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CN1818067A - Zoophobous fusion protein and use thereof - Google Patents

Zoophobous fusion protein and use thereof Download PDF

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CN1818067A
CN1818067A CN 200610049611 CN200610049611A CN1818067A CN 1818067 A CN1818067 A CN 1818067A CN 200610049611 CN200610049611 CN 200610049611 CN 200610049611 A CN200610049611 A CN 200610049611A CN 1818067 A CN1818067 A CN 1818067A
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沈志成
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Abstract

本发明公开了一种抗虫融合基因,该基因包括从5’-3’依次为含有编码BT晶体毒素的核苷酸序列和编码Vip3毒素的核苷酸序列;且上述2个核苷酸序列位于同一个开放阅读框内;BT晶体毒素为全长或是C端切除的活性毒素。本发明还公开了抗虫融合基因编码的融合蛋白,该融合蛋白从N端至C端依次为BT晶体毒素和Vip3毒素。本发明还公开了上述融合蛋白在转基因作物抗虫作物和转基因作物杀虫微生物方面的应用。

Figure 200610049611

The invention discloses an insect-resistant fusion gene, which comprises, from 5' to 3', a nucleotide sequence encoding BT crystal toxin and a nucleotide sequence encoding Vip3 toxin; and the above two nucleotide sequences Located in the same open reading frame; BT crystal toxin is a full-length or C-terminal excised active toxin. The invention also discloses a fusion protein encoded by the anti-insect fusion gene, the fusion protein is BT crystal toxin and Vip3 toxin in sequence from N terminal to C terminal. The invention also discloses the application of the above-mentioned fusion protein in transgenic crop insect-resistant crops and transgenic crop insecticidal microorganisms.

Figure 200610049611

Description

抗虫融合基因、融合蛋白及其应用Anti-insect fusion gene, fusion protein and application thereof

技术领域technical field

本发明涉及一种抗虫融合基因、此种抗虫融合基因编码的融合蛋白,及该融合蛋白的具体应用。The invention relates to an insect-resistant fusion gene, a fusion protein encoded by the insect-resistant fusion gene, and specific applications of the fusion protein.

背景技术Background technique

害虫给全球农业生产带来每年约80亿美元的损失。害虫的防治目前主要依靠使用化学农药,但是农药残留会对人体健康带来危害。因此,人们成功的选择了利用杀虫毒素转基因作物进行抗虫,目前转基因抗虫玉米和棉花已经大量种植。Pests cost global agricultural production an estimated $8 billion per year. The control of pests currently mainly relies on the use of chemical pesticides, but pesticide residues will cause harm to human health. Therefore, people have successfully selected transgenic crops using insecticidal toxins for insect resistance. At present, transgenic insect-resistant corn and cotton have been planted in large quantities.

转基因作物抗虫的关键技术是获得性能优良的杀虫蛋白质,杀虫蛋白质有多种。比较常用的是Bt晶体蛋白质(注1),例如Cry1Ab,Cry1C等,它们已被大量运用于转基因抗虫作物。但是目前已发现昆虫可以产生对晶体毒素的抗性,因此影响了这些晶体毒素抗虫性能和可利用性(注2)。另一种杀虫蛋白质是Vip3(注3),它与晶体毒素的杀虫机理不同,但对有些主要害虫的杀虫能力不高。另外,单个杀虫毒素无论是晶体毒素还是Vip3毒素,它的杀虫谱都比较窄;因此影响了害虫防治的效果,并且大量使用还容易引起产生抗性。The key technology for transgenic crops to resist insects is to obtain insecticidal proteins with excellent performance, and there are many kinds of insecticidal proteins. More commonly used are Bt crystal proteins (Note 1), such as Cry1Ab, Cry1C, etc., which have been widely used in transgenic insect-resistant crops. However, it has been found that insects can develop resistance to crystal toxins, thus affecting the insect resistance and availability of these crystal toxins (Note 2). Another insecticidal protein is Vip3 (Note 3), which has a different insecticidal mechanism from crystal toxins, but its insecticidal ability against some major pests is not high. In addition, whether a single insecticidal toxin is a crystal toxin or a Vip3 toxin, its insecticidal spectrum is relatively narrow; therefore, it affects the effect of pest control, and it is easy to cause resistance when used in large quantities.

因此,获得新型杀虫毒素,对提高杀虫能力和减缓害虫抗性的发生具有重要应用价值。Therefore, obtaining new insecticidal toxins has important application value for improving insecticidal ability and slowing down the occurrence of pest resistance.

参考文献如下:The references are as follows:

(1)、 Crickmore,N.Zeigler,D.R.Feitelson,J.Schnepf,E.Van Rie, J.Lereclus,D.Baum,J.Dean,D.H.(1998)Microbiol.Mol.Biol.Rev.62,807-813.(1), Crickmore, N. , Zeigler, DR , Feitelson, J., Schnepf, E. , Van Rie, J. , Lereclus, D. , Baum, J. & Dean, DH (1998) Microbiol.Mol.Biol .Rev.62, 807-813.

(2)、Ferre,J.& Van Rie,J.(2002)Annu.Rev.Entomol.47,501-533.(2), Ferre, J. & Van Rie, J. (2002) Annu. Rev. Entomol. 47, 501-533.

(3)、 Estruch,J.J.Warren,G.W.Mullins,M.A.Nye,G.J.Craig,J.A.&Koziel,M.G.(1996)Proc.Natl.Acad.Sci.USA 93,5389-5394.(3), Estruch, JJ , Warren, GW , Mullins, MA , Nye, GJ , Craig, JA & Koziel, MG (1996) Proc.Natl.Acad.Sci.USA 93, 5389-5394.

发明内容Contents of the invention

针对现有技术中存在的不足之处,本发明提供一种能提高杀虫能力和减缓害虫抗性的抗虫融合基因、该基因编码的融合蛋白以及该种融合蛋白的用途。Aiming at the deficiencies in the prior art, the present invention provides an insect-resistant fusion gene capable of improving insecticidal ability and slowing down pest resistance, a fusion protein encoded by the gene and an application of the fusion protein.

本发明为达到以上目的,是通过这样的技术方案来实现的:提供一种抗虫融合基因,该基因包括从5’-3’依次为含有编码BT晶体毒素的核苷酸序列和编码Vip3毒素的核苷酸序列;且上述2个核苷酸序列位于同一个开放阅读框内;BT晶体毒素为全长或是C端切除的活性毒素。In order to achieve the above object, the present invention is achieved through such a technical scheme: a kind of insect-resistant fusion gene is provided. and the above two nucleotide sequences are located in the same open reading frame; the BT crystal toxin is a full-length or C-terminal excised active toxin.

作为本发明的抗虫融合基因的一种改进:该基因包括从5’-3’依次为含有编码BT晶体毒素的核苷酸序列、任何的氨基酸多肽片断和编码Vip3毒素的核苷酸序列。As an improvement of the anti-insect fusion gene of the present invention: the gene includes, from 5' to 3', a nucleotide sequence encoding BT crystal toxin, any amino acid polypeptide fragment and a nucleotide sequence encoding Vip3 toxin.

作为本发明的抗虫融合基因的进一步改进:BT晶体毒素为Cry1Ab、Cry1Ac、Cry2或Cry3,Vip3毒素为Vip3A、Vip3B、Vip3C、Vip3D或Vip3H。As a further improvement of the insect-resistant fusion gene of the present invention: the BT crystal toxin is Cry1Ab, Cry1Ac, Cry2 or Cry3, and the Vip3 toxin is Vip3A, Vip3B, Vip3C, Vip3D or Vip3H.

作为本发明的抗虫融合基因的进一步改进:当BT晶体毒素为Cry1Ab、Vip3毒素为Vip3H时,基因的核苷酸序列为SEQ ID NO:1;当BT晶体毒素为Cry1Ab、Vip3毒素为Vip3A时,基因的核苷酸序列为SEQ ID NO:2。As a further improvement of the insect-resistant fusion gene of the present invention: when the BT crystal toxin is Cry1Ab and the Vip3 toxin is Vip3H, the nucleotide sequence of the gene is SEQ ID NO: 1; when the BT crystal toxin is Cry1Ab and the Vip3 toxin is Vip3A , the nucleotide sequence of the gene is SEQ ID NO:2.

本发明还提供了上述抗虫融合基因编码的融合蛋白,该融合蛋白从N端至C端依次为BT晶体毒素和Vip3毒素。The present invention also provides a fusion protein encoded by the above-mentioned anti-insect fusion gene, the fusion protein is BT crystal toxin and Vip3 toxin in sequence from N-terminus to C-terminus.

作为本发明的融合蛋白的一种改进:当BT晶体毒素为Cry1Ab、Vip3毒素为Vip3H时,融合蛋白的氨基酸序列为SEQ ID NO:3;当BT晶体毒素为Cry1Ab、Vip3毒素为Vip3A时,融合蛋白的氨基酸序列为SEQ ID NO:4。As an improvement of the fusion protein of the present invention: when the BT crystal toxin is Cry1Ab and the Vip3 toxin is Vip3H, the amino acid sequence of the fusion protein is SEQ ID NO: 3; when the BT crystal toxin is Cry1Ab and the Vip3 toxin is Vip3A, the fusion The amino acid sequence of the protein is SEQ ID NO:4.

本发明还提供了上述融合蛋白在转基因作物抗虫作物和转基因作物杀虫微生物方面的应用。The present invention also provides the application of the above-mentioned fusion protein in transgenic crop insect-resistant crops and transgenic crop insecticidal microorganisms.

本发明所设计的用一个Bt晶体毒素与一个Vip3毒素融合成的人工蛋白质分子,与原先的晶体蛋白质和Vip3蛋白质相比,具有如下优点:杀虫谱广,能杀灭粘虫、甜菜夜蛾、玉米螟、二化螟等害虫,杀虫率高达100%;而且可以有效的减缓害虫抗性的发生。Compared with the original crystal protein and Vip3 protein, the artificial protein molecule designed by the present invention, which is fused with a Bt crystal toxin and a Vip3 toxin, has the following advantages: it has a wide insecticidal spectrum and can kill armyworms and beet armyworms , corn borer, stem borer and other pests, the insecticidal rate is as high as 100%; and it can effectively slow down the occurrence of pest resistance.

附图说明Description of drawings

图1是本发明的融合杀虫蛋白的结构图;Fig. 1 is the structural diagram of fusion insecticidal protein of the present invention;

图2是融合毒素基因的制备过程图。Fig. 2 is a diagram of the preparation process of the fusion toxin gene.

具体实施方式Detailed ways

参照上述附图,对本发明的具体实施方式进行详细说明。Specific embodiments of the present invention will be described in detail with reference to the above-mentioned drawings.

实施例1、Cry1Ab-Vip3H融合毒素基因的制备:Example 1, Preparation of Cry1Ab-Vip3H fusion toxin gene:

编码Cry1Ab和Vip3H杀虫蛋白的基因均由上海生工合成,其DNA序列分别为SEQ ID NO:5和SEQ ID NO:6,并克隆在PET28a表达载体的限制性内切酶BamHI和SacI的位点之间。The genes encoding Cry1Ab and Vip3H insecticidal proteins were synthesized by Shanghai Sangong, and their DNA sequences were respectively SEQ ID NO: 5 and SEQ ID NO: 6, and were cloned at the positions of the restriction enzymes BamHI and SacI of the PET28a expression vector between points.

Cry1Ab-Vip3H合成过程如图2所示,具体步骤如下:The synthesis process of Cry1Ab-Vip3H is shown in Figure 2, and the specific steps are as follows:

1、由如下二引物经过PCR而获得Vip3H基因片断:V3HN 5’CTCCCC CGG GCC AGG TGG AAG TAA GCT CTC CAC CCG CGC CCT C,和V3HC 5’TCT TGA GCT CCT ACT TGA TGC TCA CGT CGT AGA AGT GCA。这二个引物分别包含限制性内切酶XmaI和SacI的位点。PCR的模板是Vip3H(SEQ ID NO:6)。1. The Vip3H gene fragment was obtained by PCR with the following two primers: V3HN 5'CTCCCC CGG GCC AGG TGG AAG TAA GCT CTC CAC CCG CGC CCT C, and V3HC 5'TCT TGA GCT CCT ACT TGA TGC TCA CGT CGT AGA AGT GCA. These two primers contain sites for the restriction enzymes XmaI and SacI, respectively. The template for PCR was Vip3H (SEQ ID NO: 6).

2、用XmaI和SacI处理PCR产物,并与用同样酶处理过的pET28a-Cry1Ab载体连接。2. Treat the PCR product with XmaI and SacI, and connect it with the pET28a-Cry1Ab vector treated with the same enzyme.

3、转入大肠杆菌,获得质粒为pET28a-Cry1Ab-Vip3H。融合毒素基因Cry1Ab-Vip3H(DNA序列3)被克隆在表达载体pET28a中。这个人工合成的Cry1Ab-Vip3H融合毒素基因的开放阅读框能表达一个分子量大约为150kD融合蛋白质。3. Transform into Escherichia coli to obtain the plasmid pET28a-Cry1Ab-Vip3H. The fusion toxin gene Cry1Ab-Vip3H (DNA sequence 3) was cloned in the expression vector pET28a. The open reading frame of the artificially synthesized Cry1Ab-Vip3H fusion toxin gene can express a fusion protein with a molecular weight of about 150kD.

实施例2、Cry1Ab-Vip3A融合毒素基因的制备:Example 2, Preparation of Cry1Ab-Vip3A fusion toxin gene:

编码Cry1Ab和Vip3A杀虫蛋白的基因均由上海生工合成,其DNA序列分别为SEQ ID NO:5和SEQ ID NO:7,并克隆在PET28a表达载体的限制性内切酶BamHI和SacI的位点之间。The genes encoding Cry1Ab and Vip3A insecticidal proteins were synthesized by Shanghai Sangong, and their DNA sequences were respectively SEQ ID NO: 5 and SEQ ID NO: 7, and were cloned at the positions of the restriction enzymes BamHI and SacI of the PET28a expression vector between points.

Cry1Ab-Vip3A合成过程如图2所示,具体步骤如下:The synthesis process of Cry1Ab-Vip3A is shown in Figure 2, and the specific steps are as follows:

1、由如下二引物经过PCR而获得Vip3H基因片断:V3AN 5’GGCCCC GGG ACC AAG CTG AGC ACC AGG GCC,和V3AC 5’TCT TGA GCTCCT ACT TGA TGC TCA CGT CGT AGA ACT TCA CG。这二个引物分别包含限制性内切酶XmaI和SacI的位点。PCR的模板是Vip3H(SEQ IDNO:7)。1. The Vip3H gene fragment was obtained by PCR with the following two primers: V3AN 5'GGCCCC GGG ACC AAG CTG AGC ACC AGG GCC, and V3AC 5'TCT TGA GCTCCT ACT TGA TGC TCA CGT CGT AGA ACT TCA CG. These two primers contain sites for the restriction enzymes XmaI and SacI, respectively. The template for PCR was Vip3H (SEQ ID NO: 7).

2、用XmaI和SacI处理PCR产物,并与用同样酶处理过的pET28a-Cry1Ab载体连接。2. Treat the PCR product with XmaI and SacI, and connect it with the pET28a-Cry1Ab vector treated with the same enzyme.

3、转入大肠杆菌,获得质粒为pET28a-Cry1Ab-Vip3A。融合毒素基因Cry1Ab-Vip3H(DNA序列3)被克隆在表达载体pET28a中。这个人工合成的Cry1Ab-Vip3A融合毒素基因的开放阅读框能表达一个分子量大约为150kD的融合蛋白质。3. Transform into Escherichia coli to obtain the plasmid pET28a-Cry1Ab-Vip3A. The fusion toxin gene Cry1Ab-Vip3H (DNA sequence 3) was cloned in the expression vector pET28a. The open reading frame of the artificially synthesized Cry1Ab-Vip3A fusion toxin gene can express a fusion protein with a molecular weight of about 150kD.

实施例3、Cry1Ab-Vip3H融合蛋白的制备:Example 3, Preparation of Cry1Ab-Vip3H fusion protein:

利用通用标准方法将含融合蛋白基因的表达载体pET28a-Cry1Ab-Vip3H被转入大肠杆菌BL21star.单个菌落接种到100毫升LB细菌培养液,37℃震动培养至OD600=0.6,加IPTG到0.5mM,继续在同样的条件下培养4小时。培养液5000g离心10分钟沉淀大肠杆菌细胞,然后弃上清收集沉淀。沉淀中加30毫升20mM Tris-HCl缓冲液,超声粉碎后即可用于杀虫活性的测定。The expression vector pET28a-Cry1Ab-Vip3H containing the fusion protein gene was transformed into Escherichia coli BL21star using a general standard method. A single colony was inoculated into 100 ml of LB bacterial culture medium, cultured with shaking at 37°C until OD 600 =0.6, and added IPTG to 0.5mM , and continued to incubate for 4 hours under the same conditions. The culture solution was centrifuged at 5000 g for 10 minutes to pellet the E. coli cells, and then the supernatant was discarded to collect the pellet. Add 30 ml of 20mM Tris-HCl buffer solution to the precipitate and ultrasonically pulverize it for the determination of insecticidal activity.

实施例4、Cry1Ab-Vip3A融合蛋白的制备:Example 4, Preparation of Cry1Ab-Vip3A fusion protein:

利用通用标准方法将含融合蛋白基因的表达载体pET28a-Cry1Ab-Vip3A被转入大肠杆菌BL21star.单个菌落接种到100毫升LB细菌培养液,37℃震动培养至OD600=0.6,加IPTG到0.5mM,继续在同样的条件下培养4小时。培养液5000g离心10分钟沉淀大肠杆菌细胞,然后弃上清收集沉淀。沉淀中加30毫升20mM Tris-HCl缓冲液,超声粉碎后即可用于杀虫活性的测定。The expression vector pET28a-Cry1Ab-Vip3A containing the fusion protein gene was transformed into Escherichia coli BL21star using a general standard method. A single colony was inoculated into 100 ml of LB bacterial culture medium, cultured with shaking at 37°C until OD 600 =0.6, and added IPTG to 0.5mM , and continued to incubate for 4 hours under the same conditions. The culture solution was centrifuged at 5000 g for 10 minutes to pellet the E. coli cells, and then the supernatant was discarded to collect the pellet. Add 30 ml of 20mM Tris-HCl buffer solution to the precipitate and ultrasonically pulverize it for the determination of insecticidal activity.

