CN113646328B - 一种免疫细胞因子及其制备与用途 - Google Patents

一种免疫细胞因子及其制备与用途 Download PDF

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CN113646328B
CN113646328B CN202080009757.0A CN202080009757A CN113646328B CN 113646328 B CN113646328 B CN 113646328B CN 202080009757 A CN202080009757 A CN 202080009757A CN 113646328 B CN113646328 B CN 113646328B
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王峰
郑花鸯
张雨菡
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Nantong Yichen Biomedical Technology Co ltd
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Abstract

本发明提供了一种IL‑15与IL‑15Ra分别融合在靶向细胞表面抗原的抗体的免疫细胞因子，可有效地将IL‑15与IL‑15Ra的复合物特异性靶向肿瘤微环境，激活肿瘤内或附近的相关免疫细胞，达到特异性杀伤肿瘤的目标，同时可以避免因全身性过度激活NK细胞诱导的免疫毒性。

Description

一种免疫细胞因子及其制备与用途
技术领域
本发明属于生物制药领域，具体涉及一种IL-15与IL-15Ra分别融合于抗体的免疫细胞因子或者IL-15单独与抗体融合的免疫细胞因子及其制备和用途。
背景技术
在过去几年中，免疫疗法已被用于治疗人类的各种肿瘤。免疫疗法利用人体的免疫系统去攻击或杀死恶性肿瘤细胞，同时对健康组织无影响。免疫系统具有识别和清除恶性肿瘤细胞的能力，但是，肿瘤进化出多种逃避免疫监视的机制。因此，免疫疗法的挑战在于开发出能有效、安全地增强机体抗肿瘤免疫反应的策略。目前正在进行和开发的肿瘤免疫治疗策略主要有细胞因子治疗、过继细胞转移、肿瘤疫苗、单克隆抗体等。其中刺激或活化肿瘤特异性的T细胞或NK的免疫反应，发挥T细胞或NK细胞对肿瘤的杀伤作用是特别令人感兴趣的[The Potential and Promise of IL-15in Immuno-Oncogenic Therapies]。
IL-15是一种具有与IL-2类似的结构的细胞因子，其可有效调节效应天然杀伤细胞(NK)、记忆CD8+T细胞的发育、增殖和活化。IL-15Ra是与IL-15具有高亲和力的跨膜蛋白，其与IL-15结合后通过反式递呈作用将IL-15递呈至表达IL2R beta和gamma链的NK细胞和T细胞表面，促进这些细胞的增殖和活化，增强这些细胞的肿瘤杀伤活性。另外，与IL-2不同，IL-15不会导致Treg细胞的激活，目前作为肿瘤免疫治疗制剂正在进行广泛的临床前和临床研究。
IL-15与IL-15Ra形成的复合物(IL-15超激动剂)进一步加快了以IL-15为基础的肿瘤免疫治疗的步伐。与单体IL-15相比，IL-15超激动剂具有突出的优势：如更高的血液循环浓度、更长的体内半衰期以及增强的刺激NK和CD8T细胞的能力。目前正在开发的IL-15超激动剂主要有两大类：IL-15通过linker与IL-15Ra融合形成的RLI(如Cytune的CYP0150)、以及IL-15与IL-15Ra形成的分子内复合物(如诺华的NIZ985、Altor的ALT-803、Xencer的XmAb24306)。CYP0150，由于不含有Fc，在体内易被清除，半衰期很短，需频繁给药；NIZ985和ALT-803分子中，IL-15和IL-15Ra通过分子间的作用力形成复合物，不仅分子本身不稳定，而且制备工艺较繁琐。XmAb24306通过将IL-15和IL-15Ra分别融合在Fc的N端，形成的分子内复合物较为稳定，而且具有较长的体内半衰期。大量的临床前研究表明，与天然IL-15相比，IL-15超激动剂的生理活性及抗肿瘤活性大大增强。一些研究表明，其他免疫疗法如Nivolumab(anti-PD-1单抗)、Rituximab(anti-CD20单抗)可有效增强ALT-803对于进展性肿瘤患者的抗肿瘤效应。另外，全身性施用IL-15超激动剂可偏向性地扩增淋巴器官中促炎症(CD11bhighCD27high)NK细胞亚群，这些细胞亚群分泌的大量IFNγ等促炎症因子可能会导致诸如体温过低、体重减少、肝损伤等免疫毒性作用。
本发明人发现，将IL-15与IL-15Ra分别融合在靶向肿瘤抗原的抗体形成的免疫细胞因子，可以特异性靶向肿瘤微环境。在肿瘤微环境内，该免疫细胞因子中的IL-15/IL15Ra形成的复合物，可以激活肿瘤内或附近的相关免疫细胞，发挥肿瘤微环境内T细胞或者NK细胞对肿瘤的特异性杀伤作用，同时可以避免全身性过度激活T细胞或者NK细胞诱导的免疫毒性。
本发明简述
本发明人发现，将IL15与IL-15Ra分别融合在靶向治疗相关细胞表面抗原的抗体形成的免疫细胞因子，可以有效地将免疫细胞因子特异性靶向肿瘤微环境，激活肿瘤内或附近的相关免疫细胞，达到特异性杀伤肿瘤的目标，同时可以避免因全身性过度激活NK细胞诱导的免疫毒性。
本发明的一个方面，提供了一种免疫细胞因子，所述免疫细胞因子包括：
(A)白介素-15(IL-15)；
(B)白介素-15受体a亚基(IL-15Ra)；
(C)靶向治疗相关细胞表面抗原的抗体；
其中，所述IL-15直接或通过连接肽与所述抗体的重链可变区N端连接，所述IL-15Ra直接或通过连接肽与所述抗体的轻链可变区N端连接；或者，所述IL-15直接或通过连接肽与所述抗体的轻链可变区N端连接，所述IL-15Ra直接或通过连接肽与所述抗体的重链可变区N端连接；或者，所述IL-15直接或通过连接肽与所述抗体的轻链恒定区CL的C端连接，所述IL-15Ra直接或通过连接肽与所述抗体的重链恒定区CH1的C端连接；或者所述IL-15直接或通过连接肽与所述抗体的重链恒定区CH1的C端连接，所述IL-15Ra直接或通过连接肽与所述抗体的轻链恒定区CL的C端连接。在一些实施方案中，所述连接肽为裂解性连接肽或非裂解性连接肽。在一些实施方案中，其中所述连接肽独立地选自但不限于GGGGSGGGGSGGGGSG、GSPLGVRGS、GSPLGVR、PLGVR、GGGGSGPLGVRGGGGSG或GGGGSGPLGVR等。
