CN113773372A - 重组蛋白及其制备方法和应用 - Google Patents

重组蛋白及其制备方法和应用 Download PDF

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CN113773372A
CN113773372A CN202110933826.3A CN202110933826A CN113773372A CN 113773372 A CN113773372 A CN 113773372A CN 202110933826 A CN202110933826 A CN 202110933826A CN 113773372 A CN113773372 A CN 113773372A
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高强
胡雅灵
王琳
朱朗
卜祥利
李育蓉
胡一凡
尹卫东
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Abstract

本文公开一种重组表面刺突(S)蛋白及其制备方法和应用，所述重组S蛋白来源于严重急性呼吸系统综合症冠状病毒(SARS‑CoV‑2)，且包含在N末端结构域中的缺失和弗林酶切位点结构域的缺失。

Description

重组蛋白及其制备方法和应用
技术领域
本公开属于生物技术领域，具体涉及一种重组蛋白，及其制备方法和应用。
背景技术
严重急性呼吸系统综合症冠状病毒(SARS-CoV-2，新冠病毒)是一种有包膜的正义单链 RNA病毒，可导致新型冠状病毒病(COVID-19)，引发机体产生发热、乏力、干咳等症状，严重的还容易引起呼吸困难，最终导致死亡。
新冠病毒颗粒的结构包括入侵宿主细胞所需的遗传物质RNA和结构蛋白。新冠病毒侵染 细胞后，遗传物质RNA被用来编码构成病毒颗粒的结构蛋白，指导病毒组装、转录、复制和 宿主控制的非结构蛋白，以及功能尚未确定的辅助蛋白。SARS-CoV-2的结构蛋白包括包膜(E) 蛋白、表面刺突(S)蛋白、膜(M)蛋白和核衣壳(N)蛋白。S蛋白位于病毒颗粒的外部， 介导新冠病毒颗粒的附着和进入宿主细胞，是新冠疫苗开发、抗体疗法和基于抗原的诊断测试 的主要靶标。
S蛋白是新冠病毒的主要免疫原区域，绝大多数疫苗免疫后产生的中和抗体及恢复期患者 血清中的中和抗体均由S蛋白的受体结合结构域(RBD)产生。最近有报道发现，S蛋白的 S1/S2连接处的弗林酶切位点缺失或突变会引起新冠病毒在Vero细胞中呈现复制增强，在动物 中呈现毒力减弱的状态，且这种含有弗林酶切位点缺失的病毒能够诱导产生很强的体液免疫和 细胞免疫反应。
目前，已有灭活疫苗、重组蛋白疫苗、mRNA疫苗、腺病毒载体疫苗、减毒流感病毒载体疫苗等新冠疫苗陆续上市或进入临床试验阶段。在保证安全性的前提下，如何获得一种免疫 原性更好的新冠疫苗，是新冠疫苗开发设计的重要目标。
发明内容
为了解决现有技术中存在的上述技术问题之一，本公开对新冠病毒SARS-CoV-2中的S 蛋白的序列进行了改造，提供了一种免疫原性得到显著提高的重组S蛋白，可用于新冠疫苗的 开发。
根据本公开的一个方面，提供了一种重组表面刺突(S)蛋白，其特征在于，所述重组S 蛋白来源于严重急性呼吸系统综合症冠状病毒(SARS-CoV-2)，且包含在N末端结构域中的 缺失和弗林酶切位点结构域的缺失。本公开的重组S蛋白具有与新冠病毒野生型毒株的S蛋 白相比显著提高的免疫原性。
根据本公开的一些实施方式，所述SARS-CoV-2可以选自Wuhan-Hu-1病毒株、P.1病毒 株、P.2病毒株、B.1.351病毒株、B.1.1.7病毒株、C.37病毒株或B.1.617.2病毒株。根据本公 开的一些实施方式，所述重组S蛋白可以具有如SEQ ID NO:1～7中任一项所示的氨基酸序列。 根据本公开的一些实施方式，所述重组S蛋白可以具有与SEQ ID NO:1～7中任一项所示的氨 基酸序列具有至少85％同一性的氨基酸序列，例如，具有与SEQ ID NO:1～7中任一项所示的 氨基酸序列具有至少85％，86％，87％，88％，89％，90％，91％，92％，93％，94％，95％， 96％，97％，98％或99％同一性的序列。
根据本公开的一些实施方式，所述N末端结构域中可以包括如IX1X2SGTNX3X4所示的序 列的缺失，其中X1不存在或者选自组氨酸，X2不存在或者选自缬氨酸，X3选自甘氨酸或缬氨 酸，和/或X4选自苏氨酸或异亮氨酸。根据本公开的一些实施方式，所述N末端结构域中可以 包括如SEQ ID NO:8～10中任一项所示的氨基酸序列的缺失。
根据本公开的一些实施方式，所述弗林酶切位点结构域的缺失包括如X5RRAR所示的序 列的缺失，其中X5选自组氨酸、精氨酸或脯氨酸。根据本公开的一些实施方式，所述弗林酶 切位点结构域的缺失包括如SEQ ID NO:11～13中任一项所示的氨基酸序列的缺失。
根据本公开的一些实施方式，所述重组S蛋白可以具有如SEQ ID NO:*～*中任一项所示 的氨基酸序列。根据本公开的一些实施方式，所述重组S蛋白可以具有与SEQ IDNO:*～*中 任一项所示的氨基酸序列具有至少85％同一性的氨基酸序列，例如，具有与SEQID NO:*～* 中任一项所示的氨基酸序列具有至少85％，86％，87％，88％，89％，90％，91％，92％，93％， 94％，95％，96％，97％，98％或99％同一性的序列。
根据本公开的另一方面，提供了一种编码如上所述的重组S蛋白的核酸序列。根据本公开 的一个实施方式，编码如上所述的重组S蛋白的核酸序列具有如SEQ ID NO:22所示的核酸序 列。
根据本公开的又一方面，提供了一种表达载体，所述表达载体包括如上所述的核酸序列。 根据本公开的一些实施方式，所示表达载体包括包括腺病毒载体、痘病毒载体、流感病毒载体 等。
根据本公开的又一方面，提供了一种宿主细胞，所述宿主细胞包括如上所述的核酸序列或 如上所述的表达载体。
根据本公开的又一方面，提供了如上所述的重组S蛋白、如上所述的核酸序列、如上所述 的表达载体或如上所述的宿主细胞，在制备用于对象的SARS-CoV-2疫苗中的用途。根据本公 开的一些实施方式，所述对象可以包括哺乳动物，优选为人、猴、骆驼、牛、马、山羊、绵羊、 猪、猫、狗、兔、小鼠或大鼠。
根据本公开的又一方面，提供了一种用于制备如上所述的重组S蛋白的方法。根据本公开 的一些实施方式，所述方法包括：对来源于严重急性呼吸系统综合症冠状病毒(SARS-CoV-2) 的重组S蛋白，进行N末端结构域和弗林酶切位点结构域的缺失。
根据本公开的一些方式，所示方法包括以下步骤：在编码上述S蛋白的核苷酸序列的5’- 端加入编码信号肽的序列，3’-端加上终止密码子进行克隆表达，筛选正确的重组子，用重组 子转染表达系统的细胞进行表达，收集表达后细胞上清，纯化得到含有上述氨基酸序列的新冠 病毒抗原。
上述方法所述表达系统的细胞包括哺乳动物细胞(293细胞或CHO细胞)、昆虫细胞、酵 母细胞或细菌细胞(大肠杆菌)。
本公开获得的重组S蛋白变体相比于新冠病毒原型株S蛋白的免疫原性提高10倍以上， 因此是作为免疫原或抗原用于免疫对象的理想疫苗候选蛋白。
定义
除非另有定义，否则本公开使用的所有技术术语和科技术语都具有如在本公开所属领域中 通常使用的相同含义。出于解释本说明书的目的，将应用以下定义，并且在适当时，以单数形 式使用的术语也将包括复数形式，反之亦然。
除非上下文另有明确说明，否则本文所用的表述“一种”和“一个”包括复数指代。例如， 提及“一个细胞”包括多个这样的细胞及本领域技术人员可知晓的等同物等等。
本文所用的术语“约”表示其后的数值的±20％的范围。在一些实施方式中，术语“约” 表示其后的数值的±10％的范围。在一些实施方式中，术语“约”表示其后的数值的±5％的 范围。
SARS-CoV-2病毒颗粒的S蛋白与细胞表面受体血管紧张素转化酶2(ACE2)结合，以促进其进入细胞。由于S蛋白对于病毒进入至关重要，因此它已成为疫苗开发和治疗性抗体干 预的目标。SARS-CoV-2的S蛋白被弗林酶(Furin)切割，产生S1和S2片段。S1蛋白包括 N末端结构域(NTD)和受体结合结构域域(RBD)，而S2蛋白促进膜融合。
目前发现了七株SARS-CoV-2病毒，即Wuhan-Hu-1病毒株、P.1(Gamma)病毒株、P.2(Zeta)病毒株、B.1.351(Beta)病毒株、B.1.1.7(Alpha)病毒株、C.37(Lambda)病毒株 或B.1.617.2(Delta)病毒株。Wuhan-Hu-1病毒株的S蛋白具有如SEQ ID NO:1所示的氨基 酸序列。P.1(Gamma)病毒株的S蛋白具有如SEQ ID NO:2所示的氨基酸序列。P.2(Zeta) 病毒株的S蛋白具有如SEQ ID NO:3所示的氨基酸序列。B.1.351(Beta)病毒株的S蛋白具 有如SEQ ID NO:4所示的氨基酸序列。B.1.1.7(Alpha)病毒株的S蛋白具有如SEQ ID NO:5 所示的氨基酸序列。C.37(Lambda)病毒株的S蛋白具有如SEQ ID NO:6所示的氨基酸序列。B.1.617.2(Delta)病毒株的S蛋白具有如SEQ ID NO:7所示的氨基酸序列。图2中示出了这七株毒株的S蛋白的序列比对结果。
下面提供实施例和附图以帮助理解本公开。但应理解，这些实施例和附图仅用于说明本公 开，但不构成任何限制。本公开的实际保护范围在权利要求书中进行阐述。应理解，在不脱离 本公开精神的情况下，可以进行任何修改和改变。
附图说明
图1示出了由CHO细胞或汉逊酵母中表达的重组S蛋白(S-del)和野生型S蛋白(S)免疫小鼠后的中和抗体的效价。
图2示出了原始病毒株(Wuhan-Hu-1)、γ病毒株(P.1)、zeta(ζ)病毒株(P.2)、β病毒株 (B.1.351)、α病毒株(B.1.1.7)、λ病毒株(C.37)和δ病毒株(B.1.617.2)的S蛋白以及本 公开的一种重组S蛋白的氨基酸序列的对比。
具体实施方式
为使本公开的目的、技术方案及优点更加清楚明白，以下结合实施例，对本公开进行进一 步的详细说明。此处所描述的具体实施例仅用于解释本公开，并不用于构成对本公开的任何限 制。此外，在以下说明中，省略了对公知结构和技术的描述，以避免不必要地混淆本公开的概 念。这样的结构和技术在许多出版物中也进行了描述。
在以下说明中，省略了对公知技术的描述，以避免不必要地混淆本公开的概念。这样的技 术在许多出版物，例如《分子克隆实验指南(第四版)》(冷泉港实验室科学出版社)中进行了 描述。
实施例1
将SEQ ID NO:21和SEQ ID NO:22所示的核酸序列分别构建到pCHO载体上，并且通过 热激法转化DH5α感受态。通过表达载体的抗性筛选阳性克隆，挑取克隆斑进行菌液PCR检 测，并将阳性检测结果送测序，进一步确定得到目的克隆。测序正确的菌种，经过质粒提取和 纯化，转染至CHO细胞，进行目的蛋白的表达和纯化。
实施例2
将SEQ ID NO:21和SEQ ID NO:22所示的核酸序列，根据酵母表达系统的密码子偏好， 优化密码子，进行基因合成。通过设计引物将合成得到的基因扩增，使用合适的限制酶将质粒 载体线性化，通过酶切连接或者同源重组的方式将目的基因连接到载体上。用热激法转化DH5 α感受态，通过载体的抗性筛选阳性克隆。挑取克隆斑进行菌液PCR检测，并将阳性检测结 果送测序。用化学法制备酵母细胞感受态，随后将测序正确的质粒载体转化酵母细胞。通过抗 性或营养缺陷法筛选成功转化的酵母细胞，通过在酵母基因组上设计引物，进行菌液PCR检 测，鉴定目的基因是否整合到酵母基因组中。通过甲醇诱导目的基因表达，用Western印迹检 测了目的蛋白的表达。
实施例3
分别构建含有SEQ ID NO:21(编码野生型S蛋白，S)和SEQ ID NO:22(编码重组S蛋白，S-del)的载体，分别在相应的CHO细胞和汉逊酵母中表达纯化后获得目的蛋白。将纯化后获得的目的蛋白与氢氧化铝佐剂1:1混合免疫大鼠，每组10只，免疫剂量为蛋白质含量10μg/只，0、14天免疫后第28天采血进行中和抗体效价检测，结果如图1所示。
野生型S蛋白和重组S-del蛋白在不同CHO细胞和酵母中的表达产物来免疫大鼠。从图1 可以看出，血清中和抗体效价GMT，野生型S蛋白表达产物在CHO中为1:37，酵母中为1: 20；重组S-del蛋白的GMT分别为1:179和1:129。与野生型S蛋白相比，重组S-del蛋白 的表达产物血清中和抗体效价均有4～7倍的提高，这种提高在不同表达系统中的差异均显著。
本公开的技术方案不限于上述具体实施例的限制，凡是根据本公开的技术方案做出的技术 变形，均落入本公开的保护范围之内。
序列表
<110> 北京科兴中维生物技术有限公司
<120> 重组蛋白及其制备方法和应用
<160> 22
<170> SIPOSequenceListing 1.0
<210> 1
<211> 1273
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 1
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp
65 70 75 80
Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu
85 90 95
Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser
100 105 110
Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile
115 120 125
Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr
130 135 140
Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr
145 150 155 160
Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu
165 170 175
Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe
180 185 190
Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr
195 200 205
Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu
210 215 220
Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr
225 230 235 240
Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser
245 250 255
Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro
260 265 270
Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala
275 280 285
Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys
290 295 300
Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val
305 310 315 320
Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys
325 330 335
Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala
340 345 350
Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu
355 360 365
Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro
370 375 380
Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe
385 390 395 400
Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly
405 410 415
Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys
420 425 430
Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn
435 440 445
Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe
450 455 460
Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys
465 470 475 480
Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly
485 490 495
Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val
500 505 510
Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys
515 520 525
Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn
530 535 540
Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu
545 550 555 560
Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val
565 570 575
Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe
580 585 590
Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val
595 600 605
Ala Val Leu Tyr Gln Asp Val Asn Cys Thr Glu Val Pro Val Ala Ile
610 615 620
His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser
625 630 635 640
Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val
645 650 655
Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala
660 665 670
Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala
675 680 685
Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser
690 695 700
Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile
705 710 715 720
Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val
725 730 735
Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu
740 745 750
Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr
755 760 765
Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln
770 775 780
Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe
785 790 795 800
Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser
805 810 815
Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly
820 825 830
Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp
835 840 845
Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu
850 855 860
Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly
865 870 875 880
Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile
885 890 895
Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr
900 905 910
Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn
915 920 925
Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala
930 935 940
Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn
945 950 955 960
Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val
965 970 975
Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln
980 985 990
Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val
995 1000 1005
Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu
1010 1015 1020
Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val
1025 1030 1035 1040
Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala
1045 1050 1055
Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu
1060 1065 1070
Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His
1075 1080 1085
Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val
1090 1095 1100
Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr
1105 1110 1115 1120
Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr
1125 1130 1135
Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu
1140 1145 1150
Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp
1155 1160 1165
Ile Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp
1170 1175 1180
Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu
1185 1190 1195 1200
Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile
1205 1210 1215
Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile
1220 1225 1230
Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys
1235 1240 1245
Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val
1250 1255 1260
Leu Lys Gly Val Lys Leu His Tyr Thr
1265 1270
<210> 2
<211> 1273
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 2
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Phe Thr Asn Arg Thr Gln Leu Pro Ser Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp
65 70 75 80
Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu
85 90 95
Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser
100 105 110
Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile
115 120 125
Lys Val Cys Glu Phe Gln Phe Cys Asn Tyr Pro Phe Leu Gly Val Tyr
130 135 140
Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr
145 150 155 160
Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu
165 170 175
Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Ser Glu Phe
180 185 190
Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr
195 200 205
Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu
210 215 220
Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr
225 230 235 240
Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser
245 250 255
Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro
260 265 270
Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala
275 280 285
Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys
290 295 300
Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val
305 310 315 320
Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys
325 330 335
Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala
340 345 350
Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu
355 360 365
Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro
370 375 380
Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe
385 390 395 400
Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly
405 410 415
Thr Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys
420 425 430
Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn
435 440 445
Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe
450 455 460
Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys
465 470 475 480
Asn Gly Val Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly
485 490 495
Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val
500 505 510
Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys
515 520 525
Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn
530 535 540
Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu
545 550 555 560
Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val
565 570 575
Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe
580 585 590
Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val
595 600 605
Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile
610 615 620
His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser
625 630 635 640
Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu Tyr Val
645 650 655
Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala
660 665 670
Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala
675 680 685
Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser
690 695 700
Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile
705 710 715 720
Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val
725 730 735
Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu
740 745 750
Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr
755 760 765
Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln
770 775 780
Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe
785 790 795 800
Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser
805 810 815
Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly
820 825 830
Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp
835 840 845
Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu
850 855 860
Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly
865 870 875 880
Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile
885 890 895
Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr
900 905 910
Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn
915 920 925
Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala
930 935 940
Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn
945 950 955 960
Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val
965 970 975
Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln
980 985 990
Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val
995 1000 1005
Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu
1010 1015 1020
Ala Ala Ile Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val
1025 1030 1035 1040
Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala
1045 1050 1055
Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu
1060 1065 1070
Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His
1075 1080 1085
Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val
1090 1095 1100
Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr
1105 1110 1115 1120
Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr
1125 1130 1135
Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu
1140 1145 1150
Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp
1155 1160 1165
Ile Ser Gly Ile Asn Ala Ser Phe Val Asn Ile Gln Lys Glu Ile Asp
1170 1175 1180
Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu
1185 1190 1195 1200
Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile
1205 1210 1215
Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile
1220 1225 1230
Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys
1235 1240 1245
Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val
1250 1255 1260
Leu Lys Gly Val Lys Leu His Tyr Thr
1265 1270
<210> 3
<211> 1273
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 3
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp
65 70 75 80
Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu
85 90 95
Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser
100 105 110
Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile
115 120 125
Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr
130 135 140
Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr
145 150 155 160
Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu
165 170 175
Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe
180 185 190
Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr
195 200 205
Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu
210 215 220
Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr
225 230 235 240
Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser
245 250 255
Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro
260 265 270
Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala
275 280 285
Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys
290 295 300
Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val
305 310 315 320
Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys
325 330 335
Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala
340 345 350
Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu
355 360 365
Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro
370 375 380
Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe
385 390 395 400
Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly
405 410 415
Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys
420 425 430
Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn
435 440 445
Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe
450 455 460
Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys
465 470 475 480
Asn Gly Val Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly
485 490 495
Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val
500 505 510
Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys
515 520 525
Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn
530 535 540
Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu
545 550 555 560
Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val
565 570 575
Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe
580 585 590
Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val
595 600 605
Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile
610 615 620
His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser
625 630 635 640
Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val
645 650 655
Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala
660 665 670
Ser Tyr Gln Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala
675 680 685
Ser Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser
690 695 700
Val Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile
705 710 715 720
Ser Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val
725 730 735
Asp Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu
740 745 750
Leu Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr
755 760 765
Gly Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln
770 775 780
Val Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe
785 790 795 800
Asn Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser
805 810 815
Phe Ile Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly
820 825 830
Phe Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp
835 840 845
Leu Ile Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu
850 855 860
Leu Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly
865 870 875 880
Thr Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile
885 890 895
Pro Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr
900 905 910
Gln Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn
915 920 925
Ser Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala
930 935 940
Leu Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn
945 950 955 960
Thr Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val
965 970 975
Leu Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln
980 985 990
Ile Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val
995 1000 1005
Thr Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu
1010 1015 1020
Ala Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val
1025 1030 1035 1040
Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala
1045 1050 1055
Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu
1060 1065 1070
Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His
1075 1080 1085
Phe Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val
1090 1095 1100
Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr
1105 1110 1115 1120
Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr
1125 1130 1135
Val Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu
1140 1145 1150
Asp Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp
1155 1160 1165
Ile Ser Gly Ile Asn Ala Ser Phe Val Asn Ile Gln Lys Glu Ile Asp
1170 1175 1180
Arg Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu
1185 1190 1195 1200
Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile
1205 1210 1215
Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile
1220 1225 1230
Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys
1235 1240 1245
Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val
1250 1255 1260
Leu Lys Gly Val Lys Leu His Tyr Thr
1265 1270
<210> 4
<211> 1270
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 4
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Phe Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Ala
65 70 75 80
Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu
85 90 95
Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser
100 105 110
Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile
115 120 125
Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr
130 135 140
Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr
145 150 155 160
Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu
165 170 175
Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe
180 185 190
Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr
195 200 205
Pro Ile Asn Leu Val Arg Gly Leu Pro Gln Gly Phe Ser Ala Leu Glu
210 215 220
Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr
225 230 235 240
Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr
245 250 255
Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe
260 265 270
Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys
275 280 285
Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr
290 295 300
Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr
305 310 315 320
Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly
325 330 335
Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg
340 345 350
Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser
355 360 365
Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu
370 375 380
Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg
385 390 395 400
Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Asn Ile Ala
405 410 415
Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala
420 425 430
Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr
435 440 445
Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp
450 455 460
Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val
465 470 475 480
Lys Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro
485 490 495
Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe
500 505 510
Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr
515 520 525
Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr
530 535 540
Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln
545 550 555 560
Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro
565 570 575
Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val
580 585 590
Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu
595 600 605
Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp
610 615 620
Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe
625 630 635 640
Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser
645 650 655
Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln
660 665 670
Thr Gln Thr Asn Ser Pro Arg Arg Ala Arg Ser Val Ala Ser Gln Ser
675 680 685
Ile Ile Ala Tyr Thr Met Ser Leu Gly Val Glu Asn Ser Val Ala Tyr
690 695 700
Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr
705 710 715 720
Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr
725 730 735
Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln
740 745 750
Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala
755 760 765
Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln
770 775 780
Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser
785 790 795 800
Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu
805 810 815
Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys
820 825 830
Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys
835 840 845
Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp
850 855 860
Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr
865 870 875 880
Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala
885 890 895
Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val
900 905 910
Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile
915 920 925
Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys
930 935 940
Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val
945 950 955 960
Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp
965 970 975
Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp Arg
980 985 990
Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln
995 1000 1005
Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr
1010 1015 1020
Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys
1025 1030 1035 1040
Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly
1045 1050 1055
Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe
1060 1065 1070
Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg
1075 1080 1085
Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg
1090 1095 1100
Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser
1105 1110 1115 1120
Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp
1125 1130 1135
Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr
1140 1145 1150
Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly
1155 1160 1165
Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn
1170 1175 1180
Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu
1185 1190 1195 1200
Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly
1205 1210 1215
Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys
1220 1225 1230
Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly
1235 1240 1245
Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly
1250 1255 1260
Val Lys Leu His Tyr Thr
1265 1270
<210> 5
<211> 1270
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 5
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Ile Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp Asn Pro
65 70 75 80
Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu Lys Ser
85 90 95
Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser Lys Thr
100 105 110
Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile Lys Val
115 120 125
Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr His Lys
130 135 140
Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala
145 150 155 160
Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp Leu
165 170 175
Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe Lys
180 185 190
Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile Asn
195 200 205
Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu Val
210 215 220
Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala
225 230 235 240
Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr
245 250 255
Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe
260 265 270
Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys
275 280 285
Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr
290 295 300
Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr
305 310 315 320
Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly
325 330 335
Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg
340 345 350
Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser
355 360 365
Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu
370 375 380
Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg
385 390 395 400
Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala
405 410 415
Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala
420 425 430
Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr
435 440 445
Leu Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp
450 455 460
Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val
465 470 475 480
Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro
485 490 495
Thr Tyr Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe
500 505 510
Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr
515 520 525
Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr
530 535 540
Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln
545 550 555 560
Gln Phe Gly Arg Asp Ile Asp Asp Thr Thr Asp Ala Val Arg Asp Pro
565 570 575
Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val
580 585 590
Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu
595 600 605
Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp
610 615 620
Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe
625 630 635 640
Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser
645 650 655
Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln
660 665 670
Thr Gln Thr Asn Ser His Arg Arg Ala Arg Ser Val Ala Ser Gln Ser
675 680 685
Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr
690 695 700
Ser Asn Asn Ser Ile Ala Ile Pro Ile Asn Phe Thr Ile Ser Val Thr
705 710 715 720
Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr
725 730 735
Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln
740 745 750
Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala
755 760 765
Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln
770 775 780
Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser
785 790 795 800
Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu
805 810 815
Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys
820 825 830
Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys
835 840 845
Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp
850 855 860
Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr
865 870 875 880
Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala
885 890 895
Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val
900 905 910
Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile
915 920 925
Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys
930 935 940
Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val
945 950 955 960
Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp
965 970 975
Ile Leu Ala Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp Arg
980 985 990
Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln
995 1000 1005
Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr
1010 1015 1020
Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys
1025 1030 1035 1040
Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly
1045 1050 1055
Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe
1060 1065 1070
Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg
1075 1080 1085
Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg
1090 1095 1100
Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr His Asn Thr Phe Val Ser
1105 1110 1115 1120
Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp
1125 1130 1135
Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr
1140 1145 1150
Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly
1155 1160 1165
Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn
1170 1175 1180
Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu
1185 1190 1195 1200
Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly
1205 1210 1215
Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys
1220 1225 1230
Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly
1235 1240 1245
Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly
1250 1255 1260
Val Lys Leu His Tyr Thr
1265 1270
<210> 6
<211> 1266
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 6
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Ile His Val Ser Gly Thr Asn Val Ile Lys Arg Phe Asp
65 70 75 80
Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu
85 90 95
Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser
100 105 110
Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile
115 120 125
Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr
130 135 140
Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr
145 150 155 160
Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu
165 170 175
Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe
180 185 190
Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr
195 200 205
Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu
210 215 220
Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr
225 230 235 240
Leu Leu Ala Leu His Asn Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala
245 250 255
Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr
260 265 270
Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro
275 280 285
Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly
290 295 300
Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val
305 310 315 320
Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn
325 330 335
Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser
340 345 350
Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser
355 360 365
Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys
370 375 380
Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val
385 390 395 400
Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr
405 410 415
Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn
420 425 430
Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Gln Tyr Arg Leu
435 440 445
Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu
450 455 460
Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn
465 470 475 480
Cys Tyr Ser Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val
485 490 495
Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His
500 505 510
Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys
515 520 525
Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val
530 535 540
Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg
545 550 555 560
Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu
565 570 575
Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr
580 585 590
Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Gly Val
595 600 605
Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro
610 615 620
Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala
625 630 635 640
Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp
645 650 655
Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Asn
660 665 670
Ser Pro Arg Arg Ala Arg Ser Val Ala Ser Gln Ser Ile Ile Ala Tyr
675 680 685
Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn Asn Ser
690 695 700
Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile Leu
705 710 715 720
Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile Cys
725 730 735
Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser Phe
740 745 750
Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln Asp
755 760 765
Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys Thr
770 775 780
Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu Pro
785 790 795 800
Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu Phe
805 810 815
Asn Lys Leu Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly Asp
820 825 830
Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys Phe
835 840 845
Asn Gly Leu Asn Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile Ala
850 855 860
Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp Thr
865 870 875 880
Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met Ala
885 890 895
Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu Asn
900 905 910
Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile Gln
915 920 925
Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp Val
930 935 940
Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu Ser
945 950 955 960
Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser Arg
965 970 975
Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr Gly
980 985 990
Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg Ala
995 1000 1005
Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser Glu
1010 1015 1020
Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly Tyr
1025 1030 1035 1040
His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe Leu
1045 1050 1055
His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala Pro
1060 1065 1070
Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val Phe
1075 1080 1085
Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr Glu
1090 1095 1100
Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys Asp
1105 1110 1115 1120
Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln Pro
1125 1130 1135
Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn His
1140 1145 1150
Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala Ser
1155 1160 1165
Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala Lys
1170 1175 1180
Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr Glu
1185 1190 1195 1200
Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala Gly
1205 1210 1215
Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys Cys Met Thr Ser
1220 1225 1230
Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys Cys Lys
1235 1240 1245
Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys Leu His
1250 1255 1260
Tyr Thr
1265
<210> 7
<211> 1271
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 7
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Leu Arg Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Ile His Val Ser Gly Thr Asn Gly Thr Lys Arg Phe Asp
65 70 75 80
Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Ile Glu
85 90 95
Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser
100 105 110
Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile
115 120 125
Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr
130 135 140
Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Gly Val Tyr Ser Ser
145 150 155 160
Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu Met Asp
165 170 175
Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe Val Phe
180 185 190
Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr Pro Ile
195 200 205
Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu Pro Leu
210 215 220
Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr Leu Leu
225 230 235 240
Ala Leu His Arg Ser Tyr Leu Thr Pro Gly Asp Ser Ser Ser Gly Trp
245 250 255
Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr
260 265 270
Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp
275 280 285
Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe
290 295 300
Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro
305 310 315 320
Thr Glu Ser Ile Val Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe
325 330 335
Gly Glu Val Phe Asn Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn
340 345 350
Arg Lys Arg Ile Ser Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn
355 360 365
Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys
370 375 380
Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile
385 390 395 400
Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile
405 410 415
Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile
420 425 430
Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn
435 440 445
Tyr Arg Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg
450 455 460
Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Lys Pro Cys Asn Gly
465 470 475 480
Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln
485 490 495
Pro Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser
500 505 510
Phe Glu Leu Leu His Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser
515 520 525
Thr Asn Leu Val Lys Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu
530 535 540
Thr Gly Thr Gly Val Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe
545 550 555 560
Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp
565 570 575
Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly
580 585 590
Val Ser Val Ile Thr Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val
595 600 605
Leu Tyr Gln Gly Val Asn Cys Thr Glu Val Pro Val Ala Ile His Ala
610 615 620
Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val
625 630 635 640
Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn
645 650 655
Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr
660 665 670
Gln Thr Gln Thr Asn Ser Arg Arg Arg Ala Arg Ser Val Ala Ser Gln
675 680 685
Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala
690 695 700
Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val
705 710 715 720
Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys
725 730 735
Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu
740 745 750
Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile
755 760 765
Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys
770 775 780
Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe
785 790 795 800
Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile
805 810 815
Glu Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile
820 825 830
Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile
835 840 845
Cys Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr
850 855 860
Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile
865 870 875 880
Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe
885 890 895
Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn
900 905 910
Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala
915 920 925
Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly
930 935 940
Lys Leu Gln Asn Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu
945 950 955 960
Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn
965 970 975
Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp
980 985 990
Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln
995 1000 1005
Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala
1010 1015 1020
Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe
1025 1030 1035 1040
Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His
1045 1050 1055
Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn
1060 1065 1070
Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro
1075 1080 1085
Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln
1090 1095 1100
Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val
1105 1110 1115 1120
Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr
1125 1130 1135
Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys
1140 1145 1150
Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser
1155 1160 1165
Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu
1170 1175 1180
Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu
1185 1190 1195 1200
Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu
1205 1210 1215
Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu
1220 1225 1230
Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys
1235 1240 1245
Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys
1250 1255 1260
Gly Val Lys Leu His Tyr Thr
1265 1270
<210> 8
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 8
Ile His Val Ser Gly Thr Asn Gly Thr
1 5
<210> 9
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 9
Ile Ser Gly Thr Asn Gly Thr
1 5
<210> 10
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 10
Ile His Val Ser Gly Thr Asn Val Ile
1 5
<210> 11
<211> 5
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 11
Pro Arg Arg Ala Arg
1 5
<210> 12
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 12
Asn Ser Pro Arg Arg Ala Arg Ser Val Ala
1 5 10
<210> 13
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 13
Asn Ser Arg Arg Arg Ala Arg Ser Val Ala
1 5 10
<210> 14
<211> 1254
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 14
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly
65 70 75 80
Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile
85 90 95
Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn
100 105 110
Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn
115 120 125
Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met
130 135 140
Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu
145 150 155 160
Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn
165 170 175
Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe
180 185 190
Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro
195 200 205
Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile
210 215 220
Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu
225 230 235 240
Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr
245 250 255
Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu
260 265 270
Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser
275 280 285
Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr
290 295 300
Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe
305 310 315 320
Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr
325 330 335
Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys
340 345 350
Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe
355 360 365
Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr
370 375 380
Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln
385 390 395 400
Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu
405 410 415
Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu
420 425 430
Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg
435 440 445
Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr
450 455 460
Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr
465 470 475 480
Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr
485 490 495
Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro
500 505 510
Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys
515 520 525
Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr
530 535 540
Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile
545 550 555 560
Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu
565 570 575
Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly
580 585 590
Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Asp Val Asn Cys
595 600 605
Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp
610 615 620
Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys
625 630 635 640
Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro
645 650 655
Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Ser Gln Ser
660 665 670
Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr
675 680 685
Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr
690 695 700
Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr
705 710 715 720
Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln
725 730 735
Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala
740 745 750
Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln
755 760 765
Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser
770 775 780
Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu
785 790 795 800
Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys
805 810 815
Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys
820 825 830
Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp
835 840 845
Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr
850 855 860
Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala
865 870 875 880
Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val
885 890 895
Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile
900 905 910
Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys
915 920 925
Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val
930 935 940
Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp
945 950 955 960
Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp Arg
965 970 975
Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln
980 985 990
Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr
995 1000 1005
Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys
1010 1015 1020
Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly
1025 1030 1035 1040
Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe
1045 1050 1055
Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg
1060 1065 1070
Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg
1075 1080 1085
Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser
1090 1095 1100
Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp
1105 1110 1115 1120
Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr
1125 1130 1135
Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly
1140 1145 1150
Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn
1155 1160 1165
Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu
1170 1175 1180
Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly
1185 1190 1195 1200
Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys
1205 1210 1215
Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly
1220 1225 1230
Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly
1235 1240 1245
Val Lys Leu His Tyr Thr
1250
<210> 15
<211> 1254
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 15
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Phe Thr Asn Arg Thr Gln Leu Pro Ser Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly
65 70 75 80
Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile
85 90 95
Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn
100 105 110
Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn
115 120 125
Tyr Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met
130 135 140
Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu
145 150 155 160
Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn
165 170 175
Phe Lys Asn Leu Ser Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe
180 185 190
Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro
195 200 205
Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile
210 215 220
Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu
225 230 235 240
Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr
245 250 255
Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu
260 265 270
Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser
275 280 285
Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr
290 295 300
Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe
305 310 315 320
Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr
325 330 335
Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys
340 345 350
Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe
355 360 365
Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr
370 375 380
Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln
385 390 395 400
Ile Ala Pro Gly Gln Thr Gly Thr Ile Ala Asp Tyr Asn Tyr Lys Leu
405 410 415
Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu
420 425 430
Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg
435 440 445
Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr
450 455 460
Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Lys Gly Phe Asn Cys Tyr
465 470 475 480
Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Tyr Gly Val Gly Tyr
485 490 495
Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro
500 505 510
Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys
515 520 525
Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr
530 535 540
Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile
545 550 555 560
Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu
565 570 575
Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly
580 585 590
Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Gly Val Asn Cys
595 600 605
Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp
610 615 620
Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys
625 630 635 640
Leu Ile Gly Ala Glu Tyr Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro
645 650 655
Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Ser Gln Ser
660 665 670
Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr
675 680 685
Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr
690 695 700
Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr
705 710 715 720
Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln
725 730 735
Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala
740 745 750
Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln
755 760 765
Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser
770 775 780
Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu
785 790 795 800
Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys
805 810 815
Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys
820 825 830
Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp
835 840 845
Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr
850 855 860
Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala
865 870 875 880
Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val
885 890 895
Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile
900 905 910
Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys
915 920 925
Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val
930 935 940
Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp
945 950 955 960
Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp Arg
965 970 975
Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln
980 985 990
Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Ile
995 1000 1005
Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys
1010 1015 1020
Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly
1025 1030 1035 1040
Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe
1045 1050 1055
Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg
1060 1065 1070
Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg
1075 1080 1085
Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser
1090 1095 1100
Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp
1105 1110 1115 1120
Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr
1125 1130 1135
Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly
1140 1145 1150
Ile Asn Ala Ser Phe Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn
1155 1160 1165
Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu
1170 1175 1180
Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly
1185 1190 1195 1200
Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys
1205 1210 1215
Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly
1220 1225 1230
Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly
1235 1240 1245
Val Lys Leu His Tyr Thr
1250
<210> 16
<211> 1254
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 16
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly
65 70 75 80
Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile
85 90 95
Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn
100 105 110
Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn
115 120 125
Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met
130 135 140
Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu
145 150 155 160
Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn
165 170 175
Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe
180 185 190
Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro
195 200 205
Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile
210 215 220
Asn Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu
225 230 235 240
Thr Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr
245 250 255
Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu
260 265 270
Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser
275 280 285
Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr
290 295 300
Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe
305 310 315 320
Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr
325 330 335
Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys
340 345 350
Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe
355 360 365
Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr
370 375 380
Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln
385 390 395 400
Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu
405 410 415
Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu
420 425 430
Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg
435 440 445
Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr
450 455 460
Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Lys Gly Phe Asn Cys Tyr
465 470 475 480
Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr
485 490 495
Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro
500 505 510
Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys
515 520 525
Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr
530 535 540
Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile
545 550 555 560
Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu
565 570 575
Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly
580 585 590
Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Gly Val Asn Cys
595 600 605
Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp
610 615 620
Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys
625 630 635 640
Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro
645 650 655
Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Ser Gln Ser
660 665 670
Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr
675 680 685
Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr
690 695 700
Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr
705 710 715 720
Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln
725 730 735
Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala
740 745 750
Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln
755 760 765
Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser
770 775 780
Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu
785 790 795 800
Asp Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys
805 810 815
Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys
820 825 830
Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp
835 840 845
Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr
850 855 860
Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala
865 870 875 880
Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val
885 890 895
Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile
900 905 910
Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys
915 920 925
Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val
930 935 940
Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp
945 950 955 960
Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp Arg
965 970 975
Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln
980 985 990
Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr
995 1000 1005
Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys
1010 1015 1020
Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly
1025 1030 1035 1040
Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe
1045 1050 1055
Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg
1060 1065 1070
Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg
1075 1080 1085
Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser
1090 1095 1100
Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp
1105 1110 1115 1120
Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr
1125 1130 1135
Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly
1140 1145 1150
Ile Asn Ala Ser Phe Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn
1155 1160 1165
Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu
1170 1175 1180
Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly
1185 1190 1195 1200
Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys
1205 1210 1215
Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly
1220 1225 1230
Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly
1235 1240 1245
Val Lys Leu His Tyr Thr
1250
<210> 17
<211> 1251
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 17
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Phe Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Lys Arg Phe Ala Asn Pro Val Leu Pro Phe Asn Asp Gly
65 70 75 80
Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile
85 90 95
Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn
100 105 110
Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn
115 120 125
Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met
130 135 140
Glu Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu
145 150 155 160
Tyr Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn
165 170 175
Phe Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe
180 185 190
Lys Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Gly Leu Pro
195 200 205
Gln Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile
210 215 220
Asn Ile Thr Arg Phe Gln Thr Leu His Arg Ser Tyr Leu Thr Pro Gly
225 230 235 240
Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val Gly
245 250 255
Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly Thr
260 265 270
Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr Lys
275 280 285
Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr Ser
290 295 300
Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn Ile
305 310 315 320
Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe Ala
325 330 335
Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp
340 345 350
Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys Tyr
355 360 365
Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val Tyr
370 375 380
Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro
385 390 395 400
Gly Gln Thr Gly Asn Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp Asp
405 410 415
Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys
420 425 430
Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys Ser Asn
435 440 445
Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly
450 455 460
Ser Thr Pro Cys Asn Gly Val Lys Gly Phe Asn Cys Tyr Phe Pro Leu
465 470 475 480
Gln Ser Tyr Gly Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln Pro Tyr
485 490 495
Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr Val
500 505 510
Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val Asn
515 520 525
Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser Asn
530 535 540
Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp Thr
545 550 555 560
Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile Thr
565 570 575
Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn Thr
580 585 590
Ser Asn Gln Val Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu Val
595 600 605
Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val Tyr
610 615 620
Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile Gly
625 630 635 640
Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly Ala
645 650 655
Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Ser Gln Ser Ile Ile Ala
660 665 670
Tyr Thr Met Ser Leu Gly Val Glu Asn Ser Val Ala Tyr Ser Asn Asn
675 680 685
Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu Ile
690 695 700
Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr Ile
705 710 715 720
Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly Ser
725 730 735
Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu Gln
740 745 750
Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr Lys
755 760 765
Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile Leu
770 775 780
Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu Leu
785 790 795 800
Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr Gly
805 810 815
Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln Lys
820 825 830
Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met Ile
835 840 845
Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly Trp
850 855 860
Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln Met
865 870 875 880
Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr Glu
885 890 895
Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys Ile
900 905 910
Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln Asp
915 920 925
Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln Leu
930 935 940
Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu Ser
945 950 955 960
Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp Arg Leu Ile Thr
965 970 975
Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile Arg
980 985 990
Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met Ser
995 1000 1005
Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys Gly
1010 1015 1020
Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val Phe
1025 1030 1035 1040
Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr Ala
1045 1050 1055
Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly Val
1060 1065 1070
Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe Tyr
1075 1080 1085
Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn Cys
1090 1095 1100
Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu Gln
1105 1110 1115 1120
Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys Asn
1125 1130 1135
His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn Ala
1140 1145 1150
Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val Ala
1155 1160 1165
Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys Tyr
1170 1175 1180
Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile Ala
1185 1190 1195 1200
Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys Cys Met Thr
1205 1210 1215
Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys Cys
1220 1225 1230
Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys Leu
1235 1240 1245
His Tyr Thr
1250
<210> 18
<211> 1253
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 18
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly
65 70 75 80
Val Tyr Phe Ala Ser Thr Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile
85 90 95
Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn
100 105 110
Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn
115 120 125
Asp Pro Phe Leu Gly Val Tyr His Lys Asn Asn Lys Ser Trp Met Glu
130 135 140
Ser Glu Phe Arg Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr
145 150 155 160
Val Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe
165 170 175
Lys Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys
180 185 190
Ile Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln
195 200 205
Gly Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn
210 215 220
Ile Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr
225 230 235 240
Pro Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr
245 250 255
Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn
260 265 270
Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu
275 280 285
Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln
290 295 300
Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro
305 310 315 320
Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg
325 330 335
Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val
340 345 350
Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys
355 360 365
Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn
370 375 380
Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile
385 390 395 400
Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro
405 410 415
Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp
420 425 430
Ser Lys Val Gly Gly Asn Tyr Asn Tyr Leu Tyr Arg Leu Phe Arg Lys
435 440 445
Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln
450 455 460
Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe
465 470 475 480
Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Tyr Gly Val Gly Tyr Gln
485 490 495
Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala
500 505 510
Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys
515 520 525
Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu
530 535 540
Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Asp
545 550 555 560
Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp
565 570 575
Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr
580 585 590
Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Gly Val Asn Cys Thr
595 600 605
Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg
610 615 620
Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu
625 630 635 640
Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile
645 650 655
Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Ser Gln Ser Ile
660 665 670
Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser
675 680 685
Asn Asn Ser Ile Ala Ile Pro Ile Asn Phe Thr Ile Ser Val Thr Thr
690 695 700
Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met
705 710 715 720
Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr
725 730 735
Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val
740 745 750
Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile
755 760 765
Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln
770 775 780
Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp
785 790 795 800
Leu Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln
805 810 815
Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala
820 825 830
Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu
835 840 845
Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser
850 855 860
Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met
865 870 875 880
Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu
885 890 895
Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly
900 905 910
Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu
915 920 925
Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys
930 935 940
Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile
945 950 955 960
Leu Ala Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp Arg Leu
965 970 975
Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu
980 985 990
Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys
995 1000 1005
Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly
1010 1015 1020
Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val
1025 1030 1035 1040
Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr
1045 1050 1055
Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu
1060 1065 1070
Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn
1075 1080 1085
Phe Tyr Glu Pro Gln Ile Ile Thr Thr His Asn Thr Phe Val Ser Gly
1090 1095 1100
Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro
1105 1110 1115 1120
Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe
1125 1130 1135
Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile
1140 1145 1150
Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu
1155 1160 1165
Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly
1170 1175 1180
Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe
1185 1190 1195 1200
Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys Cys
1205 1210 1215
Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly Ser
1220 1225 1230
Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly Val
1235 1240 1245
Lys Leu His Tyr Thr
1250
<210> 19
<211> 1256
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 19
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Ile His Val Ser Gly Thr Asn Val Ile Lys Arg Phe Asp
65 70 75 80
Asn Pro Val Leu Pro Phe Asn Asp Gly Val Tyr Phe Ala Ser Thr Glu
85 90 95
Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe Gly Thr Thr Leu Asp Ser
100 105 110
Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val Val Ile
115 120 125
Lys Val Cys Glu Phe Gln Phe Cys Asn Asp Pro Phe Leu Gly Val Tyr
130 135 140
Tyr His Lys Asn Asn Lys Ser Trp Met Glu Ser Glu Phe Arg Val Tyr
145 150 155 160
Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val Ser Gln Pro Phe Leu
165 170 175
Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys Asn Leu Arg Glu Phe