实施例5、在大肠杆菌中表达的Cry1Ab-Vip3H融合毒素对多种鳞翅目昆虫有杀伤作用:Example 5. The Cry1Ab-Vip3H fusion toxin expressed in Escherichia coli has killing effects on various Lepidoptera insects:

实施例3和实施例4所获得的Cry1Ab-Vip3H和Cry1Ab-Vip3A融合蛋白涂在昆虫人工饲料的表面,新生一龄幼虫用来进行杀虫活性测定。阴性对照的准备方法与实施例3相同,但质粒为不含任何插入DNA的pET28a载体本身。杀虫活性结果如表1所示:The Cry1Ab-Vip3H and Cry1Ab-Vip3A fusion proteins obtained in Example 3 and Example 4 were coated on the surface of the insect artificial diet, and the newborn first instar larvae were used to measure the insecticidal activity. The preparation method of the negative control was the same as in Example 3, but the plasmid was the pET28a vector itself without any inserted DNA. The insecticidal activity results are shown in Table 1:

            表1、Cry1Ab-Vip3H的杀虫率   粘虫   玉米螟   甜菜夜蛾   Cry1Ab   0%   100%   60%   Vip3H   100%   0%   100%   Vip3A   100%   0%   100%   Cry1Ab-Vip3H   100%   100%   100%   Cry1Ab-Vip3A   100%   100%   100%   阴性对照   0%   0%   0% Table 1. Insecticidal rate of Cry1Ab-Vip3H Armyworm corn borer beet armyworm Cry1Ab 0% 100% 60% Vip3H 100% 0% 100% Vip3A 100% 0% 100% Cry1Ab-Vip3H 100% 100% 100% Cry1Ab-Vip3A 100% 100% 100% negative control 0% 0% 0%

实施例6、转基因水稻Embodiment 6, transgenic rice

Cry1Ab-VipH转基因水稻的获得步骤如下:The steps for obtaining Cry1Ab-VipH transgenic rice are as follows:

1、Cry1Ab-Vip3H基因从pET28a-Cry1Ab-Vip3H(实施例1)利用BamHI和SacI切出。玉米Ubiqutin启动子用PCR方法从玉米基因组获得(其5’设有HindIII位点,3’设有BamHI位点),并用HindIII和BamHI处理。载体pCAM1300经过HindIII和SacI处理。以上3个DNA片段经连接酶而获得pCAMUbi-Cry1Ab-Vip3H植物转基因质粒。1. The Cry1Ab-Vip3H gene was excised from pET28a-Cry1Ab-Vip3H (Example 1) using BamHI and SacI. The maize Ubiqutin promoter was obtained from the maize genome (with a HindIII site at the 5' and a BamHI site at the 3') by PCR, and treated with HindIII and BamHI. Vector pCAM1300 was treated with HindIII and SacI. The above three DNA fragments are subjected to ligase to obtain the pCAMUbi-Cry1Ab-Vip3H plant transgenic plasmid.

2、应用基因枪把pCAMUbi-Cry1Ab-Vip3H打入水稻愈伤组织。应用目前已成熟的技术,以50mg/L hygromycin进行思想和培养,获得转基因水稻。2. Inject pCAMUbi-Cry1Ab-Vip3H into rice callus by gene gun. Apply the currently mature technology to obtain transgenic rice by thinking and cultivating with 50mg/L hygromycin.

实施例7、Cry1Ab-VipH在植物中表达可以杀虫:Example 7, expression of Cry1Ab-VipH in plants can kill insects:

Cry1Ab-Vip3H被克隆在玉米Ubiqutin启动子的控制下,用基因枪转入水稻,水稻的叶片的提取物可以杀死稻纵卷叶螟,二化螟,粘虫和玉米螟等害虫,杀虫效果如表2所示:Cry1Ab-Vip3H was cloned under the control of the corn Ubiqutin promoter and transferred into rice with a gene gun. The extract of rice leaves can kill rice leaf rollers, rice stem borers, armyworms and corn borers and other pests. The effect is shown in Table 2:

         表2   害虫   杀虫率   粘虫   100%   甜菜夜蛾   100%   玉米螟   100%   二化螟   100% Table 2 pest Insecticidal rate Armyworm 100% beet armyworm 100% corn borer 100% Chilo borer 100%

最后,还需要注意的是,以上列举的仅是本发明的若干个具体实施例。显然,本发明不限于以上实施例,还可以有许多变形。本领域的普通技术人员能从本发明公开的内容直接导出或联想到的所有变形,均应认为是本发明的保护范围。Finally, it should be noted that the above examples are only some specific embodiments of the present invention. Obviously, the present invention is not limited to the above embodiments, and many variations are possible. All deformations that can be directly derived or associated by those skilled in the art from the content disclosed in the present invention should be considered as the protection scope of the present invention.

                             序列表Sequence Listing

SEQ ID NO:1SEQ ID NO: 1

   1  ATGGACAACA ACCCCAACAT CAACGAGTGC ATCCCCTACA ACTGCCTGAG CAACCCCGAG1 ATGGACAACA ACCCCAACAT CAACGAGTGC ATCCCCTACA ACTGCCTGAG CAACCCCCGAG

  61  GTGGAGGTGC TGGGCGGCGA GCGCATCGAG ACCGGCTACA CCCCCATCGA CATCAGCCTG61 GTGGAGGTGC TGGGCGGCGA GCGCATCGAG ACCGGCTACA CCCCCATCGA CATCAGCCTG

 121  AGCCTGACCC AGTTCCTGCT GAGCGAGTTC GTGCCCGGCG CCGGCTTCGT GCTGGGCCTG121 AGCCTGACCC AGTTCCTGCT GAGCGAGTTC GTGCCCGGCG CCGGCTTCGT GCTGGGCCTG

 181  GTGGACATCA TCTGGGGCAT CTTCGGCCCC AGCCAGTGGG ACGCCTTCCT GGTGCAGATC181 GTGGACATCA TCTGGGGCAT CTTCGGCCCC AGCCAGTGGG ACGCCTTCCT GGTGCAGATC

 241  GAGCAGCTGA TCAACCAGCG CATCGAGGAG TTCGCCCGCA ACCAGGCCAT CAGCCGCCTG241 GAGCAGCTGA TCAACCAGCG CATCGAGGAG TTCGCCCGCA ACCAGGCCAT CAGCCGCCTG

 301  GAGGGCCTGA GCAACCTGTA CCAAATCTAC GCCGAGAGCT TCCGCGAGTG GGAGGCCGAC301 GAGGGCCTGA GCAACCTGTA CCAAATCTAC GCCGAGAGCT TCCGCGAGTG GGAGGCCGAC

 361  CCCACCAACC CCGCCCTGCG CGAGGAGATG CGCATCCAGT TCAACGACAT GAACAGCGCC361 CCCACCAACC CCGCCCTGCG CGAGGAGATG CGCATCCAGT TCAACGACAT GAACAGCGCC

 421  CTGACCACCG CCATCCCCCT GTTCGCCGTG CAGAACTACC AGGTGCCCCT GCTGAGCGTG421 CTGACCACCG CCATCCCCCT GTTCGCCGTG CAGAACTACC AGGTGCCCCT GCTGAGCGTG

 481  TACGTGCAGG CCGCCAACCT GCACCTGAGC GTGCTGCGCG ACGTCAGCGT GTTCGGCCAG481 TACGTGCAGG CCGCCAACCT GCACCTGAGC GTGCTGCGCG ACGTCAGCGT GTTCGGCCAG

 541  CGCTGGGGCT TCGACGCCGC CACCATCAAC AGCCGCTACA ACGACCTGAC CCGCCTGATC541 CGCTGGGGCT TCGACGCCGC CACCATCAAC AGCCGCTACA ACGACCTGAC CCGCCTGATC

 601  GGCAACTACA CCGACCACGC CGTGCGCTGG TACAACACCG GCCTGGAGCG CGTGTGGGGT601 GGCAACTACA CCGACCACGC CGTGCGCTGG TACAACACCG GCCTGGAGCG CGTGTGGGGT

 661  CCCGACAGCC GCGACTGGAT CAGGTACAAC CAGTTCCGCC GCGAGCTGAC CCTGACCGTG661 CCCGACAGCC GCGACTGGAT CAGGTACAAC CAGTTCCGCC GCGAGCTGAC CCTGACCGTG

 721  CTGGACATCG TGAGCCTGTT CCCCAACTAC GACAGCCGCA CCTACCCCAT CCGCACCGTG721 CTGGACATCG TGAGCCTGTT CCCCAACTAC GACAGCCGCA CCTACCCCAT CCGCACCGTG

 781  AGCCAGCTGA CCCGCGAGAT TTACACCAAC CCCGTGCTGG AGAACTTCGA CGGCAGCTTC781 AGCCAGCTGA CCCGCGAGAT TTACACCAAC CCCGTGCTGG AGAACTTCGA CGGCAGCTTC

 841  CGCGGCAGCG CCCAGGGCAT CGAGGGCAGC ATCCGCAGCC CCCACCTGAT GGACATCCTG841 CGCGGCAGCG CCCAGGGCAT CGAGGGCAGC ATCCGCAGCC CCCACCTGAT GGACATCCTG

 901  AACAGCATCA CCATCTACAC CGACGCCCAC CGCGGCGAGT ACTACTGGAG CGGCCACCAG901 AACAGCATCA CCATCTACAC CGACGCCCAC CGCGGCGAGT ACTACTGGAG CGGCCACCAG

 961  ATCATGGCCA GCCCCGTCGG CTTCAGCGGC CCCGAGTTCA CCTTCCCCCT GTACGGCACC961 ATCATGGCCA GCCCCGTCGG CTTCAGCGGC CCCGAGTTCA CCTTCCCCCT GTACGGCACC

1021  ATGGGCAACG CTGCACCTCA GCAGCGCATA GTGGCACAGC TGGGCCAGGG AGTGTACCGC1021 ATGGGCAACG CTGCACCTCA GCAGCGCATA GTGGCACAGC TGGGCCAGGG AGTGTACCGC

1081  ACCCTGAGCA GCACCCTGTA CCGTCGACCT TTCAACATCG GCATCAACAA CCAGCAGCTG1081 ACCCTGAGCA GCACCCTGTA CCGTCGACCT TTCAACATCG GCATCAACAA CCAGCAGCTG

1141  AGCGTGCTGG ACGGCACCGA GTTCGCCTAC GGCACCAGCA GCAACCTGCC CAGCGCCGTG1141 AGCGTGCTGG ACGGCACCGA GTTCGCCTAC GGCACCAGCA GCAACCTGCC CAGCGCCGTG

1201  TACCGCAAGA GCGGCACCGT GGACAGCCTG GACGAGATCC CCCCTCAGAA CAACAACGTG1201 TACCGCAAGA GCGGCACCGT GGACAGCCTG GACGAGATCC CCCCTCAGAA CAACAACGTG

1261  CCACCTCGAC AGGGCTTCAG CCACCGTCTG AGCCACGTGA GCATGTTCCG CAGTGGCTTC1261 CCACCTCGAC AGGGCTTCAG CCACCGTCTG AGCCACGTGA GCATGTTCCG CAGTGGCTTC

1321  AGCAACAGCA GCGTGAGCAT CATCCGTGCA CCTATGTTCA GCTGGATTCA CCGCAGTGCC1321 AGCAACAGCA GCGTGAGCAT CATCCGTGCA CCTATGTTCA GCTGGATTCA CCGCAGTGCC

1381  GAGTTCAACA ACATCATCCC CAGCAGCCAG ATCACCCAGA TCCCCCTGAC CAAGAGCACC1381 GAGTTCAACA ACATCATCCC CAGCAGCCAG ATCACCCAGA TCCCCCTGAC CAAGAGCACC

1441  AACCTGGGCA GCGGCACCAG CGTGGTGAAG GGCCCCGGCT TCACCGGCGG CGACATCCTG1441 AACCTGGGCA GCGGCACCAG CGTGGTGAAG GGCCCCGGCT TCACCGGCGG CGACATCCTG

1501  CGCCGCACCA GCCCCGGCCA GATCAGCACC CTGCGCGTGA ACATCACCGC CCCCCTGAGC1501 CGCCGCACCA GCCCCGGCCA GATCAGCACC CTGCGCGTGA ACATCACCGC CCCCCTGAGC

1561  CAGCGCTACC GCGTCCGCAT CCGCTACGCC AGCACCACCA ACCTGCAGTT CCACACCAGC1561 CAGCGCTACC GCGTCCGCAT CCGCTACGCC AGCACCACCA ACCTGCAGTT CCACACCAGC

1621  ATCGACGGCC GCCCCATCAA CCAGGGCAAC TTCAGCGCCA CCATGAGCAG CGGCAGCAAC1621 ATCGACGGCC GCCCCATCAA CCAGGGCAAC TTCAGCGCCA CCATGAGCAG CGGCAGCAAC

1681  CTGCAGAGCG GCAGCTTCCG CACCGTGGGC TTCACCACCC CCTTCAACTT CAGCAACGGC1681 CTGCAGAGCG GCAGCTTCCG CACCGTGGGC TTCACCACCC CCTTCAACTT CAGCAACGGC

1741  AGCAGCGTGT TCACCCTGAG CGCCCACGTG TTCAACAGCG GCAACGAGGT GTACATCGAC1741 AGCAGCGTGT TCACCCTGAG CGCCCACGTG TTCAACAGCG GCAACGAGGT GTACATCGAC

1801  CGCATCGAGT TCGTGCCCGC CGAGGTGACC TTCGAGGCCG AGTACGACCT GGAGAGGGCT1801 CGCATCGAGT TCGTGCCCGC CGAGGTGACC TTCGAGGCCG AGTACGACCT GGAGAGGGCT

1861  CAGAAGGCCG TGAACGAGCT GTTCACCAGC AGCAACCAGA TCGGCCTGAA GACCGACGTG1861 CAGAAGGCCG TGAACGAGCT GTTCACCAGC AGCAACCAGA TCGGCCTGAA GACCGACGTG

1921  ACCGACTACC ACATCGATCA GGTGCGAGGC CCCGGGCCAG GTGGAAGTAA GCTCTCCACC1921 ACCGACTACC ACATCGATCA GGTGCGAGGC CCCGGGCCAG GTGGAAGTAA GCTCTCCACC

1981  CGCGCCCTCC CGTCCTTCAT CGACTACTTC AACGGCATCT ACGGCTTCGC CACCGGCATC1981 CGCGCCCTCC CGTCCTTCAT CGACTACTTC AACGGCATCT ACGGCTTCGC CACCGGCATC

2041  AAGGACATCA TGAACATGAT CTTCAAGACC GACACCGGCG GCAACGTCAC CCTCGACGAG2041 AAGGACATCA TGAACATGAT CTTCAAGACC GACACCGGCG GCAACGTCAC CCTCGACGAG

2101  ATCCTCAAGA ACCAGCAGCT CCTCAACGAG ATCAGCGGCA AGCTCGACGG CGTGAACGGC2101 ATCCTCAAGA ACCAGCAGCT CCTCAACGAG ATCAGCGGCA AGCTCGACGG CGTGAACGGC

2161  TCCCTCAACG AGCTCATCGC CCAGGTCAAC CTCAACACCG AGCTGTCCAA GGAGATCCTC2161 TCCCTCAACG AGCTCATCGC CCAGGTCAAC CTCAACACCG AGCTGTCCAA GGAGATCCTC

2221  AAGATCTCCA ACGAGCAGAA CCAGGTGCTC AACGACGTGA ACAACAAGCT GGACGCCATC2221 AAGATCTCCA ACGAGCAGAA CCAGGTGCTC AACGACGTGA ACAACAAGCT GGACGCCATC

2281  AACACCATGC TGCACATCTA CCTCCCGAAG ATCACCTCCA TGCTCTCCGA CGTGATGAAG2281 AACACCATGC TGCACATCTA CCTCCCGAAG ATCACCTCCA TGCTCTCCGA CGTGATGAAG

2341  CAGAACTACG CCCTCTCCCT CCAGATCGAG TACCTCTCCA AGCAGCTCCA GGAGATCAGC2341 CAGAACTACG CCCTCTCCCT CCAGATCGAG TACCTCTCCA AGCAGTCCA GGAGATCAGC

2401  GACAAGCTCG ACATCATCAA CGTGAACGTG CTCATCAACT CCACCCTCAC CGAGATCACC2401 GACAAGCTCG ACATCATCAA CGTGAACGTG CTCATCAACT CCACCCTCAC CGAGATCACC

2461  CCGGCCTACC AGCGCATCAA GTACGTGAAC GAGAAGTTCG AGGAGCTGAC CTTCGCCACC2461 CCGGCCTACC AGCGCATCAA GTACGTGAAC GAGAAGTTCG AGGAGCTGAC CTTCGCCACC

2521  GAGACCACCC TCAAGGTGAA GAAGGACTCC TCCCCGGCCG ACATCCTCGA CGAGCTGACC2521 GAGACCACCC TCAAGGTGAA GAAGGACTCC TCCCCGGCCG ACATCCTCGA CGAGCTGACC

2581  GAGCTGACCG AGCTGGCCAA GTCCGTGACC AAGAACGACG TGGACGGCTT CGAGTTCTAC2581 GAGCTGACCG AGCTGGCCAA GTCCGTGACC AAGAACGACG TGGACGGCTT CGAGTTCTAC