在一些实施方案中，所述IL-15为哺乳动物细胞IL-15，优选灵长类IL-15，更优选人类IL-15。在一些实施方案中，所述IL-15为野生型IL-15或IL-15衍生物。在一些实施方案中，所述IL-15具有如SEQ ID NO：71所示的核酸序列和SEQ ID NO：72所示的氨基酸序列；在一些实施方案中，所述IL-15具有如SEQ ID NO：111所示的核酸序列和SEQ ID NO：112所示的氨基酸序列。在另外的一些实施方案中，所述IL-15具有如与SEQ ID NO：72或SEQ ID NO：11285％-100％同源的氨基酸序列。
在一些实施方案中，所述IL-15Ra为IL-15Ra。在一些实施方案中，所述IL-15Ra为IL-15Ra的Sushi结构域。在一些实施方案中，所述IL-15Ra为IL-15RaSushi结构域的变异体或者衍生物。在一些实施方案中，所述IL-15Ra具有如SEQ ID NO：73所示的核酸序列和SEQID NO：74所示的氨基酸序列。在一些实施方案中，所述IL-15Ra具有如SEQ ID NO：87所示的核酸序列或SEQ ID NO：88所示的氨基酸序列。在另外的一些实施方案中，所述IL-15Ra具有与SEQ ID NO：74或SEQ ID NO：8885％-100％同源的氨基酸序列。
在一些实施方案中，所述治疗相关细胞表面抗原为CD抗原。在一些实施方案中，所述CD抗原选自但不限于CD19、CD20、CD47、CD40、CD73、CD33、CD38、CD123、CD30、CD3、CD22、CD25、CD133、CD27、CD39、CD138、CD46、CD56、CD70、CD32、CD11b、CD135、CD171、CD174、CD147、CD155、CD16、CD162、CD16a、CD200、CD21、CD28、CD44、CD52、CD54、CD7、CD80、CD88、CD13、CD130、CD150、CD160、CD200R1、CD267、CD29、CD3E、CD4、CD51或CD8等。
在一些实施方案中，所述治疗相关细胞表面抗原为免疫监测点蛋白。在一些实施方案中，所述免疫监测点蛋白选自但不限于PD-1、PD-L1、CTLA-4、LAG-3、OX40、CD28、CD40、CD47、CD70、CD80、CD122、GTIR、A2AR、B7-H3(CD276)、B7-H4、IDO、KIR、Tim-3或4-1BB(CD137)等。在一些实施方案中，所述免疫监测点蛋白为PD-1。在一些实施方案中，靶向免疫监测点蛋白PD-1的抗体具有如SEQ ID NO：76所示的重链氨基酸序列中所含的HCDR1、HCDR2和HCDR3序列，以及如SEQ ID NO：78所示的轻链氨基酸序列中所含的LCDR1、LCDR2和LCDR3序列，或者具有如SEQ ID NO：76所示的重链氨基酸序列中所含的vH序列，以及如SEQ ID NO：78所示的轻链氨基酸序列中所含的VL序列。在一些实施方案中，所述靶向免疫监测点蛋白PD-1的抗体具有如SEQ ID NO：75所示的重链核酸序列和SEQ ID NO：77所示的轻链核酸序列，或者具有如SEQ ID NO：76所示的重链氨基酸序列和SEQ ID NO：78所示的轻链氨基酸序列。
在一些实施方案中，所述免疫监测点蛋白为PD-L1。在一些实施方案中，所述靶向免疫监测点蛋白PD-L1的抗体具有SEQ ID NO：36所示的重链氨基酸序列中所含的HCDR1、HCDR2和HCDR3序列，以及如SEQ ID NO：38所示的轻链氨基酸序列中所含的LCDR1、LCDR2和LCDR3序列；或者具有SEQ ID NO：80所示的重链氨基酸序列中所含的HCDR1、HCDR2和HCDR3序列，以及如SEQ ID NO：82所示的轻链氨基酸序列中所含的LCDR1、LCDR2和LCDR3序列。在一些实施方案中，所述靶向免疫监测点蛋白PD-L1的抗体具有SEQ ID NO：36所示的氨基酸序列中所含的VH序列，以及如SEQ ID NO：38所示的氨基酸序列中所含的VL序列；或者具有SEQ ID NO：80所示的重链氨基酸序列中所含的VH序列，以及如SEQ ID NO：82所示的轻链氨基酸序列中所含的VL序列。在一些实施方案中，所述靶向免疫监测点蛋白PD-L1的抗体具有如SEQ ID NO：35所示的重链核酸序列和SEQ ID NO：37所示的轻链核酸序列，或者具有如SEQ ID NO：36所示的重链氨基酸序列和SEQ ID NO：38所示的轻链氨基酸序列。在一些实施方案中，所述靶向免疫监测点蛋白PD-L1的抗体具有如SEQ ID NO：79所示的重链核酸序列和SEQ ID NO：81所示的轻链核酸序列，具有如SEQ ID NO：80所示的重链氨基酸序列和SEQID NO：82所示的轻链氨基酸序列。
在一些实施方案中，所述治疗相关细胞表面抗原选自肿瘤表面抗原。在一些实施方案中，所述肿瘤表面抗原选自但不限于EGFR、HER2、HER3、HER4、NY-ESO-1、GPC-3、CLL-1、BCMA、GD2、EpCAM、化学趋化因子受体家族(CCRl、CCR2、CCR3、CCR4、CCR5、CCR6、CCR7、CCR8、CCR9、CCR10、CCL27、CCL28、CX3CR1、CXCR1、CXCR2、CXCR3、CXCR4、CXCR5、CXCR6)、mucin家族(MUC1、MUC2、MUC3A、MUC3B、MUC4、MUC5AC、MUC5B、MUC6、MUC7、MUC8、MUC12、MUC13、MUC15、MUC16、MUC17、MUC19、MUC20)、PSMA、CEA、HDAC6、Mesothelin、TERT、TLR、TLR9、TLR4、CD33、GITR、Survivin、CD123、TIGIT、成纤维细胞生长因子受体(FGFR)、血管内皮生长因子受体(FLT1、KDR/Flk-1、VEGFR-3)、肝细胞生长因子受体(HGFR)、神经生长因子受体(NGFR)、胰岛素样生长因子受体(IGFR)、血小板衍生生长因子受体(PDGFR)或激素受体(黑皮质素1受体(MC1R，MSHR)等。