180 185 190
Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile Tyr Ser Lys His Thr
195 200 205
Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly Phe Ser Ala Leu Glu
210 215 220
Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile Thr Arg Phe Gln Thr
225 230 235 240
Leu Leu Ala Leu His Asn Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala
245 250 255
Ala Tyr Tyr Val Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr
260 265 270
Asn Glu Asn Gly Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro
275 280 285
Leu Ser Glu Thr Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly
290 295 300
Ile Tyr Gln Thr Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val
305 310 315 320
Arg Phe Pro Asn Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn
325 330 335
Ala Thr Arg Phe Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser
340 345 350
Asn Cys Val Ala Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser
355 360 365
Thr Phe Lys Cys Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys
370 375 380
Phe Thr Asn Val Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val
385 390 395 400
Arg Gln Ile Ala Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr
405 410 415
Lys Leu Pro Asp Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn
420 425 430
Asn Leu Asp Ser Lys Val Gly Gly Asn Tyr Asn Tyr Gln Tyr Arg Leu
435 440 445
Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu
450 455 460
Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe Asn
465 470 475 480
Cys Tyr Ser Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val
485 490 495
Gly Tyr Gln Pro Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His
500 505 510
Ala Pro Ala Thr Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys
515 520 525
Asn Lys Cys Val Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val
530 535 540
Leu Thr Glu Ser Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg
545 550 555 560
Asp Ile Ala Asp Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu
565 570 575
Ile Leu Asp Ile Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr
580 585 590
Pro Gly Thr Asn Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Gly Val
595 600 605
Asn Cys Thr Glu Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro
610 615 620
Thr Trp Arg Val Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala
625 630 635 640
Gly Cys Leu Ile Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp
645 650 655
Ile Pro Ile Gly Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Ser
660 665 670
Gln Ser Ile Ile Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val
675 680 685
Ala Tyr Ser Asn Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser
690 695 700
Val Thr Thr Glu Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp
705 710 715 720
Cys Thr Met Tyr Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu
725 730 735
Leu Gln Tyr Gly Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly
740 745 750
Ile Ala Val Glu Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val
755 760 765
Lys Gln Ile Tyr Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn
770 775 780
Phe Ser Gln Ile Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe
785 790 795 800
Ile Glu Asp Leu Leu Phe Asn Lys Leu Thr Leu Ala Asp Ala Gly Phe
805 810 815
Ile Lys Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu
820 825 830
Ile Cys Ala Gln Lys Phe Asn Gly Leu Asn Val Leu Pro Pro Leu Leu
835 840 845
Thr Asp Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr
850 855 860
Ile Thr Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro
865 870 875 880
Phe Ala Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln
885 890 895
Asn Val Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser
900 905 910
Ala Ile Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu
915 920 925
Gly Lys Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr
930 935 940
Leu Val Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu
945 950 955 960
Asn Asp Ile Leu Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile
965 970 975
Asp Arg Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr
980 985 990
Gln Gln Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala
995 1000 1005
Ala Thr Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp
1010 1015 1020
Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro
1025 1030 1035 1040
His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys
1045 1050 1055
Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe
1060 1065 1070
Pro Arg Glu Gly Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr
1075 1080 1085
Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe
1090 1095 1100
Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val
1105 1110 1115 1120
Tyr Asp Pro Leu Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp
1125 1130 1135
Lys Tyr Phe Lys Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile
1140 1145 1150
Ser Gly Ile Asn Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg
1155 1160 1165
Leu Asn Glu Val Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln
1170 1175 1180
Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp
1185 1190 1195 1200
Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met
1205 1210 1215
Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser
1220 1225 1230
Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu
1235 1240 1245
Lys Gly Val Lys Leu His Tyr Thr
1250 1255
<210> 20
<211> 1252
<212> PRT
<213> 人工序列(Artificial Sequence)
<400> 20
Met Phe Val Phe Leu Val Leu Leu Pro Leu Val Ser Ser Gln Cys Val
1 5 10 15
Asn Leu Arg Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser Phe
20 25 30
Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val Phe Arg Ser Ser Val Leu
35 40 45
His Ser Thr Gln Asp Leu Phe Leu Pro Phe Phe Ser Asn Val Thr Trp
50 55 60
Phe His Ala Lys Arg Phe Asp Asn Pro Val Leu Pro Phe Asn Asp Gly
65 70 75 80
Val Tyr Phe Ala Ser Ile Glu Lys Ser Asn Ile Ile Arg Gly Trp Ile
85 90 95
Phe Gly Thr Thr Leu Asp Ser Lys Thr Gln Ser Leu Leu Ile Val Asn
100 105 110
Asn Ala Thr Asn Val Val Ile Lys Val Cys Glu Phe Gln Phe Cys Asn
115 120 125
Asp Pro Phe Leu Gly Val Tyr Tyr His Lys Asn Asn Lys Ser Trp Met
130 135 140
Glu Ser Gly Val Tyr Ser Ser Ala Asn Asn Cys Thr Phe Glu Tyr Val
145 150 155 160
Ser Gln Pro Phe Leu Met Asp Leu Glu Gly Lys Gln Gly Asn Phe Lys
165 170 175
Asn Leu Arg Glu Phe Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys Ile
180 185 190
Tyr Ser Lys His Thr Pro Ile Asn Leu Val Arg Asp Leu Pro Gln Gly
195 200 205
Phe Ser Ala Leu Glu Pro Leu Val Asp Leu Pro Ile Gly Ile Asn Ile
210 215 220
Thr Arg Phe Gln Thr Leu Leu Ala Leu His Arg Ser Tyr Leu Thr Pro
225 230 235 240
Gly Asp Ser Ser Ser Gly Trp Thr Ala Gly Ala Ala Ala Tyr Tyr Val
245 250 255
Gly Tyr Leu Gln Pro Arg Thr Phe Leu Leu Lys Tyr Asn Glu Asn Gly
260 265 270
Thr Ile Thr Asp Ala Val Asp Cys Ala Leu Asp Pro Leu Ser Glu Thr
275 280 285
Lys Cys Thr Leu Lys Ser Phe Thr Val Glu Lys Gly Ile Tyr Gln Thr
290 295 300
Ser Asn Phe Arg Val Gln Pro Thr Glu Ser Ile Val Arg Phe Pro Asn
305 310 315 320
Ile Thr Asn Leu Cys Pro Phe Gly Glu Val Phe Asn Ala Thr Arg Phe
325 330 335
Ala Ser Val Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala
340 345 350
Asp Tyr Ser Val Leu Tyr Asn Ser Ala Ser Phe Ser Thr Phe Lys Cys
355 360 365
Tyr Gly Val Ser Pro Thr Lys Leu Asn Asp Leu Cys Phe Thr Asn Val
370 375 380
Tyr Ala Asp Ser Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala
385 390 395 400
Pro Gly Gln Thr Gly Lys Ile Ala Asp Tyr Asn Tyr Lys Leu Pro Asp
405 410 415
Asp Phe Thr Gly Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser
420 425 430
Lys Val Gly Gly Asn Tyr Asn Tyr Arg Tyr Arg Leu Phe Arg Lys Ser
435 440 445
Asn Leu Lys Pro Phe Glu Arg Asp Ile Ser Thr Glu Ile Tyr Gln Ala
450 455 460
Gly Ser Lys Pro Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro
465 470 475 480
Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln Pro
485 490 495
Tyr Arg Val Val Val Leu Ser Phe Glu Leu Leu His Ala Pro Ala Thr
500 505 510
Val Cys Gly Pro Lys Lys Ser Thr Asn Leu Val Lys Asn Lys Cys Val
515 520 525
Asn Phe Asn Phe Asn Gly Leu Thr Gly Thr Gly Val Leu Thr Glu Ser
530 535 540
Asn Lys Lys Phe Leu Pro Phe Gln Gln Phe Gly Arg Asp Ile Ala Asp
545 550 555 560
Thr Thr Asp Ala Val Arg Asp Pro Gln Thr Leu Glu Ile Leu Asp Ile
565 570 575
Thr Pro Cys Ser Phe Gly Gly Val Ser Val Ile Thr Pro Gly Thr Asn
580 585 590
Thr Ser Asn Gln Val Ala Val Leu Tyr Gln Gly Val Asn Cys Thr Glu
595 600 605
Val Pro Val Ala Ile His Ala Asp Gln Leu Thr Pro Thr Trp Arg Val
610 615 620
Tyr Ser Thr Gly Ser Asn Val Phe Gln Thr Arg Ala Gly Cys Leu Ile
625 630 635 640
Gly Ala Glu His Val Asn Asn Ser Tyr Glu Cys Asp Ile Pro Ile Gly
645 650 655
Ala Gly Ile Cys Ala Ser Tyr Gln Thr Gln Thr Ser Gln Ser Ile Ile
660 665 670
Ala Tyr Thr Met Ser Leu Gly Ala Glu Asn Ser Val Ala Tyr Ser Asn
675 680 685
Asn Ser Ile Ala Ile Pro Thr Asn Phe Thr Ile Ser Val Thr Thr Glu
690 695 700
Ile Leu Pro Val Ser Met Thr Lys Thr Ser Val Asp Cys Thr Met Tyr
705 710 715 720
Ile Cys Gly Asp Ser Thr Glu Cys Ser Asn Leu Leu Leu Gln Tyr Gly
725 730 735
Ser Phe Cys Thr Gln Leu Asn Arg Ala Leu Thr Gly Ile Ala Val Glu
740 745 750
Gln Asp Lys Asn Thr Gln Glu Val Phe Ala Gln Val Lys Gln Ile Tyr
755 760 765
Lys Thr Pro Pro Ile Lys Asp Phe Gly Gly Phe Asn Phe Ser Gln Ile
770 775 780
Leu Pro Asp Pro Ser Lys Pro Ser Lys Arg Ser Phe Ile Glu Asp Leu
785 790 795 800
Leu Phe Asn Lys Val Thr Leu Ala Asp Ala Gly Phe Ile Lys Gln Tyr
805 810 815
Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp Leu Ile Cys Ala Gln
820 825 830
Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu Leu Thr Asp Glu Met
835 840 845
Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly Thr Ile Thr Ser Gly
850 855 860
Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile Pro Phe Ala Met Gln
865 870 875 880
Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr Gln Asn Val Leu Tyr
885 890 895
Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn Ser Ala Ile Gly Lys
900 905 910
Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala Leu Gly Lys Leu Gln
915 920 925
Asn Val Val Asn Gln Asn Ala Gln Ala Leu Asn Thr Leu Val Lys Gln
930 935 940
Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val Leu Asn Asp Ile Leu
945 950 955 960
Ser Arg Leu Asp Lys Val Glu Ala Glu Val Gln Ile Asp Arg Leu Ile
965 970 975
Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val Thr Gln Gln Leu Ile
980 985 990
Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu Ala Ala Thr Lys Met
995 1000 1005
Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val Asp Phe Cys Gly Lys
1010 1015 1020
Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala Pro His Gly Val Val
1025 1030 1035 1040
Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu Lys Asn Phe Thr Thr
1045 1050 1055
Ala Pro Ala Ile Cys His Asp Gly Lys Ala His Phe Pro Arg Glu Gly
1060 1065 1070
Val Phe Val Ser Asn Gly Thr His Trp Phe Val Thr Gln Arg Asn Phe
1075 1080 1085
Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr Phe Val Ser Gly Asn
1090 1095 1100
Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr Val Tyr Asp Pro Leu
1105 1110 1115 1120
Gln Pro Glu Leu Asp Ser Phe Lys Glu Glu Leu Asp Lys Tyr Phe Lys
1125 1130 1135
Asn His Thr Ser Pro Asp Val Asp Leu Gly Asp Ile Ser Gly Ile Asn
1140 1145 1150
Ala Ser Val Val Asn Ile Gln Lys Glu Ile Asp Arg Leu Asn Glu Val
1155 1160 1165
Ala Lys Asn Leu Asn Glu Ser Leu Ile Asp Leu Gln Glu Leu Gly Lys
1170 1175 1180
Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile Trp Leu Gly Phe Ile
1185 1190 1195 1200
Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile Met Leu Cys Cys Met
1205 1210 1215
Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys Ser Cys Gly Ser Cys
1220 1225 1230
Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val Leu Lys Gly Val Lys
1235 1240 1245
Leu His Tyr Thr
1250
<210> 21
<211> 3822
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 21
atgtttgttt ttcttgtttt attgccacta gtctctagtc agtgtgttaa tcttacaacc 60
agaactcaat taccccctgc atacactaat tctttcacac gtggtgttta ttaccctgac 120
aaagttttca gatcctcagt tttacattca actcaggact tgttcttacc tttcttttcc 180