2641  CTCAACACCT TCCACGACGT GATGGTGGGC AACAACCTCT TCGGCCGCTC CGCCCTCAAG2641 CTCAACACCT TCCACGACGT GATGGTGGGC AACAACCTCT TCGGCCGCTC CGCCCTCAAG

2701  ACCGCCTCCG AGCTGATCGC CAAGGAGAAC GTGAAGACCT CCGGCTCCGA GGTGGGCAAC2701 ACCGCCTCCG AGCTGATCGC CAAGGAGAAC GTGAAGACCT CCGGCTCCGA GGTGGGCAAC

2761  GTGTACAACT TCCTCATCGT GCTCACCGCC CTGCAGGCCA AGGCCTTCCT CACCCTCACC2761 GTGTACAACT TCCTCATCGT GCTCACCGCC CTGCAGGCCA AGGCCTTCCT CACCCTCACC

2821  ACCTGCCGCA AGCTCCTCGG CCTCGCCGGC ATCGACTACA CCTCCATCAT GAACGAGCAC2821 ACCTGCCGCA AGCTCCTCGG CCTCGCCGGC ATCGACTACA CCTCCATCAT GAACGAGCAC

2881  CTCAACAAGG AGAAGGAGGA GTTCCGCGTG AACATCCTCC CGACCCTCTC CAACACCTTC2881 CTCAACAAGG AGAAGGAGGA GTTCCGCGTG AACATCCTCC CGACCTCTCCAACACCTTC

2941  TCCAACCCGA ACTACGCCAA GGTGAAGGGC TCCGACGAGG ACGCCAAGAT GATCGTGGAG2941 TCCAACCCGA ACTACGCCAA GGTGAAGGGC TCCGACGAGG ACGCCAAGAT GATCGTGGAG

3001  GCCAAGCCGG GCCACGCCCT CGTGGGCTTC GAGATGTCCA ACGACTCCAT CACCGTGCTC3001 GCCAAGCCGG GCCACGCCCT CGTGGGCTTC GAGATGTCCA ACGACTCCAT CACCGTGCTC

3061  AAGGTGTACG AGGCCAAGCT CAAGCAGAAC TACCAGGTGG ACAAGGACTC CCTCTCCGAG3061 AAGGTGTACG AGGCCAAGCT CAAGCAGAAC TACCAGGTGG ACAAGGACTC CCTCTCCGAG

3121  GTGATCTACG GCGACACCGA CAAGCTCTTC TGCCCGGACC AGTCCGAGCA GATATACTAC3121 GTGATCTACG GCGACACCGA CAAGCTCTTC TGCCCGGACC AGTCCGAGCA GATATACTAC

3181  ACCAACAACA TCGTGTTCCC GAACGAGTAC GTGATCACCA AGATCGACTT CACCAAGAAG3181 ACCAACAACA TCGTGTTCCC GAACGAGTAC GTGATCACCA AGATCGACTT CACCAAGAAG

3241  ATGAAGACCC TCCGCTACGA GGTGACCGCC AACTTCTACG ACTCCTCCAC CGGCGAGATC3241 ATGAAGACCC TCCGCTACGA GGTGACCGCC AACTTCTACG ACTCCTCCAC CGGCGAGATC

3301  GACCTCAACA AGAAGAAGGT GGAGTCCTCC GAGGCCGAGT ACCGCACCCT CTCCGCCAAC3301 GACCTCAACA AGAAGAAGGT GGAGTCCTCC GAGGCCGAGT ACCGCACCCT CTCCGCCAAC

3361  GACGACGGCG TGTACATGCC GCTCGGCGTG ATCTCCGAAA CCTTCCTCAC CCCGATCAAC3361 GACGACGGCG TGTACATGCC GCTCGGCGTG ATCTCCGAAA CCTTCCTCAC CCCGATCAAC

3421  GGCTTCGGCC TCCAGGCCGA CGAGAACTCC CGCCTCATCA CCCTCACCTG CAAGTCCTAC3421 GGCTTCGGCC TCCAGGCCGA CGAGAACTCC CGCCTCATCA CCCTCACCTG CAAGTCCTAC

3481  CTCCGCGAGC TGCTCCTCGC CACCGACCTC TCCAACAAGG AGACCAAGCT CATCGTGCCG3481 CTCCGCGAGC TGCTCCTCGC CACCGACCTC TCCAACAAGG AGACCAAGCT CATCGTGCCG

3541  CCGTCCGGCT TCATCTCCAA CATCGTGGAG AACGGCGCCA TCGAGGAGGA CAACCTCGAG3541 CCGTCCGGCT TCATCTCCAA CATCGTGGAG AACGGCGCCA TCGAGGAGGA CAACCTCGAG

3601  CCGTGGAAGG CCAACAACAA GAACGCCTAC GTGGACCACA CCGGCGGCGT GAACGGCACC3601 CCGTGGAAGG CCAACAACAA GAACGCCTAC GTGGACCACA CCGGCGGCGT GAACGGCACC

3661  AAGGCCCTCT ACGTGCACAA GGACGGCGGC TTCTCCCAGT TCATCGGCGA CAAGCTCAAG3661 AAGGCCCTCT ACGTGCACAA GGACGGCGGC TTCTCCCAGT TCATCGGCGA CAAGCTCAAG

3721  CCGAAGACCG AGTACGTGAT CCAGTACACC GTGAAGGGCA AGGCCAGCAT CTACCTGAAG3721 CCGAAGACCG AGTACGTGAT CCAGTACACC GTGAAGGGCA AGGCCAGCAT CTACCTGAAG

3781  GACGAGAAGA ACAACGAGGG CATCTACGAG GAGATCAACA ACGACCTGGA GGACTTCCAG3781 GACGAGAAGA ACAACGAGGG CATCTACGAG GAGATCAACA ACGACCTGGA GGACTTCCAG

3841  ACCGTGACCA AGAGGTTCAT CACCGGCACC GACAGCAGCG GCGTGCACCT GATCTTCACC3841 ACCGTGACCA AGAGGTTCAT CACCGGCACC GACAGCAGCG GCGTGCACCT GATTCTTCACC

3901  AGCCAGAACG GCGACGAGGC CTTCGGCGGC AACTTCATCA TCAGCGAGAT CAGGAGCAGC3901 AGCCAGAACG GCGACGAGGC CTTCGGCGGC AACTTCATCA TCAGCGAGAT CAGGAGCAGC

3961  GAGGAGCTGC TGAGCCCGGA GCTGATCAAG AGCGACGCCT GGGTGGGCAG CCAGGGCACC3961 GAGGAGCTGC TGAGCCCGGA GCTGATCAAG AGCGACGCCT GGGTGGGCAG CCAGGGCACC

4021  TGGATCAGCG GCAACAGCCT GACCATCAAC AGCAACGCCA ACGGCACCTT CAGGCAGAAC4021 TGGATCAGCG GCAACAGCT GACCATCAAC AGCAACGCCA ACGGCACCTT CAGGCAGAAC

4081  CTGCCGCTGG AGAGCTACAG CACCTACAGC ATGAACTTCA ACGTGAACGG CTTCGCCAAG4081 CTGCCGCTGG AGAGCTACAG CACCTACAGC ATGAACTTCA ACGTGAACGG CTTCGCCAAG

4141  GTGACCGTGA GGAACAGCAG GGAGGTGCTG TTCGAGAAGA ACTTCAGCCA GCTGAGCCCG4141 GTGACCGTGA GGAACAGCAG GGAGGTGCTG TTCGAGAAGA ACTTCAGCCA GCTGAGCCCG

4201  AAGGACTACA GCGAGAAGTT CACCACCGCC GCCAACAACA CCGGCTTCTA CGTGGAGCTG4201 AAGGACTACA GCGAGAAGTT CACCACCGCC GCCAACAACA CCGGCTTCTA CGTGGAGCTG

4261  AGCAGGGGCA CCCAGGGCGG CAACATCACC TTCAGGGACT TCAGCATCAA GTAA4261 AGCAGGGGCA CCCAGGGCGG CAACATCACC TTCAGGGACT TCAGCATCAA GTAA

SEQ ID NO:2SEQ ID NO: 2

   1  ATGGACAACA ACCCCAACAT CAACGAGTGC ATCCCCTACA ACTGCCTGAG CAACCCCGAG1 ATGGACAACA ACCCCAACAT CAACGAGTGC ATCCCCTACA ACTGCCTGAG CAACCCCCGAG

  61  GTGGAGGTGC TGGGCGGCGA GCGCATCGAG ACCGGCTACA CCCCCATCGA CATCAGCCTG61 GTGGAGGTGC TGGGCGGCGA GCGCATCGAG ACCGGCTACA CCCCCATCGA CATCAGCCTG

 121  AGCCTGACCC AGTTCCTGCT GAGCGAGTTC GTGCCCGGCG CCGGCTTCGT GCTGGGCCTG121 AGCCTGACCC AGTTCCTGCT GAGCGAGTTC GTGCCCGGCG CCGGCTTCGT GCTGGGCCTG

 181  GTGGACATCA TCTGGGGCAT CTTCGGCCCC AGCCAGTGGG ACGCCTTCCT GGTGCAGATC181 GTGGACATCA TCTGGGGCAT CTTCGGCCCC AGCCAGTGGG ACGCCTTCCT GGTGCAGATC

 241  GAGCAGCTGA TCAACCAGCG CATCGAGGAG TTCGCCCGCA ACCAGGCCAT CAGCCGCCTG241 GAGCAGCTGA TCAACCAGCG CATCGAGGAG TTCGCCCGCA ACCAGGCCAT CAGCCGCCTG

 301  GAGGGCCTGA GCAACCTGTA CCAAATCTAC GCCGAGAGCT TCCGCGAGTG GGAGGCCGAC301 GAGGGCCTGA GCAACCTGTA CCAAATCTAC GCCGAGAGCT TCCGCGAGTG GGAGGCCGAC

 361  CCCACCAACC CCGCCCTGCG CGAGGAGATG CGCATCCAGT TCAACGACAT GAACAGCGCC361 CCCACCAACC CCGCCCTGCG CGAGGAGATG CGCATCCAGT TCAACGACAT GAACAGCGCC

 421  CTGACCACCG CCATCCCCCT GTTCGCCGTG CAGAACTACC AGGTGCCCCT GCTGAGCGTG421 CTGACCACCG CCATCCCCCT GTTCGCCGTG CAGAACTACC AGGTGCCCCT GCTGAGCGTG

 481  TACGTGCAGG CCGCCAACCT GCACCTGAGC GTGCTGCGCG ACGTCAGCGT GTTCGGCCAG481 TACGTGCAGG CCGCCAACCT GCACCTGAGC GTGCTGCGCG ACGTCAGCGT GTTCGGCCAG

 541  CGCTGGGGCT TCGACGCCGC CACCATCAAC AGCCGCTACA ACGACCTGAC CCGCCTGATC541 CGCTGGGGCT TCGACGCCGC CACCATCAAC AGCCGCTACA ACGACCTGAC CCGCCTGATC

 601  GGCAACTACA CCGACCACGC CGTGCGCTGG TACAACACCG GCCTGGAGCG CGTGTGGGGT601 GGCAACTACA CCGACCACGC CGTGCGCTGG TACAACACCG GCCTGGAGCG CGTGTGGGGT

 661  CCCGACAGCC GCGACTGGAT CAGGTACAAC CAGTTCCGCC GCGAGCTGAC CCTGACCGTG661 CCCGACAGCC GCGACTGGAT CAGGTACAAC CAGTTCCGCC GCGAGCTGAC CCTGACCGTG

 721  CTGGACATCG TGAGCCTGTT CCCCAACTAC GACAGCCGCA CCTACCCCAT CCGCACCGTG721 CTGGACATCG TGAGCCTGTT CCCCAACTAC GACAGCCGCA CCTACCCCAT CCGCACCGTG

 781  AGCCAGCTGA CCCGCGAGAT TTACACCAAC CCCGTGCTGG AGAACTTCGA CGGCAGCTTC781 AGCCAGCTGA CCCGCGAGAT TTACACCAAC CCCGTGCTGG AGAACTTCGA CGGCAGCTTC

 841  CGCGGCAGCG CCCAGGGCAT CGAGGGCAGC ATCCGCAGCC CCCACCTGAT GGACATCCTG841 CGCGGCAGCG CCCAGGGCAT CGAGGGCAGC ATCCGCAGCC CCCACCTGAT GGACATCCTG

 901  AACAGCATCA CCATCTACAC CGACGCCCAC CGCGGCGAGT ACTACTGGAG CGGCCACCAG901 AACAGCATCA CCATCTACAC CGACGCCCAC CGCGGCGAGT ACTACTGGAG CGGCCACCAG

 961  ATCATGGCCA GCCCCGTCGG CTTCAGCGGC CCCGAGTTCA CCTTCCCCCT GTACGGCACC961 ATCATGGCCA GCCCCGTCGG CTTCAGCGGC CCCGAGTTCA CCTTCCCCCT GTACGGCACC

1021  ATGGGCAACG CTGCACCTCA GCAGCGCATA GTGGCACAGC TGGGCCAGGG AGTGTACCGC1021 ATGGGCAACG CTGCACCTCA GCAGCGCATA GTGGCACAGC TGGGCCAGGG AGTGTACCGC

1081  ACCCTGAGCA GCACCCTGTA CCGTCGACCT TTCAACATCG GCATCAACAA CCAGCAGCTG1081 ACCCTGAGCA GCACCCTGTA CCGTCGACCT TTCAACATCG GCATCAACAA CCAGCAGCTG

1141  AGCGTGCTGG ACGGCACCGA GTTCGCCTAC GGCACCAGCA GCAACCTGCC CAGCGCCGTG1141 AGCGTGCTGG ACGGCACCGA GTTCGCCTAC GGCACCAGCA GCAACCTGCC CAGCGCCGTG

1201  TACCGCAAGA GCGGCACCGT GGACAGCCTG GACGAGATCC CCCCTCAGAA CAACAACGTG1201 TACCGCAAGA GCGGCACCGT GGACAGCCTG GACGAGATCC CCCCTCAGAA CAACAACGTG

1261  CCACCTCGAC AGGGCTTCAG CCACCGTCTG AGCCACGTGA GCATGTTCCG CAGTGGCTTC1261 CCACCTCGAC AGGGCTTCAG CCACCGTCTG AGCCACGTGA GCATGTTCCG CAGTGGCTTC

1321  AGCAACAGCA GCGTGAGCAT CATCCGTGCA CCTATGTTCA GCTGGATTCA CCGCAGTGCC1321 AGCAACAGCA GCGTGAGCAT CATCCGTGCA CCTATGTTCA GCTGGATTCA CCGCAGTGCC

1381  GAGTTCAACA ACATCATCCC CAGCAGCCAG ATCACCCAGA TCCCCCTGAC CAAGAGCACC1381 GAGTTCAACA ACATCATCCC CAGCAGCCAG ATCACCCAGA TCCCCCTGAC CAAGAGCACC

1441  AACCTGGGCA GCGGCACCAG CGTGGTGAAG GGCCCCGGCT TCACCGGCGG CGACATCCTG1441 AACCTGGGCA GCGGCACCAG CGTGGTGAAG GGCCCCGGCT TCACCGGCGG CGACATCCTG

1501  CGCCGCACCA GCCCCGGCCA GATCAGCACC CTGCGCGTGA ACATCACCGC CCCCCTGAGC1501 CGCCGCACCA GCCCCGGCCA GATCAGCACC CTGCGCGTGA ACATCACCGC CCCCCTGAGC

1561  CAGCGCTACC GCGTCCGCAT CCGCTACGCC AGCACCACCA ACCTGCAGTT CCACACCAGC1561 CAGCGCTACC GCGTCCGCAT CCGCTACGCC AGCACCACCA ACCTGCAGTT CCACACCAGC

1621  ATCGACGGCC GCCCCATCAA CCAGGGCAAC TTCAGCGCCA CCATGAGCAG CGGCAGCAAC1621 ATCGACGGCC GCCCCATCAA CCAGGGCAAC TTCAGCGCCA CCATGAGCAG CGGCAGCAAC

1681  CTGCAGAGCG GCAGCTTCCG CACCGTGGGC TTCACCACCC CCTTCAACTT CAGCAACGGC1681 CTGCAGAGCG GCAGCTTCCG CACCGTGGGC TTCACCACCC CCTTCAACTT CAGCAACGGC

1741  AGCAGCGTGT TCACCCTGAG CGCCCACGTG TTCAACAGCG GCAACGAGGT GTACATCGAC1741 AGCAGCGTGT TCACCCTGAG CGCCCACGTG TTCAACAGCG GCAACGAGGT GTACATCGAC

1801  CGCATCGAGT TCGTGCCCGC CGAGGTGACC TTCGAGGCCG AGTACGACCT GGAGAGGGCT1801 CGCATCGAGT TCGTGCCCGC CGAGGTGACC TTCGAGGCCG AGTACGACCT GGAGAGGGCT

1861  CAGAAGGCCG TGAACGAGCT GTTCACCAGC AGCAACCAGA TCGGCCTGAA GACCGACGTG1861 CAGAAGGCCG TGAACGAGCT GTTCACCAGC AGCAACCAGA TCGGCCTGAA GACCGACGTG

1921  ACCGACTACC ACATCGATCA GGTGCGAGGC CCCGGGACCA AGCTGAGCAC CAGGGCCCTG1921 ACCGACTACC ACATCGATCA GGTGCGAGGC CCCGGGACCA AGCTGAGCAC CAGGGCCCTG

1981  CCGAGCTTCA TCGACTACTT CAACGGCATC TACGGCTTCG CCACCGGCAT CAAGGACATC1981 CCGAGCTTCA TCGACTACTT CAACGGCATC TACGGCTTCG CCACCGGCAT CAAGGACATC