在一些实施方案中，所述肿瘤表面抗原为EGFR。在一些实施方案中，所述靶向肿瘤表面抗原EGFR的抗体具有如SEQ ID NO：32所示的重链氨基酸序列中所含的HCDR1、HCDR2和HCDR3序列，以及如SEQ ID NO：34所示的轻链氨基酸序列中所含的LCDR1、LCDR2和LCDR3序列，或者具有如SEQ ID NO：32所示的重链氨基酸序列中所含的VH序列，以及如SEQ ID NO：34所示的轻链氨基酸序列中所含的VL序列。在一些实施方案中，所述靶向肿瘤表面抗原EGFR的抗体具有如SEQ ID NO：29所示的重链核酸序列和SEQ ID NO：33所示的轻链核酸序列，或者具有如SEQ ID NO：30所示的重链氨基酸序列和SEQ ID NO：34所示的轻链氨基酸序列。在一些实施方案中，所述靶向肿瘤表面抗原EGFR的抗体具有如SEQ ID NO：31所示的重链核酸序列和SEQ ID NO：33所示的轻链核酸序列，或者具有如SEQ ID NO：32所示的重链氨基酸序列和SEQ ID NO：34所示的轻链氨基酸序列。
在一些实施方案中，所述肿瘤表面抗原为HER2。在一些实施方案中，靶向HER2的抗体具有如SEQ ID NO：18所示的重链氨基酸序列中所含的HCDR1、HCDR2和HCDR3序列，以及如SEQ ID NO：20所示的轻链氨基酸序列中所含的LCDR1、LCDR2和LCDR3序列，或者靶向HER2的抗体具有如SEQ ID NO：18所示的重链氨基酸序列中所含的VH序列，以及如SEQ ID NO：20所示的轻链氨基酸序列中所含的VL序列。在一些实施方案中，靶向HER2的抗体具有如SEQ IDNO：17所示的重链核酸序列和SEQ ID NO：19所示的轻链核酸序列，或者具有如SEQ ID NO：18所示的重链氨基酸序列和SEQ ID NO：20所示的轻链氨基酸序列。
在一些实施方案中，所述细胞表面抗原选自病毒相关抗原。在一些实施方案中，所述病毒相关抗原选自但不限于RSV F、HPV E6、HPV E7、HPV L2、HPV 16、HPV E6/7、HPV L1、HPV16 E6、HPV16 E7等。在一些具体的实施方案中，所述病毒相关抗原为RSV F。在一些实施方案中，靶向RSV病毒F蛋白的抗体具有SEQ ID NO：54所示的重链氨基酸序列中所含的HCDR1、HCDR2和HCDR3序列，以及如SEQ ID NO：56所示的轻链氨基酸序列中所含的LCDR1、LCDR2和LCDR3序列；或者具有SEQ ID NO：54所示的重链氨基酸序列中所含的VH序列，以及如SEQ ID NO：56所示的轻链氨基酸序列中所含的VL序列。在一些实施方案中，靶向病毒相关抗原RSV F蛋白的抗体具有如SEQ ID NO：53所示的重链核酸序列和SEQ ID NO：55所示的轻链核酸序列，或者具有如SEQ ID NO：54所示的重链氨基酸序列和SEQ ID NO：56所示的轻链氨基酸序列。
在一些实施方案中，所述免疫细胞因子由分别具有如下氨基酸序列的重链和轻链组成：SEQ ID NO：2和SEQ ID NO：8；SEQ ID NO：6和SEQ ID NO：4；SEQ ID NO：68和SEQ IDNO：8；SEQ ID NO：70和SEQ ID NO：4；SEQ ID NO：10和SEQ ID NO：12；SEQ ID NO：14和SEQID NO：16；SEQ ID NO：22和SEQ ID NO：24；SEQ ID NO：26和SEQ ID NO：28；SEQ ID NO：40和SEQ ID NO：24；SEQ ID NO：44和SEQ ID NO：28；SEQ ID NO：46和SEQ ID NO：48；SEQ ID NO：42和SEQ ID NO：58；SEQ ID NO：84和SEQ ID NO：86；SEQ ID NO：60和SEQ ID NO：62；SEQ IDNO：64和SEQ ID NO：66；SEQ ID NO：115和SEQ ID NO：116；SEQ ID NO：117和SEQ ID NO：118；SEQ ID NO：119和SEQ ID NO：12；SEQ ID NO：120和SEQ ID NO：16。本领域技术人员容易理解，本发明的免疫细胞因子的“重链”指包含靶向治疗相关细胞表面抗原的抗体的重链可变区及与之连接的IL-15或IL-15Ra的多肽链，免疫细胞因子的“轻链”指包含靶向治疗相关细胞表面抗原的抗体的轻链可变区及与之连接的IL-15Ra或IL-15的多肽链。
在一些实施方案中，所述免疫细胞因子由分别具有如下氨基酸序列的重链和轻链组成：SEQ ID NO：1和SEQ ID NO：7；SEQ ID NO：5和SEQ ID NO：3；SEQ ID NO：67和SEQ IDNO：7；SEQ ID NO：69和SEQ ID NO：3；SEQ ID NO：9和SEQ ID NO：11；SEQ ID NO：13和SEQ IDNO：15；SEQ ID NO：21和SEQ ID NO：23；SEQ ID NO：25和SEQ ID NO：27；SEQ ID NO：39和SEQID NO：23；SEQ ID NO：43和SEQ ID NO：27；SEQ ID NO：45和SEQ ID NO：47；SEQ ID NO：41和SEQ ID NO：57；SEQ ID NO：83和SEQ ID NO：85；SEQ ID NO：59和SEQ ID NO：61；SEQ ID NO：63和SEQ ID NO：65。
本发明的一个方面，提供了一种免疫细胞因子，所述免疫细胞因子包括：
(A)白介素-15(IL-15)；
(B)靶向治疗相关细胞表面抗原的抗体；
其中，所述IL-15直接或者通过连接肽与所述抗体重链可变区的N端和/或轻链可变区的N端连接；或者，所述IL-15直接或者通过连接肽与所述抗体重链恒定区的C端或轻链恒定区的C端连接。
