG, GACATCGCCC, TCGCCTGGTC, 480ACCACCCTGC, CGCTGTACAC, CACCCAACTG, TTCGTCAGGC, AACTCGCTGC, GGGCAATCTG, 540ATCAACGCGA, TCGGCTATCC, CCTGGCGGCC, ACCGTAGGTT, TAGGCACGAT, CGATAGCGGG, 600CGGCGTGGAA, TTGCTCACCC, TCCTCGCGGC, GGCCTCGGAC, ACCGTTCGAA, ACATCGAGGG, 660CCTCGTCACC, TAACGGATTC, CCGACGGCAT, 690, (2) SEQ, ID, the information of NO:173:

(i) sequence signature:

(A) length: 407 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 173: ACGGTGACGG CGGTACTGGC GGCGGCCACG GCGGCAACGG CGGGAATCCC GGGTGGCTCT 60TGGGCACAGC CGGGGGTGGC GGCAACGGTG GCGCCGGCAG CACCGGTACT GCAGGTGGCG 120GCTCTGGGGG CACCGGCGGC GACGGCGGGA CCGGCGGGCG TGGCGGCCTG TTAATGGGCG 180CCGGCGCCGG CGGGCACGGT GGCACTGGCG GCGCGGGCGG TGCCGGTGTC GACGGTGGCG 240GCGCCGGCGG GGCCGGCGGG GCCGGCGGCA ACGGCGGCGC CGGGGGTCAA GCCGCCCTGC 300TGTTCGGGCG CGGCGGCACC GGCGGAGCCG GCGGCTACGG CGGCGATGGC GGTGGCGGCG 360GTGACGGCTT CGACGGCACG ATGGCCGGCC TGGGTGGTAC CGGTGGC 407 (2) SEQ ID NO: 174 information:

(i) sequence signature:

(A) length: 468 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(, xi, ), sequence description: SEQ, ID, NO:174:GATCGGTCAG, CGCATCGCCC, TCGGCGGCAA, GCGATTCCGC, GGTCTCACCG, AAGAACATCG, 60TGCACGCGGC, GGCGCGGACC, AGCCCGCTGC, GCTGCGGCGC, GTCGAACGCC, TCCAGCAGGC, 120ACAGCCAGTC, CTTGGCGGCC, TGCGAGGCGA, ACACGTCGGT, GTCACCGGTG, TAGATCGCCG, 180GGATGCCCGC, CTCCGCCAAC, GCATTCCGGC, ACGCCCGCGC, GTCTTTGTGA, TGCTCGACGA, 240TCACCGCGAT, GTCTGCGGCC, ACCACGGGCC, GCCCGGCGAA, GGTGGCCCCG, CTGGCCAGTA, 300GCGCCGCGAC, GTCGGCGGCC, AGGTCGTCGG, GGATGTGCCG, GCGCAGCGCT, CCGGCGCGAC, 360GCCCGAAAAA, CGACCCCTCA, CCCAGCTGGG, TCCCGCTGGC, ATATCCCTTG, CCGTCCTGGG, 420CGATATTGGA, CGCGCATGCC, CCGACCGCGT, ACAGGCCGGC, CACCACCG, 468, (, 2, ), SEQ, ID, the information of NO:175:

(i) sequence signature:

(A) length: 219 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ ID NO:175:GGTGGTAACG GCGGCCAGGG TGGCATCGGC GGCGCCGGCG AGAGAGGCGC CGACGGCGCC 60GGCCCCAATG CTAACGGCGC AAACGGCGAG AACGGCGGTA GCGGTGGTAA CGGTGGCGAC 120GGCGGCGCCG GCGGCAATGG CGGCGCGGGC GGCAACGCGC AGGCGGCCGG GTACACCGAC 180GGCGCCACGG GCACCGGCGG CGACGGCGGC AACGGCGGC 219, (2) information of SEQ ID NO:176:

(i) sequence signature:

(A) length: 494 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ, ID, NO:176:TAGCTCCGGC, GAGGGCGGCA, AGGGCGGCGA, CGGTGGCCAC, GGCGGTGACG, GCGTCGGCGG, 60CAACAGTTCC, GTCACCCAAG, GCGGCAGCGG, CGGTGGCGGC, GGCGCCGGCG, GCGCCGGCGG, 120CAGCGGCTTT, TTCGGCGGCA, AGGGCGGCTT, CGGCGGCGAC, GGCGGTCAGG, GCGGCCCCAA, 180CGGCGGCGGT, ACCGTCGGCA, CCGTGGCCGG, TGGCGGCGGC, AACGGCGGTG, TCGGCGGCCG, 240GGGCGGCGAC, GGCGTCTTTG, CCGGTGCCGG, CGGCCAGGGC, GGCCTCGGTG, GGCAGGGCGG, 300CAATGGCGGC, GGCTCCACCG, GCGGCAACGG, CGGCCTTGGC, GGCGCGGGCG, GTGGCGGAGG, 360CAACGCCCCG, GCTCGTGCCG, AATCCGGGCT, GACCATGGAC, AGCGCGGCCA, AGTTCGCTGC, 420CATCGCATCA, GGCGCGTACT, GCCCCGAACA, CCTGGAACAT, CACCCGAGTT, AGCGGGGCGC, 480ATTTCCTGAT, CACC, 494, (2) SEQ, ID, the information of NO:177:

(i) sequence signature:

(A) length: 220 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ ID NO:177:GGGCCGGTGG TGCCGCGGGC CAGCTCTTCA GCGCCGGAGG CGCGGCGGGT GCCGTTGGGG 60TTGGCGGCAC CGGCGGCCAG GGTGGGGCTG GCGGTGCCGG AGCGGCCGGC GCCGACGCCC 120CCGCCAGCAC AGGTCTAACC GGTGGTACCG GGTTCGCTGG CGGGGCCCGC GGCGTCGGCG 180GCCAGAGCGG CAACGCCATT GCCGGCGGCA TCAACGGCTC 220, (2) information of SEQ ID NO:178:

(i) sequence signature:

(A) length: 388 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 178: ATGGCGGCAA CGGGGGCCCC GGCGGTGCTG GCGGGGCCGG CGACTACAAT TTCCAACGGC 60GGGCAGGGTG GTGCCGGCGG CCAAGGCGGC CAAGGCGGCC TGGGCGGGGC AAGCACCACC 120TGATCGGCCT AGCCGCACCC GGGAAAGCCG ATCCAACAGG CGACGATGCC GCCTTCCTTG 180CCGCGTTGGA CCAGGCCGGC ATCACCTACG CTGACCCAGG CCACGCCATA ACGGCCGCCA 240AGGCGATGTG TGGGCTGTGT GCTAACGGCG TAACAGGTCT ACAGCTGGTC GCGGACCTGC 300GGGACTACAA TCCCGGGCTG ACCATGGACA GCGCGGCCAA GTTCGCTGCC ATCGCATCAG 360GCGCGTACTG CCCCGAACAC CTGGAACA 388 (2) SEQ ID NO: 179 information:

(i) sequence signature:

(A) length: 400 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 179: GCAAAGGCGG CACCGGCGGG GCCGGCATGA ACAGCCTCGA CCCGCTGCTA GCCGCCCAAG 60ACGGCGGCCA AGGCGGCACC GGCGGCACCG GCGGCAACGC CGGCGCCGGC GGCACCAGCT 120TCACCCAAGG CGCCGACGGC AACGCCGGCA ACGGCGGTGA CGGCGGGGTC GGCGGCAACG 180GCGGAAACGG CGGAAACGGC GCAGACAACA CCACCACCGC CGCCGCCGGC ACCACAGGCG 240GCGACGGCGG GGCCGGCGGG GCCGGCGGAA CCGGCGGAAC CGGCGGAGCC GCCGGCACCG 300GCACCGGCGG CCAACAAGGC AACGGCGGCA ACGGCGGCAC CGGCGGCAAA GGCGGCACCG 360GCGGCGACGG TGCACTCTCA GGCAGCACCG GTGGTGCCGG 400 (2) SEQ ID NO: 180 information:

(i) sequence signature:

(A) length: 538 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ, ID, NO:180:GGCAACGGCG, GCAACGGCGG, CATCGCCGGC, ATTGGGCGGC, AACGGCGTTC, CGGGACGGGC, 60AGCGGCAACG, GCGGCCAACG, GCGGCAGCGG, CGGCAACGGC, GGCAACGCCG, GCATGGGCGG, 120CAACAGCGGC, ACCGGCAGCG, GCGACGGCGG, TGCCGGCGGG, AACGGCGGCG, CGGCGGGCAC, 180GGGCGGCACC, GGCGGCGACG, GCGGCCTCAC, CGGTACTGGC, GGCACCGGCG, GCAGCGGTGG, 240CACCGGCGGT, GACGGCGGTA, ACGGCGGCAA, CGGAGCAGAT, AACACCGCAA, ACATGACTGC, 300GCAGGCGGGC, GGTGACGGTG, GCAACGGCGG, CGACGGTGGC, TTCGGCGGCG, GGGCCGGGGC, 360CGGCGGCGGT, GGCTTGACCG, CTGGCGCCAA, CGGCACCGGC, GGGCAAGGCG, GCGCCGGCGG, 420CGATGGCGGC, AACGGGGCCA, TCGGCGGCCA, CGGCCCACTC, ACTGACGACC, CCGGCGGCAA, 480CGGGGGCACC, GGCGGCAACG, GCGGCACCGG, CGGCACCGGC, GGCGCGGGCA, TCGGCAGC, 538, (2) SEQ, ID, the information of NO:181:

(i) sequence signature:

(A) length: 239 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

, (xi) sequence description: SEQ ID NO:181:GGGCCGGTGG TGCCGCGGGC CAGCTCTTCA GCGCCGGAGG CGCGGCGGGT GCCGTTGGGG 60TTGGCGGCAC CGGCGGCCAG GGTGGGGCTG GCGGTGCCGG AGCGGCCGGC GCCGACGCCC 120CCGCCAGCAC AGGTCTAACC GGTGGTACCG GGTTCGCTGG CGGGGCCGGC GGCGTCGGCG 180GCCACGGCGG CAACGCCATT GCCGGCGGCA TCAACGGCTC CGGTGGTGCC GGCGGCACC 239, (2) information of SEQ ID NO:182:

(i) sequence signature:

(A) length: 985 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ, ID, NO:182:AGCAGCGCTA, CCGGTGGCGC, CGGGTTCGCC, GGCGGCGCCG, GCGGAGAAGG, CGGAGCGGGC, 60GGCAACAGCG, GTGTGGGCGG, CACCAACGGC, TCCGGCGGCG, CCGGCGGTGC, AGGGGGCAAG, 120GGCGGCACCG, GAGGTGCCGG, CGGGTCCGGC, GCGGACAACC, CCACCGGTGC, TGGTTTCGCC, 180GGTGGCGCCG, GCGGCACAGG, TGGCGCGGCC, GGCGCCGGCG, GGGCCGGCGG, GGCGACCGGT, 240ACCGGCGGCA, CCGGCGGCGT, TGTCGGCGCC, ACCGGTAGTG, CAGGCATCGG, CGGGGCCGGC, 300GGCCGCGGCG, GTGACGGCGG, CGATGGGGCC, AGCGGTCTCG, GCCTGGGCCT, CTCCGGCTTT, 360GACGGCGGCC, AAGGCGGCCA, AGGCGGGGCC, GGCGGCAGCG, CCGGCGCCGG, CGGCATCAAC, 420GGGGCCGGCG, GGGCCGGCGG, CAACGGCGGC, GACGGCGGGG, ACGGCGCAAC, CGGTGCCGCA, 480GGTCTCGGCG, ACAACGGCGG, GGTCGGCGGT, GACGGTGGGG, CCGGTGGCGC, CGCCGGCAAC, 540GGCGGCAACG, CGGGCGTCGG, CCTGACAGCC, AAGGCCGGCG, ACGGCGGCGC, CGCGGGCAAT, 600GGCGGCAACG, GGGGCGCCGG, CGGTGCTGGC, GGGGCCGGCG, ACAACAATTT, CAACGGCGGC, 660CAGGGTGGTG, CCGGCGGCCA, AGGCGGCCAA, GGCGGCTTGG, GCGGGGCAAG, CACCACCTGA, 720TCGGCCTAGC, CGCACCCGGG, AAAGCCGATC, CAACAGGCGA, CGATGCCGCC, TTCCTTGCCG, 780CGTTGGACCA, GGCCGGCATC, ACCTACGCTG, ACCCAGGCCA, CGCCATAACG, GCCGCCAAGG, 840CGATGTGTGG, GCTGTGTGCT, AACGGCGTAA, CAGGTCTACA, GCTGGTCGCG, GACCTGCGGG, 900AATACAATCC, CGGGCTGACC, ATGGACAGCG, CGGCCAAGTT, CGCTGCCATC, GCATCAGGCG, 960CGTACTGCCC, CGAACACCTG, GAACA, 985, (2) SEQ, ID, the information of NO:183:

(i) sequence signature:

(A) length: 2138 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ, ID, NO:183:CGGCACGAGG, ATCGGTACCC, CGCGGCATCG, GCAGCTGCCG, ATTCGCCGGG, TTTCCCCACC, 60CGAGGAAAGC, CGCTACCAGA, TGGCGCTGCC, GAAGTAGGGC, GATCCGTTCG, CGATGCCGGC, 120ATGAACGGGC, GGCATCAAAT, TAGTGCAGGA, ACCTTTCAGT, TTAGCGACGA, TAATGGCTAT, 180AGCACTAAGG, AGGATGATCC, GATATGACGC, AGTCGCAGAC, CGTGACGGTG, GATCAGCAAG, 240AGATTTTGAA, CAGGGCCAAC, GAGGTGGAGG, CCCCGATGGC, GGACCCACCG, ACTGATGTCC, 300CCATCACACC, GTGCGAACTC, ACGGCGGCTA, AAAACGCCGC, CCAACAGCTG, GTATTGTCCG, 360CCGACAACAT, GCGGGAATAC, CTGGCGGCCG, GTGCCAAAGA, GCGGCAGCGT, CTGGCGACCT, 420CGCTGCGCAA, CGCGGCCAAG, GCGTATGGCG, AGGTTGATGA, GGAGGCTGCG, ACCGCGCTGG, 480ACAACGACGG, CGAAGGAACT, GTGCAGGCAG, AATCGGCCGG, GGCCGTCGGA, GGGGACAGTT, 540CGGCCGAACT, AACCGATACG, CCGAGGGTGG, CCACGGCCGG, TGAACCCAAC, TTCATGGATC, 600TCAAAGAAGC, GGCAAGGAAG, CTCGAAACGG, GCGACCAAGG, CGCATCGCTC, GCGCACTTTG, 660CGGATGGGTG, GAACACTTTC, AACCTGACGC, TGCAAGGCGA, CGTCAAGCGG, TTCCGGGGGT, 720TTGACAACTG, GGAAGGCGAT, GCGGCTACCG, CTTGCGAGGC, TTCGCTCGAT, CAACAACGGC, 780AATGGATACT, CCACATGGCC, AAATTGAGCG, CTGCGATGGC, CAAGCAGGCT, CAATATGTCG, 840CGCAGCTGCA, CGTGTGGGCT, AGGCGGGAAC, ATCCGACTTA, TGAAGACATA, GTCGGGCTCG, 900AACGGCTTTA, CGCGGAAAAC, CCTTCGGCCC, GCGACCAAAT, TCTCCCGGTG, TACGCGGAGT, 960ATCAGCAGAG, GTCGGAGAAG, GTGCTGACCG, AATACAACAA, CAAGGCAGCC, CTGGAACCGG, 1020TAAACCCGCC, GAAGCCTCCC, CCCGCCATCA, AGATCGACCC, GCCCCCGCCT, CCGCAAGAGC, 1080AGGGATTGAT, CCCTGGCTTC, CTGATGCCGC, CGTCTGACGG, CTCCGGTGTG, ACTCCCGGTA, 1140CCGGGATGCC, AGCCGCACCG, ATGGTTCCGC, CTACCGGATC, GCCGGGTGGT, GGCCTCCCGG, 1200CTGACACGGC, GGCGCAGCTG, ACGTCGGCTG, GGCGGGAAGC, CGCAGCGCTG, TCGGGCGACG, 1260TGGCGGTCAA, AGCGGCATCG, CTCGGTGGCG, GTGGAGGCGG, CGGGGTGCCG, TCGGCGCCGT, 1320TGGGATCCGC, GATCGGGGGC, GCCGAATCGG, TGCGGCCCGC, TGGCGCTGGT, GACATTGCCG, 1380GCTTAGGCCA, GGGAAGGGCC, GGCGGCGGCG, CCGCGCTGGG, CGGCGGTGGC, ATGGGAATGC, 1440CGATGGGTGC, CGCGCATCAG, GGACAAGGGG, GCGCCAAGTC, CAAGGGTTCT, CAGCAGGAAG, 1500ACGAGGCGCT, CTACACCGAG, GATCGGGCAT, GGACCGAGGC, CGTCATTGGT, AACCGTCGGC, 1560GCCAGGACAG, TAAGGAGTCG, AAGTGAGCAT, GGACGAATTG, GACCCGCATG, TCGCCCGGGC, 1620GTTGACGCTG, GCGGCGCGGT, TTCAGTCGGC, CCTAGACGGG, ACGCTCAATC, AGATGAACAA, 1680CGGATCCTTC, CGCGCCACCG, ACGAAGCCGA, GACCGTCGAA, GTGACGATCA, ATGGGCACCA, 1740GTGGCTCACC, CGCCTGCGCA, TCGAAGATGG, TTTGCTGAAG, AAGCTGGGTG, CCGAGGCGGT, 1800GGCTCAGCGG, GTCAACGAGG, CGCTGCACAA, TGCGCAGGCC, GCGGCGTCCG, CGTATAACGA, 1860CGCGGCGGGC, GAGCAGCTGA, CCGCTGCGTT, ATCGGCCATG, TCCCGCGCGA, TGAACGAAGG, 1920AATGGCCTAA, GCCCATTGTT, GCGGTGGTAG, CGACTACGCA, CCGAATGAGC, GCCGCAATGC, 1980GGTCATTCAG, CGCGCCCGAC, ACGGCGTGAG, TACGCATTGT, CAATGTTTTG, ACATGGATCG, 2040GCCGGGTTCG, GAGGGCGCCA, TAGTCCTGGT, CGCCAATATT, GCCGCAGCTA, GCTGGTCTTA, 2100GGTTCGGTTA, CGCTGGTTAA, TTATGACGTC, CGTTACCA, 2138, (2) SEQ, ID, the information of NO:184:

(i) sequence signature:

(A) length: 460 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linearity

(xi) sequence description: SEQ ID NO:184:Met Thr Gln Ser Gln Thr Val Thr Val Asp Gln Gln Glu Ile Leu Asn1 5 10 15Arg Ala Asn Glu Val Glu Ala Pro Mat Ala Asp Pro Pro Thr Asp Val

20??????????????????25??????????????????30Pro?Ile?Thr?Pro?Cys?Glu?Leu?Thr?Ala?Ala?Lys?Asn?Ala?Ala?Gln?Gln

35??????????????????40??????????????????45Leu?Val?Leu?Ser?Ala?Asp?Asn?Met?Arg?Glu?Tyr?Leu?Ala?Ala?Gly?Ala

50??????????????????55??????????????????60Lys?Glu?Arg?Gln?Arg?Leu?Ala?Thr?Ser?Leu?Arg?Asn?Ala?Ala?Lys?Ala65???????????????????70??????????????????75??????????????????80Tyr?Gly?Glu?Val?Asp?Glu?Glu?Ala?Ala?Thr?Ala?Leu?Asp?Asn?Asp?Gly

85??????????????????90??????????????????95Glu?Gly?Thr?Val?Gln?Ala?Glu?Ser?Ala?Gly?Ala?Val?Gly?Gly?Asp?Ser

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

115?????????????????120?????????????????125Asn?Phe?Met?Asp?Leu?Lys?Glu?Ala?Ala?Arg?Lys?Leu?Glu?Thr?Gly?Asp

130?????????????????135?????????????????140???Gln?Gly?Ala?Ser?Leu?Ala?His?Phe?Ala?Asp?Gly?Trp?Asn?Thr?Phe?Asn???145?????????????????150?????????????????155?????????????????160???Leu?Thr?Leu?Gln?Gly?Asp?Val?Lys?Arg?Phe?Arg?Gly?Phe?Asp?Asn?Trp

165?????????????????170?????????????????175???Glu?Gly?Asp?Ala?Ala?Thr?Ala?Cys?Glu?Ala?Ser?Leu?Asp?Gln?Gln?Arg

180?????????????????185?????????????????190???Gln?Trp?Ile?Leu?His?Met?Ala?Lys?Leu?Ser?Ala?Ala?Met?Ala?Lys?Gln

195?????????????????200?????????????????205???Ala?Gln?Tyr?Val?Ala?Gln?Leu?His?Val?Trp?Ala?Arg?Arg?Glu?His?Pro

210?????????????????215?????????????????220???Thr?Tyr?Glu?Asp?Ile?Val?Gly?Leu?Glu?Arg?Leu?Tyr?Ala?Glu?Asn?Pro???225?????????????????230?????????????????235?????????????????240???Ser?Ala?Arg?Asp?Gln?Ile?Leu?Pro?Val?Tyr?Ala?Glu?Tyr?Gln?Gln?Arg

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

260?????????????????265?????????????????270???Val?Asn?Pro?Pro?Lys?Pro?Pro?Pro?Ala?Ile?Lys?Ile?Asp?Pro?Pro?Pro

275?????????????????280?????????????????285???Pro?Pro?Gln?Glu?Gln?Gly?Leu?Ile?Pro?Gly?Phe?Leu?Met?Pro?Pro?Ser

290?????????????????295?????????????????300???Asp?Gly?Ser?Gly?Val?Thr?Pro?Gly?Thr?Gly?Met?Pro?Ala?Ala?Pro?Met???305?????????????????310?????????????????315?????????????????320???Val?Pro?Pro?Thr?Gly?Ser?Pro?Gly?Gly?Gly?Leu?Pro?Ala?Asp?Thr?Ala

325?????????????????330?????????????????335???Ala?Gln?Leu?Thr?Ser?Ala?Gly?Arg?Glu?Ala?Ala?Ala?Leu?Ser?Gly?Asp

340?????????????????345?????????????????350???Val?Ala?Val?Lys?Ala?Ala?Ser?Leu?Gly?Gly?Gly?Gly?Gly?Gly?Gly?Val

355?????????????????360?????????????????365???Pro?Ser?Ala?Pro?Leu?Gly?Ser?Ala?Ile?Gly?Gly?Ala?Glu?Ser?Val?Arg

370?????????????????375?????????????????380???Pro?Ala?Gly?Ala?Gly?Asp?Ile?Ala?Gly?Leu?Gly?Gln?Gly?Arg?Ala?Gly???385?????????????????390?????????????????395?????????????????400???Gly?Gly?Ala?Ala?Leu?Gly?Gly?Gly?Gly?Met?Gly?Met?Pro?Met?Gly?Ala

405?????????????????410?????????????????415???Ala?His?Gln?Gly?Gln?Gly?Gly?Ala?Lys?Ser?Lys?Gly?Ser?Gln?Gln?Glu

420?????????????????425?????????????????430???Asp?Glu?Ala?Leu?Tyr?Thr?Glu?Asp?Arg?Ala?Trp?Thr?Glu?Ala?Val?Ile

435?????????????????440?????????????????445???Gly?Asn?Arg?Arg?Arg?Gln?Asp?Ser?Lys?Glu?Ser?Lys

450 455 460 (2) INFORMATION FOR SEQ ID NO:185:(2) information of SEQ ID NO:185:

(i) sequence signature:

(A) length: 277 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linearity

(xi) sequence description: SEQ ID NO:185:Ala Gly Asn Val Thr Ser Ala Ser Gly Pro His Arg Phe Gly Ala Pro1 5 10 15Asp Arg Gly Ser Gln Arg Arg Arg Arg His Pro Ala Ala Ser Thr Ala

20??????????????????25??????????????????30Thr?Glu?Arg?Cys?Arg?Phe?Asp?Arg?His?Val?Ala?Arg?Gln?Arg?Cys?Gly

35??????????????????40??????????????????45Phe?Pro?Pro?Ser?Arg?Arg?Gln?Leu?Arg?Arg?Arg?Val?Ser?Arg?Glu?Ala

50??????????????????55??????????????????60Thr?Thr?Arg?Arg?Ser?Gly?Arg?Arg?Asn?His?Arg?Cys?Gly?Trp?His?Pro65???????????????????70??????????????????75??????????????????80Gly?Thr?Gly?Ser?His?Thr?Gly?Ala?Val?Arg?Arg?Arg?His?Gln?Glu?Ala

85??????????????????90??????????????????95Arg?Asp?Gln?Ser?Leu?Leu?Leu?Arg?Arg?Arg?Gly?Arg?Val?Asp?Leu?Asp

100?????????????????105?????????????????110Gly?Gly?Gly?Arg?Leu?Arg?Arg?Val?Tyr?Arg?Phe?Gln?Gly?Cys?Leu?Val

115?????????????????120?????????????????125Val?Val?Phe?Gly?Gln?His?Leu?Leu?Arg?Pro?Leu?Leu?Ile?Leu?Arg?Val

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

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

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

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

210?????????????????215?????????????????220Pro?Leu?Asp?Val?Ala?Leu?Gln?Arg?Gln?Val?Glu?Ser?Val?Pro?Pro?Ile225?????????????????230?????????????????235?????????????????240Arg?Lys?Val?Arg?Glu?Arg?Cys?Ala?Leu?Val?Ala?Arg?Phe?Glu?Leu?Pro

245?????????????????250?????????????????255Cys?Arg?Phe?Phe?Glu?Ile?His?Glu?Val?Gly?Phe?Thr?Gly?Arg?Gly?His

260????????????????265?????????????????270Pro?Arg?Arg?Ile?Gly

The information of 275 (2) SEQ ID NO:186:

(i) sequence signature:

(A) length: 192 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linearity

(xi) sequence description: SEQ ID NO:186:Arg Val Ala Ala Ser Phe Ile Asp Trp Leu Asp Ser Pro Asp Ser Pro1 5 10 15Leu Asp Pro Ser Leu Val Ser Ser Leu Leu Asn Ala Val Ser Cys Gly

20??????????????????25??????????????????30Ala?Glu?Ser?Ser?Ala?Ser?Ser?Ser?Ala?Arg?Ser?Gly?Asn?Gly?Ser?Arg

35??????????????????40??????????????????45Trp?Thr?Ser?Met?Pro?Ser?Gly?Thr?Arg?Pro?Gly?Pro?Arg?Arg?Ala?Thr

50??????????????????55??????????????????60Ser?Arg?Asp?Asp?Arg?Arg?Ser?Ala?Thr?Ser?Val?Ile?Pro?Ser?Arg?Arg65??????????????????70??????????????????75??????????????????80Ser?Val?Ala?Pro?Arg?Ala?Glu?Phe?Gly?Thr?Arg?Leu?Ala?Ser?His?Arg

85??????????????????90??????????????????95Ala?Ser?Pro?Ser?Asn?Ala?Cys?Pro?Val?Arg?Ile?Val?Thr?Ser?Ala?Ser

100?????????????????105?????????????????110Gly?Arg?Pro?Ile?Ser?Ser?Pro?Pro?Ile?Val?Arg?Ser?Arg?Ser?Cys?Val

115?????????????????120?????????????????125Asp?Lys?Asn?Gly?Arg?Arg?Cys?Ala?Ser?Gly?Tyr?Arg?Arg?Leu?Asn?Arg

130?????????????????135?????????????????140Ala?Arg?Ser?Ser?Ser?Ile?Ala?Ala?Arg?Cys?Arg?Thr?Ile?Gly?Thr?Phe145?????????????????150?????????????????155?????????????????160Arg?Arg?Ser?Arg?Tyr?Ser?Ala?Ser?Met?Arg?Val?Ser?Thr?Asn?Ser?Pro

165?????????????????170?????????????????175His?Val?Thr?His?Gly?Val?Ala?Pro?Gly?Val?Thr?Arg?Arg?Ile?Gly?Gly

The information of 180 185 190 (2) SEQ ID NO:187:

(i) sequence signature:

(A) length: 196 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linearity

(xi) sequence description: SEQ ID NO:187:Gln Glu Arg Pro Gln Met Cys Gln Arg Val Ser Glu Ile Glu Pro Arg1 5 10 15Thr Gln Phe Phe Asn Arg Cys Ala Leu Pro His Tyr Trp His Phe Pro

20??????????????????25??????????????????30Ala?Val?Ala?Val?Phe?Ser?Lys?His?Ala?Ser?Leu?Asp?Glu?Leu?Ala?Pro

35??????????????????40??????????????????45Arg?Asn?Pro?Arg?Arg?Ser?Ser?Arg?Arg?Asp?Ala?Glu?Asp?Arg?Arg?Val

50??????????????????55??????????????????60Ile?Phe?Ala?Ala?Thr?Leu?Val?Ala?Val?Asp?Pro?Pro?Leu?Arg?Gly?Ala5???????????????????70??????????????????75??????????????????80Gly?Gly?Glu?Ala?Asp?Gln?Leu?Ile?Asp?Leu?Gly?Val?Cys?Arg?Arg?Gln

85??????????????????90??????????????????95Ala?Gly?Arg?Val?Arg?Arg?Gly?Gln?Glu?Leu?His?His?Arg?His?Arg?His

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

115?????????????????120?????????????????125Gln?Gln?His?Arg?Arg?Leu?Gln?Arg?Val?Arg?Gln?Leu?Arg?Arg?Tyr?Val

130?????????????????135?????????????????140Gln?Thr?Ala?His?His?Arg?Arg?Phe?Ala?Arg?Thr?Asp?Arg?Val?Arg?His145?????????????????150?????????????????155?????????????????160His?Val?Arg?Gly?Pro?Ser?Asn?His?Arg?Arg?Arg?Arg?Val?Tyr?Arg?Gly

165?????????????????170?????????????????175Arg?His?Ser?Gly?Ala?Gly?Gly?Cys?Pro?Ala?Gly?Gly?Ala?Gly?Ser?Val

180?????????????????185?????????????????190Gly?Gly?Ser?Ala

The information of 195 (2) SEQ ID NO:188:

(i) sequence signature:

(A) length: 311 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linearity

(xi) sequence description: SEQ ID NO:188:Val Arg Cys Gly Thr Leu Val Pro Val Pro Met Val Glu Phe Leu Thr1 5 10 15Ser Thr Asn Ala Pro Ser Leu Pro Ser Ala Tyr Ala Glu Val Asp Lys

20??????????????????25??????????????????30Leu?Ile?Gly?Leu?Pro?Ala?Gly?Thr?Ala?Lys?Arg?Trp?Ile?Asn?Gly?Tyr

35??????????????????40??????????????????45Glu?Arg?Gly?Gly?Lys?Asp?His?Pro?Pro?Ile?Leu?Arg?Val?Thr?Pro?Gly

50??????????????????55??????????????????60Ala?Thr?Pro?Trp?Val?Thr?Trp?Gly?Glu?Phe?Val?Glu?Thr?Arg?Met?Leu65??????????????????70??????????????????75??????????????????80Ala?Glu?Tyr?Arg?Asp?Arg?Arg?Lys?Val?Pro?Ile?Val?Arg?Gln?Arg?Ala

85??????????????????90??????????????????95Ala?Ile?Glu?Glu?Leu?Arg?Ala?Arg?Phe?Asn?Leu?Arg?Tyr?Pro?Leu?Ala

100?????????????????105?????????????????110His?Leu?Arg?Pro?Phe?Leu?Ser?Thr?His?Glu?Arg?Asp?Leu?Thr?Met?Gly

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

130?????????????????135?????????????????140Gln?Ala?Leu?Leu?Gly?Asp?Ala?Arg?Trp?Leu?Ala?Ser?Leu?Val?Pro?Asn145?????????????????150?????????????????155?????????????????160Ser?Ala?Arg?Gly?Ala?Thr?Leu?Arg?Arg?Leu?Gly?Ile?Thr?Asp?Val?Ala

165?????????????????170?????????????????175Asp?Leu?Arg?Ser?Ser?Arg?Glu?Val?Ala?Arg?Arg?Gly?Pro?Gly?Arg?Val

180?????????????????185?????????????????190Pro?Asp?Gly?Ile?Asp?Val?His?Leu?Leu?Pro?Phe?Pro?Asp?Leu?Ala?Asp

195?????????????????200?????????????????205Asp?Asp?Ala?Asp?Asp?Ser?Ala?Pro?His?Glu?Thr?Ala?Phe?Lys?Arg?Leu

210?????????????????215?????????????????220Leu?Thr?Asn?Asp?Gly?Ser?Asn?Gly?Glu?Ser?Gly?Glu?Ser?Ser?Gln?Ser225?????????????????230?????????????????235?????????????????240Ile?Asn?Asp?Ala?Ala?Thr?Arg?Tyr?Met?Thr?Asp?Glu?Tyr?Arg?Gln?Phe

245?????????????????250?????????????????255Pro?Thr?Arg?Asn?Gly?Ala?Gln?Arg?Ala?Leu?His?Arg?Val?Val?Thr?Leu