2041  ATGAACATGA TCTTCAAGAC CGACACCGGC GGCGACCTGA CCCTGGACGA GATCCTGAAG2041 ATGAACATGA TCTTCAAGAC CGACACCGGC GGCGACCTGA CCCTGGACGA GATCCTGAAG

2101  AACCAGCAGC TGCTGAACGA CATCAGCGGC AAGCTGGACG GCGTGAACGG CAGCCTGAAC2101 AACCAGCAGC TGCTGAACGA CATCAGCGGC AAGCTGGACG GCGTGAACGG CAGCCTGAAC

2161  GACCTGATCG CCCAGGGCAA CCTGAACACC GAGCTGAGCA AGGAGATCCT GAAGATCGCC2161 GACCTGATCG CCCAGGGCAA CCTGAACACC GAGCTGAGCA AGGAGATCCT GAAGATCGCC

2221  AACGAGCAGA ACCAGGTGCT GAACGACGTG AACAACAAGC TGGACGCCAT CAACACCATG2221 AACGAGCAGA ACCAGGTGCT GAACGACGTG AACAACAAGC TGGACGCCAT CAACACCATG

2281  CTGAGGGTGT ACCTGCCGAA GATCACCAGC ATGCTGAGCG ACGTGATGAA GCAGAACTAC2281 CTGAGGGTGT ACCTGCCGAA GATCACCAGC ATGCTGAGCG ACGTGATGAA GCAGAACTAC

2341  GCCCTGAGCC TGCAGATCGA GTACCTGAGC AAGCAGCTGC AGGAGATCAG CGACAAGCTG2341 GCCCTGAGCC TGCAGATCGA GTACCTGAGC AAGCAGCTGC AGGAGATCAG CGACAAGCTG

2401  GACATCATCA ACGTGAACGT GCTGATCAAC AGCACCCTGA CCGAGATCAC CCCGGCCTAC2401 GACATCATCA ACGTGAACGT GCTGATCAAC AGCACCCTGA CCGAGATCAC CCCGGCCTAC

2461  CAGAGGATCA AGTACGTGAA CGAGAAGTTC GAGGAGCTGA CCTTCGCCAC CGAGACCAGC2461 CAGAGGATCA AGTACGTGAA CGAGAAGTTC GAGGAGCTGA CCTTCGCCAC CGAGACCAGC

2521  AGCAAGGTGA AGAAGGACGG CAGCCCGGCC GACATCCTGG ACGAGCTGAC CGAGCTGACC2521 AGCAAGGTGA AGAAGGACGG CAGCCCGGCC GACATCCTGG ACGAGCTGAC CGAGCTGACC

2581  GGCCTGGCCA AGAGCGTGCC GAAGAACGAC GTGGACGGCT TCGAGTTCTA CCTGAACACC2581 GGCCTGGCCA AGAGCGTGCC GAAGAACGAC GTGGACGGCT TCGAGTTCTA CCTGAACACC

2641  TTCCACGACG TGATGGTGGG CAACAACCTG TTCGGCAGGA GCGCCCTGAA GACCGCCAGC2641 TTCCACGACG TGATGGTGGG CAACAACCTG TTCGGCAGGA GCGCCCTGAA GACCGCCAGC

2701  GAGCTGATCA CCAAGGAGAA CGTGAAGACC AGCGGCAGCG AGGTGGGCAA CGTGTACAAC2701 GAGCTGATCA CCAAGGAGAA CGTGAAGACC AGCGGCAGCG AGGTGGGCAA CGTGTACAAC

2761  AGCCTGATCG TGCTGACCCT GCTGCAGGCC AAGGCCTTCC TGACCCTGAC CACCTGCAGG2761 AGCCTGATCG TGCTGACCCT GCTGCAGGCC AAGGCCTTCC TGACCCTGAC CACCTGCAGG

2821  AAGCTGCTGG GCCTGGCCGA CATCGACTAC ACCAGCATCA TGAACGAGCA CCTGAACAAG2821 AAGCTGCTGG GCCTGGCCGA CATCGACTAC ACCAGCATCA TGAACGAGCA CCTGAACAAG

2881  GAGAAGGAGG AGTTCAGGGT GAACATCCCG CCGACCCTGA GCAACACCTT CAGCAACCCG2881 GAGAAGGAGG AGTTCAGGGT GAACATCCCG CCGACCCTGA GCAACACCTT CAGCAACCCG

2941  AACTACGCCA AGGTGAAGGG CAGCGACGAG GACGCCAAGA TGATCGTGGA GGCCAAGCCG2941 AACTACGCCA AGGTGAAGGG CAGCGACGAG GACGCCAAGA TGATCGTGGA GGCCAAGCCG

3001  GGCCACGCCC TGGTGGGCTT CGAGATCAGC AACGACAGCA TCACCGTGCT GAAGGTGTAC3001 GGCCACGCCC TGGTGGGCTT CGAGATCAGC AACGACAGCA TCACCGTGCT GAAGGTGTAC

3061  GAGGCCAAGC TGAAGCAGAA CTACCAGGTG GACAAGGACA GCCTGAGCGA GGTGATCTAC3061 GAGGCCAAGC TGAAGCAGAA CTACCAGGTG GACAAGGACA GCCTGAGCGA GGTGATCTAC

3121  GGCGACATGG ACAAGCTGCT GGGCCCGGAC CAGAGCGGCC CGATCTACTA CCCGAACAAC3121 GGCGACATGG ACAAGCTGCT GGGCCCGGAC CAGAGCGGCC CGATCTACTA CCCGAACAAC

3181  ATCGTGTTCC CGAACGAGTA CGTGATCACC AAGATCGACT TCACCAAGAA GATGAAGACC3181 ATCGTGTTCC CGAACGAGTA CGTGATCACC AAGATCGACT TCACCAAGAA GATGAAGACC

3241  CTGAGGTACG AGGTGACCGC CAACTTCTAC GACAGCAGCA CCGGCGAGAT CGACCTGAAC3241 CTGAGGTACG AGGTGACCGC CAACTTCTAC GACAGCAGCA CCGGCGAGAT CGACCTGAAC

3301  AAGAAGAAGG TGGAGAGCAG CGAGGCCGAG TACAGGACCC TGAGCGCCAA CGACGACGGC3301 AAGAAGAAGG TGGAGAGCAG CGAGGCCGAG TACAGGACCC TGAGCGCCAA CGACGACGGC

3361  GTGTACATGC CGCTGGGCGT GATCAGCGAG ACCTTCCTGA CCCCGATCAA CGGCTTCGGC3361 GTGTACATGC CGCTGGGCGT GATCAGCGAG ACCTTCCTGA CCCCGATCAA CGGCTTCGGC

3421  CTGCAGGCCG ACGAGAACAG CAGGCTGATC ACCCTGACCT GCAAGAGCTA CCTGAGGGAG3421 CTGCAGGCCG ACGAGAACAG CAGGCTGATC ACCCTGACCT GCAAGAGCTA CCTGAGGGAG

3481  CTGCTGCTGG CCACCGACCT GAGCAACAAG GAGACCAAGC TGATCGTGCC GCCGAGCGGC3481 CTGCTGCTGG CCACCGACCT GAGCAACAAG GAGACCAAGC TGATCGTGCC GCCGAGCGGC

3541  TTCATCAAGA ACATCGTGGA GAACGGCAGC ATCGAGGAGG ACAACCTGGA GCCGTGGAAG3541 TTCATCAAGA ACATCGTGGA GAACGGCAGC ATCGAGGAGG ACAACCTGGA GCCGTGGAAG

3601  GCCAACAACA AGAACGCCTA CGTGGACCAC ACCGGCGGCG TGAACGGCAC CAAGGCCCTG3601 GCCAACAACA AGAACGCCTA CGTGGACCAC ACCGGCGGCG TGAACGGCAC CAAGGCCCTG

3661  TACGTGCACA AGGACGGCGG CATCAGCCAG TTCATCGGCG ACAAGCTGAA GCCGAAGACC3661 TACGTGCACA AGGACGGCGG CATCAGCCAG TTCATCGGCG ACAAGCTGAA GCCGAAGACC

3721  GAGTACGTGA TCCAGTACAC CGTGAAGGGC AAGCCGAGCA TCCACCTGAA GGACGAGAAC3721 GAGTACGTGA TCCAGTACAC CGTGAAGGGC AAGCCGAGCA TCCACCTGAA GGACGAGAAC

3781  ACCGGCTACA TCCACTACGA GGACACCAAC AACAACCTGG AGGACTACCA GACCATCACC3781 ACCGGCTACA TCCACTACGA GGACACCAAC AACAACCTGG AGGACTACCA GACCATCACC

3841  AAGAGGTTCA CCACCGGCAC CGACCTGAAG GGCGTGTACC TGATCCTGAA GAGCCAGAAC3841 AAGAGGTTCA CCACCGGCAC CGACCTGAAG GGCGTGTACC TGATCCTGAA GAGCCAGAAC

3901  GGCGACGAGG CCTGGGGCGA CAACTTCATC ATCCTGGAGA TCAGCCCGAG CGAGAAGCTG3901 GGCGACGAGG CCTGGGGCGA CAACTTCATC ATCCTGGAGA TCAGCCCGAG CGAGAAGCTG

3961  CTGAGCCCGG AGCTGATCAA CACCAACAAC TGGACCAGCA CCGGCAGCAC CAACATCAGC3961 CTGAGCCCGG AGCTGATCAA CACCAACAAC TGGACCAGCA CCGGCAGCAC CAACATCAGC

4021  GGCAACACCC TGACCCTGTA CCAGGGCGGC AGGGGCATCC TGAAGCAGAA CCTGCAGCTG4021 GGCAACACCC TGACCCTGTA CCAGGGCGGC AGGGGCATCC TGAAGCAGAA CCTGCAGCTG

4081  GACAGCTTCA GCACCTACAG GGTGTACTTC AGCGTGAGCG GCGACGCCAA CGTGAGGATC4081 GACAGCTTCA GCACCTACAG GGTGTACTTC AGCGTGAGCG GCGACGCCAA CGTGAGGATC

4141  AGGAACAGCA GGGAGGTGCT GTTCGAGAAG AGGTACATGA GCGGCGCCAA GGACGTGAGC4141 AGGAACAGCA GGGAGGTGCT GTTCGAGAAG AGGTACATGA GCGGCGCCAA GGACGTGAGC

4201  GAGATCTTCA CCACCAAGCT GGGCAAGGAC AACTTCTACA TCGAGCTGAG CCAGGGCAAC4201 GAGATCTTCA CCACCAAGCT GGGCAAGGAC AACTTCTACA TCGAGCTGAG CCAGGGCAAC

4261  AACCTGAACG GCGGCCCGAT CGTGAAGTTC TACGACGTGA GCATCAAGTA A4261 AACCTGAACG GCGGCCCGAT CGTGAAGTTC TACGACGTGA GCATCAAGTA A

SEQ ID NO:3SEQ ID NO: 3

Met Asp Asn Asn Pro Asn Ile Asn Glu Cys Ile Pro Tyr Asn Cys Leu Ser Asn Pro GluMet Asp Asn Asn Pro Asn Ile Asn Glu Cys Ile Pro Tyr Asn Cys Leu Ser Asn Pro Glu

Val Glu Val Leu Gly Gly Glu Arg Ile Glu Thr Gly Tyr Thr Pro Ile Asp Ile Ser LeuVal Glu Val Leu Gly Gly Glu Arg Ile Glu Thr Gly Tyr Thr Pro Ile Asp Ile Ser Leu

Ser Leu Thr Gln Phe Leu Leu Ser Glu Phe Val Pro Gly Ala Gly Phe Val Leu Gly LeuSer Leu Thr Gln Phe Leu Leu Ser Glu Phe Val Pro Gly Ala Gly Phe Val Leu Gly Leu

Val Asp Ile Ile Trp Gly Ile Phe Gly Pro Ser Gln Trp Asp Ala Phe Leu Val Gln IleVal Asp Ile Ile Trp Gly Ile Phe Gly Pro Ser Gln Trp Asp Ala Phe Leu Val Gln Ile

Glu Gln Leu Ile Asn Gln Arg Ile Glu Glu Phe Ala Arg Asn Gln Ala Ile Ser Arg LeuGlu Gln Leu Ile Asn Gln Arg Ile Glu Glu Phe Ala Arg Asn Gln Ala Ile Ser Arg Leu

Glu Gly Leu Ser Asn Leu Tyr Gln Ile Tyr Ala Glu Ser Phe Arg Glu Trp Glu Ala AspGlu Gly Leu Ser Asn Leu Tyr Gln Ile Tyr Ala Glu Ser Phe Arg Glu Trp Glu Ala Asp

Pro Thr Asn Pro Ala Leu Arg Glu Glu Met Arg Ile Gln Phe Asn Asp Met Asn Ser AlaPro Thr Asn Pro Ala Leu Arg Glu Glu Met Arg Ile Gln Phe Asn Asp Met Asn Ser Ala

Leu Thr Thr Ala Ile Pro Leu Phe Ala Val Gln Asn Tyr Gln Val Pro Leu Leu Ser ValLeu Thr Thr Ala Ile Pro Leu Phe Ala Val Gln Asn Tyr Gln Val Pro Leu Leu Ser Val

Tyr Val Gln Ala Ala Asn Leu His Leu Ser Val Leu Arg Asp Val Ser Val Phe Gly GlnTyr Val Gln Ala Ala Asn Leu His Leu Ser Val Leu Arg Asp Val Ser Val Phe Gly Gln

Arg Trp Gly Phe Asp Ala Ala Thr Ile Asn Ser Arg Tyr Asn Asp Leu Thr Arg Leu IleArg Trp Gly Phe Asp Ala Ala Thr Ile Asn Ser Arg Tyr Asn Asp Leu Thr Arg Leu Ile

Gly Asn Tyr Thr Asp His Ala Val Arg Trp Tyr Asn Thr Gly Leu Glu Arg Val Trp GlyGly Asn Tyr Thr Asp His Ala Val Arg Trp Tyr Asn Thr Gly Leu Glu Arg Val Trp Gly

Pro Asp Ser Arg Asp Trp Ile Arg Tyr Asn Gln Phe Arg Arg Glu Leu Thr Leu Thr ValPro Asp Ser Arg Asp Trp Ile Arg Tyr Asn Gln Phe Arg Arg Glu Leu Thr Leu Thr Val

Leu Asp Ile Val Ser Leu Phe Pro Asn Tyr Asp Ser Arg Thr Tyr Pro Ile Arg Thr ValLeu Asp Ile Val Ser Leu Phe Pro Asn Tyr Asp Ser Arg Thr Tyr Pro Ile Arg Thr Val

Ser Gln Leu Thr Arg Glu Ile Tyr Thr Asn Pro Val Leu Glu Asn Phe Asp Gly Ser PheSer Gln Leu Thr Arg Glu Ile Tyr Thr Asn Pro Val Leu Glu Asn Phe Asp Gly Ser Phe

Arg Gly Ser Ala Gln Gly Ile Glu Gly Ser Ile Arg Ser Pro His Leu Met Asp Ile LeuArg Gly Ser Ala Gln Gly Ile Glu Gly Ser Ile Arg Ser Pro His Leu Met Asp Ile Leu

Asn Ser Ile Thr Ile Tyr Thr Asp Ala His Arg Gly Glu Tyr Tyr Trp Ser Gly His GlnAsn Ser Ile Thr Ile Tyr Thr Asp Ala His Arg Gly Glu Tyr Tyr Trp Ser Gly His Gln

Ile Met Ala Ser Pro Val Gly Phe Ser Gly Pro Glu Phe Thr Phe Pro Leu Tyr Gly ThrIle Met Ala Ser Pro Val Gly Phe Ser Gly Pro Glu Phe Thr Phe Pro Leu Tyr Gly Thr

Met Gly Asn Ala Ala Pro Gln Gln Arg Ile Val Ala Gln Leu Gly Gln Gly Val Tyr ArgMet Gly Asn Ala Ala Pro Gln Gln Arg Ile Val Ala Gln Leu Gly Gln Gly Val Tyr Arg

Thr Leu Ser Ser Thr Leu Tyr Arg Arg Pro Phe Asn Ile Gly Ile Asn Asn Gln Gln LeuThr Leu Ser Ser Thr Leu Tyr Arg Arg Pro Phe Asn Ile Gly Ile Asn Asn Gln Gln Leu

Ser Val Leu Asp Gly Thr Glu Phe Ala Tyr Gly Thr Ser Ser Asn Leu Pro Ser Ala ValSer Val Leu Asp Gly Thr Glu Phe Ala Tyr Gly Thr Ser Ser Asn Leu Pro Ser Ala Val

Tyr Arg Lys Ser Gly Thr Val Asp Ser Leu Asp Glu Ile Pro Pro Gln Asn Asn Asn ValTyr Arg Lys Ser Gly Thr Val Asp Ser Leu Asp Glu Ile Pro Pro Gln Asn Asn Asn Asn Val

Pro Pro Arg Gln Gly Phe Ser His Arg Leu Ser His Val Ser Met Phe Arg Ser Gly PhePro Pro Arg Gln Gly Phe Ser His Arg Leu Ser His Val Ser Met Phe Arg Ser Gly Phe

Ser Asn Ser Ser Val Ser Ile Ile Arg Ala Pro Met Phe Ser Trp Ile His Arg Ser AlaSer Asn Ser Ser Ser Val Ser Ile Ile Arg Ala Pro Met Phe Ser Trp Ile His Arg Ser Ala

Glu Phe Asn Asn Ile Ile Pro Ser Ser Gln Ile Thr Gln Ile Pro Leu Thr Lys Ser ThrGlu Phe Asn Asn Ile Ile Pro Ser Ser Gln Ile Thr Gln Ile Pro Leu Thr Lys Ser Thr