在一些实施方案中，所述连接肽为裂解性连接肽或非裂解性连接肽。在一些实施方案中，其中所述连接肽独立地选自但不限于GGGGSGGGGSGGGGSG、GSPLGVRGS、GSPLGVR、PLGVR、GGGGSGPLGVRGGGGSG或GGGGSGPLGVR等。
在一些实施方案中，所述IL-15为哺乳动物细胞IL-15，优选灵长类IL-15，更优选人类IL-15。在一些实施方案中，所述IL-15为野生型IL-15或IL-15衍生物。在一些实施方案中，所述IL-15具有如SEQ ID NO：71所示的核酸序列和SEQ ID NO：72所示的氨基酸序列；在一些实施方案中，所述IL-15具有如SEQ ID NO：111所示的核酸序列和SEQ ID NO：112所示的氨基酸序列。在另外的一些实施方案中，所述IL-15具有如与SEQ ID NO：72或SEQ ID NO：11285％-100％同源的氨基酸序列。
在一些实施方案中，所述治疗相关细胞表面抗原选自肿瘤表面抗原。在一些实施方案中，所述肿瘤表面抗原选自但不限于EGFR、HER2、HER3、HER4、NY-ESO-1、GPC-3、CLL-1、BCMA、GD2、EpCAM、化学趋化因子受体家族(CCR1、CCR2、CCR3、CCR4、CCR5、CCR6、CCR7、CCR8、CCR9、CCR10、CCL27、CCL28、CX3CR1、CXCR1、CXCR2、CXCR3、CXCR4、CXCR5、CXCR6)、mucin家族(MUC1、MUC2、MUC3A、MUC3B、MUC4、MUC5AC、MUC5B、MUC6、MUC7、MUC8、MUC12、MUC13、MUC15、MUC16、MUC17、MUC19、MUC20)、PSMA、CEA、HDAC6、Mesothelin、TERT、TLR、TLR9、TLR4、CD33、GITR、Survivin、CD123、TIGIT、成纤维细胞生长因子受体(FGFR)、血管内皮生长因子受体(FLT1、KDR/Flk-1、VEGFR-3)、肝细胞生长因子受体(HGFR)、神经生长因子受体(NGFR)、胰岛素样生长因子受体(IGFR)、血小板衍生生长因子受体(PDGFR)或激素受体(黑皮质素1受体(MC1R，MSHR)等。
在一些实施方案中，所述肿瘤表面抗原为EGFR。在一些实施方案中，所述靶向肿瘤表面抗原EGFR的抗体具有如SEQ ID NO：32所示的重链氨基酸序列中所含的HCDR1、HCDR2和HCDR3序列，以及如SEQ ID NO：34所示的轻链氨基酸序列中所含的LCDR1、LCDR2和LCDR3序列，或者具有如SEQ ID NO：32所示的重链氨基酸序列中所含的VH序列，以及如SEQ ID NO：34所示的轻链氨基酸序列中所含的vL序列。在一些实施方案中，所述靶向肿瘤表面抗原EGFR的抗体具有如SEQ ID NO：29所示的重链核酸序列和SEQ ID NO：33所示的轻链核酸序列，或者具有如SEQ ID NO：30所示的重链氨基酸序列和SEQ ID NO：34所示的轻链氨基酸序列。在一些实施方案中，所述靶向肿瘤表面抗原EGFR的抗体具有如SEQ ID NO：31所示的重链核酸序列和SEQ ID NO：33所示的轻链核酸序列，或者具有如SEQ ID NO：32所示的重链氨基酸序列和SEQ ID NO：34所示的轻链氨基酸序列。
在一些实施方案中，所述肿瘤表面抗原为HER2。在一些实施方案中，靶向HER2的抗体具有如SEQ ID NO：18所示的重链氨基酸序列中所含的HCD R1、HCDR2和HCDR3序列，以及如SEQ ID NO：20所示的轻链氨基酸序列中所含的LCD R1、LCDR2和LCDR3序列，或者靶向HER2的抗体具有如SEQ ID NO：18所示的重链氨基酸序列中所含的VH序列，以及如SEQ IDNO：20所示的轻链氨基酸序列中所含的VL序列。在一些实施方案中，靶向HER2的抗体具有如SEQ ID NO：17所示的重链核酸序列和SEQ ID NO：19所示的轻链核酸序列，或者具有如SEQID NO：18所示的重链氨基酸序列和SEQ ID NO：20所示的轻链氨基酸序列。
在一些实施方案中，所述免疫细胞因子由分别具有如下氨基酸序列的重链和轻链组成：SEQ ID NO：90和SEQ ID NO：34；SEQ ID NO：92和SEQ ID NO：34；SEQ ID NO：94和SEQID NO：34；SEQ ID NO：96和SEQ ID NO：34；SEQ ID NO：98和SEQ ID NO：20；SEQ ID NO：100和SEQ ID NO：20；SEQ ID NO：110和SEQ ID NO：102；SEQ ID NO：110和SEQ ID NO：104；SEQID NO：98和SEQ ID NO：102；SEQ ID NO：98和SEQ ID NO：104；SEQ ID NO：100和SEQ ID NO：102；SEQ ID NO：100和SEQ ID NO：104；SEQ ID NO：106和SEQ ID NO：20；SEQ ID NO：110和SEQ ID NO：108；SEQ ID NO：106和SEQ ID NO：108；SEQ ID NO：113和SEQ ID NO：34；SEQ IDNO：114和SEQ ID NO：34。
在一些实施方案中，所述免疫细胞因子由分别具有如下氨基酸序列的重链和轻链组成：SEQ ID NO：89和SEQ ID NO：33；SEQ ID NO：91和SEQ ID NO：33；SEQ ID NO：93和SEQID NO：33；SEQ ID NO：95和SEQ ID NO：33；SEQ ID NO：97和SEQ ID NO：19；SEQ ID NO：99和SEQ ID NO：19；SEQ ID NO：109和SEQ ID NO：101；SEQ ID NO：109和SEQ ID NO：103；SEQ IDNO：97和SEQ ID NO：101；SEQ ID NO：97和SEQ ID NO：103；SEQ ID NO：99和SEQ ID NO：101；SEQ ID NO：99和SEQ ID NO：103；SEQ ID NO：105和SEQ ID NO：19；SEQ ID NO：109和SEQ IDNO：107；SEQ ID NO：105和SEQ ID NO：107。