aatgttactt ggttccatgc tatacatgtc tctgggacca atggtactaa gaggtttgat 240
aaccctgtcc taccatttaa tgatggtgtt tattttgctt ccactgagaa gtctaacata 300
ataagaggct ggatttttgg tactacttta gattcgaaga cccagtccct acttattgtt 360
aataacgcta ctaatgttgt tattaaagtc tgtgaatttc aattttgtaa tgatccattt 420
ttgggtgttt attaccacaa aaacaacaaa agttggatgg aaagtgagtt cagagtttat 480
tctagtgcga ataattgcac ttttgaatat gtctctcagc cttttcttat ggaccttgaa 540
ggaaaacagg gtaatttcaa aaatcttagg gaatttgtgt ttaagaatat tgatggttat 600
tttaaaatat attctaagca cacgcctatt aatttagtgc gtgatctccc tcagggtttt 660
tcggctttag aaccattggt agatttgcca ataggtatta acatcactag gtttcaaact 720
ttacttgctt tacatagaag ttatttgact cctggtgatt cttcttcagg ttggacagct 780
ggtgctgcag cttattatgt gggttatctt caacctagga cttttctatt aaaatataat 840
gaaaatggaa ccattacaga tgctgtagac tgtgcacttg accctctctc agaaacaaag 900
tgtacgttga aatccttcac tgtagaaaaa ggaatctatc aaacttctaa ctttagagtc 960
caaccaacag aatctattgt tagatttcct aatattacaa acttgtgccc ttttggtgaa 1020
gtttttaacg ccaccagatt tgcatctgtt tatgcttgga acaggaagag aatcagcaac 1080
tgtgttgctg attattctgt cctatataat tccgcatcat tttccacttt taagtgttat 1140
ggagtgtctc ctactaaatt aaatgatctc tgctttacta atgtctatgc agattcattt 1200
gtaattagag gtgatgaagt cagacaaatc gctccagggc aaactggaaa gattgctgat 1260
tataattata aattaccaga tgattttaca ggctgcgtta tagcttggaa ttctaacaat 1320
cttgattcta aggttggtgg taattataat tacctgtata gattgtttag gaagtctaat 1380
ctcaaacctt ttgagagaga tatttcaact gaaatctatc aggccggtag cacaccttgt 1440
aatggtgttg aaggttttaa ttgttacttt cctttacaat catatggttt ccaacccact 1500
aatggtgttg gttaccaacc atacagagta gtagtacttt cttttgaact tctacatgca 1560
ccagcaactg tttgtggacc taaaaagtct actaatttgg ttaaaaacaa atgtgtcaat 1620
ttcaacttca atggtttaac aggcacaggt gttcttactg agtctaacaa aaagtttctg 1680
cctttccaac aatttggcag agacattgct gacactactg atgctgtccg tgatccacag 1740
acacttgaga ttcttgacat tacaccatgt tcttttggtg gtgtcagtgt tataacacca 1800
ggaacaaata cttctaacca ggttgctgtt ctttatcagg atgttaactg cacagaagtc 1860
cctgttgcta ttcatgcaga tcaacttact cctacttggc gtgtttattc tacaggttct 1920
aatgtttttc aaacacgtgc aggctgttta ataggggctg aacatgtcaa caactcatat 1980
gagtgtgaca tacccattgg tgcaggtata tgcgctagtt atcagactca gactaattct 2040
cctcggcggg cacgtagtgt agctagtcaa tccatcattg cctacactat gtcacttggt 2100
gcagaaaatt cagttgctta ctctaataac tctattgcca tacccacaaa ttttactatt 2160
agtgttacca cagaaattct accagtgtct atgaccaaga catcagtaga ttgtacaatg 2220
tacatttgtg gtgattcaac tgaatgcagc aatcttttgt tgcaatatgg cagtttttgt 2280
acacaattaa accgtgcttt aactggaata gctgttgaac aagacaaaaa cacccaagaa 2340
gtttttgcac aagtcaaaca aatttacaaa acaccaccaa ttaaagattt tggtggtttt 2400
aatttttcac aaatattacc agatccatca aaaccaagca agaggtcatt tattgaagat 2460
ctacttttca acaaagtgac acttgcagat gctggcttca tcaaacaata tggtgattgc 2520
cttggtgata ttgctgctag agacctcatt tgtgcacaaa agtttaacgg ccttactgtt 2580
ttgccacctt tgctcacaga tgaaatgatt gctcaataca cttctgcact gttagcgggt 2640
acaatcactt ctggttggac ctttggtgca ggtgctgcat tacaaatacc atttgctatg 2700
caaatggctt ataggtttaa tggtattgga gttacacaga atgttctcta tgagaaccaa 2760
aaattgattg ccaaccaatt taatagtgct attggcaaaa ttcaagactc actttcttcc 2820
acagcaagtg cacttggaaa acttcaagat gtggtcaacc aaaatgcaca agctttaaac 2880
acgcttgtta aacaacttag ctccaatttt ggtgcaattt caagtgtttt aaatgatatc 2940
ctttcacgtc ttgacaaagt tgaggctgaa gtgcaaattg ataggttgat cacaggcaga 3000
cttcaaagtt tgcagacata tgtgactcaa caattaatta gagctgcaga aatcagagct 3060
tctgctaatc ttgctgctac taaaatgtca gagtgtgtac ttggacaatc aaaaagagtt 3120
gatttttgtg gaaagggcta tcatcttatg tccttccctc agtcagcacc tcatggtgta 3180
gtcttcttgc atgtgactta tgtccctgca caagaaaaga acttcacaac tgctcctgcc 3240
atttgtcatg atggaaaagc acactttcct cgtgaaggtg tctttgtttc aaatggcaca 3300
cactggtttg taacacaaag gaatttttat gaaccacaaa tcattactac agacaacaca 3360
tttgtgtctg gtaactgtga tgttgtaata ggaattgtca acaacacagt ttatgatcct 3420
ttgcaacctg aattagactc attcaaggag gagttagata aatattttaa gaatcataca 3480
tcaccagatg ttgatttagg tgacatctct ggcattaatg cttcagttgt aaacattcaa 3540
aaagaaattg accgcctcaa tgaggttgcc aagaatttaa atgaatctct catcgatctc 3600
caagaacttg gaaagtatga gcagtatata aaatggccat ggtacatttg gctaggtttt 3660
atagctggct tgattgccat agtaatggtg acaattatgc tttgctgtat gaccagttgc 3720
tgtagttgtc tcaagggctg ttgttcttgt ggatcctgct gcaaatttga tgaagacgac 3780
tctgagccag tgctcaaagg agtcaaatta cattacacat aa 3822
<210> 22
<211> 3765
<212> DNA/RNA
<213> 人工序列(Artificial Sequence)
<400> 22
atgtttgttt ttcttgtttt attgccacta gtctctagtc agtgtgttaa tcttacaacc 60
agaactcaat taccccctgc atacactaat tctttcacac gtggtgttta ttaccctgac 120
aaagttttca gatcctcagt tttacattca actcaggact tgttcttacc tttcttttcc 180
aatgttactt ggttccatgc taagaggttt gataaccctg tcctaccatt taatgatggt 240
gtttattttg cttccactga gaagtctaac ataataagag gctggatttt tggtactact 300
ttagattcga agacccagtc cctacttatt gttaataacg ctactaatgt tgttattaaa 360
gtctgtgaat ttcaattttg taatgatcca tttttgggtg tttattacca caaaaacaac 420
aaaagttgga tggaaagtga gttcagagtt tattctagtg cgaataattg cacttttgaa 480
tatgtctctc agccttttct tatggacctt gaaggaaaac agggtaattt caaaaatctt 540
agggaatttg tgtttaagaa tattgatggt tattttaaaa tatattctaa gcacacgcct 600
attaatttag tgcgtgatct ccctcagggt ttttcggctt tagaaccatt ggtagatttg 660
ccaataggta ttaacatcac taggtttcaa actttacttg ctttacatag aagttatttg 720
actcctggtg attcttcttc aggttggaca gctggtgctg cagcttatta tgtgggttat 780
cttcaaccta ggacttttct attaaaatat aatgaaaatg gaaccattac agatgctgta 840
gactgtgcac ttgaccctct ctcagaaaca aagtgtacgt tgaaatcctt cactgtagaa 900
aaaggaatct atcaaacttc taactttaga gtccaaccaa cagaatctat tgttagattt 960
cctaatatta caaacttgtg cccttttggt gaagttttta acgccaccag atttgcatct 1020
gtttatgctt ggaacaggaa gagaatcagc aactgtgttg ctgattattc tgtcctatat 1080
aattccgcat cattttccac ttttaagtgt tatggagtgt ctcctactaa attaaatgat 1140
ctctgcttta ctaatgtcta tgcagattca tttgtaatta gaggtgatga agtcagacaa 1200
atcgctccag ggcaaactgg aaagattgct gattataatt ataaattacc agatgatttt 1260
acaggctgcg ttatagcttg gaattctaac aatcttgatt ctaaggttgg tggtaattat 1320
aattacctgt atagattgtt taggaagtct aatctcaaac cttttgagag agatatttca 1380
actgaaatct atcaggccgg tagcacacct tgtaatggtg ttgaaggttt taattgttac 1440
tttcctttac aatcatatgg tttccaaccc actaatggtg ttggttacca accatacaga 1500
gtagtagtac tttcttttga acttctacat gcaccagcaa ctgtttgtgg acctaaaaag 1560
tctactaatt tggttaaaaa caaatgtgtc aatttcaact tcaatggttt aacaggcaca 1620
ggtgttctta ctgagtctaa caaaaagttt ctgcctttcc aacaatttgg cagagacatt 1680
gctgacacta ctgatgctgt ccgtgatcca cagacacttg agattcttga cattacacca 1740
tgttcttttg gtggtgtcag tgttataaca ccaggaacaa atacttctaa ccaggttgct 1800
gttctttatc aggatgttaa ctgcacagaa gtccctgttg ctattcatgc agatcaactt 1860
actcctactt ggcgtgttta ttctacaggt tctaatgttt ttcaaacacg tgcaggctgt 1920
ttaatagggg ctgaacatgt caacaactca tatgagtgtg acatacccat tggtgcaggt 1980
atatgcgcta gttatcagac tcagactagt caatccatca ttgcctacac tatgtcactt 2040
ggtgcagaaa attcagttgc ttactctaat aactctattg ccatacccac aaattttact 2100
attagtgtta ccacagaaat tctaccagtg tctatgacca agacatcagt agattgtaca 2160
atgtacattt gtggtgattc aactgaatgc agcaatcttt tgttgcaata tggcagtttt 2220
tgtacacaat taaaccgtgc tttaactgga atagctgttg aacaagacaa aaacacccaa 2280
gaagtttttg cacaagtcaa acaaatttac aaaacaccac caattaaaga ttttggtggt 2340
tttaattttt cacaaatatt accagatcca tcaaaaccaa gcaagaggtc atttattgaa 2400
gatctacttt tcaacaaagt gacacttgca gatgctggct tcatcaaaca atatggtgat 2460
tgccttggtg atattgctgc tagagacctc atttgtgcac aaaagtttaa cggccttact 2520
gttttgccac ctttgctcac agatgaaatg attgctcaat acacttctgc actgttagcg 2580
ggtacaatca cttctggttg gacctttggt gcaggtgctg cattacaaat accatttgct 2640
atgcaaatgg cttataggtt taatggtatt ggagttacac agaatgttct ctatgagaac 2700
caaaaattga ttgccaacca atttaatagt gctattggca aaattcaaga ctcactttct 2760
tccacagcaa gtgcacttgg aaaacttcaa gatgtggtca accaaaatgc acaagcttta 2820
aacacgcttg ttaaacaact tagctccaat tttggtgcaa tttcaagtgt tttaaatgat 2880
atcctttcac gtcttgacaa agttgaggct gaagtgcaaa ttgataggtt gatcacaggc 2940
agacttcaaa gtttgcagac atatgtgact caacaattaa ttagagctgc agaaatcaga 3000
gcttctgcta atcttgctgc tactaaaatg tcagagtgtg tacttggaca atcaaaaaga 3060
gttgattttt gtggaaaggg ctatcatctt atgtccttcc ctcagtcagc acctcatggt 3120
gtagtcttct tgcatgtgac ttatgtccct gcacaagaaa agaacttcac aactgctcct 3180
gccatttgtc atgatggaaa agcacacttt cctcgtgaag gtgtctttgt ttcaaatggc 3240
acacactggt ttgtaacaca aaggaatttt tatgaaccac aaatcattac tacagacaac 3300
acatttgtgt ctggtaactg tgatgttgta ataggaattg tcaacaacac agtttatgat 3360
cctttgcaac ctgaattaga ctcattcaag gaggagttag ataaatattt taagaatcat 3420
acatcaccag atgttgattt aggtgacatc tctggcatta atgcttcagt tgtaaacatt 3480
caaaaagaaa ttgaccgcct caatgaggtt gccaagaatt taaatgaatc tctcatcgat 3540
ctccaagaac ttggaaagta tgagcagtat ataaaatggc catggtacat ttggctaggt 3600
tttatagctg gcttgattgc catagtaatg gtgacaatta tgctttgctg tatgaccagt 3660
tgctgtagtt gtctcaaggg ctgttgttct tgtggatcct gctgcaaatt tgatgaagac 3720
gactctgagc cagtgctcaa aggagtcaaa ttacattaca cataa 3765

Claims (10)

1.一种重组表面刺突(S)蛋白，其特征在于，所述重组S蛋白来源于严重急性呼吸系统综合症冠状病毒(SARS-CoV-2)，且包含在N末端结构域中的缺失和弗林酶切位点结构域的缺失。
2.根据权利要求1所述的重组S蛋白，其特征在于，所述SARS-CoV-2选自Wuhan-Hu-1病毒株、P.1病毒株、P.2病毒株、B.1.351病毒株、B.1.1.7病毒株、C.37病毒株或B.1.617.2病毒株，
优选地，所述重组S蛋白具有如SEQ ID NO:1～7中任一项所示的氨基酸序列，或与SEQID NO:1～7中任一项所示的氨基酸序列具有至少85％同一性的氨基酸序列。
3.根据权利要求1或2所述的重组S蛋白，其特征在于，所述N末端结构域中包括如IX1X2SGTNX3X4所示的序列的缺失，其中X1不存在或者选自组氨酸，X2不存在或者选自缬氨酸，X3选自甘氨酸或缬氨酸，和/或X4选自苏氨酸或异亮氨酸；优选地，所述N末端结构域中包括如SEQ ID NO:8～10中任一项所示的氨基酸序列的缺失，
所述弗林酶切位点结构域的缺失包括如X5RRAR所示的序列的缺失，其中X5选自组氨酸、精氨酸或脯氨酸；优选地，所述弗林酶切位点结构域的缺失包括如SEQ ID NO:11～13中任一项所示的氨基酸序列的缺失。
4.根据权利要求1至3中任一项所述的重组S蛋白，其特征在于，所述重组S蛋白具有如SEQ ID NO:14～20中任一项所示的氨基酸序列，或与SEQ ID NO:14～20中任一项所示的氨基酸序列具有至少85％同一性的氨基酸序列。
5.一种编码如权利要求1至4中任一项所述的重组S蛋白的核酸序列。
6.一种表达载体，其特征在于，所述表达载体包括如权利要求5所述的核酸序列。
7.一种宿主细胞，其特征在于，所述宿主细胞包括如权利要求5所述的核酸序列或如权利要求6所述的表达载体。
8.如权利要求1至4中任一项所述的重组S蛋白、如权利要求5所述的核酸序列、如权利要求6所述的表达载体或如权利要求7所述的宿主细胞，在制备用于对象的SARS-CoV-2疫苗中的用途。
9.如权利要求8所述的用途，其特征在于，所述对象为哺乳动物，优选为人、猴、骆驼、牛、马、山羊、绵羊、猪、猫、狗、兔、小鼠或大鼠。
10.一种用于制备如权利要求1至4中任一项所述的重组S蛋白的方法，其特征在于，所述方法包括：对来源于严重急性呼吸系统综合症冠状病毒(SARS-CoV-2)的重组S蛋白，进行N末端结构域和弗林酶切位点结构域的缺失。
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023122731A3 (en) * 2021-12-22 2023-08-31 Ohio State Innovation Foundation A live attenuated mumps virus-based sars-cov-2 vaccine

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013102492A1 (en) * 2012-01-04 2013-07-11 Instytut Biochemii I Biofizyki Pan Synthetic genes encoding peptide fragments of natural myelin proteins for induction of oral tolerance, dna fragment comprising these genes, means of obtaining these peptides in a microbial (bacterial) system and their medical application
CN111896747A (zh) * 2020-08-02 2020-11-06 广州德成生物科技有限公司 检测新型冠状病毒IgM和IgG的免疫层析试纸
US10953089B1 (en) * 2020-01-27 2021-03-23 Novavax, Inc. Coronavirus vaccine formulations
WO2021154812A1 (en) * 2020-01-27 2021-08-05 Novavax, Inc. Coronavirus vaccine formulations
CN113234170A (zh) * 2021-04-13 2021-08-10 武汉大学 新型冠状病毒突变株s蛋白及其亚单位疫苗
CN113832168A (zh) * 2021-08-15 2021-12-24 北京科兴中维生物技术有限公司 mRNA疫苗及其制备方法和应用

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013102492A1 (en) * 2012-01-04 2013-07-11 Instytut Biochemii I Biofizyki Pan Synthetic genes encoding peptide fragments of natural myelin proteins for induction of oral tolerance, dna fragment comprising these genes, means of obtaining these peptides in a microbial (bacterial) system and their medical application
US10953089B1 (en) * 2020-01-27 2021-03-23 Novavax, Inc. Coronavirus vaccine formulations
WO2021154812A1 (en) * 2020-01-27 2021-08-05 Novavax, Inc. Coronavirus vaccine formulations
CN111896747A (zh) * 2020-08-02 2020-11-06 广州德成生物科技有限公司 检测新型冠状病毒IgM和IgG的免疫层析试纸
CN113234170A (zh) * 2021-04-13 2021-08-10 武汉大学 新型冠状病毒突变株s蛋白及其亚单位疫苗
CN113832168A (zh) * 2021-08-15 2021-12-24 北京科兴中维生物技术有限公司 mRNA疫苗及其制备方法和应用

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BRYAN A JOHNSON: "Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesisi", 《NATURE》, vol. 591, no. 7849, pages 293 - 299, XP037410730, DOI: 10.1038/s41586-021-03237-4 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023122731A3 (en) * 2021-12-22 2023-08-31 Ohio State Innovation Foundation A live attenuated mumps virus-based sars-cov-2 vaccine

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