260?????????????????265?????????????????270Leu?Ala?Ala?Gly?Arg?Pro?Val?Leu?Thr?His?Cys?Phe?Ala?Gly?Lys?Asp

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

The information of 290 295 300Arg Asp Val Ile Val Ala Asp305,310 (2) SEQ ID NO:189:

(i) sequence signature:

(A) length: 2072 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ, ID, NO:189:CTCGTGCCGA, TTCGGCACGA, GCTGAGCAGC, CCAAGGGGCC, GTTCGGCGAA, GTCATCGAGG, 60CATTCGCCGA, CGGGCTGGCC, GGCAAGGGTA, AGCAAATCAA, CACCACGCTG, AACAGCCTGT, 120CGCAGGCGTT, GAACGCCTTG, AATGAGGGCC, GCGGCGACTT, CTTCGCGGTG, GTACGCAGCC, 180TGGCGCTATT, CGTCAACGCG, CTACATCAGG, ACGACCAACA, GTTCGTCGCG, TTGAACAAGA, 240ACCTTGCGGA, GTTCACCGAC, AGGTTGACCC, ACTCCGATGC, GGACCTGTCG, AACGCCATCC, 300AGCAATTCGA, CAGCTTGCTC, GCCGTCGCGC, GCCCGTTCTT, CGCCAAGAAC, CGCGAGGTGC, 360TGACGCATGA, CGTCAATAAT, CTCGCGACCG, TGACCACCAC, GTTGCTGCAG, CCCGATCCGT, 420TGGATGGGTT, GGAGACCGTC, CTGCACATCT, TCCCGACGCT, GGCGGCGAAC, ATTAACCAGC, 480TTTACCATCC, GACACACGGT, GGCGTGGTGT, CGCTTTCCGC, GTTCACGAAT, TTCGCCAACC, 540CGATGGAGTT, CATCTGCAGC, TCGATTCAGG, CGGGTAGCCG, GCTCGGTTAT, CAAGAGTCGG, 600CCGAACTCTG, TGCGCAGTAT, CTGGCGCCAG, TCCTCGATGC, GATCAAGTTC, AACTACTTTC, 660CGTTCGGCCT, GAACGTGGCC, AGCACCGCCT, CGACACTGCC, TAAAGAGATC, GCGTACTCCG, 720AGCCCCGCTT, GCAGCCGCCC, AACGGGTACA, AGGACACCAC, GGTGCCCGGC, ATCTGGGTGC, 780CGGATACGCC, GTTGTCACAC, CGCAACACGC, AGCCCGGTTG, GGTGGTGGCA, CCCGGGATGC, 840AAGGGGTTCA, GGTGGGACCG, ATCACGCAGG, GTTTGCTGAC, GCCGGAGTCC, CTGGCCGAAC, 900TCATGGGTGG, TCCCGATATC, GCCCCTCCGT, CGTCAGGGCT, GCAAACCCCG, CCCGGACCCC, 960CGAATGCGTA, CGACGAGTAC, CCCGTGCTGC, CGCCGATCGG, TTTACAGGCC, CCACAGGTGC, 1020CGATACCACC, GCCGCCTCCT, GGGCCCGACG, TAATCCCGGG, TCCGGTGCCA, CCGGTCTTGG, 1080CGGCGATCGT, GTTCCCAAGA, GATCGCCCGG, CAGCGTCGGA, AAACTTCGAC, TACATGGGCC, 1140TCTTGTTGCT, GTCGCCGGGC, CTGGCGACCT, TCCTGTTCGG, GGTGTCATCT, AGCCCCGCCC, 1200GTGGAACGAT, GGCCGATCGG, CACGTGTTGA, TACCGGCGAT, CACCGGCCTG, GCGTTGATCG, 1260CGGCATTCGT, CGCACATTCG, TGGTACCGCA, CAGAACATCC, GCTCATAGAC, ATGCGCTTGT, 1320TCCAGAACCG, AGCGGTCGCG, CAGGCCAACA, TGACGATGAC, GGTGCTCTCC, CTCGGGCTGT, 1380TTGGCTCCTT, CTTGCTGCTC, CCGAGCTACC, TCCAGCAAGT, GTTGCACCAA, TCACCGATGC, 1440AATCGGGGGT, GCATATCATC, CCACAGGGCC, TCGGTGCCAT, GCTGGCGATG, CCGATCGCCG, 1500GAGCGATGAT, GGACCGACGG, GGACCGGCCA, AGATCGTGCT, GGTTGGGATC, ATGCTGATCG, 1560CTGCGGGGTT, GGGCACCTTC, GCCTTTGGTG, TCGCGCGGCA, AGCGGACTAC, TTACCCATTC, 1620TGCCGACCGG, GCTGGCAATC, ATGGGCATGG, GCATGGGCTG, CTCCATGATG, CCACTGTCCG, 1680GGGCGGCAGT, GCAGACCCTG, GCCCCACATC, AGATCGCTCG, CGGTTCGACG, CTGATCAGCG, 1740TCAACCAGCA, GGTGGGCGGT, TCGATAGGGA, CCGCACTGAT, GTCGGTGCTG, CTCACCTACC, 1800AGTTCAATCA, CAGCGAAATC, ATCGCTACTG, CAAAGAAAGT, CGCACTGACC, CCAGAGAGTG, 1860GCGCCGGGCG, GGGGGCGGCG, GTTGACCCTT, CCTCGCTACC, GCGCCAAACC, AACTTCGCGG, 1920CCCAACTGCT, GCATGACCTT, TCGCACGCCT, ACGCGGTGGT, ATTCGTGATA, GCGACCGCGC, 1980TAGTGGTCTC, GACGCTGATC, CCCGCGGCAT, TCCTGCCGAA, ACAGCAGGCT, AGTCATCGAA, 2040GAGCACCGTT, GCTATCCGCA, TGACGTCTGC, TT, 2072, (2) SEQ, ID, the information of NO:190:

(i) sequence signature:

(A) length: 1923 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ, ID, NO:190:TCACCCCGGA, GAAGTCGTTC, GTCGACGACC, TGGACATCGA, CTCGCTGTCG, ATGGTCGAGA, 60TCGCCGTGCA, GACCGAGGAC, AAGTACGGCG, TCAAGATCCC, CGACGAGGAC, CTCGCCGGTC, 120TGCGTACCGT, CGGTGACGTT, GTCGCCTACA, TCCAGAAGCT, CGAGGAAGAA, AACCCGGAGG, 180CGGCTCAGGC, GTTGCGCGCG, AAGATTGAGT, CGGAGAACCC, CGATGCGGCA, CGAGCAGATC, 240GGTGCGTTTC, ACCCACATCG, CAAGCTCGAG, ACGCCCGTCG, TCCTCTTGCA, CGCTCAGCCA, 300GGTTGGCGTG, TCGCCGCCTT, CCAGCAAGTG, TTCCCACCAC, ACGAAGGGAC, CCTCGCGAAA, 360GGTGACTGAT, CCGCGGACCA, CATAGTCGAT, GCCACCGTGG, CTGACAATTG, CGCCGGGTCC, 420GAGTTGGCGG, GGGCCGAATT, GCGGCATTGC, GTCGAAGGCC, AGCGGATCCC, GGCGCCCGCC, 480CGGCGTGGCT, GGTGTTTTGG, GCCGCCGGAT, GGCCACGACG, AGAACGACGA, TGGCGGCGAT, 540GAACAGCGCC, ACGGCAATCA, CGACCAGCAG, ATTTCCCACG, CATACCCTCT, CGTACCGCTG, 600CGCCGCGGTT, GGTCGATCGG, TCGCATATCG, ATGGCGCCGT, TTAACGTAAC, AGCTTTCGCG, 660GGACCGGGGG, TCACAACGGG, CGAGTTGTCC, GGCCGGGAAC, CCGGCAGGTC, TCGGCCGCGG, 720TCACCCCAGC, TCACTGGTGC, ACCATCCGGG, TGTCGGTGAG, CGTGCAACTC, AAACACACTC, 780AACGGCAACG, GTTTCTCAGG, TCACCAGCTC, AACCTCGACC, CGCAATCGCT, CGTACGTTTC, 840GACCGCGCGC, AGGTCGCGAG, TCAGCAGCTT, TGCGCCGGCA, GCTTTCGCCG, TGAAGCCGAC, 900CAGGGCATCG, TAGGTTGCGC, CACCGGTGAC, ATCGTGCTCG, GCGAGGTGGT, CGGTCAAGCC, 960GCGATATGAG, CAGGCATCCA, GTGCCAGGTA, GTTGCTGGAG, GTGATGTCCG, CCAAGTAGGC, 1020GTGGACGGCA, ACAGGGGCAA, TACGATGCGG, CGGTGGTAGC, CGGGTCAAGA, CCGAATAGGT, 1080TTCCACAGCC, GCGTGCGCGA, TCAGATGGAC, GCCACGGTTG, AGCGCGCGCA, CGGCGGCCTC, 1140GTGCCCTTCG, TGCCAGGTCG, CGAATCCGGC, AACCAGCACG, CTGGTGTCTG, GTGCGATCAC, 1200CGCCGTGTGC, GATCGAGCGT, TTCCCGAACG, ATTTCGTCGG, TCAACGGGGG, CAGGGGACGT, 1260TCTGGCCGTG, CGACGAGAAC, CGAGCCTTCC, CGAACGAGTT, CGACACCGGT, CGGGGCCGGC, 1320TCAATCTCGA, TGCGCCCATC, GCGCTCGGTG, ATCTCCACCT, GGTCGTTCCC, GCGCAAGCCA, 1380AGGCGCTCGC, GAATCCGCTT, GGGAATCACC, AGACGTCCTG, CGACATCGAT, GGTTGTTCGC, 1440ATGGTAGGAA, ATTTACCATC, GCACGTTCCA, TAGGCGTGTC, CTGCGCGGGA, TGTCGGGACG, 1500ATCCGCTAGC, GTATCGAACG, ATTGTTTCGG, AAATGGCTGA, GGGAGCGTGC, GGTGCGGGTG, 1560ATGGGTGTCG, ATCCCGGGTT, GACCCGATGC, GGGCTGTCGC, TCATCGAGAG, TGGGCGTGGT, 1620CGGCAGCTCA, CCGCGCTGGA, TGTCGACGTG, GTGCGCACAC, CGTCGGATGC, GGCCTTGGCG, 1680CAGCGCCTGT, TGGCCATCAG, CGATGCCGTC, GAGCACTGGC, TGGACACCCA, TCATCCGGAG, 1740GTGGTGGCTA, TCGAACGGGT, GTTCTCTCAG, CTCAACGTGA, CCACGGTGAT, GGGCACCGCG, 1800CAGGCCGGCG, GCGTGATCGC, CCTGGCGGCG, GCCAAACGTG, GTGTCGACGT, GCATTTCCAT, 1860ACCCCCAGCG, AGGTCAAGGC, GGCGGTCACT, GGCAACGGTT, CCGCAGACAA, GGCTCAGGTC, 1920ACC, 1923, (2) SEQ, ID, the information of NO:191:

(i) sequence signature:

(A) length: 1055 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ, ID, NO:191:CTGGCGTGCC, AGTGTCACCG, GCGATATGAC, GTCGGCATTC, AATTTCGCGG, CCCCGCCGGA, 60CCCGTCGCCA, CCCAATCTGG, ACCACCCGGT, CCGTCAATTG, CCGAAGGTCG, CCAAGTGCGT, 120GCCCAATGTG, GTGCTGGGTT, TCTTGAACGA, AGGCCTGCCG, TATCGGGTGC, CCTACCCCCA, 180AACAACGCCA, GTCCAGGAAT, CCGGTCCCGC, GCGGCCGATT, CCCAGCGGCA, TCTGCTAGCC, 240GGGGATGGTT, CAGACGTAAC, GGTTGGCTAG, GTCGAAACCC, GCGCCAGGGC, CGCTGGACGG, 300GCTCATGGCA, GCGAAATTAG, AAAACCCGGG, ATATTGTCCG, CGGATTGTCA, TACGATGCTG, 360AGTGCTTGGT, GGTTCGTGTT, TAGCCATTGA, GTGTGGATGT, GTTGAGACCC, TGGCCTGGAA, 420GGGGACAACG, TGCTTTTGCC, TCTTGGTCCG, CCTTTGCCGC, CCGACGCGGT, GGTGGCGAAA, 480CGGGCTGAGT, CGGGAATGCT, CGGCGGGTTG, TCGGTTCCGC, TCAGCTGGGG, AGTGGCTGTG, 540CCACCCGATG, ATTATGACCA, CTGGGCGCCT, GCGCCGGAGG, ACGGCGCCGA, TGTCGATGTC, 600CAGGCGGCCG, AAGGGGCGGA, CGCAGAGGCC, GCGGCCATGG, ACGAGTGGGA, TGAGTGGCAG, 660GCGTGGAACG, AGTGGGTGGC, GGAGAACGCT, GAACCCCGCT, TTGAGGTGCC, ACGGAGTAGC, 720AGCAGCGTGA, TTCCGCATTC, TCCGGCGGCC, GGCTAGGAGA, GGGGGCGCAG, ACTGTCGTTA, 780TTTGACCAGT, GATCGGCGGT, CTCGGTGTTC, CCGCGGCCGG, CTATGACAAC, AGTCAATGTG, 840CATGACAAGT, TACAGGTATT, AGGTCCAGGT, TCAACAAGGA, GACAGGCAAC, ATGGCAACAC, 900GTTTTATGAC, GGATCCGCAC, GCGATGCGGG, ACATGGCGGG, CCGTTTTGAG, GTGCACGCCC, 960AGACGGTGGA, GGACGAGGCT, CGCCGGATGT, GGGCGTCCGC, GCAAAACATC, TCGGGNGCGG, 1020GCTGGAGTGG, CATGGCCGAG, GCGACCTCGC, TAGAC, 1055, (2) SEQ, ID, the information of NO:192:

(i) sequence signature:

(A) length: 359 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 192: CCGCCTCGTT GTTGGCATAC TCCGCCGCGG CCGCCTCGAC CGCACTGGCC GTGGCGTGTG 60TCCGGGCTGA CCACCGGGAT CGCCGAACCA TCCGAGATCA CCTCGCAATG ATCCACCTCG 120CGCAGCTGGT CACCCAGCCA CCGGGCGGTG TGCGACAGCG CCTGCATCAC CTTGGTATAG 180CCGTCGCGCC CCAGCCGCAG GAAGTTGTAG TACTGGCCCA CCACCTGGTT ACCGGGACGG 240GAGAAGTTCA GGGTGAAGGT CGGCATGTCG CCGCCGAGGT AGTTGACCCG GAAAACCAGA 300TCCTCCGGCA GGTGCTCGGG CCCGCGCCAC ACGACAAACC CGACGCCGGG ATAGGTCAG 359 (2) SEQ ID NO: 193 information:

(i) sequence signature:

(A) length: 350 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 193: AACGGGCCCG TGGGCACCGC TCCTCTAAGG GCTCTCGTTG GTCGCATGAA GTGCTGGAAG 60GATGCATCTT GGCAGATTCC CGCCAGAGCA AAACAGCCGC TAGTCCTAGT CCGAGTCGCC 120CGCAAAGTTC CTCGAATAAC TCCGTACCCG GAGCGCCAAA CCGGGTCTCC TTCGCTAAGC 180TGCGCGAACC ACTTGAGGTT CCGGGACTCC TTGACGTCCA GACCGATTCG TTCGAGTGGC 240TGATCGGTTC GCCGCGCTGG CGCGAATCCG CCGCCGAGCG GGGTGATGTC AACCCAGTGG 300GTGGCCTGGA AGAGGTGCTC TACGAGCTGT CTCCGATCGA GGACTTCTCC 350 (2 ) SEQ ID NO: 194 information:

(i) sequence signature:

(A) length: 679 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linearity

(xi) sequence description: SEQ ID NO:194:Glu Gln Pro Lys Gly Pro Phe Gly Glu Val Ile Glu Ala Phe Ala Asp1 5 10 15Gly Leu Ala Gly Lys Gly Lys Gln Ile Asn Thr Thr Leu Asn Ser Leu

20??????????????????25??????????????????30Ser?Gln?Ala?Leu?Asn?Ala?Leu?Asn?Glu?Gly?Arg?Gly?Asp?Phe?Phe?Ala

35??????????????????40??????????????????45Val?Val?Arg?Ser?Leu?Ala?Leu?Phe?Val?Asn?Ala?Leu?His?Gln?Asp?Asp

50??????????????????55??????????????????60Gln?Gln?Phe?Val?Ala?Leu?Asn?Lys?Asn?Leu?Ala?Glu?Phe?Thr?Asp?Arg65??????????????????70??????????????????75??????????????????80Leu?Thr?His?Ser?Asp?Ala?Asp?Leu?Ser?Asn?Ala?Ile?Gln?Gln?Phe?Asp