一方面，本发明提供了编码如上所述免疫细胞因子的核酸。
一方面，本发明提供了一种含有如上所述免疫细胞因子核酸序列的载体。
一方面，本发明提供了一种宿主细胞，其包含如上所述的载体。
一方面，本发明提供了一种药物组合物，其包含药学上可接受的载体或制剂以及如上所述的免疫细胞因子。
另一方面，本发明提供了一种治疗有需要的受试者炎症性疾病或癌症的方法，所述方法包括对所述受试者施用治疗有效量的组合物，所述组合物包含药学可接受形式的如上所述的免疫细胞因子。
附图说明
构成本申请的附图用来提供对本发明的进一步理解，本发明的示意性实施例及其说明用于解释本发明，并不构成对本发明的不当限定，在附图中：
图1为基于抗体的免疫细胞因子构建体(名称参见表1)的SDS-PAGE图。各小图中M为蛋白marker，图1A和1B中泳道上方标示的A代表BSIC-01，B代表BSIC-10，C代表BSIC-09，D代表BSIC-05，E代表BSIC-06，F代表BSIC-03。“-”表示不加beta-巯基乙醇后上样，“+”表示加beta-巯基乙醇后上样。
图2为基于抗体的免疫细胞因子凝胶层析结果，其中2A为BSIC-03、2B为BSIC-05、2C为BSIC-06、2D为BSIC-09、2E为BSIC-10、2F为BSIC-24。
图3为基于抗体的免疫细胞因子与IL-15结合(图3A)或IL-15RaSushi结合(图3B)的ELISA检测结果，其中阳性1为IL-15RaSushi-Fc融合蛋白(Novoprotein)，阳性2为IL-15-Fc融合蛋白(金斯瑞生物)
图4为基于抗体的免疫细胞因子促进Mo7e细胞增殖的检测结果，其中阳性3为IL-15与IL-15RaSushi-Fc通过非共价相互作用形成的异二聚体。
图5显示了aEGFR(5A)、aHER2(5B)、aPD1(5C)、aPDL1(5D和5E)、synagis(5F)抗体重链和轻链可变区，互补决定区(CDRs)为下划线标出的部分。
图6为基于抗体的免疫细胞因子刺激脾脏(6A)和PBMC(6B)中淋巴细胞FACS检测结果，其中阳性3为IL-15与IL-15RaSushi-Fc通过非共价相互作用形成的异二聚体，阴性为DPBS。
图7为基于抗体的免疫细胞因子体内与抗原ELISA检测结果，其中7A为免疫细胞因子与抗原hEGFR的结合；7B为免疫细胞细胞因子与抗原hPD-L1的结合；7C为免疫细胞因子与抗原hHER2的结合。
本发明的详述
本发明在此通过对使用下述定义和实施例的引用进行详细描述。所有在本文中提及的专利和公开文献的内容，包括在这些专利和公开中披露的所有序列，明确地通过提述并入本文。
本文所述的“免疫细胞因子”(immunocytokines)是指细胞因子与抗体的融合物。
本文的术语“抗体”以最广泛的含义使用，并且包括各种抗体结构，包括但不限于单克隆抗体及其衍生物和工程化抗体，包括如多特异性抗体(例如DVD-Ig、CrossMab、ART-Ig、FIT-Ig、Duobody等双特异性抗体，三特异性抗体)和抗体片段，包括但不限于Fab、Fab’、(Fab’)2、Fv、Diabody等等，只要它们表现出所期望的治疗相关细胞表面抗原结合活性，且具有能够在N端与IL-15和IL-15Ra连接的重链可变区和轻链可变区。在某些情形下，例如在IL-15或IL-15Ra与轻链CL或重链CH1的C端连接的场合，抗体亦可包含重链和轻链恒定区或其部分。在这样的情形中，抗体可以是，例如，Fab的形式。
术语“CDR”是指在免疫球蛋白可变区序列内的互补决定区。对于各重链和轻可变区，在重链和轻链的各可变区中存在三个CDR，其被命名为CDR1、CDR2和CDR3。术语“CDR组”是指在能够结合抗原的单一可变区中出现的三个CDR的组。这些CDR的确切边界已根据不同系统不同地定义。由Kabat(Kabat等(1987)和(1991))描述的系统，不仅提供了可适用于抗体或结合蛋白的任何可变区的明确残基编号系统，而且还提供了定义各重链或轻链序列中的三个CDR的精确残基边界。这些CDR可以被称为Kabat CDR。Chothia和同事(Chothia和Lesk(1987)J.Mol.Biol.196：901-917；Chothia等(1989)Nature342：877-883)发现KabatCDR内的某些亚部分采取几乎相同的肽骨架构象，尽管在氨基酸序列水平上具有大的多样性。这些亚部分被命名为L1、L2和L3或H1、H2和H3，其中“L”和“H”分别指轻链和重链区域。这些区域可以被称为Chothia CDR，所述Chothia CDR具有与Kabat CDR重叠的边界。定义与Kabat CDR重叠的CDR的其它边界已由Padlan(1995)FASEB J.9：133-139和MacCallum(1996)J.Mol.Biol.262(5)：732-45)描述。还有其它CDR边界定义可以不严格遵循本文系统之一，但仍将与Kabat CDR重叠，尽管鉴于特定残基或残基组或甚至整个CDR不显著影响抗原结合的预测或实验发现，它们可以缩短或加长。本文综合了Kabat和Contact定义CDR的方法(详见http：//www.bioinf,org.uk/abs/)。
术语“同源性”或“同一性”指两个聚合物分子之间(例如，在两个核酸分子(如，两个DNA分子或两个RNA分子之间)或在两个多肽分子之间)的次级单位序列同一性。当这两个分子中的次级单位位置被相同单体性次级单位占据时，例如，若两个DNA分子中每个分子中的某位置被腺嘌呤占据，则它们在该位置是同源或相同的。两个序列之间的同一性直接随匹配位置或同源位置的数目而变化，例如，如果两个序列中一半位置(例如长度为十个次级单位的聚合物中的五个位置)是同源的，则这两个序列是同源的(亦可称具有50％同源性或50％同一性)；如果90％的位置(例如10个位置中9个位置)是匹配或同源的，则这两个序列是90％同源的(亦可称具有90％同源性或90％同一性)。