Asn Leu Gly Ser Gly Thr Ser Val Val Lys Gly Pro Gly Phe Thr Gly Gly Asp Ile LeuAsn Leu Gly Ser Gly Thr Ser Val Val Lys Gly Pro Gly Phe Thr Gly Gly Asp Ile Leu

Arg Arg Thr Ser Pro Gly Gln Ile Ser Thr Leu Arg Val Asn Ile Thr Ala Pro Leu SerArg Arg Thr Ser Pro Gly Gln Ile Ser Thr Leu Arg Val Asn Ile Thr Ala Pro Leu Ser

Gln Arg Tyr Arg Val Arg Ile Arg Tyr Ala Ser Thr Thr Asn Leu Gln Phe His Thr SerGln Arg Tyr Arg Val Arg Ile Arg Tyr Ala Ser Thr Thr Asn Leu Gln Phe His Thr Ser

Ile Asp Gly Arg Pro Ile Asn Gln Gly Asn Phe Ser Ala Thr Met Ser Ser Gly Ser AsnIle Asp Gly Arg Pro Ile Asn Gln Gly Asn Phe Ser Ala Thr Met Ser Ser Gly Ser Asn

Leu Gln Ser Gly Ser Phe Arg Thr Val Gly Phe Thr Thr Pro Phe Asn Phe Ser Asn GlyLeu Gln Ser Gly Ser Phe Arg Thr Val Gly Phe Thr Thr Pro Phe Asn Phe Ser Asn Gly

Ser Ser Val Phe Thr Leu Ser Ala His Val Phe Asn Ser Gly Asn Glu Val Tyr Ile AspSer Ser Val Phe Thr Leu Ser Ala His Val Phe Asn Ser Gly Asn Glu Val Tyr Ile Asp

Arg Ile Glu Phe Val Pro Ala Glu Val Thr Phe Glu Ala Glu Tyr Asp Leu Glu Arg AlaArg Ile Glu Phe Val Pro Ala Glu Val Thr Phe Glu Ala Glu Tyr Asp Leu Glu Arg Ala

Gln Lys Ala Val Asn Glu Leu Phe Thr Ser Ser Asn Gln Ile Gly Leu Lys Thr Asp ValGln Lys Ala Val Asn Glu Leu Phe Thr Ser Ser Asn Gln Ile Gly Leu Lys Thr Asp Val

Thr Asp Tyr His Ile Asp Gln Val Arg Gly Pro Gly Pro Gly Gly Ser Lys Leu Ser ThrThr Asp Tyr His Ile Asp Gln Val Arg Gly Pro Gly Pro Gly Gly Ser Lys Leu Ser Thr

Lys Asp Ile Met Asn Met Ile Phe Lys Thr Asp Thr Gly Gly Asn Val Thr Leu Asp GluLys Asp Ile Met Asn Met Ile Phe Lys Thr Asp Thr Gly Gly Asn Val Thr Leu Asp Glu

Lys Ile Ser Asn Glu Gln Asn Gln Val Leu Asn Asp Val Asn Asn Lys Leu Asp Ala IleLys Ile Ser Asn Glu Gln Asn Gln Val Leu Asn Asp Val Asn Asn Lys Leu Asp Ala Ile

Asn Thr Met Leu His Ile Tyr Leu Pro Lys Ile Thr Ser Met Leu Ser Asp Val Met LysAsn Thr Met Leu His Ile Tyr Leu Pro Lys Ile Thr Ser Met Leu Ser Asp Val Met Lys

Gln Asn Tyr Ala Leu Ser Leu Gln Ile Glu Tyr Leu Ser Lys Gln Leu Gln Glu Ile SerGln Asn Tyr Ala Leu Ser Leu Gln Ile Glu Tyr Leu Ser Lys Gln Leu Gln Glu Ile Ser

Asp Lys Leu Asp Ile Ile Asn Val Asn Val Leu Ile Asn Ser Thr Leu Thr Glu Ile ThrAsp Lys Leu Asp Ile Ile Asn Val Asn Val Leu Ile Asn Ser Thr Leu Thr Glu Ile Thr

Pro Ala Tyr Gln Arg Ile Lys Tyr Val Asn Glu Lys Phe Glu Glu Leu Thr Phe Ala ThrPro Ala Tyr Gln Arg Ile Lys Tyr Val Asn Glu Lys Phe Glu Glu Leu Thr Phe Ala Thr

Glu Thr Thr Leu Lys Val Lys Lys Asp Ser Ser Pro Ala Asp Ile Leu Asp Glu Leu ThrGlu Thr Thr Leu Lys Val Lys Lys Asp Ser Ser Ser Pro Ala Asp Ile Leu Asp Glu Leu Thr

Glu Leu Thr Glu Leu Ala Lys Ser Val Thr Lys Asn Asp Val Asp Gly Phe Glu Phe TyrGlu Leu Thr Glu Leu Ala Lys Ser Val Thr Lys Asn Asp Val Asp Gly Phe Glu Phe Tyr

Leu Asn Thr Phe His Asp Val Met Val Gly Asn Asn Leu Phe Gly Arg Ser Ala Leu LysLeu Asn Thr Phe His Asp Val Met Val Gly Asn Asn Leu Phe Gly Arg Ser Ala Leu Lys

Thr Ala Ser Glu Leu Ile Ala Lys Glu Asn Val Lys Thr Ser Gly Ser Glu Val Gly AsnThr Ala Ser Glu Leu Ile Ala Lys Glu Asn Val Lys Thr Ser Gly Ser Glu Val Gly Asn

Val Tyr Asn Phe Leu Ile Val Leu Thr Ala Leu Gln Ala Lys Ala Phe Leu Thr Leu ThrVal Tyr Asn Phe Leu Ile Val Leu Thr Ala Leu Gln Ala Lys Ala Phe Leu Thr Leu Thr

Thr Cys Arg Lys Leu Leu Gly Leu Ala Gly Ile Asp Tyr Thr Ser Ile Met Asn Glu HisThr Cys Arg Lys Leu Leu Gly Leu Ala Gly Ile Asp Tyr Thr Ser Ile Met Asn Glu His

Leu Asn Lys Glu Lys Glu Glu Phe Arg Val Asn Ile Leu Pro Thr Leu Ser Asn Thr PheLeu Asn Lys Glu Lys Glu Glu Phe Arg Val Asn Ile Leu Pro Thr Leu Ser Asn Thr Phe

Ser Asn Pro Asn Tyr Ala Lys Val Lys Gly Ser Asp Glu Asp Ala Lys Met Ile Val GluSer Asn Pro Asn Tyr Ala Lys Val Lys Gly Ser Asp Glu Asp Ala Lys Met Ile Val Glu

Ala Lys Pro Gly His Ala Leu Val Gly Phe Glu Met Ser Asn Asp Ser Ile Thr Val LeuAla Lys Pro Gly His Ala Leu Val Gly Phe Glu Met Ser Asn Asp Ser Ile Thr Val Leu

Lys Val Tyr Glu Ala Lys Leu Lys Gln Asn Tyr Gln Val Asp Lys Asp Ser Leu Ser GluLys Val Tyr Glu Ala Lys Leu Lys Gln Asn Tyr Gln Val Asp Lys Asp Ser Leu Ser Glu

Val Ile Tyr Gly Asp Thr Asp Lys Leu Phe Cys Pro Asp Gln Ser Glu Gln Ile Tyr TyrVal Ile Tyr Gly Asp Thr Asp Lys Leu Phe Cys Pro Asp Gln Ser Glu Gln Ile Tyr Tyr

Thr Asn Asn Ile Val Phe Pro Asn Glu Tyr Val Ile Thr Lys Ile Asp Phe Thr Lys LysThr Asn Asn Ile Val Phe Pro Asn Glu Tyr Val Ile Thr Lys Ile Asp Phe Thr Lys Lys

Met Lys Thr Leu Arg Tyr Glu Val Thr Ala Asn Phe Tyr Asp Ser Ser Thr Gly Glu IleMet Lys Thr Leu Arg Tyr Glu Val Thr Ala Asn Phe Tyr Asp Ser Ser Thr Gly Glu Ile

Asp Leu Asn Lys Lys Lys Val Glu Ser Ser Glu Ala Glu Tyr Arg Thr Leu Ser Ala AsnAsp Leu Asn Lys Lys Lys Val Glu Ser Ser Glu Ala Glu Tyr Arg Thr Leu Ser Ala Asn

Asp Asp Gly Val Tyr Met Pro Leu Gly Val Ile Ser Glu Thr Phe Leu Thr Pro Ile AsnAsp Asp Gly Val Tyr Met Pro Leu Gly Val Ile Ser Glu Thr Phe Leu Thr Pro Ile Asn

Gly Phe Gly Leu Gln Ala Asp Glu Asn Ser Arg Leu Ile Thr Leu Thr Cys Lys Ser TyrGly Phe Gly Leu Gln Ala Asp Glu Asn Ser Arg Leu Ile Thr Leu Thr Cys Lys Ser Tyr

Leu Arg Glu Leu Leu Leu Ala Thr Asp Leu Ser Asn Lys Glu Thr Lys Leu Ile Val ProLeu Arg Glu Leu Leu Leu Ala Thr Asp Leu Ser Asn Lys Glu Thr Lys Leu Ile Val Pro

Pro Ser Gly Phe Ile Ser Asn Ile Val Glu Asn Gly Ala Ile Glu Glu Asp Asn Leu GluPro Ser Gly Phe Ile Ser Asn Ile Val Glu Asn Gly Ala Ile Glu Glu Asp Asn Leu Glu

Pro Trp Lys Ala Asn Asn Lys Asn Ala Tyr Val Asp His Thr Gly Gly Val Asn Gly ThrPro Trp Lys Ala Asn Asn Lys Asn Ala Tyr Val Asp His Thr Gly Gly Val Asn Gly Thr

Lys Ala Leu Tyr Val His Lys Asp Gly Gly Phe Ser Gln Phe Ile Gly Asp Lys Leu LysLys Ala Leu Tyr Val His Lys Asp Gly Gly Phe Ser Gln Phe Ile Gly Asp Lys Leu Lys

Pro Lys Thr Glu Tyr Val Ile Gln Tyr Thr Val Lys Gly Lys Ala Ser Ile Tyr Leu LysPro Lys Thr Glu Tyr Val Ile Gln Tyr Thr Val Lys Gly Lys Ala Ser Ile Tyr Leu Lys

Asp Glu Lys Asn Asn Glu Gly Ile Tyr Glu Glu Ile Asn Asn Asp Leu Glu Asp Phe GlnAsp Glu Lys Asn Asn Glu Gly Ile Tyr Glu Glu Ile Asn Asn Asp Leu Glu Asp Phe Gln

Thr Val Thr Lys Arg Phe Ile Thr Gly Thr Asp Ser Ser Gly Val His Leu Ile Phe ThrThr Val Thr Lys Arg Phe Ile Thr Gly Thr Asp Ser Ser Gly Val His Leu Ile Phe Thr

Ser Gln Asn Gly Asp Glu Ala Phe Gly Gly Asn Phe Ile Ile Ser Glu Ile Arg Ser SerSer Gln Asn Gly Asp Glu Ala Phe Gly Gly Asn Phe Ile Ile Ser Glu Ile Arg Ser Ser

Glu Glu Leu Leu Ser Pro Glu Leu Ile Lys Ser Asp Ala Trp Val Gly Ser Gln Gly ThrGlu Glu Leu Leu Ser Pro Glu Leu Ile Lys Ser Asp Ala Trp Val Gly Ser Gln Gly Thr

Trp Ile Ser Gly Asn Ser Leu Thr Ile Asn Ser Asn Ala Asn Gly Thr Phe Arg Gln AsnTrp Ile Ser Gly Asn Ser Leu Thr Ile Asn Ser Asn Ala Asn Gly Thr Phe Arg Gln Asn

Leu Pro Leu Glu Ser Tyr Ser Thr Tyr Ser Met Asn Phe Asn Val Asn Gly Phe Ala LysLeu Pro Leu Glu Ser Tyr Ser Thr Tyr Ser Met Asn Phe Asn Val Asn Gly Phe Ala Lys

Val Thr Val Arg Asn Ser Arg Glu Val Leu Phe Glu Lys Asn Phe Ser Gln Leu Ser ProVal Thr Val Arg Asn Ser Arg Glu Val Leu Phe Glu Lys Asn Phe Ser Gln Leu Ser Pro

Lys Asp Tyr Ser Glu Lys Phe Thr Thr Ala Ala Asn Asn Thr Gly Phe Tyr Val Glu LeuLys Asp Tyr Ser Glu Lys Phe Thr Thr Ala Ala Asn Asn Thr Gly Phe Tyr Val Glu Leu

Ser Arg Gly Thr Gln Gly Gly Asn Ile Thr Phe Arg Asp Phe Ser Ile LysSer Arg Gly Thr Gln Gly Gly Asn Ile Thr Phe Arg Asp Phe Ser Ile Lys

SEQ ID NO:4SEQ ID NO: 4

Met Asp Asn Asn Pro Asn Ile Asn Glu Cys Ile Pro Tyr Asn Cys Leu Ser Asn Pro GluMet Asp Asn Asn Pro Asn Ile Asn Glu Cys Ile Pro Tyr Asn Cys Leu Ser Asn Pro Glu

Val Glu Val Leu Gly Gly Glu Arg Ile Glu Thr Gly Tyr Thr Pro Ile Asp Ile Ser LeuVal Glu Val Leu Gly Gly Glu Arg Ile Glu Thr Gly Tyr Thr Pro Ile Asp Ile Ser Leu

Ser Leu Thr Gln Phe Leu Leu Ser Glu Phe Val Pro Gly Ala Gly Phe Val Leu Gly LeuSer Leu Thr Gln Phe Leu Leu Ser Glu Phe Val Pro Gly Ala Gly Phe Val Leu Gly Leu

Val Asp Ile Ile Trp Gly Ile Phe Gly Pro Ser Gln Trp Asp Ala Phe Leu Val Gln IleVal Asp Ile Ile Trp Gly Ile Phe Gly Pro Ser Gln Trp Asp Ala Phe Leu Val Gln Ile

Glu Gln Leu Ile Asn Gln Arg Ile Glu Glu Phe Ala Arg Asn Gln Ala Ile Ser Arg LeuGlu Gln Leu Ile Asn Gln Arg Ile Glu Glu Phe Ala Arg Asn Gln Ala Ile Ser Arg Leu

Glu Gly Leu Ser Asn Leu Tyr Gln Ile Tyr Ala Glu Ser Phe Arg Glu Trp Glu Ala AspGlu Gly Leu Ser Asn Leu Tyr Gln Ile Tyr Ala Glu Ser Phe Arg Glu Trp Glu Ala Asp

Pro Thr Asn Pro Ala Leu Arg Glu Glu Met Arg Ile Gln Phe Asn Asp Met Asn Ser AlaPro Thr Asn Pro Ala Leu Arg Glu Glu Met Arg Ile Gln Phe Asn Asp Met Asn Ser Ala

Leu Thr Thr Ala Ile Pro Leu Phe Ala Val Gln Asn Tyr Gln Val Pro Leu Leu Ser ValLeu Thr Thr Ala Ile Pro Leu Phe Ala Val Gln Asn Tyr Gln Val Pro Leu Leu Ser Val

Tyr Val Gln Ala Ala Asn Leu His Leu Ser Val Leu Arg Asp Val Ser Val Phe Gly GlnTyr Val Gln Ala Ala Asn Leu His Leu Ser Val Leu Arg Asp Val Ser Val Phe Gly Gln

Arg Trp Gly Phe Asp Ala Ala Thr Ile Asn Ser Arg Tyr Asn Asp Leu Thr Arg Leu IleArg Trp Gly Phe Asp Ala Ala Thr Ile Asn Ser Arg Tyr Asn Asp Leu Thr Arg Leu Ile

Gly Asn Tyr Thr Asp His Ala Val Arg Trp Tyr Asn Thr Gly Leu Glu Arg Val Trp GlyGly Asn Tyr Thr Asp His Ala Val Arg Trp Tyr Asn Thr Gly Leu Glu Arg Val Trp Gly

Pro Asp Ser Arg Asp Trp Ile Arg Tyr Asn Gln Phe Arg Arg Glu Leu Thr Leu Thr ValPro Asp Ser Arg Asp Trp Ile Arg Tyr Asn Gln Phe Arg Arg Glu Leu Thr Leu Thr Val

Leu Asp Ile Val Ser Leu Phe Pro Asn Tyr Asp Ser Arg Thr Tyr Pro Ile Arg Thr ValLeu Asp Ile Val Ser Leu Phe Pro Asn Tyr Asp Ser Arg Thr Tyr Pro Ile Arg Thr Val

Ser Gln Leu Thr Arg Glu Ile Tyr Thr Asn Pro Val Leu Glu Asn Phe Asp Gly Ser PheSer Gln Leu Thr Arg Glu Ile Tyr Thr Asn Pro Val Leu Glu Asn Phe Asp Gly Ser Phe

Arg Gly Ser Ala Gln Gly Ile Glu Gly Ser Ile Arg Ser Pro His Leu Met Asp Ile LeuArg Gly Ser Ala Gln Gly Ile Glu Gly Ser Ile Arg Ser Pro His Leu Met Asp Ile Leu

Asn Ser Ile Thr Ile Tyr Thr Asp Ala His Arg Gly Glu Tyr Tyr Trp Ser Gly His GlnAsn Ser Ile Thr Ile Tyr Thr Asp Ala His Arg Gly Glu Tyr Tyr Trp Ser Gly His Gln

Ile Met Ala Ser Pro Val Gly Phe Ser Gly Pro Glu Phe Thr Phe Pro Leu Tyr Gly ThrIle Met Ala Ser Pro Val Gly Phe Ser Gly Pro Glu Phe Thr Phe Pro Leu Tyr Gly Thr