85??????????????????90??????????????????95Ser?Leu?Leu?Ala?Val?Ala?Arg?Pro?Phe?Phe?Ala?Lys?Asn?Arg?Glu?Val

100?????????????????105?????????????????110Leu?Thr?His?Asp?Val?Asn?Asn?Leu?Ala?Thr?Val?Thr?Thr?Thr?Leu?Leu

115?????????????????120?????????????????125Gln?Pro?Asp?Pro?Leu?Asp?Gly?Leu?Glu?Thr?Val?Leu?His?Ile?Phe?Pro

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

165?????????????????170?????????????????175Ile?Cys?Ser?Ser?Ile?Gln?Ala?Gly?Ser?Arg?Leu?Gly?Tyr?Gln?Glu?Ser

180?????????????????185?????????????????190Ala?Glu?Leu?Cys?Ala?Gln?Tyr?Leu?Ala?Pro?Val?Leu?Asp?Ala?Ile?Lys

195?????????????????200?????????????????205Phe?Asn?Tyr?Phe?Pro?Phe?Gly?Leu?Asn?Val?Ala?Ser?Thr?Ala?Ser?Thr

210?????????????????215?????????????????220Leu?Pro?Lys?Glu?Ile?Ala?Tyr?Ser?Glu?Pro?Arg?Leu?Gln?Pro?Pro?Asn225?????????????????230?????????????????235?????????????????240Gly?Tyr?Lys?Asp?Thr?Thr?Val?Pro?Gly?Ile?Trp?Val?Pro?Asp?Thr?Pro

245?????????????????250?????????????????255Leu?Ser?His?Arg?Asn?Thr?Gln?Pro?Gly?Trp?Val?Val?Ala?Pro?Gly?Met

260?????????????????265?????????????????270Gln?Gly?Val?Gln?Val?Gly?Pro?Ile?Thr?Gln?Gly?Leu?Leu?Thr?Pro?Glu

275?????????????????280?????????????????285Ser?Leu?Ala?Glu?Leu?Met?Gly?Gly?Pro?Asp?Ile?Ala?Pro?Pro?Ser?Ser

290?????????????????295?????????????????300Gly?Leu?Gln?Thr?Pro?Pro?Gly?Pro?Pro?Asn?Ala?Tyr?Asp?Glu?Tyr?Pro305?????????????????310?????????????????315?????????????????320Val?Leu?Pro?Pro?Ile?Gly?Leu?Gln?Ala?Pro?Gln?Val?Pro?Ile?Pro?Pro

325?????????????????330?????????????????335Pro?Pro?Pro?Gly?Pro?Asp?Val?Ile?Pro?Gly?Pro?Val?Pro?Pro?Val?Leu

340?????????????????345?????????????????350Ala?Ala?Ile?Val?Phe?Pro?Arg?Asp?Arg?Pro?Ala?Ala?Ser?Glu?Asn?Phe

355?????????????????360?????????????????365Asp?Tyr?Met?Gly?Leu?Leu?Leu?Leu?Ser?Pro?Gly?Leu?Ala?Thr?Phe?Leu

370?????????????????375?????????????????380Phe?Gly?Val?Ser?Ser?Ser?Pro?Ala?Arg?Gly?Thr?Met?Ala?Asp?Arg?His385?????????????????390?????????????????395?????????????????400Val?Leu?Ile?Pro?Ala?Ile?Thr?Gly?Leu?Ala?Leu?Ile?Ala?Ala?Phe?Val

405?????????????????410?????????????????415Ala?His?Ser?Trp?Tyr?Arg?Thr?Glu?His?Pro?Leu?Ile?Asp?Met?Arg?Leu

420?????????????????425?????????????????430Phe?Gln?Asn?Arg?Ala?Val?Ala?Gln?Ala?Asn?Met?Thr?Met?Thr?Val?Leu

435?????????????????440?????????????????445Ser?Leu?Gly?Leu?Phe?Gly?Ser?Phe?Leu?Leu?Leu?Pro?Ser?Tyr?Leu?Gln

450?????????????????455?????????????????460Gln?Val?Leu?His?Gln?Ser?Pro?Met?Gln?Ser?Gly?Val?His?Ile?Ile?Pro465?????????????????470?????????????????475?????????????????480Gln?Gly?Leu?Gly?Ala?Met?Leu?Ala?Met?Pro?Ile?Ala?Gly?Ala?Met?Met

485?????????????????490?????????????????495Asp?Arg?Arg?Gly?Pro?Ala?Lys?Ile?Val?Leu?Val?Gly?Ile?Met?Leu?Ile

500?????????????????505?????????????????510Ala?Ala?Gly?Leu?Gly?Thr?Phe?Ala?Phe?Gly?Val?Ala?Arg?GIn?Ala?Asp

515?????????????????520?????????????????525Tyr?Leu?Pro?Ile?Leu?Pro?Thr?Gly?Leu?Ala?Ile?Met?Gly?Met?Gly?Met

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

565?????????????????570?????????????????575Val?Gly?Gly?Ser?Ile?Gly?Thr?Ala?Leu?Met?Ser?Val?Leu?Leu?Thr?Tyr

580?????????????????585?????????????????590Gln?Phe?Asn?His?Ser?Glu?Ile?Ile?Ala?Thr?Ala?Lys?Lys?Val?Ala?Leu

595?????????????????600?????????????????605Thr?Pro?Glu?Ser?Gly?Ala?Gly?Arg?Gly?Ala?Ala?Val?Asp?Pro?Ser?Ser

610?????????????????615?????????????????620Leu?Pro?Arg?Gln?Thr?Asn?Phe?Ala?Ala?Gln?Leu?Leu?His?Asp?Leu?Ser625?????????????????630?????????????????635?????????????????640Hls?Ala?Tyr?Ala?Val?Val?Phe?Val?Ile?Ala?Thr?Ala?Leu?Val?Val?Ser

645?????????????????650?????????????????655Thr?Leu?Ile?Pro?Ala?Ala?Phe?Leu?Pro?Lys?Gln?Gln?Ala?Ser?His?Arg

660?????????????????665?????????????????670Arg?Ala?Pro?Leu?Leu?Ser?Ala

The information of 675 (2) SEQ ID NO:195:

(i) sequence signature:

(A) length: 120 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linearity

(xi) sequence description: SEQ ID NO:195:Thr Pro Glu Lys Ser Phe Val Asp Asp Leu Asp Ile Asp Ser Leu Ser1 5 10 15Met Val Glu Ile Ala Val Gln Thr Glu Asp Lys Tyr Gly Val Lys Ile

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

35??????????????????40??????????????????45Tyr?Ile?Gln?Lys?Leu?Glu?Glu?Glu?Asn?Pro?Glu?Ala?Ala?Gln?Ala?Leu

50??????????????????55??????????????????60Arg?Ala?Lys?Ile?Glu?Ser?Glu?Asn?Pro?Asp?Ala?Ala?Arg?Ala?Asp?Arg65??????????????????70??????????????????75??????????????????80Cys?Val?Ser?Pro?Thr?Ser?Gln?Ala?Arg?Asp?Ala?Arg?Arg?Pro?Leu?Ala

85??????????????????90??????????????????95Arg?Ser?Ala?Arg?Leu?Ala?Cys?Arg?Arg?Leu?Pro?Ala?Ser?Val?Pro?Thr

100?????????????????105?????????????????110Thr?Arg?Arg?Asp?Pro?Arg?Glu?Arg

The information of 115 120 (2) SEQ ID NO:196:

(i) sequence signature:

(A) length: 89 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linearity

(xi) sequence description: SEQ ID NO:196:Leu Ala Cys Gln Cys His Arg Arg Tyr Asp Val Gly Ile Gln Phe Arg1 5 10 15Gly Pro Ala Gly Pro Val Ala Thr Gln Ser Gly Pro Pro Gly Pro Ser

20??????????????????25??????????????????30Ile?Ala?Glu?Gly?Arg?Gln?Val?Arg?Ala?Gln?Cys?Gly?Ala?Gly?Phe?Leu

35??????????????????40??????????????????45Glu?Arg?Arg?Pro?Ala?Val?Ser?Gly?Ala?Leu?Pro?Pro?Asn?Asn?Ala?Ser

50??????????????????55??????????????????60Pro?Gly?Ile?Arg?Ser?Arg?Ala?Ala?Asp?Ser?Gln?Arg?His?Leu?Leu?Ala65??????????????????70??????????????????75???????????????????80Gly?Asp?Gly?Ser?Asp?Val?Thr?Val?Gly

The information of 85 (2) SEQ ID NO:197:

(i) sequence signature:

(A) length: 119 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linearity

(xi) sequence description: SEQ ID NO:197:Ala Ser Leu Leu Ala Tyr Ser Ala Ala Ala Ala Ser Thr Ala Leu Ala1 5 10 15Val Ala Cys Val Arg Ala Asp His Arg Asp Arg Arg Thr Ile Arg Asp

20??????????????????25??????????????????30His?Leu?Ala?Met?Ile?His?Leu?Ala?Gln?Leu?Val?Thr?Gln?Pro?Pro?Gly

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

50??????????????????55??????????????????60Pro?Gln?Glu?Val?Val?Val?Leu?Ala?His?His?Leu?Val?Thr?Gly?Thr?Gly65??????????????????70??????????????????75??????????????????80Glu?Val?Gln?Gly?Glu?Gly?Arg?His?Val?Ala?Ala?Glu?Val?Val?Asp?Pro

85??????????????????90??????????????????95Glu?Asn?Gln?Ile?Leu?Arg?Gln?Val?Leu?Gly?Pro?Ala?Pro?His?Asp?Lys

100?????????????????105?????????????????110Pro?Asp?Ala?Gly?Ile?Gly?Gln

The information of 115 (2) SEQ ID NO:198:

(i) sequence signature:

(A) length: 116 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linearity

(xi) sequence description: SEQ ID NO:198:Arg Ala Arg Gly His Arg Ser Ser Lys Gly Ser Arg Trp Ser His Glu1 5 10 15Val Leu Glu Gly Cys Ile Leu Ala Asp Ser Arg Gln Ser Lys Thr Ala

20??????????????????25??????????????????30Ala?Ser?Pro?Ser?Pro?Ser?Arg?Pro?Gln?Ser?Ser?Ser?Asn?Asn?Ser?Val

35??????????????????40??????????????????45Pro?Gly?Ala?Pro?Asn?Arg?Val?5er?Phe?Ala?Lys?Leu?Arg?Glu?Pro?Leu

50??????????????????55??????????????????60Glu?Val?Pro?Gly?Leu?Leu?Asp?Val?Gln?Thr?Asp?Ser?Phe?Glu?Trp?Leu65??????????????????70??????????????????75??????????????????80Ile?Gly?Ser?Pro?Arg?Trp?Arg?Glu?Ser?Ala?Ala?Glu?Arg?Gly?Asp?Val

85??????????????????90??????????????????95Asn?Pro?Val?Gly?Gly?Leu?Glu?Glu?Val?Leu?Tyr?Glu?Leu?Ser?Pro?Ile

100?????????????????105?????????????????110Glu?Asp?Phe?Ser

The information of 115 (2) SEQ ID NO:199:

(i) sequence signature:

(A) length: 811 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ, ID, NO:199:TGCTACGCAG, CAATCGCTTT, GGTGACAGAT, GTGGATGCCG, GCGTCGCTGC, TGGCGATGGC, 60GTGAAAGCCG, CCGACGTGTT, CGCCGCATTC, GGGGAGAACA, TCGAACTGCT, CAAAAGGCTG, 120GTGCGGGCCG, CCATCGATCG, GGTCGCCGAC, GAGCGCACGT, GCACGCACTG, TCAACACCAC, 180GCCGGTGTTC, CGTTGCCGTT, CGAGCTGCCA, TGAGGGTGCT, GCTGACCGGC, GCGGCCGGCT, 240TCATCGGGTC, GCGCGTGGAT, GCGGCGTTAC, GGGCTGCGGG, TCACGACGTG, GTGGGCGTCG, 300ACGCGCTGCT, GCCCGCCGCG, CACGGGCCAA, ACCCGGTGCT, GCCACCGGGC, TGCCAGCGGG, 360TCGACGTGCG, CGACGCCAGC, GCGCTGGCCC, CGTTGTTGGC, CGGTGTCGAT, CTGGTGTGTC, 420ACCAGGCCGC, CATGGTGGGT, GCCGGCGTCA, ACGCCGCCGA, CGCACCCGCC, TATGGCGGCC, 480ACAACGATTT, CGCCACCACG, GTGCTGCTGG, CGCAGATGTT, CGCCGCCGGG, GTCCGCCGTT, 540TGGTGCTGGC, GTCGTCGATG, GTGGTTTACG, GGCAGGGGCG, CTATGACTGT, CCCCAGCATG, 600GACCGGTCGA, CCCGCTGCCG, CGGCGGCGAG, CCGACCTGGA, CAATGGGGTC, TTCGAGCACC, 660GTTGCCCGGG, GTGCGGCGAG, CCAGTCATCT, GGCAATTGGT, CGACGAAGAT, GCCCCGTTGC, 720GCCCGCGCAG, CCTGTACGCG, GCAGCAAGAC, CGCGCAGGAG, CACTACGCGC, TGGCGTGGTC, 780GGAAACGAAT, GGCGGTTCCG, TGGTGGCGTT, G, 811, (2) SEQ, ID, the information of NO:200:

(i) sequence signature:

(A) length: 966 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ, ID, NO:200:GTCCCGCGAT, GTGGCCGAGC, ATGACTTTCG, GCAACACCGG, CGTAGTAGTC, GAAGATATCG, 60GACTTTGTGG, TCCCGGTGGC, GGGATAGAGC, ACCTGTCGGC, GTTGGTCAGC, GTCACCCGTT, 120GCTCGGACGC, CGAACCCATG, CTTTCAACGT, AGCCTGTCGG, TCACACAAGT, CGCGAGCGTA, 180ACGTCACGGT, CAAATATCGC, GTGGAATTTC, GCCGTGACGT, TCCGCTCGCG, GACAATCAAG, 240GCATACTCAC, TTACATGCGA, GCCATTTGGA, CGGGTTCGAT, CGCCTTCGGG, CTGGTGAACG, 300TGCCGGTCAA, GGTGTACAGC, GCTACCGCAG, ACCACGACAT, CAGGTTCCAC, CAGGTGCACG, 360CCAAGGACAA, CGGACGCATC, CGGTACAAGC, GCGTCTGCGA, GGCGTGTGGC, GAGGTGGTCG, 420ACTACCGCGA, TCTTGCCCGG, GCCTACGAGT, CCGGCGACGG, CCAAATGGTG, GCGATCACCG, 480ACGACGACAT, CGCCAGCTTG, CCTGAAGAAC, GCAGCCGGGA, GATCGAGGTG, TTGGAGTTCG, 540TCCCCGCCGC, CGACGTGGAC, CCGATGATGT, TCGACCGCAG, CTACTTTTTG, GAGCCTGATT, 600CGAAGTCGTC, GAAATCGTAT, GTGCTGCTGG, CTAAGACACT, CGCCGAGACC, GACCGGATGG, 660CGATCGTGGA, TCGCCCCACC, GGCCGTGAAT, GCAGGAAAAA, TAAGAGCCGC, TATCCACAAT, 720TCGGCGTCGA, GCTCGGCTAC, CACAAACGGT, AGAACGATCG, AGACATTCCC, GAGCTGAAGT, 780GCGGCGCTAT, AGAAGCCGCT, CTGCGCGATT, ATCAAACGCA, AAATACGCTT, ACTCATGCCA, 840TCGGCGCTGC, TCACCCGATG, CGACGTTTTT, GCCACGCTCC, ACCGCCTGCC, GCGCGACCTC, 900AAGTGGGCAT, GCATCCCACC, CGTTCCCGGA, AACCGGTTCC, GGCGGGTCGG, CTCATCGCTT, 960CATCCT, 966, (2) SEQ, ID, the information of NO:201:

(i) sequence signature:

(A) length: 2367 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ, ID, NO:201:CCGCACCGCC, GGCAATACCG, CCAGCGCCAC, CGTTACCGCC, GTTTGCGCCG, TTGCCCCCGT, 60TGCCGCCCGT, CCCGCCGGCC, CCGCCGATGG, AGTTCTCATC, GCCAAAAGTA, CTGGCGTTGC, 120CACCGGAGCC, GCCGTTGCCG, CCGTCACCGC, CAGCCCCGCC, GACTCCACCG, GCCCCACCGA, 180CTCCGCCGCT, GCCACCGTTG, CCGCCGTTGC, CGATCAACAT, GCCGCTGGCG, CCACCCTTGC, 240CACCCACGCC, ACCGGCTCCG, CCCACCCCGC, CGACACCAAG, CGAGCTGCCG, CCGGAGCCAC, 300CATCACCACC, TACGCCACCG, ACCGCCCAGA, CACCAGCGAC, CGGGTCTTCG, TGAAACGTCG, 360CGGTGCCACC, ACCGCCGCCG, TTACCGCCAA, CCCCACCGGC, AACGCCGGCG, CCGCCATCCC, 420CGCCGGCCCC, GGCGTTGCCG, CCGTTGCCGC, CGTTGCCGAA, CAACAACCCG, CCGGCGCCGC, 480CGTTGCCGCC, CGCGCCGCCG, GTCCCGCCGG, CGCCGCCGAC, GCCAAGGCCG, CTGCCGCCCT, 540TGCCGCCATC, ACCACCCTTG, CCGCCGACCA, CATCGGGTTC, TGCCTCGGGG, TCTGGGCTGT, 600CAAACCTCGC, GATGCCAGCG, TTGCCGCCGC, TTCCCCCGGG, CCCCCCCGTG, GCGCCGTCAC, 660CACCGATACC, ACCCGCGCCA, CCGGCGCCAC, CGTTGCCGCC, ATCACCGAAT, AGCAACCCGC, 720CGGCGCCACC, ATTGCCGCCA, GCTCCCCCTG, CGCCACCGTC, GGCGCCGGAG, GCGGCACTGG, 780CAGCCCCGTT, ACCACCGAAA, CCGCCGCTAC, CACCGGTAGA, GGTGGCAGTG, GCGATGTGTA, 840CGAAAGCGCC, GCCTCCGGCG, CCGCCGCTAC, CACCCCCACT, GCCGGCGGCT, ACACCGTCGG, 900ACCCGTTGCC, ACCATCACCG, CCAAAGGCGC, TCGCAATGTC, GCCCTGCGCG, ACTCCGCCGT, 960CGCCGCCGTT, GCCGCCGCCG, CCACCGGCAG, CGGCGGTACC, GCCGTCACCA, CCGGCACCGC, 1020CGGTGGCCTT, GCCCGAGCCT, GCCGTCGCGG, TGGCACCGTC, GCCGCCGGTG, CCACCGGTCG, 1080GCGTGCCGGC, AGTGCCATGG, CCGCCCGTGC, CGCCGTCGCC, GCCGGTTTGA, TCACCGATGC, 1140CGGACACATC, TGCCGGGCTG, TCCCCGGTGC, TGGCCGCGGG, GCCGGGCGTG, GGATTGACCC, 1200CGTTTGCCCC, GGCGAGGCCG, GCGCCGCCGG, TACCACCGGC, GCCGCCATGG, CCGAACAGCC, 1260CGGCGTTGCC, GCCGTTACCG, CCCGCACCCC, CGATGCCTGC, GGCCACGCTG, GTGCCGCCGA, 1320CACCGCCGTT, GCCGCCGTTG, CCCCACAACC, ACCCCCCGTT, CCCACCGGCA, CCGCCGGCCG, 1380CGCCGGTACC, ACCGGCCCCG, CCGTTGCCGC, CGTTGCCGAT, CAACCCGGCC, GCGCCTCCGC, 1440TGCCGCCGGT, TTGACCGAAC, CCGCCAGCCG, CGCCGTTGCC, ACCGTTGCCA, AACAGCAACC, 1500CGCCGGCCGC, GCCAGGCTGC, CCGGGTGCCG, TCCCGTCGGC, GCCGTTTCCG, ATCAACGGGC, 1560GCCCCAAAAG, CGCCTCGGTG, GGCGCATTCA, CCGCACCCAG, CAGACTCCGC, TCAACAGCGG, 1620CTTCAGTGCT, GGCATACCGA, CCCGCGGCCG, CAGTCAACGC, CTGCACAAAC, TGCTCGTGAA, 1680ACGCTGCCAC, CTGTACGCTG, AGCGCCTGAT, ACTGCCGAGC, ATGGGCCCCG, AACAACCCCG, 1740CAATCGCCGC, CGACACTTCA, TCGGCAGCCG, CAGCCACCAC, TTCCGTCGTC, GGGATCGCCG, 1800CGGCCGCATT, AGCCGCGCTC, ACCTGCGAAC, CAATAGTCGA, TAAATCCAAA, GCCGCAGTTG, 1860CCAGCAGCTG, CGGCGTCGCG, ATCACCAAGG, ACACCTCGCA, CCTCCGGATA, CCCCATATCG, 1920CCGCACCGTG, TCCCCAGCGG, CCACGTGACC, TTTGGTCGCT, GGCTGGCGGC, CCTGACTATG, 1980GCCGCGACGG, CCCTCGTTCT, GATTCGCCCC, GGCGCGCAGC, TTGTTGCGCG, AGTTGAAGAC, 2040GGGAGGACAG, GCCGAGCTTG, GTGTAGACGT, GGGTCAAGTG, GGAATGCACG, GTCCGCGGCG, 2100AGATGAATAG, GCGGACGCCG, ATCTCCTTGT, TGCTGAGTCC, CTCACCGACC, AGTAGAGCCA, 2160CCTCAAGCTC, TGTCGGTGTC, AACGCGCCCC, AGCCACTTGT, CGGGCGTTTC, CGTGCACCGC, 2220GGCCTCGTTG, CGCGTACGCG, ATCGCCTCAT, CGATCGATAA, CGCAGTTCCT, TCGGCCCAGG, 2280CATCGTCGAA, CTCGCTGTCA, CCCATGGATT, TTCGAAGGGT, GGCTAGCGAC, GAGTTACAGC, 2340CCGCCTGGTA, GATCCCGAAG, CGGACCG, 2367, (2) SEQ, ID, the information of NO:202:

(i) sequence signature:

(A) length: 376 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linear (xi) sequence description: SEQ ID NO:202:Gln Pro Ala Gly Ala Tnr Ile Ala Ala Ser Ser Pro Cys Ala Thr Val1 5 10 15Gly Ala Gly Gly Gly Thr Gly Ser Pro Val Thr Thr Glu Thr Ala Ala

20??????????????????25?????????????????30Thr?Thr?Gly?Arg?Gly?Gly?Ser?Gly?Asp?Val?Tyr?Glu?Ser?Ala?Ala?Ser

35??????????????????40??????????????????45Gly?Ala?Ala?Ala?Thr?Thr?Pro?Thr?Ala?Gly?Gly?Tyr?Thr?Val?Gly?Pro

50??????????????????55??????????????????60Val?Ala?Thr?Ile?Thr?Ala?Lys?Gly?Ala?Arg?Asn?Val?Ala?Leu?Arg?Asp65??????????????????70??????????????????75??????????????????80Ser?Ala?Val?Ala?Ala?Val?Ala?Ala?Ala?Ala?Thr?Gly?Ser?Gly?Gly?Thr

85??????????????????90??????????????????95Ala?Val?Thr?Thr?Gly?Thr?Ala?Gly?Gly?Leu?Ala?Arg?Ala?Cys?Arg?Arg

100?????????????????105?????????????????110Gly?Gly?Thr?Val?Ala?Ala?Gly?Ala?Thr?Gly?Arg?Arg?Ala?Gly?Ser?Ala

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

130?????????????????135?????????????????140His?Ile?Cys?Arg?Ala?Val?Pro?Gly?Ala?Gly?Arg?Gly?Ala?Gly?Arg?Gly145?????????????????150?????????????????155?????????????????160Ile?Asp?Pro?Val?Cys?Pro?Gly?Glu?Ala?Gly?Ala?Ala?Gly?Thr?Thr?Gly

165?????????????????170?????????????????175Ala?Ala?Met?Ala?Glu?Gln?Pro?Gly?Val?Ala?Ala?Val?Thr?Ala?Arg?Thr

180?????????????????185?????????????????190Pro?Asp?Ala?Cys?Gly?His?Ala?Gly?Ala?Ala?Asp?Thr?Ala?Val?Ala?Ala

195?????????????????200?????????????????205Val?Ala?Pro?Gln?Pro?Pro?Pro?Val?Pro?Thr?Gly?Thr?Ala?Gly?Arg?Ala

210?????????????????215?????????????????220Gly?Thr?Thr?Gly?Pro?Ala?Val?Ala?Ala?Val?Ala?Asp?Gln?Pro?Gly?Arg225?????????????????230?????????????????235?????????????????240Ala?Ser?Ala?Ala?Ala?Gly?Leu?Thr?Glu?Pro?Ala?Ser?Arg?Ala?Val?Ala

245?????????????????250?????????????????255Thr?Val?Ala?Lys?Gln?Gln?Pro?Ala?Gly?Arg?Ala?Arg?Leu?Pro?Gly?Cys

260?????????????????265?????????????????270Arg?Pro?Val?Gly?Ala?Val?Ser?Asp?Gln?Arg?Ala?Pro?Gln?Lys?Arg?Leu

275?????????????????280?????????????????285Gly?Gly?Arg?Ile?His?Arg?Thr?Gln?Gln?Thr?Pro?Leu?Asn?Ser?Gly?Phe

290?????????????????295?????????????????300Ser?Ala?Gly?Ile?Pro?Thr?Arg?Gly?Arg?Ser?Gln?Arg?Leu?His?Lys?Leu305?????????????????310?????????????????315?????????????????320Leu?Val?Lys?Arg?Cys?His?Leu?Tyr?Ala?Glu?Arg?Leu?Ile?Leu?Pro?Ser

325?????????????????330?????????????????335Met?Gly?Pro?Glu?Gln?Pro?Arg?Asn?Arg?Arg?Arg?His?Phe?Ile?Gly?Ser

340?????????????????345?????????????????350Arg?Ser?His?His?Phe?Arg?Arg?Arg?Asp?Arg?Arg?Gly?Arg?Ile?Ser?Arg

355?????????????????360?????????????????365Ala?His?Leu?Arg?Thr?Asn?Ser?Arg

The information of 370 375 (2) SEQ ID NO:203:

(i) sequence signature:

(A) length: 2852 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ, ID, NO:203:GGCCAAAACG, CCCCGGCGAT, CGCGGCCACC, GAGGCCGCCT, ACGACCAGAT, GTGGGCCCAG, 60GACGTGGCGG, CGATGTTTGG, CTACCATGCC, GGGGCTTCGG, CGGCCGTCTC, GGCGTTGACA, 120CCGTTCGGCC, AGGCGCTGCC, GACCGTGGCG, GGCGGCGGTG, CGCTGGTCAG, CGCGGCCGCG, 180GCTCAGGTGA, CCACGCGGGT, CTTCCGCAAC, CTGGGCTTGG, CGAACGTCCG, CGAGGGCAAC, 240GTCCGCAACG, GTAATGTCCG, GAACTTCAAT, CTCGGCTCGG, CCAACATCGG, CAACGGCAAC, 300ATCGGCAGCG, GCAACATCGG, CAGCTCCAAC, ATCGGGTTTG, GCAACGTGGG, TCCTGGGTTG, 360ACCGCAGCGC, TGAACAACAT, CGGTTTCGGC, AACACCGGCA, GCAACAACAT, CGGGTTTGGC, 420AACACCGGCA, GCAACAACAT, CGGGTTCGGC, AATACCGGAG, ACGGCAACCG, AGGTATCGGG, 480CTCACGGGTA, GCGGTTTGTT, GGGGTTCGGC, GGCCTGAACT, CGGGCACCGG, CAACATCGGT, 540CTGTTCAACT, CGGGCACCGG, AAACGTCGGC, ATCGGCAACT, CGGGTACCGG, GAACTGGGGC, 600ATTGGCAACT, CGGGCAACAG, CTACAACACC, GGTTTTGGCA, ACTCCGGCGA, CGCCAACACG, 660GGCTTCTTCA, ACTCCGGAAT, AGCCAACACC, GGCGTCGGCA, ACGCCGGCAA, CTACAACACC, 720GGTAGCTACA, ACCCGGGCAA, CAGCAATACC, GGCGGCTTCA, ACATGGGCCA, GTACAACACG, 780GGCTACCTGA, ACAGCGGCAA, CTACAACACC, GGCTTGGCAA, ACTCCGGCAA, TGTCAACACC, 840GGCGCCTTCA, TTACTGGCAA, CTTCAACAAC, GGCTTCTTGT, GGCGCGGCGA, CCACCAAGGC, 900CTGATTTTCG, GGAGCCCCGG, CTTCTTCAAC, TCGACCAGTG, CGCCGTCGTC, GGGATTCTTC, 960AACAGCGGTG, CCGGTAGCGC, GTCCGGCTTC, CTGAACTCCG, GTGCCAACAA, TTCTGGCTTC, 1020TTCAACTCTT, CGTCGGGGGC, CATCGGTAAC, TCCGGCCTGG, CAAACGCGGG, CGTGCTGGTA, 1080TCGGGCGTGA, TCAACTCGGG, CAACACCGTA, TCGGGTTTGT, TCAACATGAG, CCTGGTGGCC, 1140ATCACAACGC, CGGCCTTGAT, CTCGGGCTTC, TTCAACACCG, GAAGCAACAT, GTCGGGATTT, 1200TTCGGTGGCC, CACCGGTCTT, CAATCTCGGC, CTGGCAAACC, GGGGCGTCGT, GAACATTCTC, 1260GGCAACGCCA, ACATCGGCAA, TTACAACATT, CTCGGCAGCG, GAAACGTCGG, TGACTTCAAC, 1320ATCCTTGGCA, GCGGCAACCT, CGGCAGCCAA, AACATCTTGG, GCAGCGGCAA, CGTCGGCAGC, 1380TTCAATATCG, GCAGTGGAAA, CATCGGAGTA, TTCAATGTCG, GTTCCGGAAG, CCTGGGAAAC, 1440TACAACATCG, GATCCGGAAA, CCTCGGGATC, TACAACATCG, GTTTTGGAAA, CGTCGGCGAC, 1500TACAACGTCG, GCTTCGGGAA, CGCGGGCGAC, TTCAACCAAG, GCTTTGCCAA, CACCGGCAAC, 1560AACAACATCG, GGTTCGCCAA, CACCGGCAAC, AACAACATCG, GCATCGGGCT, GTCCGGCGAC, 1620AACCAGCAGG, GCTTCAATAT, TGCTAGCGGC, TGGAACTCGG, GCACCGGCAA, CAGCGGCCTG, 1680TTCAATTCGG, GCACCAATAA, CGTTGGCATC, TTCAACGCGG, GCACCGGAAA, CGTCGGCATC, 1740GCAAACTCGG, GCACCGGGAA, CTGGGGTATC, GGGAACCCGG, GTACCGACAA, TACCGGCATC, 1800CTCAATGCTG, GCAGCTACAA, CACGGGCATC, CTCAACGCCG, GCGACTTCAA, CACGGGCTTC, 1860TACAACACGG, GCAGCTACAA, CACCGGCGGC, TTCAACGTCG, GTAACACCAA, CACCGGCAAC, 1920TTCAACGTGG, GTGACACCAA, TACCGGCAGC, TATAACCCGG, GTGACACCAA, CACCGGCTTC, 1980TTCAATCCCG, GCAACGTCAA, TACCGGCGCT, TTCGACACGG, GCGACTTCAA, CAATGGCTTC, 2040TTGGTGGCGG, GCGATAACCA, GGGCCAGATT, GCCATCGATC, TCTCGGTCAC, CACTCCATTC, 2100ATCCCCATAA, ACGAGCAGAT, GGTCATTGAC, GTACACAACG, TAATGACCTT, CGGCGGCAAC, 2160ATGATCACGG, TCACCGAGGC, CTCGACCGTT, TTCCCCCAAA, CCTTCTATCT, GAGCGGTTTG, 2220TTCTTCTTCG, GCCCGGTCAA, TCTCAGCGCA, TCCACGCTGA, CCGTTCCGAC, GATCACCCTC, 2280ACCATCGGCG, GACCGACGGT, GACCGTCCCC, ATCAGCATTG, TCGGTGCTCT, GGAGAGCCGC, 2340ACGATTACCT, TCCTCAAGAT, CGATCCGGCG, CCGGGCATCG, GAAATTCGAC, CACCAACCCC, 2400TCGTCCGGCT, TCTTCAACTC, GGGCACCGGT, GGCACATCTG, GCTTCCAAAA, CGTCGGCGGC, 2460GGCAGTTCAG, GCGTCTGGAA, CAGTGGTTTG, AGCAGCGCGA, TAGGGAATTC, GGGTTTCCAG, 2520AACCTCGGCT, CGCTGCAGTC, AGGCTGGGCG, AACCTGGGCA, ACTCCGTATC, GGGCTTTTTC, 2580AACACCAGTA, CGGTGAACCT, CTCCACGCCG, GCCAATGTCT, CGGGCCTGAA, CAACATCGGC, 2640ACCAACCTGT, CCGGCGTGTT, CCGCGGTCCG, ACCGGGACGA, TTTTCAACGC, GGGCCTTGCC, 2700AACCTGGGCC, AGTTGAACAT, CGGCAGCGCC, TCGTGCCGAA, TTCGGCACGA, GTTAGATACG, 2760GTTTCAACAA, TCATATCCGC, GTTTTGCGGC, AGTGCATCAG, ACGAATCGAA, CCCGGGAAGC, 2820GTAAGCGAAT, AAACCGAATG, GCGGCCTGTC, AT, 2852, (2) SEQ, ID, the information of NO:204:

(i) sequence signature:

(A) length: 943 amino acid

(B) type: amino acid

(C) chain number:

(D) topology: linearity

(xi) sequence description: SEQ ID NO:204:Gly Gln Asn Ala Pro Ala Ile Ala Ala Thr Glu Ala Ala Tyr Asp Gln1 5 10 15Met Trp Ala Gln Asp Val Ala Ala Met Phe Gly Tyr His Ala Gly Ala

20??????????????????25??????????????????30Ser?Ala?Ala?Val?Ser?Ala?Leu?Thr?Pro?Phe?Gly?Gln?Ala?Leu?Pro?Thr

35??????????????????40??????????????????45Val?Ala?Gly?Gly?Gly?Ala?Leu?Val?Ser?Ala?Ala?Ala?Ala?Gln?Val?Thr

50??????????????????55??????????????????60Thr?Arg?Val?Phe?Arg?Asn?Leu?Gly?Leu?Ala?Asn?Val?Arg?Glu?Gly?Asn65??????????????????70??????????????????75??????????????????80Val?Arg?Asn?Gly?Asn?Val?Arg?Asn?Phe?Asn?Leu?Gly?Ser?Ala?Asn?Ile

85??????????????????90??????????????????95Gly?Asn?Gly?Asn?Ile?Gly?Ser?Gly?Asn?Ile?Gly?Ser?Ser?Asn?Ile?Gly

100?????????????????105?????????????????110Phe?Gly?Asn?Val?Gly?Pro?Gly?Leu?Thr?Ala?Ala?Leu?Asn?Asn?Ile?Gly

115?????????????????120?????????????????125Phe?Gly?Asn?Thr?Gly?Ser?Asn?Asn?Ile?Gly?Phe?Gly?Asn?Thr?Gly?Ser

130?????????????????135?????????????????140Asn?Asn?Ile?Gly?Phe?Gly?Asn?Thr?Gly?Asp?Gly?Asn?Arg?Gly?Ile?Gly145?????????????????150?????????????????155?????????????????160Leu?Thr?Gly?Ser?Gly?Leu?Leu?Gly?Phe?Gly?Gly?Leu?Asn?Ser?Gly?Thr

165?????????????????170?????????????????175Gly?Asn?Ile?Gly?Leu?Phe?Asn?Ser?Gly?Thr?Gly?Asn?Val?Gly?Ile?Gly

180?????????????????185?????????????????190Asn?Ser?Gly?Thr?Gly?Asn?Trp?Gly?Ile?Gly?Asn?Ser?Gly?Asn?Ser?Tyr

195?????????????????200?????????????????205Asn?Thr?Gly?Phe?Gly?Asn?Ser?Gly?Asp?Ala?Asn?Thr?Gly?Phe?Phe?Asn

210?????????????????215?????????????????220Ser?Gly?Ile?Ala?Asn?Thr?Gly?Val?Gly?Asn?Ala?Gly?Asn?Tyr?Asn?Thr225?????????????????230?????????????????235?????????????????240Gly?Ser?Tyr?Asn?Pro?Gly?Asn?Ser?Asn?Thr?Gly?Gly?Phe?Asn?Met?Gly

245?????????????????250?????????????????255Gln?Tyr?Asn?Thr?Gly?Tyr?Leu?Asn?Ser?Gly?Asn?Tyr?Asn?Thr?Gly?Leu

260?????????????????265?????????????????270Ala?Asn?Ser?Gly?Asn?Val?Asn?Thr?Gly?Ala?Phe?Ile?Thr?Gly?Asn?Phe

275?????????????????280?????????????????285Asn?Asn?Gly?Phe?Leu?Trp?Arg?Gly?Asp?His?Gln?Gly?Leu?Ile?Phe?Gly

290?????????????????295?????????????????300Ser?Pro?Gly?Phe?Phe?Asn?Ser?Thr?Ser?Ala?Pro?Ser?Ser?Gly?Phe?Phe305?????????????????310?????????????????315?????????????????320Asn?Ser?Gly?Ala?Gly?Ser?Ala?Ser?Gly?Phe?Leu?Asn?Ser?Gly?Ala?Asn

325?????????????????330?????????????????335Asn?Ser?Gly?Phe?Phe?Asn?Ser?Ser?Ser?Gly?Ala?Ile?Gly?Asn?Ser?Gly

340?????????????????345?????????????????350Leu?Ala?Asn?Ala?Gly?Val?Leu?Val?Ser?Gly?Val?Ile?Asn?Ser?Gly?Asn

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

370?????????????????375?????????????????380Ala?Leu?Ile?Ser?Gly?Phe?Phe?Asn?Thr?Gly?Ser?Asn?Met?Ser?Gly?Phe385?????????????????390?????????????????395?????????????????400Phe?Gly?Gly?Pro?Pro?Val?Phe?Asn?Leu?Gly?Leu?Ala?Asn?Arg?Gly?Val

405?????????????????410?????????????????415Val?Asn?Ile?Leu?Gly?Asn?Ala?Asn?Ile?Gly?Asn?Tyr?Asn?Ile?Leu?Gly

420?????????????????425?????????????????430Ser?Gly?Asn?Val?Gly?Asp?Phe?Asn?Ile?Leu?Gly?Ser?Gly?Asn?Leu?Gly

435?????????????????440?????????????????445Ser?Gln?Asn?Ile?Leu?Gly?Ser?Gly?Asn?Val?Gly?Ser?Phe?Asn?Ile?Gly

450?????????????????455?????????????????460Ser?Gly?Asn?Ile?Gly?Val?Phe?Asn?Val?Gly?Ser?Gly?Ser?Leu?Gly?Asn465?????????????????470?????????????????475?????????????????480Tyr?Asn?Ile?Gly?Ser?Gly?Asn?Leu?Gly?Ile?Tyr?Asn?Ile?Gly?Phe?Gly

485?????????????????490?????????????????495Asn?Val?Gly?Asp?Tyr?Asn?Val?Gly?Phe?Gly?Asn?Ala?Gly?Asp?Phe?Asn

500?????????????????505?????????????????510Gln?Gly?Phe?Ala?Asn?Thr?Gly?Asn?Asn?Asn?Ile?Gly?Phe?Ala?Asn?Thr

515?????????????????520?????????????????525Gly?Asn?Asn?Asn?Ile?Gly?Ile?Gly?Leu?Ser?Gly?Asp?Asn?Gln?Gln?Gly

530?????????????????535?????????????????540Phe?Asn?Ile?Ala?Ser?Gly?Trp?Asn?Ser?Gly?Thr?Gly?Asn?Ser?Gly?Leu545?????????????????550?????????????????555?????????????????560Phe?Asn?Ser?Gly?Thr?Asn?Asn?Val?Gly?Ile?Phe?Asn?Ala?Gly?Thr?Gly

565?????????????????570?????????????????575Asn?Val?Gly?Ile?Ala?Asn?Ser?Gly?Thr?Gly?Asn?Trp?Gly?Ile?Gly?Asn

580?????????????????585?????????????????590Pro?Gly?Thr?Asp?Asn?Thr?Gly?Ile?Leu?Asn?Ala?Gly?Ser?Tyr?Asn?Thr

595?????????????????600?????????????????605Gly?Ile?Leu?Asn?Ala?Gly?Asp?Phe?Asn?Thr?Gly?Phe?Tyr?Asn?Thr?Gly

610?????????????????615?????????????????620Ser?Tyr?Asn?Thr?Gly?Gly?Phe?Asn?Val?Gly?Asn?Thr?Asn?Thr?Gly?Asn625?????????????????630?????????????????635?????????????????640Phe?Asn?Val?Gly?Asp?Thr?Asn?Thr?Gly?Ser?Tyr?Asn?Pro?Gly?Asp?Thr

645?????????????????650?????????????????655Asn?Thr?Gly?Phe?Phe?Asn?Pro?Gly?Asn?Val?Asn?Thr?Gly?Ala?Phe?Asp

660?????????????????665?????????????????670Thr?Gly?Asp?Phe?Asn?Asn?Gly?Phe?Leu?Val?Ala?Gly?Asp?Asn?Gln?Gly

675?????????????????680?????????????????685Gln?Ile?Ala?Ile?Asp?Leu?Ser?Val?Thr?Thr?Pro?Phe?Ile?Pro?Ile?Asn

690?????????????????695?????????????????700Glu?Gln?Met?Val?Ile?Asp?Val?His?Asn?Val?Met?Thr?Phe?Gly?Gly?Asn705?????????????????710?????????????????715?????????????????720Met?Ile?Thr?Val?Thr?Glu?Ala?Ser?Thr?Val?Phe?Pro?Gln?Thr?Phe?Tyr

725?????????????????730?????????????????735Leu?Ser?Gly?Leu?Phe?Phe?Phe?Gly?Pro?Val?Asn?Leu?Ser?Ala?Ser?Thr

740?????????????????745?????????????????750Leu?Thr?Val?Pro?Thr?lle?Thr?Leu?Thr?Ile?Gly?Gly?Pro?Thr?Val?Thr

755?????????????????760?????????????????765Val?Pro?Ile?Ser?Ile?Val?Gly?Ala?Leu?Glu?Ser?Arg?Thr?Ile?Thr?Phe

770?????????????????775?????????????????780Leu?Lys?Ile?Asp?Pro?Ala?Pro?Gly?Ile?Gly?Asn?Ser?Thr?Thr?Asn?Pro785?????????????????790?????????????????795?????????????????800Ser?Ser?Gly?Phe?Phe?Asn?Ser?Gly?Thr?Gly?Gly?Thr?Ser?Gly?Phe?Gln

805?????????????????810?????????????????815Asn?Val?Gly?Gly?Gly?Ser?Ser?Gly?Val?Trp?Asn?Ser?Gly?Leu?Ser?Ser

820?????????????????825?????????????????830Ala?Ile?Gly?Asn?Ser?Gly?Phe?Gln?Asn?Leu?Gly?Ser?Leu?Gln?Ser?Gly

835?????????????????840?????????????????845Trp?Ala?Asn?Leu?Gly?Asn?Ser?Val?Ser?Gly?Phe?Phe?Asn?Thr?Ser?Thr

850?????????????????855?????????????????860Val?Asn?Leu?Ser?Thr?Pro?Ala?Asn?Val?Ser?Gly?Leu?Asn?Asn?Ile?Gly865?????????????????870?????????????????875?????????????????880Thr?Asn?Leu?Ser?Gly?Val?Phe?Arg?Gly?Pro?Thr?Gly?Thr?Ile?Phe?Asn

885?????????????????890?????????????????895Ala?Gly?Leu?Ala?Asn?Leu?Gly?Gln?Leu?Asn?Ile?Gly?Ser?Ala?Ser?Cys

900?????????????????905?????????????????910Arg?Ile?Arg?His?Glu?Leu?Asp?Thr?Val?Ser?Thr?Ile?Ile?Ser?Ala?Phe

915?????????????????920?????????????????925Cys?Gly?Ser?Ala?Ser?Asp?Glu?Ser?Asn?Pro?Gly?Ser?Val?Ser?Glu

The information of 930 935 940 (2) SEQ ID NO:205:

(i) sequence signature:

(A) length: 53 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: the information of SEQ ID NO:205:GGATCCATAT GGGCCATCAT CATCATCATC ACGTGATCGA CATCATCGGG ACC 53 (2) SEQ ID NO:206:

(i) sequence signature:

(A) length: 42 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: the information of SEQ ID NO:206:CCTGAATTCA GGCCTCGGTT GCGCCGGCCT CATCTTGAAC GA 42 (2) SEQ ID NO:207:

(i) sequence signature:

(A) length: 31 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: the information of SEQ ID NO:207:GGATCCTGCA GGCTCGAAAC CACCGAGCGG T 31 (2) SEQ ID NO:208:

(i) sequence signature:

(A) length: 31 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: the information of SEQ ID NO:208:CTCTGAATTC AGCGCTGGAA ATCGTCGCGA T 31 (2) SEQ ID NO:209:

(i) sequence signature:

(A) length: 33 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: the information of SEQ ID NO:209:GGATCCAGCG CTGAGATGAA GACCGATGCC GCT 33 (2) SEQ ID NO:210:

(i) sequence signature:

(A) length: 38 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: the information of SEQ ID NO:210:GGATATCTGC AGAATTCAGG TTTAAAGCCC ATTTGCGA 38 (2) SEQ ID NO:211:

(i) sequence signature:

(A) length: 30 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: the information of SEQ ID NO:211:CCGCATGCGA GCCACGTGCC CACAACGGCC 30 (2) SEQ ID NO:212:

(i) sequence signature:

(A) length: 37 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: the information of SEQ ID NO:212:CTTCATGGAATTCTCAGGCC GGTAAGGTCC GCTGCGG 37 (2) SEQ ID NO:213:

(i) sequence signature:

(A) length: 7676 base pairs

(B) type: nucleic acid

(C) chain number: strand

(D) topology: linearity

(Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 213: TGGCGAATGG GACGCGCCCT GTAGCGGCGC ATTAAGCGCG GCGGGTGTGG TGGTTACGCG 60 CAGCGTGACC GCTACACTTG CCAGCGCCCT AGCGCCCGCT CCTTTCGCTT TCTTCCCTTC 120 CTTTCTCGCC ACGTTCGCCG GCTTTCCCCG TCAAGCTCTA AATCGGGGGC TCCCTTTAGG 180 GTTCCGATTT AGTGCTTTAC GGCACCTCGA CCCCAAAAAA CTTGATTAGG GTGATGGTTC 240 ACGTAGTGGG CCATCGCCCT GATAGACGGT TTTTCGCCCT TTGACGTTGG AGTCCACGTT 300 CTTTAATAGT GGACTCTTGT TCCAAACTGG AACAACACTC AACCCTATCT CGGTCTATTC 360 TTTTGATTTA TAAGGGATTT TGCCGATTTC GGCCTATTGG TTAAAAAATG AGCTGATTTA 420 ACAAAAATTT AACGCGAATT TTAACAAAAT ATTAACGTTT ACAATTTCAG GTGGCACTTT 480 TCGGGGAAAT GTGCGCGGAA CCCCTATTTG TTTATTTTTC TAAATACATT CAAATATGTA 540 TCCGCTCATG AATTAATTCT TAGAAAAACT CATCGAGCAT CAAATGAAAC TGCAATTTAT 600 TCATATCAGG ATTATCAATA CCATATTTTT GAAAAAGCCG TTTCTGTAAT GAAGGAGAAA 660 ACTCACCGAG GCAGTTCCAT AGGATGGCAA GATCCTGGTA TCGGTCTGCG ATTCCGACTC 720 GTCCAACATC AATACAACCT ATTAATTTCC CCTCGTCAAA AATAAGGTTA TCAAGTGAGA 780 AATCACCATG AGTGACGACT GAATCCGGTG AGAATGGCAA AAGTTTATGC ATTTCTTTCC 840 AGACTTGTTC AACAGGCCAG CCATTACGCT CGTCATCAAA ATCACTCGCA TCAACCAAAC 900 CGTTATTCAT TCGTGATTGC GCCTGAGCGA GACGAAATAC GCGATCGCTG TTAAAAGGAC 960 AATTACAAAC AGGAATCGAA TGCAACCGGC GCAGGAACAC TGCCAGCGCA TCAACAATAT 1020 TTTCACCTGA ATCAGGATAT TCTTCTAATA CCTGGAATGC TGTTTTCCCG GGGATCGCAG 1080 TGGTGAGTAA CCATGCATCA TCAGGAGTAC GGATAAAATG CTTGATGGTC GGAAGAGGCA 1140 TAAATTCCGT CAGCCAGTTT AGTCTGACCA TCTCATCTGT AACATCATTG GCAACGCTAC 1200 CTTTGCCATG TTTCAGAAAC AACTCTGGCG CATCGGGCTT CCCATACAAT CGATAGATTG 1260 TCGCACCTGA TTGCCCGACA TTATCGCGAG CCCATTTATA CCCATATAAA TCAGCATCCA 1320 TGTTGGAATT TAATCGCGGC CTAGAGCAAG ACGTTTCCCG TTGAATATGG CTCATAACAC 1380 CCCTTGTATT ACTGTTTATG TAAGCAGACA GTTTTATTGT TCATGACCAA AATCCCTTAA 1440 CGTGAGTTTT CGTTCCACTG AGCGTCAGAC CCCGTAGAAA AGATCAAAGG ATCTTCTTGA 1500 GATCCTTTTT TTCTGCGCGT AATCTGCTGC TTGCAAACAA AAAAACCACC GCTACCAGCG 1560 GTGGTTTGTT TGCCGGATCA AGAGCTACCA ACTCTTTTTC CGAAGGTAAC TGGCTTCAGC 1620 AGAGCGCAGA TACCAAATAC TGTCCTTCTA GTGTAGCCGT AGTTAGGCCA CCACTTCAAG 1680 AACTCTGTAG CACCGCCTAC ATACCTCGCT CTGCTAATCC TGTTACCAGT GGCTGCTGCC 1740 AGTGGCGATA AGTCGTGTCT TACCGGGTTG GACTCAAGAC GATAGTTACC GGATAAGGCG 1800 CAGCGGTCGG GCTGAACGGG GGGTTCGTGC ACACAGCCCA GCTTGGAGCG AACGACCTAC 1860 ACCGAACTGA GATACCTACA GCGTGAGCTA TGAGAAAGCG CCACGCTTCC CGAAGGGAGA 1920 AAGGCGGACA GGTATCCGGT AAGCGGCAGG GTCGGAACAG GAGAGCGCAC GAGGGAGCTT 1980 CCAGGGGGAA ACGCCTGGTA TCTTTATAGT CCTGTCGGGT TTCGCCACCT CTGACTTGAG 2040 CGTCGATTTT TGTGATGCTC GTCAGGGGGG CGGAGCCTAT GGAAAAACGC CAGCAACGCG 2100 GCCTTTTTAC GGTTCCTGGC CTTTTGCTGG CCTTTTGCTC ACATGTTCTT TCCTGCGTTA 2160 TCCCCTGATT CTGTGGATAA CCGTATTACC GCCTTTGAGT GAGCTGATAC CGCTCGCCGC 2220 AGCCGAACGA CCGAGCGCAG CGAGTCAGTG AGCGAGGAAG CGGAAGAGCG CCTGATGCGG 2280 TATTTTCTCC TTACGCATCT GTGCGGTATT TCACACCGCA TATATGGTGC ACTCTCAGTA 2340 CAATCTGCTC TGATGCCGCA TAGTTAAGCC AGTATACACT CCGCTATCGC TACGTGACTG 2400 GGTCATGGCT GCGCCCCGAC ACCCGCCAAC ACCCGCTGAC GCGCCCTGAC GGGCTTGTCT 2460 GCTCCCGGCA TCCGCTTACA GACAAGCTGT GACCGTCTCC GGGAGCTGCA TGTGTCAGAG 2520 GTTTTCACCG TCATCACCGA AACGCGCGAG GCAGCTGCGG TAAAGCTCAT CAGCGTGGTC 2580 GTGAAGCGAT TCACAGATGT CTGCCTGTTC ATCCGCGTCC AGCTCGTTGA GTTTCTCCAG 2640 AAGCGTTAAT GTCTGGCTTC TGATAAAGCG GGCCATGTTA AGGGCGGTTT TTTCCTGTTT 2700 GGTCACTGAT GCCTCCGTGT AAGGGGGATT TCTGTTCATG GGGGTAATGA TACCGATGAA 2760 ACGAGAGAGG ATGCTCACGA TACGGGTTAC TGATGATGAA CATGCCCGGT TACTGGAACG 2820 TTGTGAGGGT AAACAACTGG CGGTATGGAT GCGGCGGGAC CAGAGAAAAA TCACTCAGGG 2880 TCAATGCCAG CGCTTCGTTA ATACAGATGT AGGTGTTCCA CAGGGTAGCC AGCAGCATCC 2940 TGCGATGCAG ATCCGGAACA TAATGGTGCA GGGCGCTGAC TTCCGCGTTT CCAGACTTTA 3000 CGAAACACGG AAACCGAAGA CCATTCATGT TGTTGCTCAG GTCGCAGACG TTTTGCAGCA 3060 GCAGTCGCTT CACGTTCGCT CGCGTATCGG TGATTCATTC TGCTAACCAG TAAGGCAACC 3120 CCGCCAGCCT AGCCGGGTCC TCAACGACAG GAGCACGATC ATGCGCACCC GTGGGGCCGC 3180 CATGCCGGCG ATAATGGCCT GCTTCTCGCC GAAACGTTTG GTGGCGGGAC CAGTGACGAA 3240 GGCTTGAGCG AGGGCGTGCA AGATTCCGAA TACCGCAAGC GACAGGCCGA TCATCGTCGC 3300 GCTCCAGCGA AAGCGGTCCT CGCCGAAAAT GACCCAGAGC GCTGCCGGCA CCTGTCCTAC 3360 GAGTTGCATG ATAAAGAAGA CAGTCATAAG TGCGGCGACG ATAGTCATGC CCCGCGCCCA 3420 CCGGAAGGAG CTGACTGGGT TGAAGGCTCT CAAGGGCATC GGTCGAGATC CCGGTGCCTA 3480 ATGAGTGAGC TAACTTACAT TAATTGCGTT GCGCTCACTG CCCGCTTTCC AGTCGGGAAA 3540 CCTGTCGTGC CAGCTGCATT AATGAATCGG CCAACGCGCG GGGAGAGGCG GTTTGCGTAT 3600 TGGGCGCCAG GGTGGTTTTT CTTTTCACCA GTGAGAGGGG CAACAGCTGA TTGCCCTTCA 3660 CCGCCTGGCC CTGAGAGAGT TGCAGCAAGC GGTCCACGCT GGTTTGCCCC AGCAGGCGAA 3720 AATCCTGTTT GATGGTGGTT AACGGCGGGA TATAACATGA GCTGTCTTCG GTATCGTCGT 3780 ATCCCACTAC CGAGATATCC GCACCAACGC GCAGCCCGGA CTCGGTAATG GCGCGCATTG 3840 CGCCCAGCGC CATCTGATCG TTGGCAACCA GCATCGCAGT GGGAACGATG CCCTCATTCA 3900 GCATTTGCAT GGTTTGTTGA AAACCGGACA TGGCACTCCA GTCGCCTTCC CGTTCCGCTA 3960 TCGGCTGAAT TTGATTGCGA GTGAGATATT TATGCCAGCC AGCCAGACGC AGACGCGCCG 4020 AGACAGAACT TAATGGGCCC GCTAACAGCG CGATTTGCTG GTGACCCAAT GCGACCAGAT 4080 GCTCCACGCC CAGTCGCGTA CCGTCTTCAT GGGAGAAAAT AATACTGTTG ATGGGTGTCT 4140 GGTCAGAGAC ATCAAGAAAT AACGCCGGAA CATTAGTGCA GGCAGCTTCC ACAGCAATGG 4200 CATCCTGGTC ATCCAGCGGA TAGTTAATGA TCAGCCCACT GACGCGTTGC GCGAGAAGAT 4260 TGTGCACCGC CGCTTTACAG GCTTCGACGC CGCTTCGTTC TACCATCGAC ACCACCACGC 4320 TGGCACCCAG TTGATCGGCG CGAGATTTAA TCGCCGCGAC AATTTGCGAC GGCGCGTGCA 4380 GGGCCAGACT GGAGGTGGCA ACGCCAATCA GCAACGACTG TTTGCCCGCC AGTTGTTGTG 4440 CCACGCGGTT GGGAATGTAA TTCAGCTCCG CCATCGCCGC TTCCACTTTT TCCCGCGTTT 4500 TCGCAGAAAC GTGGCTGGCC TGGTTCACCA CGCGGGAAAC GGTCTGATAA GAGACACCGG 4560 CATACTCTGC GACATCGTAT AACGTTACTG GTTTCACATT CACCACCCTG AATTGACTCT 4620 CTTCCGGGCG CTATCATGCC ATACCGCGAA AGGTTTTGCG CCATTCGATG GTGTCCGGGA 4680 TCTCGACGCT CTCCCTTATG CGACTCCTGC ATTAGGAAGC AGCCCAGTAG TAGGTTGAGG 4740 CCGTTGAGCA CCGCCGCCGC AAGGAATGGT GCATGCAAGG AGATGGCGCC CAACAGTCCC 4800 CCGGCCACGG GGCCTGCCAC CATACCCACG CCGAAACAAG CGCTCATGAG CCCGAAGTGG 4860 CGAGCCCGAT CTTCCCCATC GGTGATGTCG GCGATATAGG CGCCAGCAAC CGCACCTGTG 4920 GCGCCGGTGA TGCCGGCCAC GATGCGTCCG GCGTAGAGGA TCGAGATCTC GATCCCGCGA 4980 AATTAATACG ACTCACTATA GGGGAATTGT GAGCGGATAA CAATTCCCCT CTAGAAATAA 5040 TTTTGTTTAA CTTTAAGAAG GAGATATACA TATGGGCCAT CATCATCATC ATCACGTGAT 5100 CGACATCATC GGGACCAGCC CCACATCCTG GGAACAGGCG GCGGCGGAGG CGGTCCAGCG 5160 GGCGCGGGAT AGCGTCGATG ACATCCGCGT CGCTCGGGTC ATTGAGCAGG ACATGGCCGT 5220 GGACAGCGCC GGCAAGATCA CCTACCGCAT CAAGCTCGAA GTGTCGTTCA AGATGAGGCC 5280 GGCGCAACCG AGGGGCTCGA AACCACCGAG CGGTTCGCCT GAAACGGGCG CCGGCGCCGG 5340 TACTGTCGCG ACTACCCCCG CGTCGTCGCC GGTGACGTTG GCGGAGACCG GTAGCACGCT 5400 GCTCTACCCG CTGTTCAACC TGTGGGGTCC GGCCTTTCAC GAGAGGTATC CGAACGTCAC 5460 GATCACCGCT CAGGGCACCG GTTCTGGTGC CGGGATCGCG CAGGCCGCCG CCGGGACGGT 5520 CAACATTGGG GCCTCCGACG CCTATCTGTC GGAAGGTGAT ATGGCCGCGC ACAAGGGGCT 5580 GATGAACATC GCGCTAGCCA TCTCCGCTCA GCAGGTCAAC TACAACCTGC CCGGAGTGAG 5640 CGAGCACCTC AAGCTGAACG GAAAAGTCCT GGCGGCCATG TACCAGGGCA CCATCAAAAC 5700 CTGGGACGAC CCGCAGATCG CTGCGCTCAA CCCCGGCGTG AACCTGCCCG GCACCGCGGT 5760 AGTTCCGCTG CACCGCTCCG ACGGGTCCGG TGACACCTTC TTGTTCACCC AGTACCTGTC 5820 CAAGCAAGAT CCCGAGGGCT GGGGCAAGTC GCCCGGCTTC GGCACCACCG TCGACTTCCC 5880 GGCGGTGCCG GGTGCGCTGG GTGAGAACGG CAACGGCGGC ATGGTGACCG GTTGCGCCGA 5940 GACACCGGGC TGCGTGGCCT ATATCGGCAT CAGCTTCCTC GACCAGGCCA GTCAACGGGG 6000 ACTCGGCGAG GCCCAACTAG GCAATAGCTC TGGCAATTTC TTGTTGCCCG ACGCGCAAAG 6060 CATTCAGGCC GCGGCGGCTG GCTTCGCATC GAAAACCCCG GCGAACCAGG CGATTTCGAT 6120 GATCGACGGG CCCGCCCCGG ACGGCTACCC GATCATCAAC TACGAGTACG CCATCGTCAA 6180 CAACCGGCAA AAGGACGCCG CCACCGCGCA GACCTTGCAG GCATTTCTGC ACTGGGCGAT 6240 CACCGACGGC AACAAGGCCT CGTTCCTCGA CCAGGTTCAT TTCCAGCCGC TGCCGCCCGC 6300 GGTGGTGAAG TTGTCTGACG CGTTGATCGC GACGATTTCC AGCGCTGAGA TGAAGACCGA 6360 TGCCGCTACC CTCGCGCAGG AGGCAGGTAA TTTCGAGCGG ATCTCCGGCG ACCTGAAAAC 6420 CCAGATCGAC CAGGTGGAGT CGACGGCAGG TTCGTTGCAG GGCCAGTGGC GCGGCGCGGC 6480 GGGGACGGCC GCCCAGGCCG CGGTGGTGCG CTTCCAAGAA GCAGCCAATA AGCAGAAGCA 6540 GGAACTCGAC GAGATCTCGA CGAATATTCG TCAGGCCGGC GTCCAATACT CGAGGGCCGA 6600 CGAGGAGCAG CAGCAGGCGC TGTCCTCGCA AATGGGCTTT GTGCCCACAA CGGCCGCCTC 6660 GCCGCCGTCG ACCGCTGCAG CGCCACCCGC ACCGGCGACA CCTGTTGCCC CCCCACCACC 6720 GGCCGCCGCC AACACGCCGA ATGCCCAGCC GGGCGATCCC AACGCAGCAC CTCCGCCGGC 6780 CGACCCGAAC GCACCGCCGC CACCTGTCAT TGCCCCAAAC GCACCCCAAC CTGTCCGGAT 6840 CGACAACCCG GTTGGAGGAT TCAGCTTCGC GCTGCCTGCT GGCTGGGTGG AGTCTGACGC 6900 CGCCCACTTC GACTACGGTT CAGCACTCCT CAGCAAAACC ACCGGGGACC CGCCATTTCC 6960 CGGACAGCCG CCGCCGGTGG CCAATGACAC CCGTATCGTG CTCGGCCGGC TAGACCAAAA 7020 GCTTTACGCC AGCGCCGAAG CCACCGACTC CAAGGCCGCG GCCCGGTTGG GCTCGGACAT 7080 GGGTGAGTTC TATATGCCCT ACCCGGGCAC CCGGATCAAC CAGGAAACCG TCTCGCTTGA 7140 CGCCAACGGG GTGTCTGGAA GCGCGTCGTA TTACGAAGTC AAGTTCAGCG ATCCGAGTAA 7200 GCCGAACGGC CAGATCTGGA CGGGCGTAAT CGGCTCGCCC GCGGCGAACG CACCGGACGC 7260 CGGGCCCCCT CAGCGCTGGT TTGTGGTATG GCTCGGGACC GCCAACAACC CGGTGGACAA 7320 GGGCGCGGCC AAGGCGCTGG CCGAATCGAT CCGGCCTTTG GTCGCCCCGC CGCCGGCGCC 7380 GGCACCGGCT CCTGCAGAGC CCGCTCCGGC GCCGGCGCCG GCCGGGGAAG TCGCTCCTAC 7440 CCCGACGACA CCGACACCGC AGCGGACCTT ACCGGCCTGA GAATTCTGCA GATATCCATC 7500 ACACTGGCGG CCGCTCGAGC ACCACCACCA CCACCACTGA GATCCGGCTG CTAACAAAGC 7560 CCGAAAGGAA GCTGAGTTGG CTGCTGCCAC CGCTGAGCAA TAACTAGCAT AACCCCTTGG 7620 GGCCTCTAAA CGGGTCTTGA GGGGTTTTTT GCTGAAAGGA GGAACTATAT CCGGAT 7676 (2) SEQ ID NO: 214 Information: ...