本发明的“IL-15”为哺乳动物细胞白介素15(IL-15)，优选灵长类IL-15，更优选IL-15。本发明的“IL-1 5”指具有与选自由SEQ ID NO：72氨基酸序列至少85％(即，相当于约20个氨基酸改变)的同一性百分数的氨基酸序列，优选地至少99％(相当于约1个氨基酸改变)，但仍保持与野生型IL-15相当的生理活性的IL-15衍生物或变体。本领域技术人员可基于其知识和本专利申请的教导鉴定这样的衍生物。也应当理解天然氨基酸可以被化学修饰的氨基酸所替代。通常，这样的化学修饰的氨基酸提高多肽半衰期(见国际专利申请WO/2015/131994)。如前述使用的两个氨基酸序列之间“同一性百分数”的定义参加国际专利申请WO/2015/131994。
优选地，IL-15衍生物或变体为IL-15激动剂或超激动剂。本领域技术人员可以基于现有技术的方法鉴定IL-15激动剂或超激动剂。作为IL-15超激动剂或超激动剂的实例，可以引用在国际申请WO2005/085282或Zhu等的(J.Immunol，vol.183(6)，p：3598-607，2009)中公开的那些。
更优先地，所述IL-15激动剂或超激动剂包括选自下组的取代：L45D、L45E、S51D、L52D、N72D、N72E、N72A、N72S、N72Y和N72P(上述氨基酸位点参照人IL-15的序列，SEQ IDNO.：72)。
本发明的“IL-15Ra的Sushi结构域”具有本领域中一般公知的含义。所述Sushi结构域为哺乳动物IL-15Ra的Sushi结构域，优选灵长类IL-15Ra的Sushi结构域，更优选人IL-15Ra的Sushi结构域。优选地，包括人IL-15Ra的sushi结构域具有如SEQ ID NO.：74所示的氨基酸序列。
如本文使用，术语“IL-15Ra的sushi结构域的衍生物”是指与SEQ ID NO：74所示氨基酸序列至少85％(即相当于约10个氨基酸改变)的同一性百分数的氨基酸序列，优选地至少99％(相当于约1个氨基酸改变)的IL-15Ra的sushi结构域的衍生物。本领域技术人员可基于其个人的知识和本专利申请的教导鉴定这样的衍生物。也应当理解天然氨基酸可以被化学修饰的氨基酸所替代。通常，这样的化学修饰的氨基酸可提高多肽半衰期(见国际专利申请WO/2015/131994)。如前述使用的两个氨基酸序列之间“同一性百分数”的定义，参见例如WO/2015/131994。
本发明的“治疗相关细胞表面抗原”指表达在细胞表面的、可以被靶向以进行IL-15介导的疾病治疗的抗原。本发明的“治疗相关细胞表面抗原”包括CD抗原、免疫监测点抗原、肿瘤相关抗原、肿瘤特异性抗原、病毒诱发的肿瘤抗原，且可选自但不限于下面所述抗原：CD19、PD-1、PD-L1、HER2、STAT3、STEAP1、CTLA-4、IDO、NY-ESO-1、CD40、CSF1R、BCMA、MUC1、ADORA2A、CD20、GD2、TLR7、WT1、IFNAR1、CD47；Neoantigen、EGFR、LAG-3、OX40、PSMA、Mesothelin、TERT、TLR、TLR9、4-1BB、IL2R、TLR4、CD33、GITR、HPV E6、Survivin、CD123、TIGITTIM-3、CD73、HPVE7、TLR3、CD38、EBV、STING、CD22、GPC3、HDAC1、CXCR4、GMCSFR、CD30、CEACAM5、HDAC6、HPV、CD3、MAGE-A3、TNF、PSA、CD25、CEA、EPCAM、CMV、IL12、PRAME、IL12R、5T4、Beta catenin、CCR2、PMEL、CXCL12、IGF1、CD46、CXCR1、GMCSF、IL15R、ROR1、TGFBR2、CCR4、FLT-3、FOLR1、GCSFR、ICOS、JAK2、KRAS、VISTA、CD133、CD27、CD39、CEACAM6、NKG2D、STAT5、TGFB1、TLR2、USP7、ANG1、ANG2、B7-H3、CLEC12A、IL13RA2、RIG-I、TRP2、VEGF、AFP、Alpha-Gal、COX-2、EPHA2、gp96、MUC16、p53、TGF-β、CD138、CDw136、CS1、CXCR2、EGFRvIII、Gelactin-3、Globo H、GR、IFNAR2、IFNGR1、IL6、JAK1、MLANA、RAS、SLAMF7、TDO、TGFB2、TLR8、ALK、Arginase、CCR1、CD56、CD70、FAP、GD3、IDH1、IL6R、IRAK4、MAGE-A4、MERTK、MIF、PSCA、PTGER4、SIRPA、TGFB、TGFBR1、ACPP、ADORA2B、AR、Brachyury、CA19-9、CD32、CEACAM1、Gastrin、HDAC、HPVL2、IFNAR、IFNGR、IGF1R、IGF2、IL15、IL17R、IL1B、IL7R、JAK、MAGE-A、MAGE-A1、MAGE-A6、P38、、RORC、TLR5、VEGFR2、ADORA3、ATRT、B7-H4、c-KIT、CCR7、CD11b、CD135、CD171、CD174、CDH3、CX3CR1、Gelactin-1、GM3、HLA-A2、HSP70、IL10、IL17、IL2RB、JAK3、MDA5、NKG2A、PBF、PVRIG、SPAM1、URLC10、VEGFR1、ABCB5、ADABP、ADAM17、ADP、AEG1、Alpha-lactalbumin、AMHR2、ASPH、AXL、BCL2、BTE6-LX-8b、BTE6-X-15-7、Carbohydrateantigens、CCL20、CCL3、CCNB1、CD147、CD155、CD16、CD162、CD16a、CD200、CD21、CD28、CD44、CD52、CD54、CD7、CD80、CD88、Claudin 18、cMET、COX2、CSF1、CTCFL、CXCR5、CXCR7、E1A、EIF2AK3、ERG、FGF2、FN1、GC、GM2、gPA33、HBV、Hemagglutinin、HER3、HILPDA、HLA-DR、HMW-MAA、HP59、HPV 16、HPV E6/7、HPV