Met Gly Asn Ala Ala Pro Gln Gln Arg Ile Val Ala Gln Leu Gly Gln Gly Val Tyr ArgMet Gly Asn Ala Ala Pro Gln Gln Arg Ile Val Ala Gln Leu Gly Gln Gly Val Tyr Arg

Thr Leu Ser Ser Thr Leu Tyr Arg Arg Pro Phe Asn Ile Gly Ile Asn Asn Gln Gln LeuThr Leu Ser Ser Thr Leu Tyr Arg Arg Pro Phe Asn Ile Gly Ile Asn Asn Gln Gln Leu

Ser Val Leu Asp Gly Thr Glu Phe Ala Tyr Gly Thr Ser Ser Asn Leu Pro Ser Ala ValSer Val Leu Asp Gly Thr Glu Phe Ala Tyr Gly Thr Ser Ser Asn Leu Pro Ser Ala Val

Tyr Arg Lys Ser Gly Thr Val Asp Ser Leu Asp Glu Ile Pro Pro Gln Asn Asn Asn ValTyr Arg Lys Ser Gly Thr Val Asp Ser Leu Asp Glu Ile Pro Pro Gln Asn Asn Asn Asn Val

Pro Pro Arg Gln Gly Phe Ser His Arg Leu Ser His Val Ser Met Phe Arg Ser Gly PhePro Pro Arg Gln Gly Phe Ser His Arg Leu Ser His Val Ser Met Phe Arg Ser Gly Phe

Ser Asn Ser Ser Val Ser Ile Ile Arg Ala Pro Met Phe Ser Trp Ile His Arg Ser AlaSer Asn Ser Ser Ser Val Ser Ile Ile Arg Ala Pro Met Phe Ser Trp Ile His Arg Ser Ala

Glu Phe Asn Asn Ile Ile Pro Ser Ser Gln Ile Thr Gln Ile Pro Leu Thr Lys Ser ThrGlu Phe Asn Asn Ile Ile Pro Ser Ser Gln Ile Thr Gln Ile Pro Leu Thr Lys Ser Thr

Asn Leu Gly Ser Gly Thr Ser Val Val Lys Gly Pro Gly Phe Thr Gly Gly Asp Ile LeuAsn Leu Gly Ser Gly Thr Ser Val Val Lys Gly Pro Gly Phe Thr Gly Gly Asp Ile Leu

Arg Arg Thr Ser Pro Gly Gln Ile Ser Thr Leu Arg Val Asn Ile Thr Ala Pro Leu SerArg Arg Thr Ser Pro Gly Gln Ile Ser Thr Leu Arg Val Asn Ile Thr Ala Pro Leu Ser

Gln Arg Tyr Arg Val Arg Ile Arg Tyr Ala Ser Thr Thr Asn Leu Gln Phe His Thr SerGln Arg Tyr Arg Val Arg Ile Arg Tyr Ala Ser Thr Thr Asn Leu Gln Phe His Thr Ser

Ile Asp Gly Arg Pro Ile Asn Gln Gly Asn Phe Ser Ala Thr Met Ser Ser Gly Ser AsnIle Asp Gly Arg Pro Ile Asn Gln Gly Asn Phe Ser Ala Thr Met Ser Ser Gly Ser Asn

Leu Gln Ser Gly Ser Phe Arg Thr Val Gly Phe Thr Thr Pro Phe Asn Phe Ser Asn GlyLeu Gln Ser Gly Ser Phe Arg Thr Val Gly Phe Thr Thr Pro Phe Asn Phe Ser Asn Gly

Ser Ser Val Phe Thr Leu Ser Ala His Val Phe Asn Ser Gly Asn Glu Val Tyr Ile AspSer Ser Val Phe Thr Leu Ser Ala His Val Phe Asn Ser Gly Asn Glu Val Tyr Ile Asp

Arg Ile Glu Phe Val Pro Ala Glu Val Thr Phe Glu Ala Glu Tyr Asp Leu Glu Arg AlaArg Ile Glu Phe Val Pro Ala Glu Val Thr Phe Glu Ala Glu Tyr Asp Leu Glu Arg Ala

Gln Lys Ala Val Asn Glu Leu Phe Thr Ser Ser Asn Gln Ile Gly Leu Lys Thr Asp ValGln Lys Ala Val Asn Glu Leu Phe Thr Ser Ser Asn Gln Ile Gly Leu Lys Thr Asp Val

Thr Asp Tyr His Ile Asp Gln Val Arg Gly Pro Gly Thr Lys Leu Ser Thr Arg Ala LeuThr Asp Tyr His Ile Asp Gln Val Arg Gly Pro Gly Thr Lys Leu Ser Thr Arg Ala Leu

Pro Ser Phe Ile Asp Tyr Phe Asn Gly Ile Tyr Gly Phe Ala Thr Gly Ile Lys Asp IlePro Ser Phe Ile Asp Tyr Phe Asn Gly Ile Tyr Gly Phe Ala Thr Gly Ile Lys Asp Ile

Met Asn Met Ile Phe Lys Thr Asp Thr Gly Gly Asp Leu Thr Leu Asp Glu Ile Leu LyMet Asn Met Ile Phe Lys Thr Asp Thr Gly Gly Asp Leu Thr Leu Asp Glu Ile Leu Ly

Asn Gln Gln Leu Leu Asn Asp Ile Ser Gly Lys Leu Asp Gly Val Asn Gly Ser Leu AsnAsn Gln Gln Leu Leu Asn Asp Ile Ser Gly Lys Leu Asp Gly Val Asn Gly Ser Leu Asn

Asp Leu Ile Ala Gln Gly Asn Leu Asn Thr Glu Leu Ser Lys Glu Ile Leu Lys Ile AlaAsp Leu Ile Ala Gln Gly Asn Leu Asn Thr Glu Leu Ser Lys Glu Ile Leu Lys Ile Ala

Asn Glu Gln Asn Gln Val Leu Asn Asp Val Asn Asn Lys Leu Asp Ala Ile Asn Thr MetAsn Glu Gln Asn Gln Val Leu Asn Asp Val Asn Asn Lys Leu Asp Ala Ile Asn Thr Met

Leu Arg Val Tyr Leu Pro Lys Ile Thr Ser Met Leu Ser Asp Val Met Lys Gln Asn TyrLeu Arg Val Tyr Leu Pro Lys Ile Thr Ser Met Leu Ser Asp Val Met Lys Gln Asn Tyr

Ala Leu Ser Leu Gln Ile Glu Tyr Leu Ser Lys Gln Leu Gln Glu Ile Ser Asp Lys LeuAla Leu Ser Leu Gln Ile Glu Tyr Leu Ser Lys Gln Leu Gln Glu Ile Ser Asp Lys Leu

Asp Ile Ile Asn Val Asn Val Leu Ile Asn Ser Thr Leu Thr Glu Ile Thr Pro Ala TyrAsp Ile Ile Asn Val Asn Val Leu Ile Asn Ser Thr Leu Thr Glu Ile Thr Pro Ala Tyr

Gln Arg Ile Lys Tyr Val Asn Glu Lys Phe Glu Glu Leu Thr Phe Ala Thr Glu Thr SerGln Arg Ile Lys Tyr Val Asn Glu Lys Phe Glu Glu Leu Thr Phe Ala Thr Glu Thr Ser

Ser Lys Val Lys Lys Asp Gly Ser Pro Ala Asp Ile Leu Asp Glu Leu Thr Glu Leu ThrSer Lys Val Lys Lys Asp Gly Ser Pro Ala Asp Ile Leu Asp Glu Leu Thr Glu Leu Thr

Gly Leu Ala Lys Ser Val Pro Lys Asn Asp Val Asp Gly Phe Glu Phe Tyr Leu Asn ThrGly Leu Ala Lys Ser Val Pro Lys Asn Asp Val Asp Gly Phe Glu Phe Tyr Leu Asn Thr

Phe His Asp Val Met Val Gly Asn Asn Leu Phe Gly Arg Ser Ala Leu Lys Thr Ala SerPhe His Asp Val Met Val Gly Asn Asn Leu Phe Gly Arg Ser Ala Leu Lys Thr Ala Ser

Glu Leu Ile Thr Lys Glu Asn Val Lys Thr Ser Gly Ser Glu Val Gly Asn Val Tyr AsnGlu Leu Ile Thr Lys Glu Asn Val Lys Thr Ser Gly Ser Glu Val Gly Asn Val Tyr Asn

Ser Leu Ile Val Leu Thr Leu Leu Gln Ala Lys Ala Phe Leu Thr Leu Thr Thr Cys ArgSer Leu Ile Val Leu Thr Leu Leu Gln Ala Lys Ala Phe Leu Thr Leu Thr Thr Cys Arg

Lys Leu Leu Gly Leu Ala Asp Ile Asp Tyr Thr Ser Ile Met Asn Glu His Leu Asn LysLys Leu Leu Gly Leu Ala Asp Ile Asp Tyr Thr Ser Ile Met Asn Glu His Leu Asn Lys

Glu Lys Glu Glu Phe Arg Val Asn Ile Pro Pro Thr Leu Ser Asn Thr Phe Ser Asn ProGlu Lys Glu Glu Phe Arg Val Asn Ile Pro Pro Thr Leu Ser Asn Thr Phe Ser Asn Pro

Asn Tyr Ala Lys Val Lys Gly Ser Asp Glu Asp Ala Lys Met Ile Val Glu Ala Lys ProAsn Tyr Ala Lys Val Lys Gly Ser Asp Glu Asp Ala Lys Met Ile Val Glu Ala Lys Pro

Gly His Ala Leu Val Gly Phe Glu Ile Ser Asn Asp Ser Ile Thr Val Leu Lys Val TyrGly His Ala Leu Val Gly Phe Glu Ile Ser Asn Asp Ser Ile Thr Val Leu Lys Val Tyr

Glu Ala Lys Leu Lys Gln Asn Tyr Gln Val Asp Lys Asp Ser Leu Ser Glu Val Ile TyrGlu Ala Lys Leu Lys Gln Asn Tyr Gln Val Asp Lys Asp Ser Leu Ser Glu Val Ile Tyr

Gly Asp Met Asp Lys Leu Leu Gly Pro Asp Gln Ser Gly Pro Ile Tyr Tyr Pro Asn AsnGly Asp Met Asp Lys Leu Leu Gly Pro Asp Gln Ser Gly Pro Ile Tyr Tyr Pro Asn Asn

Ile Val Phe Pro Asn Glu Tyr Val Ile Thr Lys Ile Asp Phe Thr Lys Lys Met Lys ThrIle Val Phe Pro Asn Glu Tyr Val Ile Thr Lys Ile Asp Phe Thr Lys Lys Met Lys Thr

Leu Arg Tyr Glu Val Thr Ala Asn Phe Tyr Asp Ser Ser Thr Gly Glu Ile Asp Leu AsnLeu Arg Tyr Glu Val Thr Ala Asn Phe Tyr Asp Ser Ser Thr Gly Glu Ile Asp Leu Asn

Lys Lys Lys Val Glu Ser Ser Glu Ala Glu Tyr Arg Thr Leu Ser Ala Asn Asp Asp GlyLys Lys Lys Val Glu Ser Ser Glu Ala Glu Tyr Arg Thr Leu Ser Ala Asn Asp Asp Gly

Val Tyr Met Pro Leu Gly Val Ile Ser Glu Thr Phe Leu Thr Pro Ile Asn Gly Phe GlyVal Tyr Met Pro Leu Gly Val Ile Ser Glu Thr Phe Leu Thr Pro Ile Asn Gly Phe Gly

Leu Gln Ala Asp Glu Asn Ser Arg Leu Ile Thr Leu Thr Cys Lys Ser Tyr Leu Arg GluLeu Gln Ala Asp Glu Asn Ser Arg Leu Ile Thr Leu Thr Cys Lys Ser Tyr Leu Arg Glu

Leu Leu Leu Ala Thr Asp Leu Ser Asn Lys Glu Thr Lys Leu Ile Val Pro Pro Ser GlyLeu Leu Leu Ala Thr Asp Leu Ser Asn Lys Glu Thr Lys Leu Ile Val Pro Pro Ser Gly

Phe Ile Lys Asn Ile Val Glu Asn Gly Ser Ile Glu Glu Asp Asn Leu Glu Pro Trp LysPhe Ile Lys Asn Ile Val Glu Asn Gly Ser Ile Glu Glu Asp Asn Leu Glu Pro Trp Lys

Ala Asn Asn Lys Asn Ala Tyr Val Asp His Thr Gly Gly Val Asn Gly Thr Lys Ala LeuAla Asn Asn Lys Asn Ala Tyr Val Asp His Thr Gly Gly Val Asn Gly Thr Lys Ala Leu

Tyr Val His Lys Asp Gly Gly Ile Ser Gln Phe Ile Gly Asp Lys Leu Lys Pro Lys ThrTyr Val His Lys Asp Gly Gly Ile Ser Gln Phe Ile Gly Asp Lys Leu Lys Pro Lys Thr

Glu Tyr Val Ile Gln Tyr Thr Val Lys Gly Lys Pro Ser Ile His Leu Lys Asp Glu AsnGlu Tyr Val Ile Gln Tyr Thr Val Lys Gly Lys Pro Ser Ile His Leu Lys Asp Glu Asn

Thr Gly Tyr Ile His Tyr Glu Asp Thr Asn Asn Asn Leu Glu Asp Tyr Gln Thr Ile ThrThr Gly Tyr Ile His Tyr Glu Asp Thr Asn Asn Asn Leu Glu Asp Tyr Gln Thr Ile Thr

Lys Arg Phe Thr Thr Gly Thr Asp Leu Lys Gly Val Tyr Leu Ile Leu Lys Ser Gln AsnLys Arg Phe Thr Thr Gly Thr Asp Leu Lys Gly Val Tyr Leu Ile Leu Lys Ser Gln Asn

Gly Asp Glu Ala Trp Gly Asp Asn Phe Ile Ile Leu Glu Ile Ser Pro Ser Glu Lys LeuGly Asp Glu Ala Trp Gly Asp Asn Phe Ile Ile Leu Glu Ile Ser Pro Ser Glu Lys Leu

Leu Ser Pro Glu Leu Ile Asn Thr Asn Asn Trp Thr Ser Thr Gly Ser Thr Asn Ile SerLeu Ser Pro Glu Leu Ile Asn Thr Asn Asn Trp Thr Ser Thr Gly Ser Thr Asn Ile Ser

Gly Asn Thr Leu Thr Leu Tyr Gln Gly Gly Arg Gly Ile Leu Lys Gln Asn Leu Gln LeuGly Asn Thr Leu Thr Leu Tyr Gln Gly Gly Arg Gly Ile Leu Lys Gln Asn Leu Gln Leu

Asp Ser Phe Ser Thr Tyr Arg Val Tyr Phe Ser Val Ser Gly Asp Ala Asn Val Arg IleAsp Ser Phe Ser Thr Tyr Arg Val Tyr Phe Ser Val Ser Gly Asp Ala Asn Val Arg Ile

Arg Asn Ser Arg Glu Val Leu Phe Glu Lys Arg Tyr Met Ser Gly Ala Lys Asp Val SerArg Asn Ser Arg Glu Val Leu Phe Glu Lys Arg Tyr Met Ser Gly Ala Lys Asp Val Ser

Glu Ile Phe Thr Thr Lys Leu Gly Lys Asp Asn Phe Tyr Ile Glu Leu Ser Gln Gly AsnGlu Ile Phe Thr Thr Lys Leu Gly Lys Asp Asn Phe Tyr Ile Glu Leu Ser Gln Gly Asn

Asn Leu Asn Gly Gly Pro Ile Val Lys Phe Tyr Asp Val Ser Ile LysAsn Leu Asn Gly Gly Pro Ile Val Lys Phe Tyr Asp Val Ser Ile Lys

SEQ ID NO:5SEQ ID NO: 5

   1  ATGGACAACA ACCCCAACAT CAACGAGTGC ATCCCCTACA ACTGCCTGAG CAACCCCGAG1 ATGGACAACA ACCCCAACAT CAACGAGTGC ATCCCCTACA ACTGCCTGAG CAACCCCCGAG

  61  GTGGAGGTGC TGGGCGGCGA GCGCATCGAG ACCGGCTACA CCCCCATCGA CATCAGCCTG61 GTGGAGGTGC TGGGCGGCGA GCGCATCGAG ACCGGCTACA CCCCCATCGA CATCAGCCTG

 121  AGCCTGACCC AGTTCCTGCT GAGCGAGTTC GTGCCCGGCG CCGGCTTCGT GCTGGGCCTG121 AGCCTGACCC AGTTCCTGCT GAGCGAGTTC GTGCCCGGCG CCGGCTTCGT GCTGGGCCTG

 181  GTGGACATCA TCTGGGGCAT CTTCGGCCCC AGCCAGTGGG ACGCCTTCCT GGTGCAGATC181 GTGGACATCA TCTGGGGCAT CTTCGGCCCC AGCCAGTGGG ACGCCTTCCT GGTGCAGATC

 241  GAGCAGCTGA TCAACCAGCG CATCGAGGAG TTCGCCCGCA ACCAGGCCAT CAGCCGCCTG241 GAGCAGCTGA TCAACCAGCG CATCGAGGAG TTCGCCCGCA ACCAGGCCAT CAGCCGCCTG

 301  GAGGGCCTGA GCAACCTGTA CCAAATCTAC GCCGAGAGCT TCCGCGAGTG GGAGGCCGAC301 GAGGGCCTGA GCAACCTGTA CCAAATCTAC GCCGAGAGCT TCCGCGAGTG GGAGGCCGAC

 361  CCCACCAACC CCGCCCTGCG CGAGGAGATG CGCATCCAGT TCAACGACAT GAACAGCGCC361 CCCACCAACC CCGCCCTGCG CGAGGAGATG CGCATCCAGT TCAACGACAT GAACAGCGCC