(i) sequence signature:

(A) length: 802 amino acid

(B) type: amino acid

(C) chain number: strand

(D) topology: linearity

(xi) sequence description: SEQ ID NO:214:Met Gly His His His His His His Val Ile Asp Ile Ile Gly Thr Ser1 5 10 15Pro Thr Ser Trp Glu Gln Ala Ala Ala Glu Ala Val Gln Arg Ala Arg

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

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

50??????????????????55??????????????????60Ser?Phe?Lys?Met?Arg?Pro?Ala?Gln?Pro?Arg?Gly?Ser?Lys?Pro?Pro?Ser65??????????????????70??????????????????75??????????????????80Gly?Ser?Pro?Glu?Thr?Gly?Ala?Gly?Ala?Gly?Thr?Val?Ala?Thr?Thr?Pro

85??????????????????90??????????????????95Ala?Ser?Ser?Pro?Val?Thr?Leu?Ala?Glu?Thr?Gly?Ser?Thr?Leu?Leu?Tyr

100?????????????????105?????????????????110Pro?Leu?Phe?Asn?Leu?Trp?Gly?Pro?Ala?Phe?His?Glu?Arg?Tyr?Pro?Asn

115?????????????????120?????????????????125Val?Thr?Ile?Thr?Ala?Gln?Gly?Thr?Gly?Ser?Gly?Ala?Gly?Ile?Ala?Gln

130?????????????????135?????????????????140Ala?Ala?Ala?Gly?Thr?Val?Asn?Ile?Gly?Ala?Ser?Asp?Ala?Tyr?Leu?Ser145?????????????????150?????????????????155?????????????????160Glu?Gly?Asp?Met?Ala?Ala?His?Lys?Gly?Leu?Met?Asn?Ile?Ala?Leu?Ala

165?????????????????170?????????????????175Ile?Ser?Ala?Gln?Gln?Val?Asn?Tyr?Asn?Leu?Pro?Gly?Val?Ser?Glu?His

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

195?????????????????200?????????????????205Lys?Thr?Trp?Asp?Asp?Pro?Gln?Ile?Ala?Ala?Leu?Asn?Pro?Gly?Val?Asn

210?????????????????215?????????????????220Leu?Pro?Gly?Thr?Ala?Val?Val?Pro?Leu?His?Arg?Ser?Asp?Gly?Ser?Gly225?????????????????230?????????????????235?????????????????240Asp?Thr?Phe?Leu?Phe?Thr?Gln?Tyr?Leu?Ser?Lys?Gln?Asp?Pro?Glu?Gly

245?????????????????250?????????????????255Trp?Gly?Lys?Ser?Pro?Gly?Phe?Gly?Thr?Thr?Val?Asp?Phe?Pro?Ala?Val

260?????????????????265?????????????????270Pro?Gly?Ala?Leu?Gly?Glu?Asn?Gly?Asn?Gly?Gly?Met?Val?Thr?Gly?Cys

275?????????????????280?????????????????285Ala?Glu?Thr?Pro?Gly?Cys?Val?Ala?Tyr?Ile?Gly?Ile?Ser?Phe?Leu?Asp

290?????????????????295?????????????????300Gln?Ala?Ser?Gln?Arg?Gly?Leu?Gly?Glu?Ala?Gln?Leu?Gly?Asn?Ser?Ser305?????????????????310?????????????????315?????????????????320Gly?Asn?Phe?Leu?Leu?Pro?Asp?Ala?Gln?Ser?Ile?Gln?Ala?Ala?Ala?Ala

325?????????????????330?????????????????335Gly?Phe?Ala?Ser?Lys?Thr?Pro?Ala?Asn?Gln?Ala?Ile?Ser?Met?Ile?Asp

340?????????????????345?????????????????350Gly?Pro?Ala?Pro?Asp?Gly?Tyr?Pro?Ile?Ile?Asn?Tyr?Glu?Tyr?Ala?Ile

355?????????????????360?????????????????365Val?Asn?Asn?Arg?Gln?Lys?Asp?Ala?Ala?Thr?Ala?Gln?Thr?Leu?Gln?Ala

370?????????????????375?????????????????380Phe?Leu?His?Trp?Ala?Ile?Thr?Asp?Gly?Asn?Lys?Ala?Ser?Phe?Leu?Asp385?????????????????390?????????????????395?????????????????400Cln?Val?His?Phe?Gln?Pro?Leu?Pro?Pro?Ala?Val?Val?Lys?Leu?Ser?Asp

405?????????????????410?????????????????415Ala?Leu?Ile?Ala?Thr?lle?Ser?Ser?Ala?Glu?Met?Lys?Thr?Asp?Ala?Ala

420?????????????????425?????????????????430Thr?Leu?Ala?Gln?Glu?Ala?Gly?Asn?Phe?Glu?Arg?Ile?Ser?Gly?Asp?Leu

435?????????????????440?????????????????445Lys?Thr?Gln?Ile?Asp?Gln?Val?Glu?Ser?Thr?Ala?Gly?Ser?Leu?Gln?Gly

450?????????????????455?????????????????460Gln?Trp?Arg?Gly?Ala?Ala?Gly?Thr?Ala?Ala?Gln?Ala?Ala?Val?Val?Arg465?????????????????470?????????????????475?????????????????480Phe?Gln?Glu?Ala?Ala?Asn?Lys?Gln?Lys?Gln?Glu?Leu?Asp?Glu?Ile?Ser

485?????????????????490?????????????????495Thr?Asn?Ile?Arg?Gln?Ala?Gly?Val?Gln?Tyr?Ser?Arg?Ala?Asp?Glu?Glu

500?????????????????505?????????????????510Gln?Gln?Gln?Ala?Leu?Ser?Ser?Gln?Met?Gly?Phe?Val?Pro?Thr?Thr?Ala

515?????????????????520?????????????????525Ala?Ser?Pro?Pro?Ser?Thr?Ala?Ala?Ala?Pro?Pro?Ala?Pro?Ala?Thr?Pro

530?????????????????535?????????????????540Val?Ala?Pro?Pro?Pro?Pro?Ala?Ala?Ala?Asn?Thr?Pro?Asn?Ala?Gln?Pro545?????????????????550?????????????????555?????????????????560Gly?Asp?Pro?Asn?Ala?Ala?Pro?Pro?Pro?Ala?Asp?Pro?Asn?Ala?Pro?Pro

565?????????????????570?????????????????575Pro?Pro?Val?Ile?Ala?Pro?Asn?Ala?Pro?Gln?Pro?Val?Arg?Ile?Asp?Asn

580?????????????????585?????????????????590Pro?Val?Gly?Gly?Phe?Ser?Phe?Ala?Leu?Pro?Ala?Gly?Trp?Val?Glu?Ser

595?????????????????600?????????????????605Asp?Ala?Ala?His?Phe?Asp?Tyr?Gly?Ser?Ala?Leu?Leu?Ser?Lys?Thr?Thr

610?????????????????615?????????????????620Gly?Asp?Pro?Pro?Phe?Pro?Gly?Gln?Pro?Pro?Pro?Val?Ala?Asn?Asp?Thr625?????????????????630?????????????????635?????????????????640Arg?Ile?Val?Leu?Gly?Arg?Leu?Asp?Gln?Lys?Leu?Tyr?Ala?Ser?Ala?Glu

645?????????????????650?????????????????655Ala?Thr?Asp?Ser?Lys?Ala?Ala?Ala?Arg?Leu?Gly?Ser?Asp?Met?Gly?Glu

660?????????????????665?????????????????670Phe?Tyr?Met?Pro?Tyr?Pro?Gly?Thr?Arg?Ile?Asn?Gln?Glu?Thr?Val?Ser

675?????????????????680?????????????????685Leu?Asp?Ala?Asn?Gly?Val?Ser?Gly?Ser?Ala?Ser?Tyr?Tyr?Glu?Val?Lys

690?????????????????695?????????????????700Phe?Ser?Asp?Pro?Ser?Lys?Pro?Asn?Gly?Gln?Ile?Trp?Thr?Gly?Val?Ile705?????????????????710?????????????????715?????????????????720Gly?Ser?Pro?Ala?Ala?Asn?Ala?Pro?Asp?Ala?Gly?Pro?Pro?Gln?Arg?Trp

725?????????????????730?????????????????735?Phe?Val?Val?Trp?Leu?Gly?Thr?Ala?Asn?Asn?Pro?Val?Asp?Lys?Gly?Ala

740?????????????????745?????????????????750Ala?Lys?Ala?Leu?Ala?Glu?Ser?Ile?Arg?Pro?Leu?Val?Ala?Pro?Pro?Pro

755?????????????????760?????????????????765Ala?Pro?Ala?Pro?Ala?Pro?Ala?Glu?Pro?Ala?Pro?Ala?Pro?Ala?Pro?Ala

770?????????????????775?????????????????780Gly?Glu?Val?Ala?Pro?Thr?Pro?Thr?Thr?Pro?Thr?Pro?Gln?Arg?Thr?Leu785?????????????????790?????????????????795?????????????????800Pro?Ala

Claims (37)

1. A polypeptide comprising an immunogenic part of a soluble Mycobacterium tuberculosis antigen or a variant of such an antigen that differs only in conservative substitutions and/or modifications, wherein the antigen has an N-terminal sequence selected from the group consisting of: (a) Asp-Pro-Val-Asp-Ala-Val-Ile-Asn-Thr-Thr-Cys-Asn-Tyr-Gly-Gln- Val-Val-Ala-Ala-Leu; (SEQ ID No.120) (b) Ala-Val-Glu-Ser-Gly-Met-Leu-Ala-Leu-Gly-Thr-Pro-Ala-Pro-Ser; (SEQ ID No.121)(c) Ala-Ala-Met-Lys-Pro-Arg-Thr-Gly-Asp-Gly-Pro-Leu-Glu-Ala-Ala- Lys-Glu-Gly-Arg; (SEQ ID No.122)(d) Tyr-Tyr-Trp-Cys-Pro-Gly-Gln-Pro-Phe-Asp-Pro-Ala-Trp-Gly-Pro; (SEQ ID No.123)(e) Asp-Ile-Gly-Ser-Glu-Ser-Thr-Glu-Asp-Gln-Gln-Xaa-Ala-Val; (SEQ ID No.124)(f) Ala-Glu-Glu-Ser-Ile-Ser-Thr-Xaa-Glu-Xaa-Ile-Val-Pro; (SEQ ID No. 125)(g) Asp-Pro-Glu-Pro-Ala-Pro-Pro-Val-Pro-Thr-Thr-Ala-Ala-Ser-Pro-Pro- Ser; (SEQ ID No.126)(h) Ala-Pro-Lys-Thr-Tyr-Xaa-Glu-Glu-Leu-Lys-Gly-Thr-Asp-Thr-Gly; (SEQ ID No.127)(i) Asp-Pro-Ala-Ser-Ala-Pro-Asp-Val-Pro-Thr-Ala-Ala-Gln-Leu-Thr-Ser- Leu-Leu-Asn-Ser-Leu-Ala-Asp-Pro-Asn-Val-Ser-Phe-Ala-Asn; (SEQ ID No.128) and (j) Ala-Pro-Glu-Ser-Gly-Ala-Gly-Leu-Gly-Gly-Thr-Val-Gln-Ala-Gly; (SEQ ID No.136) wherein Xaa can be any amino acid. 2. A polypeptide comprising an immunogenic part of a Mycobacterium tuberculosis antigen or a variant of such an antigen that differs only in conservative substitutions and/or modifications, wherein the antigen has an N-terminal sequence selected from the group consisting of: ( a) Asp-Pro-Pro-Asp-Pro-His-Gln-Xaa-Asp-Met-Thr-Lys-Gly-Tyr-Tyr- Pro-Gly-Gly-Arg-Arg-Xaa-Phe; (SEQ ID No. 129) and (b) Xaa-Tyr-Ile-Ala-Tyr-Xaa-Thr-Thr-Ala-Gly-Ile-Val-Pro -Gly-Lys-Ile- Asn-Val-His-Leu-Val; (SEQ ID No.137), wherein Xaa can be any amino acid. 3. A polypeptide comprising an immunogenic portion of a soluble Mycobacterium tuberculosis antigen or a variant of said antigen that differs only in conservative substitutions and/or modifications, wherein said antigen comprises a polypeptide selected from the group consisting of SEQ ID Nos.: 1, 2, 4-10, 13-25, 52, 99 and 101 listed sequences, complementary sequences of said sequences and under moderately stringent conditions with SEQ ID Nos.: 1, 2, 4-10, 13-25, The amino acid sequence encoded by the DNA sequence hybridizing to the sequences listed in 52, 99 and 101 or its complement. 4. A polypeptide comprising an immunogenic portion of a Mycobacterium tuberculosis antigen or a variant of said antigen that differs only in conservative substitutions and/or modifications, wherein said antigen comprises a polypeptide selected from the group consisting of SEQ ID Nos.: 26-51, The sequences listed in 138, 139, 163-183 and 201, the complementary sequences of said sequences and the sequences listed in SEQ ID Nos.: 26-51, 138, 139, 163-183 and 201 hybridize under moderately stringent conditions The amino acid sequence encoded by the DNA sequence of the DNA sequence or its complementary sequence. 5. A DNA molecule comprising a nucleotide sequence encoding a polypeptide according to any one of claims 1-4. 6. An expression vector comprising the DNA molecule of claim 5. 7. A host cell transformed with the expression vector of claim 6. 8. The host cell of claim 7, wherein the host cell is selected from the group consisting of Escherichia coli, yeast and mammalian cells. 9. A pharmaceutical composition comprising one or more polypeptides according to any one of claims 1-4 and a physiologically acceptable carrier. 10. A pharmaceutical composition comprising one or more DNA molecules according to claim 5 and a physiologically acceptable carrier. 11. A pharmaceutical composition comprising one or more DNA sequences of SEQ ID Nos: 3, 11, 12, 140 and 141; and a physiologically acceptable carrier. 12. A vaccine comprising one or more polypeptides according to any one of claims 1-4 and a non-specific immune response enhancer. 13. A vaccine comprising: A polypeptide having an N-terminal sequence selected from the sequences listed in SEQ ID No.: 134 and 135; and Non-specific immune response enhancer. 14. A vaccine comprising: One or more sequences selected from SEQ ID Nos.: 3, 11, 12, 140 and 141 listed, the complementary sequence of said sequence and SEQ ID Nos.: 3, 11, 12, 140 and 141 listed The sequence of the DNA sequence hybridizes to the DNA sequence encoding the polypeptide; and Non-specific immune response enhancer. 15. The vaccine of claims 12-14, wherein the non-specific immune response enhancer is an adjuvant. 16. A vaccine comprising one or more DNA molecules of claim 5 and a non-specific immune response enhancer. 17. A vaccine comprising one or more DNA sequences of SEQ ID Nos: 3, 11, 12, 140 and 141; and a non-specific immune response enhancer. 18. The vaccine of claim 16 or 17, wherein the non-specific immune response enhancer is an adjuvant. 19. The pharmaceutical composition according to any one of claims 9-11, for the preparation of a medicament for inducing protective immunity in a patient. 20. The vaccine according to any one of claims 12-18, for use in the manufacture of a medicament for inducing protective immunity in a patient. 21. A fusion protein comprising two or more polypeptides according to any one of claims 1-4. 22. A fusion protein comprising one or more polypeptides according to any one of claims 1-4 and ESAT-6. 23. A fusion protein comprising one or more polypeptides according to any one of claims 1-4 and Mycobacterium tuberculosis antigen 38kD (SEQ ID NO: 155). 24. A pharmaceutical composition comprising the fusion protein of any one of claims 21-23 and a pharmaceutically acceptable carrier. 25. A vaccine comprising a fusion protein according to any one of claims 21-23 and a non-specific immune response enhancer. 26. The vaccine of claim 25, wherein the non-specific immune response enhancer is an adjuvant. 27. The pharmaceutical composition according to claim 24, for the preparation of a medicament for inducing protective immunity in a patient. 28. The vaccine of claim 25 or 26 for use in the manufacture of a medicament for inducing protective immunity in a patient. 29. A method for diagnosing tuberculosis in a patient, comprising: (a) contacting a patient's skin cells with one or more of the polypeptides of any one of claims 1-4; and (b) Examining the immune response to the patient's skin to diagnose tuberculosis in the patient. 30. A method for diagnosing tuberculosis in a patient, comprising: (a) contacting the patient's skin cells with a polypeptide having an N-terminal sequence selected from the sequences shown in SEQ ID NO: 134 and 135; and (b) Examining the immune response to the patient's skin to diagnose tuberculosis in the patient. 31. A method for diagnosing tuberculosis in a patient, comprising: (a) using a sequence selected from SEQ ID Nos.: 3, 11, 12, 140, 141, 156-160, 189-193, 199, 200 and 203, the complementary sequence of said sequence and SEQ ID Nos.: 3, 11, 12, 140, 141, 156-160, 189-193, 199, 200, and 203 one or more polypeptides encoded by a DNA sequence that hybridizes to the sequences listed in 203 contact the patient's skin cells; and (b) Examining the immune response to the patient's skin to diagnose tuberculosis in the patient. 32. The method of any one of claims 29-31, wherein the immune response is induration. 33. Diagnostic kit, comprising: (a) the polypeptide of any one of claims 1-4; and (b) means sufficient to bring the polypeptide into contact with the patient's skin cells. 34. Diagnostic kit, comprising: (a) have the polypeptide that is selected from the N-terminal sequence of sequence shown in SEQ ID NO:134 and 135; With (b) means sufficient to bring the polypeptide into contact with the patient's skin cells. 35. Diagnostic kit, comprising: (a) a sequence selected from SEQ ID Nos.: 3, 11, 12, 140, 141, 156-160, 189-193, 199, 200 and 203, the complementary sequence of said sequence and SEQ ID Nos.: 3 , 11, 12, 140, 141, 156-160, 189-193, 199, 200, and 203 the polypeptides encoded by the DNA sequences hybridized to the DNA sequences; and (b) means sufficient to bring the polypeptide into contact with the patient's skin cells. 36. Diagnostic kit, comprising: (a) the fusion protein of any one of claims 21-23; and (b) means sufficient to bring the fusion protein into contact with the patient's skin cells. 37. The fusion protein of claim 23, comprising an amino acid sequence selected from the sequences listed in SEQ ID NO: 153 and 209.

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