L1、HSP105、HSP65、HVEM、Hyaluronan、IL13RA1、IL2、IL21R、IL8、KIF20A、KIR2DL1、KIR2DL3、LXR、MAGE-A10、MAGE-C2、MammaglobinA、MAPK、MICA、MiHA、MMP-11、MVP、Myeloblastin、N-Myc、NKp46、NLRP3、NR2F6、Oncofetal Antigen、P2RX7、RhoC、SIM-2、SSTR2、SSX2、STAT1、STn、TAG72、TAMA、TFDP3、TGFBR、TSA、TYK2、Tyrosinase、VEGFA、5′Nucleotidase(Ecto 5′Nucleotidase or CD73 or NT5E or EC 3.1.3.5)、ADAM9、AIM2、B7-H6、BAFF-R、BAI1、BARD1、BOB-1、CA9、Cancertestis antigen、CB2、CBLB、CCR9、CD13、CD130、CD150、CD160、CD200R1、CD267、CD29、CD3E、CD4、CD51、CD8、CGEN-XXXX、Claudin 6、CLEC2D、COX、COX-1、CPEB4、CPEG4、CRBN、CRLF2、CSPG4、CTA、CXCL1、CXCR3、Cytosine deaminase、DCK、DKK1、DLL3、DR3、DR5、EBNA3C、EGF、EGFR5、ELVAL4、EPHA3、EPS8、EVI1、FAIM-3、FasR、FCU1、FLT3、FOLR、FOXM1、FSHR、Galectin-3、GalNAc、GARP、Gelactin-9、Gelatcin-1/3/9、GLD18、GNRHR、GP160、GP73、H3.3K27M、HAGE、HDAC2、HDAC8、HPV16 E6、HPV16 E7、HSP、Hypoxia、ICAM、ICAM7、IDO1、IFNG、IFNGR2、IGF2R、IGFBP2、IGK、IL10RA、IL12RB1、IL13、IL13R、IL13Ralpha2、IL15RA、IL17A、IL17B、IL1A、IL1R1、IL1R3、IL21、IL22R、IL27R、IL2RA、IL35、IL9R、Integrinbeta-7、IRAK1、ITGB5、Kappamyelomaantigen、KIR2DL2、Kynurenine、L1CAM、Lambda Myeloma Antigen、LAMP、LLO、LXRA、LXRB、Masreceptor、MG7、MHCI、MHCII、MIC、MOSPD2、MRP-3、MRP1、MRP3765、muGNTP01、MYB、MYBL2、NFAT、NGcGM3、Nrf2、p38 MAP Kinase(EC 2.7.11.24)、P55、PAM4、PAP、PASD1、PCDH18、PD-L2、PI3K-delta、POTE、PPT、Protein tolemerase、PTGER2、RANKL、RBL001、RNF43、ROR2、S100A9、SEREX、SLAMF1、STAT、TACSTD2、TASTD2、TDO2、TEM、thymidine kinase、Thymidylatesynthase、TIE2、TIMP3、TM4SF5、TOP1、TRBC1、TRBC2、TRIF、Tryptophan、TSHR、TWEAK、UTA2-1、VDBP、VRP、VSIG-4、XAGE1、XAGE1A、ZP1、ZP3。
本发明的术语“连接肽”是指用于连接2个多肽的氨基酸残基或包含2个或更多个通过肽键连接的氨基酸残基的多肽。这样的接头多肽是本领域众所周知的(参见，例如，Holliger等人(1993)Proc.Natl.Acad.Sci.USA 90：6444-6448；Poljak等人(1994)Structure2：1121-1123)。合适的，非免疫原性的连接肽包括例如GS，(G4S)n，(SG4)n，(G4S)n或G4(SG4)n肽接头。“n”一般是1至10，通常是2至4的整数。在某些实施方案中，所述连接肽是可裂解的连接肽，例如，可自断裂、可酶促断裂或可化学断裂的连接肽。参见WO2011/034605，将其全部按引用并入本文中。例如，但不限于，连接肽的酶断裂可以包括使用内肽酶或外肽酶。内肽酶的非限制性实例包括MMP2(基质金属蛋白酶2)、尿激酶、Lys-C、Asp-N、Arg-C、V8、Glu-C、胰凝乳蛋白酶、胰蛋白酶、胃蛋白酶、木瓜蛋白酶、凝血酶、Genenase、因子Xa、TEv(烟草蚀刻病毒半胱氨酸蛋白酶)、肠激酶、HRV C3(人鼻病毒C3蛋白酶)、ininogenase、枯草芽孢杆菌蛋白酶样前蛋白转化酶(例如，Furin(PC1)、PC2或PC3)和N-精氨酸二碱基转化酶(N-arginine dibasic convertase)。外肽酶的非限制性实例包括羧基肽酶A、羧基肽酶B、羧基肽酶D、羧基肽酶E(也称为羧基肽酶H)、羧基肽酶M、羧基肽酶N或羧基肽酶Z。在某些实施方案中，可以通过使用羟胺、N-氯代琥珀酰亚胺、N-溴代琥珀酰亚胺或溴化氰，进行化学断裂。
实施例
需要说明的是，在不冲突的情况下，本申请中的实施例仅为举例说明，不旨在对本发明造成任何方式上的限制。
实施例
实施例1基于抗体的免疫细胞因子的构建
分别合成编码抗EGFR抗体(aEGFR)、Palivizumab(Syn)、抗PD-1抗体(aPD-1)、抗PD-L1抗体(aPD-L1)、抗HER2抗体(aHER2)的重链(H)和轻链(L)，以及IL-15、IL-15Ra、IL-15RaSushi的基因片段，采用标准分子生物学技术通过连接肽将IL-15融合在前述抗体重链的可变区的N端或CH1的C端，将IL-15Ra融合在前述抗体轻链的可变区N端或恒定区的C端，或者将IL-15融合在前述抗体轻链的可变区的N端或恒定区的C端，将IL-15Ra融合在前述抗体重链的可变区N端或CH1的C端，所有的序列都通过测序验证(见表1的序列)。
表1基于抗体的免疫细胞因子的序列
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注：null表示Fc无ADCC和CDC功能或者具有减弱的ADCC和CDC功能.