 421  CTGACCACCG CCATCCCCCT GTTCGCCGTG CAGAACTACC AGGTGCCCCT GCTGAGCGTG421 CTGACCACCG CCATCCCCCT GTTCGCCGTG CAGAACTACC AGGTGCCCCT GCTGAGCGTG

 481  TACGTGCAGG CCGCCAACCT GCACCTGAGC GTGCTGCGCG ACGTCAGCGT GTTCGGCCAG481 TACGTGCAGG CCGCCAACCT GCACCTGAGC GTGCTGCGCG ACGTCAGCGT GTTCGGCCAG

 541  CGCTGGGGCT TCGACGCCGC CACCATCAAC AGCCGCTACA ACGACCTGAC CCGCCTGATC541 CGCTGGGGCT TCGACGCCGC CACCATCAAC AGCCGCTACA ACGACCTGAC CCGCCTGATC

 601  GGCAACTACA CCGACCACGC CGTGCGCTGG TACAACACCG GCCTGGAGCG CGTGTGGGGT601 GGCAACTACA CCGACCACGC CGTGCGCTGG TACAACACCG GCCTGGAGCG CGTGTGGGGT

 661  CCCGACAGCC GCGACTGGAT CAGGTACAAC CAGTTCCGCC GCGAGCTGAC CCTGACCGTG661 CCCGACAGCC GCGACTGGAT CAGGTACAAC CAGTTCCGCC GCGAGCTGAC CCTGACCGTG

 721  CTGGACATCG TGAGCCTGTT CCCCAACTAC GACAGCCGCA CCTACCCCAT CCGCACCGTG721 CTGGACATCG TGAGCCTGTT CCCCAACTAC GACAGCCGCA CCTACCCCAT CCGCACCGTG

 781  AGCCAGCTGA CCCGCGAGAT TTACACCAAC CCCGTGCTGG AGAACTTCGA CGGCAGCTTC781 AGCCAGCTGA CCCGCGAGAT TTACACCAAC CCCGTGCTGG AGAACTTCGA CGGCAGCTTC

 841  CGCGGCAGCG CCCAGGGCAT CGAGGGCAGC ATCCGCAGCC CCCACCTGAT GGACATCCTG841 CGCGGCAGCG CCCAGGGCAT CGAGGGCAGC ATCCGCAGCC CCCACCTGAT GGACATCCTG

 901  AACAGCATCA CCATCTACAC CGACGCCCAC CGCGGCGAGT ACTACTGGAG CGGCCACCAG901 AACAGCATCA CCATCTACAC CGACGCCCAC CGCGGCGAGT ACTACTGGAG CGGCCACCAG

 961  ATCATGGCCA GCCCCGTCGG CTTCAGCGGC CCCGAGTTCA CCTTCCCCCT GTACGGCACC961 ATCATGGCCA GCCCCGTCGG CTTCAGCGGC CCCGAGTTCA CCTTCCCCCT GTACGGCACC

1021  ATGGGCAACG CTGCACCTCA GCAGCGCATA GTGGCACAGC TGGGCCAGGG AGTGTACCGC1021 ATGGGCAACG CTGCACCTCA GCAGCGCATA GTGGCACAGC TGGGCCAGGG AGTGTACCGC

1081  ACCCTGAGCA GCACCCTGTA CCGTCGACCT TTCAACATCG GCATCAACAA CCAGCAGCTG1081 ACCCTGAGCA GCACCCTGTA CCGTCGACCT TTCAACATCG GCATCAACAA CCAGCAGCTG

1141  AGCGTGCTGG ACGGCACCGA GTTCGCCTAC GGCACCAGCA GCAACCTGCC CAGCGCCGTG1141 AGCGTGCTGG ACGGCACCGA GTTCGCCTAC GGCACCAGCA GCAACCTGCC CAGCGCCGTG

1201  TACCGCAAGA GCGGCACCGT GGACAGCCTG GACGAGATCC CCCCTCAGAA CAACAACGTG1201 TACCGCAAGA GCGGCACCGT GGACAGCCTG GACGAGATCC CCCCTCAGAA CAACAACGTG

1261  CCACCTCGAC AGGGCTTCAG CCACCGTCTG AGCCACGTGA GCATGTTCCG CAGTGGCTTC1261 CCACCTCGAC AGGGCTTCAG CCACCGTCTG AGCCACGTGA GCATGTTCCG CAGTGGCTTC

1321  AGCAACAGCA GCGTGAGCAT CATCCGTGCA CCTATGTTCA GCTGGATTCA CCGCAGTGCC1321 AGCAACAGCA GCGTGAGCAT CATCCGTGCA CCTATGTTCA GCTGGATTCA CCGCAGTGCC

1381  GAGTTCAACA ACATCATCCC CAGCAGCCAG ATCACCCAGA TCCCCCTGAC CAAGAGCACC1381 GAGTTCAACA ACATCATCCC CAGCAGCCAG ATCACCCAGA TCCCCCTGAC CAAGAGCACC

1441  AACCTGGGCA GCGGCACCAG CGTGGTGAAG GGCCCCGGCT TCACCGGCGG CGACATCCTG1441 AACCTGGGCA GCGGCACCAG CGTGGTGAAG GGCCCCGGCT TCACCGGCGG CGACATCCTG

1501  CGCCGCACCA GCCCCGGCCA GATCAGCACC CTGCGCGTGA ACATCACCGC CCCCCTGAGC1501 CGCCGCACCA GCCCCGGCCA GATCAGCACC CTGCGCGTGA ACATCACCGC CCCCCTGAGC

1561  CAGCGCTACC GCGTCCGCAT CCGCTACGCC AGCACCACCA ACCTGCAGTT CCACACCAGC1561 CAGCGCTACC GCGTCCGCAT CCGCTACGCC AGCACCACCA ACCTGCAGTT CCACACCAGC

1621  ATCGACGGCC GCCCCATCAA CCAGGGCAAC TTCAGCGCCA CCATGAGCAG CGGCAGCAAC1621 ATCGACGGCC GCCCCATCAA CCAGGGCAAC TTCAGCGCCA CCATGAGCAG CGGCAGCAAC

1681  CTGCAGAGCG GCAGCTTCCG CACCGTGGGC TTCACCACCC CCTTCAACTT CAGCAACGGC1681 CTGCAGAGCG GCAGCTTCCG CACCGTGGGC TTCACCACCC CCTTCAACTT CAGCAACGGC

1741  AGCAGCGTGT TCACCCTGAG CGCCCACGTG TTCAACAGCG GCAACGAGGT GTACATCGAC1741 AGCAGCGTGT TCACCCTGAG CGCCCACGTG TTCAACAGCG GCAACGAGGT GTACATCGAC

1801  CGCATCGAGT TCGTGCCCGC CGAGGTGACC TTCGAGGCCG AGTACGACCT GGAGAGGGCT1801 CGCATCGAGT TCGTGCCCGC CGAGGTGACC TTCGAGGCCG AGTACGACCT GGAGAGGGCT

1861  CAGAAGGCCG TGAACGAGCT GTTCACCAGC AGCAACCAGA TCGGCCTGAA GACCGACGTG1861 CAGAAGGCCG TGAACGAGCT GTTCACCAGC AGCAACCAGA TCGGCCTGAA GACCGACGTG

1921  ACCGACTACC ACATCGATCA GGTGCGAGGC CCCGGG1921 ACCGACTACC ACATCGATCA GGTGCGAGGC CCCGGG

SEQ ID NO:6SEQ ID NO: 6

   1  ATGAACAAGA ACAACAGTAA GCTCTCCACC CGCGCCCTCC CGTCCTTCAT CGACTACTTC1 ATGAACAAGA ACAACAGTAA GCTCTCCACC CGCGCCCTCC CGTCCTTCAT CGACTACTTC

  61  AACGGCATCT ACGGCTTCGC CACCGGCATC AAGGACATCA TGAACATGAT CTTCAAGACC61 AACGGCATCT ACGGCTTCGC CACCGGCATC AAGGACATCA TGAACATGAT CTTCAAGACC

 121  GACACCGGCG GCAACGTCAC CCTCGACGAG ATCCTCAAGA ACCAGCAGCT CCTCAACGAG121 GACACCGGCG GCAACGTCAC CCTCGACGAG ATCCTCAAGA ACCAGCAGCT CCTCAACGAG

 181  ATCAGCGGCA AGCTCGACGG CGTGAACGGC TCCCTCAACG AGCTCATCGC CCAGGTCAAC181 ATCAGCGGCA AGCTCGACGG CGTGAACGGC TCCCTCAACG AGCTCATCGC CCAGGTCAAC

 241  CTCAACACCG AGCTGTCCAA GGAGATCCTC AAGATCTCCA ACGAGCAGAA CCAGGTGCTC241 CTCAACACCG AGCTGTCCAA GGAGATCCTC AAGATCTCCA ACGAGCAGAA CCAGGTGCTC

 301  AACGACGTGA ACAACAAGCT GGACGCCATC AACACCATGC TGCACATCTA CCTCCCGAAG301 AACGACGTGA ACAACAAGCT GGACGCCATC AACACCATGC TGCACATCTA CCTCCCGAAG

 361  ATCACCTCCA TGCTCTCCGA CGTGATGAAG CAGAACTACG CCCTCTCCCT CCAGATCGAG361 ATCACCTCCA TGCTCTCCGA CGTGATGAAG CAGAACTACG CCCTCTCCCT CCAGATCGAG

 421  TACCTCTCCA AGCAGCTCCA GGAGATCAGC GACAAGCTCG ACATCATCAA CGTGAACGTG421 TACCTCTCCA AGCAGCTCCA GGAGATCAGC GACAAGCTCG ACATCATCAA CGTGAACGTG

 481  CTCATCAACT CCACCCTCAC CGAGATCACC CCGGCCTACC AGCGCATCAA GTACGTGAAC481 CTCATCAACT CCACCCTCAC CGAGATCACC CCGGCCTACC AGCGCATCAA GTACGTGAAC

 541  GAGAAGTTCG AGGAGCTGAC CTTCGCCACC GAGACCACCC TCAAGGTGAA GAAGGACTCC541 GAGAAGTTCG AGGAGCTGAC CTTCGCCACC GAGACCACCC TCAAGGTGAA GAAGGACTCC

 601  TCCCCGGCCG ACATCCTCGA CGAGCTGACC GAGCTGACCG AGCTGGCCAA GTCCGTGACC601 TCCCCGGCCG ACATCCTCGA CGAGCTGACC GAGCTGACCG AGCTGGCCAA GTCCGTGACC

 661  AAGAACGACG TGGACGGCTT CGAGTTCTAC CTCAACACCT TCCACGACGT GATGGTGGGC661 AAGAACGACG TGGACGGCTT CGAGTTCTAC CTCAACACCT TCCACGACGT GATGGTGGGC

 721  AACAACCTCT TCGGCCGCTC CGCCCTCAAG ACCGCCTCCG AGCTGATCGC CAAGGAGAAC721 AACAACCTCT TCGGCCGCTC CGCCCTCAAG ACCGCCTCCG AGCTGATCGC CAAGGAGAAC

 781  GTGAAGACCT CCGGCTCCGA GGTGGGCAAC GTGTACAACT TCCTCATCGT GCTCACCGCC781 GTGAAGACCT CCGGCTCCGA GGTGGGCAAC GTGTACAACT TCCTCATCGT GCTCACCGCC

 841  CTGCAGGCCA AGGCCTTCCT CACCCTCACC ACCTGCCGCA AGCTCCTCGG CCTCGCCGGC841 CTGCAGGCCA AGGCCTTCCT CACCCTCACC ACCTGCCGCA AGCTCCTCGG CCTCGCCGGC

 901  ATCGACTACA CCTCCATCAT GAACGAGCAC CTCAACAAGG AGAAGGAGGA GTTCCGCGTG901 ATCGACTACA CCTCCATCAT GAACGAGCAC CTCAACAAGG AGAAGGAGGA GTTCCGCGTG

 961  AACATCCTCC CGACCCTCTC CAACACCTTC TCCAACCCGA ACTACGCCAA GGTGAAGGGC961 AACATCCTCC CGACCTCTC CAACACCTTC TCCAACCCGA ACTACGCCAA GGTGAAGGGC

1021  TCCGACGAGG ACGCCAAGAT GATCGTGGAG GCCAAGCCGG GCCACGCCCT CGTGGGCTTC1021 TCCGACGAGG ACGCCAAGAT GATCGTGGAG GCCAAGCCGG GCCACGCCCT CGTGGGCTTC

1081  GAGATGTCCA ACGACTCCAT CACCGTGCTC AAGGTGTACG AGGCCAAGCT CAAGCAGAAC1081 GAGATGTCCA ACGACTCCAT CACCGTGCTC AAGGTGTACG AGGCCAAGCT CAAGCAGAAC

1141  TACCAGGTGG ACAAGGACTC CCTCTCCGAG GTGATCTACG GCGACACCGA CAAGCTCTTC1141 TACCAGGTGG ACAAGGACTC CCTCTCCGAG GTGATCTACG GCGACACCGA CAAGCTCTTC

1201  TGCCCGGACC AGTCCGAGCA GATATACTAC ACCAACAACA TCGTGTTCCC GAACGAGTAC1201 TGCCCGGACC AGTCCGAGCA GATATACTAC ACCAACAACA TCGTGTTCCC GAACGAGTAC

1261  GTGATCACCA AGATCGACTT CACCAAGAAG ATGAAGACCC TCCGCTACGA GGTGACCGCC1261 GTGATCACCA AGATCGACTT CACCAAGAAG ATGAAGACCC TCCGCTACGA GGTGACCGCC

1321  AACTTCTACG ACTCCTCCAC CGGCGAGATC GACCTCAACA AGAAGAAGGT GGAGTCCTCC1321 AACTTCTACG ACTCCTCCAC CGGCGAGATC GACCTCAACA AGAAGAAGGT GGAGTCCTCC

1381  GAGGCCGAGT ACCGCACCCT CTCCGCCAAC GACGACGGCG TGTACATGCC GCTCGGCGTG1381 GAGGCCGAGT ACCGCACCCT CTCCGCCAAC GACGACGGCG TGTACATGCC GCTCGGCGTG

1441  ATCTCCGAAA CCTTCCTCAC CCCGATCAAC GGCTTCGGCC TCCAGGCCGA CGAGAACTCC1441 ATCTCCGAAA CCTTCCTCAC CCCGATCAAC GGCTTCGGCC TCCAGGCCGA CGAGAACTCC

1501  CGCCTCATCA CCCTCACCTG CAAGTCCTAC CTCCGCGAGC TGCTCCTCGC CACCGACCTC1501 CGCCTCATCA CCCTCACCTG CAAGTCCTAC CTCCGCGAGC TGCTCCTCGC CACCGACCTC

1561  TCCAACAAGG AGACCAAGCT CATCGTGCCG CCGTCCGGCT TCATCTCCAA CATCGTGGAG1561 TCCAACAAGG AGACCAAGCT CATCGTGCCG CCGTCCGGCT TCATCTCCAA CATCGTGGAG

1621  AACGGCGCCA TCGAGGAGGA CAACCTCGAG CCGTGGAAGG CCAACAACAA GAACGCCTAC1621 AACGGCGCCA TCGAGGAGGA CAACCTCGAG CCGTGGAAGG CCAACAACAA GAACGCCTAC

1681  GTGGACCACA CCGGCGGCGT GAACGGCACC AAGGCCCTCT ACGTGCACAA GGACGGCGGC1681 GTGGACCACA CCGGCGGCGT GAACGGCACC AAGGCCCTCT ACGTGCACAA GGACGGCGGC

1741  TTCTCCCAGT TCATCGGCGA CAAGCTCAAG CCGAAGACCG AGTACGTGAT CCAGTACACC1741 TTCTCCCAGT TCATCGGCGA CAAGCTCAAG CCGAAGACCG AGTACGTGAT CCAGTACACC

1801  GTGAAGGGCA AGGCCAGCAT CTACCTGAAG GACGAGAAGA ACAACGAGGG CATCTACGAG1801 GTGAAGGGCA AGGCCAGCAT CTACCTGAAG GACGAGAAGA ACAACGAGGG CATCTACGAG

1861  GAGATCAACA ACGACCTGGA GGACTTCCAG ACCGTGACCA AGAGGTTCAT CACCGGCACC1861 GAGATCAACA ACGACCTGGA GGACTTCCAG ACCGTGACCA AGAGGTTCAT CACCGGCACC

1921  GACAGCAGCG GCGTGCACCT GATCTTCACC AGCCAGAACG GCGACGAGGC CTTCGGCGGC1921 GACAGCAGCG GCGTGCACCT GATTCTTCACC AGCCAGAACG GCGACGAGGC CTTCGGCGGC

1981  AACTTCATCA TCAGCGAGAT CAGGAGCAGC GAGGAGCTGC TGAGCCCGGA GCTGATCAAG1981 AACTTCATCA TCAGCGAGAT CAGGAGCAGC GAGGAGCTGC TGAGCCCGGA GCTGATCAAG

2041  AGCGACGCCT GGGTGGGCAG CCAGGGCACC TGGATCAGCG GCAACAGCCT GACCATCAAC2041 AGCGACGCCT GGGTGGGCAG CCAGGGCACC TGGATCAGCG GCAACAGCT GACCATCAAC

2101  AGCAACGCCA ACGGCACCTT CAGGCAGAAC CTGCCGCTGG AGAGCTACAG CACCTACAGC2101 AGCAACGCCA ACGGCACCTT CAGGCAGAAC CTGCCGCTGG AGAGCTACAG CACCTACAGC

2161  ATGAACTTCA ACGTGAACGG CTTCGCCAAG GTGACCGTGA GGAACAGCAG GGAGGTGCTG2161 ATGAACTTCA ACGTGAACGG CTTCGCCAAG GTGACCGTGA GGAACAGCAG GGAGGTGCTG

2221  TTCGAGAAGA ACTTCAGCCA GCTGAGCCCG AAGGACTACA GCGAGAAGTT CACCACCGCC2221 TTCGAGAAGA ACTTCAGCCA GCTGAGCCCG AAGGACTACA GCGAGAAGTT CACCACCGCC

2281  GCCAACAACA CCGGCTTCTA CGTGGAGCTG AGCAGGGGCA CCCAGGGCGG CAACATCACC2281 GCCAACAACA CCGGCTTCTA CGTGGAGCTG AGCAGGGGCA CCCAGGGCGG CAACATCACC

2341  TTCAGGGACT TCAGCATCAA GTAA2341 TTCAGGGACT TCAGCATCAA GTAA

SEQ ID NO:7SEQ ID NO: 7

   1  ATGAACAAGA ACAACACCAA GCTGAGCACC AGGGCCCTGC CGAGCTTCAT CGACTACTTC1 ATGAACAAGA ACAACACCAA GCTGAGCACC AGGGCCCTGC CGAGCTTCAT CGACTACTTC

  61  AACGGCATCT ACGGCTTCGC CACCGGCATC AAGGACATCA TGAACATGAT CTTCAAGACC61 AACGGCATCT ACGGCTTCGC CACCGGCATC AAGGACATCA TGAACATGAT CTTCAAGACC

 121  GACACCGGCG GCGACCTGAC CCTGGACGAG ATCCTGAAGA ACCAGCAGCT GCTGAACGAC121 GACACCGGCG GCGACCTGAC CCTGGACGAG ATCCTGAAGA ACCAGCAGCT GCTGAACGAC

 181  ATCAGCGGCA AGCTGGACGG CGTGAACGGC AGCCTGAACG ACCTGATCGC CCAGGGCAAC181 ATCAGCGGCA AGCTGGACGG CGTGAACGGC AGCCTGAACG ACCTGATCGC CCAGGGCAAC

 241  CTGAACACCG AGCTGAGCAA GGAGATCCTG AAGATCGCCA ACGAGCAGAA CCAGGTGCTG241 CTGAACACCG AGCTGAGCAA GGAGATCCTG AAGATCGCCA ACGAGCAGAA CCAGGTGCTG

 301  AACGACGTGA ACAACAAGCT GGACGCCATC AACACCATGC TGAGGGTGTA CCTGCCGAAG301 AACGACGTGA ACAACAAGCT GGACGCCATC AACACCATGC TGAGGGTGTA CCTGCCGAAG

 361  ATCACCAGCA TGCTGAGCGA CGTGATGAAG CAGAACTACG CCCTGAGCCT GCAGATCGAG361 ATCACCAGCA TGCTGAGCGA CGTGATGAAG CAGAACTACG CCCTGAGCCT GCAGATCGAG

 421  TACCTGAGCA AGCAGCTGCA GGAGATCAGC GACAAGCTGG ACATCATCAA CGTGAACGTG421 TACCTGAGCA AGCAGCTGCA GGAGATCAGC GACAAGCTGG ACATCATCAA CGTGAACGTG

 481  CTGATCAACA GCACCCTGAC CGAGATCACC CCGGCCTACC AGAGGATCAA GTACGTGAAC481 CTGATCAACA GCACCCTGAC CGAGATCACC CCGGCCTACC AGAGGATCAA GTACGTGAAC

 541  GAGAAGTTCG AGGAGCTGAC CTTCGCCACC GAGACCAGCA GCAAGGTGAA GAAGGACGGC541 GAGAAGTTCG AGGAGCTGAC CTTCGCCACC GAGACCAGCA GCAAGGTGAA GAAGGACGGC

 601  AGCCCGGCCG ACATCCTGGA CGAGCTGACC GAGCTGACCG GCCTGGCCAA GAGCGTGCCG601 AGCCCGGCCG ACATCCTGGA CGAGCTGACC GAGCTGACCG GCCTGGCCAA GAGCGTGCCG

 661  AAGAACGACG TGGACGGCTT CGAGTTCTAC CTGAACACCT TCCACGACGT GATGGTGGGC661 AAGAACGACG TGGACGGCTT CGAGTTCTAC CTGAACACCT TCCACGACGT GATGGTGGGC

 721  AACAACCTGT TCGGCAGGAG CGCCCTGAAG ACCGCCAGCG AGCTGATCAC CAAGGAGAAC721 AACAACCTGT TCGGCAGGAG CGCCCTGAAG ACCGCCAGCG AGCTGATCAC CAAGGAGAAC

 781  GTGAAGACCA GCGGCAGCGA GGTGGGCAAC GTGTACAACA GCCTGATCGT GCTGACCCTG781 GTGAAGACCA GCGGCAGCGA GGTGGGCAAC GTGTACAACA GCCTGATCGT GCTGACCCTG

 841  CTGCAGGCCA AGGCCTTCCT GACCCTGACC ACCTGCAGGA AGCTGCTGGG CCTGGCCGAC841 CTGCAGGCCA AGGCCTTCCT GACCCTGACC ACCTGCAGGA AGCTGCTGGG CCTGGCCGAC

 901  ATCGACTACA CCAGCATCAT GAACGAGCAC CTGAACAAGG AGAAGGAGGA GTTCAGGGTG901 ATCGACTACA CCAGCATCAT GAACGAGCAC CTGAACAAGG AGAAGGAGGA GTTCAGGGTG

 961  AACATCCCGC CGACCCTGAG CAACACCTTC AGCAACCCGA ACTACGCCAA GGTGAAGGGC961 AACATCCCGC CGACCCTGAG CAACACCTTC AGCAACCCGA ACTACGCCAA GGTGAAGGGC

1021  AGCGACGAGG ACGCCAAGAT GATCGTGGAG GCCAAGCCGG GCCACGCCCT GGTGGGCTTC1021 AGCGACGAGG ACGCCAAGAT GATCGTGGAG GCCAAGCCGG GCCACGCCCT GGTGGGCTTC

1081  GAGATCAGCA ACGACAGCAT CACCGTGCTG AAGGTGTACG AGGCCAAGCT GAAGCAGAAC1081 GAGATCAGCA ACGACAGCAT CACCGTGCTG AAGGTGTACG AGGCCAAGCT GAAGCAGAAC

1141  TACCAGGTGG ACAAGGACAG CCTGAGCGAG GTGATCTACG GCGACATGGA CAAGCTGCTG1141 TACCAGGTGG ACAAGGACAG CCTGAGCGAG GTGATCTACG GCGACATGGA CAAGCTGCTG

1201  GGCCCGGACC AGAGCGGCCC GATCTACTAC CCGAACAACA TCGTGTTCCC GAACGAGTAC1201 GGCCCGGACC AGAGCGGCCC GATCTACTAC CCGAACAACA TCGTGTTCCC GAACGAGTAC

1261  GTGATCACCA AGATCGACTT CACCAAGAAG ATGAAGACCC TGAGGTACGA GGTGACCGCC1261 GTGATCACCA AGATCGACTT CACCAAGAAG ATGAAGACCC TGAGGTACGA GGTGACCGCC

1321  AACTTCTACG ACAGCAGCAC CGGCGAGATC GACCTGAACA AGAAGAAGGT GGAGAGCAGC1321 AACTTCTACG ACAGCAGCAC CGGCGAGATC GACCTGAACA AGAAGAAGGT GGAGAGCAGC

1381  GAGGCCGAGT ACAGGACCCT GAGCGCCAAC GACGACGGCG TGTACATGCC GCTGGGCGTG1381 GAGGCCGAGT ACAGGACCCT GAGCGCCAAC GACGACGGCG TGTACATGCC GCTGGGCGTG

1441  ATCAGCGAGA CCTTCCTGAC CCCGATCAAC GGCTTCGGCC TGCAGGCCGA CGAGAACAGC1441 ATCAGCGAGA CCTTCCTGAC CCCGATCAAC GGCTTCGGCC TGCAGGCCGA CGAGAACAGC

1501  AGGCTGATCA CCCTGACCTG CAAGAGCTAC CTGAGGGAGC TGCTGCTGGC CACCGACCTG1501 AGGCTGATCA CCCTGACCTG CAAGAGCTAC CTGAGGGAGC TGCTGCTGGC CACCGACCTG

1561  AGCAACAAGG AGACCAAGCT GATCGTGCCG CCGAGCGGCT TCATCAAGAA CATCGTGGAG1561 AGCAACAAGG AGACCAAGCT GATCGTGCCG CCGAGCGGCT TCATCAAGAA CATCGTGGAG

1621  AACGGCAGCA TCGAGGAGGA CAACCTGGAG CCGTGGAAGG CCAACAACAA GAACGCCTAC1621 AACGGCAGCA TCGAGGAGGA CAACCTGGAG CCGTGGAAGG CCAACAACAA GAACGCCTAC

1681  GTGGACCACA CCGGCGGCGT GAACGGCACC AAGGCCCTGT ACGTGCACAA GGACGGCGGC1681 GTGGACCACA CCGGCGGCGT GAACGGCACC AAGGCCCTGT ACGTGCACAA GGACGGCGGC

1741  ATCAGCCAGT TCATCGGCGA CAAGCTGAAG CCGAAGACCG AGTACGTGAT CCAGTACACC1741 ATCAGCCAGT TCATCGGCGA CAAGCTGAAG CCGAAGACCG AGTACGTGAT CCAGTACACC

1801  GTGAAGGGCA AGCCGAGCAT CCACCTGAAG GACGAGAACA CCGGCTACAT CCACTACGAG1801 GTGAAGGGCA AGCCGAGCAT CCACCTGAAG GACGAGAACA CCGGCTACAT CCACTACGAG

1861  GACACCAACA ACAACCTGGA GGACTACCAG ACCATCACCA AGAGGTTCAC CACCGGCACC1861 GACACCAACA ACAACCTGGA GGACTACCAG ACCATCACCA AGAGGTTCAC CACCGGCACC

1921  GACCTGAAGG GCGTGTACCT GATCCTGAAG AGCCAGAACG GCGACGAGGC CTGGGGCGAC1921 GACCTGAAGG GCGTGTACCT GATCCTGAAG AGCCAGAACG GCGACGAGGC CTGGGGCGAC

1981  AACTTCATCA TCCTGGAGAT CAGCCCGAGC GAGAAGCTGC TGAGCCCGGA GCTGATCAAC1981 AACTTCATCA TCCTGGAGAT CAGCCCGAGC GAGAAGCTGC TGAGCCCGGA GCTGATCAAC

2041  ACCAACAACT GGACCAGCAC CGGCAGCACC AACATCAGCG GCAACACCCT GACCCTGTAC2041 ACCAACAACT GGACCAGCACC CGGCAGCACC AACATCAGCG GCAACACCCCT GACCCTGTAC

2101  CAGGGCGGCA GGGGCATCCT GAAGCAGAAC CTGCAGCTGG ACAGCTTCAG CACCTACAGG2101 CAGGGCGGCA GGGGCATCCT GAAGCAGAAC CTGCAGCTGG ACAGCTTCAG CACCTACAGG

2161  GTGTACTTCA GCGTGAGCGG CGACGCCAAC GTGAGGATCA GGAACAGCAG GGAGGTGCTG2161 GTGTACTTCA GCGTGAGCGG CGACGCCAAC GTGAGGATCA GGAACAGCAG GGAGGTGCTG

2221  TTCGAGAAGA GGTACATGAG CGGCGCCAAG GACGTGAGCG AGATCTTCAC CACCAAGCTG2221 TTCGAGAAGA GGTACATGAG CGGCGCCAAG GACGTGAGCG AGATCTTCAC CACCAAGCTG

2281  GGCAAGGACA ACTTCTACAT CGAGCTGAGC CAGGGCAACA ACCTGAACGG CGGCCCGATC2281 GGCAAGGACA ACTTCTACAT CGAGCTGAGC CAGGGCAACA ACCTGAACGG CGGCCCGATC

2341  GTGAAGTTCT ACGACGTGAG CATCAAGTAA2341 GTGAAGTTCT ACGACGTGAG CATCAAGTAA

Claims (7)

1、一种抗虫融合基因,其特征是:所述基因包括从5’-3’依次为含有编码BT晶体毒素的核苷酸序列和编码Vip3毒素的核苷酸序列;且上述2个核苷酸序列位于同一个开放阅读框内;所述BT晶体毒素为全长或是C端切除的活性毒素。1. An insect-resistant fusion gene, characterized in that: the gene includes, from 5' to 3', a nucleotide sequence encoding a BT crystal toxin and a nucleotide sequence encoding a Vip3 toxin; The nucleotide sequences are located in the same open reading frame; the BT crystal toxin is full-length or a C-terminal excised active toxin. 2、根据权利要求1所述的抗虫融合基因,其特征是:所述基因包括从5’-3’依次为含有编码BT晶体毒素的核苷酸序列、任何的氨基酸多肽片断和编码Vip3毒素的核苷酸序列。2. The anti-insect fusion gene according to claim 1, characterized in that: the gene includes, from 5' to 3', the nucleotide sequence encoding BT crystal toxin, any amino acid polypeptide fragment and Vip3 toxin the nucleotide sequence. 3、根据权利要求1或2所述的抗虫融合基因,其特征是:所述BT晶体毒素为Cry1Ab、Cry1Ac、Cry2或Cry3,所述Vip3毒素为Vip3A、Vip3B、Vip3C、Vip3D或Vip3H。3. The anti-insect fusion gene according to claim 1 or 2, characterized in that: the BT crystal toxin is Cry1Ab, Cry1Ac, Cry2 or Cry3, and the Vip3 toxin is Vip3A, Vip3B, Vip3C, Vip3D or Vip3H. 4、根据权利要求3所述的抗虫融合基因,其特征是:当所述BT晶体毒素为Cry1Ab、所述Vip3毒素为Vip3H时,基因的核苷酸序列为SEQ ID NO:1;当所述BT晶体毒素为Cry1Ab、所述Vip3毒素为Vip3A时,基因的核苷酸序列为SEQ IDNO:2。4. The anti-insect fusion gene according to claim 3, characterized in that: when the BT crystal toxin is Cry1Ab and the Vip3 toxin is Vip3H, the nucleotide sequence of the gene is SEQ ID NO: 1; When the BT crystal toxin is Cry1Ab and the Vip3 toxin is Vip3A, the nucleotide sequence of the gene is SEQ ID NO: 2. 5、如权利要求1的抗虫融合基因编码的融合蛋白,其特征是:所述融合蛋白从N端至C端依次为BT晶体毒素和Vip3毒素。5. The fusion protein encoded by the anti-insect fusion gene according to claim 1, characterized in that: said fusion protein is BT crystal toxin and Vip3 toxin in order from N-terminal to C-terminal. 6、根据权利要求5所述的融合蛋白,其特征是:当所述BT晶体毒素为Cry1Ab、所述Vip3毒素为Vip3H时,融合蛋白的氨基酸序列为SEQ ID NO:3;当所述BT晶体毒素为Cry1Ab、所述Vip3毒素为Vip3A时,融合蛋白的氨基酸序列为SEQ IDNO:4。6. The fusion protein according to claim 5, characterized in that: when the BT crystal toxin is Cry1Ab and the Vip3 toxin is Vip3H, the amino acid sequence of the fusion protein is SEQ ID NO: 3; when the BT crystal toxin is When the toxin is Cry1Ab and the Vip3 toxin is Vip3A, the amino acid sequence of the fusion protein is SEQ ID NO: 4. 7、如权利要求5或6所述的融合蛋白,在转基因作物抗虫作物和转基因作物杀虫微生物方面的应用。7. The application of the fusion protein according to claim 5 or 6 in transgenic crop insect-resistant crops and transgenic crop insecticidal microorganisms.
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CN105624177A (en) * 2016-02-04 2016-06-01 浙江大学 Insect-fusion-resistant gene, coding protein, carrier and application thereof
CN106834318A (en) * 2016-12-31 2017-06-13 浙江大学 A kind of insect-resistant fusion gene, encoding proteins and its application
CN106834318B (en) * 2016-12-31 2020-05-29 浙江大学 Insect-resistant fusion gene, encoding protein and application thereof
CN106832001A (en) * 2017-01-21 2017-06-13 浙江大学 A kind of desinsection fusion protein, encoding gene and its application
CN106832001B (en) * 2017-01-21 2020-12-22 浙江大学 A kind of insecticidal fusion protein, encoding gene and application thereof
CN107383177B (en) * 2017-08-16 2020-08-14 中国农业大学 Artificial synthesis of Bt insecticidal gene mcry1Ab for transgenic insect-resistant plants
CN107383177A (en) * 2017-08-16 2017-11-24 中国农业大学 The artificial synthesized Bt killing genes mcry1Ab for transgenic anti-insect plants
CN107723303A (en) * 2017-09-29 2018-02-23 杭州瑞丰生物科技有限公司 Insect-resistant fusion gene, encoding proteins, carrier and its application
CN111088265A (en) * 2019-12-16 2020-05-01 广州小草农业科技有限公司 Insect-resistant fusion gene, encoding protein thereof, expression vector thereof and application thereof
CN111440814A (en) * 2020-02-26 2020-07-24 中国农业科学院作物科学研究所 Insect-resistant fusion gene mCry1AbVip3A, expression vector and application thereof
CN112390893A (en) * 2020-07-16 2021-02-23 杭州瑞丰生物科技有限公司 Efficient fusion protein for resisting spodoptera frugiperda and application thereof
CN113793639A (en) * 2021-08-03 2021-12-14 杭州瑞丰生物科技有限公司 Method for managing resistance of corn borers to Bt toxins
CN113793639B (en) * 2021-08-03 2024-01-05 杭州瑞丰生物科技有限公司 Method for managing resistance of corn borers to Bt toxins
CN114853858A (en) * 2022-03-29 2022-08-05 河南大学 Insect-resistant cyiron toxin protein gene, expression vector and application
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