实施例2基于抗体的免疫细胞因子的表达、纯化和凝胶排阻层析
将实施例1构建好的含有免疫细胞因子的抗体重链和轻链的表达载体瞬时转染Expi293细胞(ThermoFisher)分别共转染，转染时重链的质粒和轻链的质粒用量为摩尔比1∶1)：将40ml Expi293(3-4×106细胞/ml)接种至125ml细胞培养瓶，80ug质粒用2mlOpti-MEM(Invitrogen)稀释后加至2ml含120μl PEI(Polysciences)的Opti-MEM中，室温静置30min，将质粒-PEI mixture加至细胞培养液中125rpm，37℃，5％CO2培养。于转染后96h收集细胞培养上清，使用Protein A Resin(Genscript)纯化，SDS-PAGE检测。
将获得的Protein A resin纯化后的免疫细胞因子用GE的AKTA chromatography过柱分析，所用的层析柱为：Superdex 200Increase 10/300GL凝胶排阻层析柱。凝胶排阻层析所用的溶液为PBS缓冲液(0.010M phosphate buffer，0.0027M KCl，0.14M NaCl，pH7.4)。从图1的SDS胶图和图2的色谱图说明免疫细胞因子复合物具有相当的纯度，可通过层析柱有效分离。
实施例3基于抗体的免疫细胞因子体外活性验证
3.1 IL-15或IL-15RaSushi结合活性
包被hIL-15(SinoBiological)或IL-15RaSushi(Miltenyi)(100ng/孔)(DPBSbuffer，pH7.4)于96孔板，4℃孵育过夜；含2％脱脂奶粉的DPBST室温封闭1小时，含0.05％Tween-20的DPBS洗3次后，分别加入梯度稀释的免疫细胞因子室温孵育2h，含0.05％Tween-20的DPBS洗4-5次后，加入HRP conjugated anti-human kappa light chain(Cat.A18853，Thermo Fisher Scientific，1∶2000)二抗室温孵育2h，含0.05％Tween-20的DPBS洗4-5次后，TMB(BioLegend)显色后于OD450处读数。Prizm Graphpad软件用log(agonist)vs.response模型对数据进行非线性回归。
结果如图3所示。与positive-1(IL-15RaSushi-Fc)相比，BSIC-01(IL15-SynH(null)：IL15RaSushi-SynL)和BSIC-02(IL15RaShi-SynH(null)：IL15-SynL)对IL-15的亲和力相对较低(3A)，说明BSIC-01(IL15-SynH(null)：IL15RaSushi-SynL)与BSIC-02(IL15RaShi-SynH(null)：IL15-SynL)分子内的IL-15和IL-15RaSushi形成稳定的复合物。与positive-2(IL-15-Fc)相比，BSIC-01(IL15-SynH(null)：IL15RaSushi-SynL)对IL-15的亲和力较低(3B)，与骨架抗体BSIC-13Syn(null)基本一致，说明BSIC-01(IL15-SynH(null)：IL15RaSushi-SynL)分子内的IL-15和IL-15RaSushi形成非常稳定的复合物；BSIC-27(IL-15RaSushi-SynH(null))对IL-15RaSushi的亲和力较高。
3.2抗原结合活性
包被hEGFR-his(SinoBiological)、hHER2(ACRO)或hPDL1(100ng/孔)于96孔板，4℃孵育过夜；含2％脱脂奶粉的PBST(0.5％Tween-20in PBS)室温封闭1小时，分别加入梯度稀释的免疫细胞因子室温孵育2h，含2％脱脂奶粉的PBST洗4-5次后，加入HRP anti-humankappa light chain(Invitorgen)二抗室温孵育1h，含2％脱脂奶粉的PBST洗4-5次后，TMB显色试剂(BioLegend，Cat.421101)显色后于450nm处读数，或者QuantaBlu荧光过氧化物酶底物(Life technologies，Cat.15169)显色后于325nm和420nm处读数。Prizm Graphpad软件用specific binding model对数据进行非线性回归。结果如图7所示，基于抗体的免疫细胞因子对抗原具有较好的亲和力。
实施例4 Mo7e促增殖实验
培养Mo7e细胞(协和细胞资源中心)(培养条件：RPMI 1640培养基+10％胎牛血清+双抗+10ng/ml GMCSF(Peprotech))，实验之前台盼蓝检测细胞活率，确保Mo7e细胞活率超过95％方可进行后续的增殖实验。用RPMI 1640(10％FBS+双抗)培养基洗2次后将细胞重悬至密度为40,000/100ul，加入到96孔板(全黑色底部不透明)中，每孔50ul。配制含有免疫细胞因子的RPMI 1640(10％FBS+双抗)培养基，按照预先设定好的浓度梯度进行配制。将配制好的含免疫细胞因子的培养基加入到96孔板中，每孔50ul，每个梯度做三个复孔；完成后，轻轻震荡96孔板，让含有细胞因子的培养基与预先铺好的Mo7e细胞混合均匀，放入细胞培养箱培养，条件同上。72h后，根据厂家提供的说明书，通过MTS(Promega)显色后于OD490处读数或者通过Cell TiterGLO(Promega)显色后读取荧光值。Prizm Graphpad软件用log(agonist)vs.response模型对数据进行非线性回归。
结果如图4所示。BSIC-01(IL15-SynH(null)：IL15RaSushi-SynL)促进Mo7e增殖的效果弱于positive-3(IL-15与IL-15RaSushi-Fc通过非共价相互作用形成的异二聚体)和rhIL-15，但是强于BSIC-27(图4A)，提示IL-15和IL-15Rasushi通过非共价相互作用形成的分子内复合物可有效促进Mo7e细胞的增殖。BSIC-07(IL15-aEGFRH(null)：IL15RaSushi-aEGFRL)和BSIC-08IL15RaSushi-aEGFRH(null)：IL15-aEGFRL促进Mo7e增殖的效果类似，但是稍弱于rhIL-15。BSIC-03(IL15-aHER2H(WT)：IL15RaSushi-aHER2L)和BSIC-04(IL15RaSushi-aHER2(WT)：IL15-aHER2L)促进Mo7e增殖的效果强于BSIC-24(IL-15-aHER2H(WT))或IL-15-aHER2L(WT)(IL-15-aHER2H(WT))，与Palivizumab或aEGFR融合的趋势一致。
实施例5淋巴细胞激活实验
将DPBS或免疫细胞因子融合蛋白腹腔注射雌性C57BL/6小鼠(6-7周)，4天后后，后眼窝采集静脉血分离PBMC，同时处死小鼠取小鼠脾脏，制备脾脏细胞单细胞悬液，用流式抗体染色后检测PBMC及脾脏中不同免疫细胞的阳性率。所用的流式抗体如下：PE rat anti-mouse CD19、APC rat anti-mouse CD45、FITC rat anti-mouse CD335、FITC rat anti-mouse CD3、PE rat anti-mouse CD4、PE rat anti-mouse CD8、TruStain FcX plus(anti-mouse CD16/32)，均购自Biolegend公司。结果如图6所示，基于抗体的免疫细胞因子能够有效激活小鼠体内的CD8+T细胞和NK细胞等免疫细胞。
SEQUENCE LISTING
<110> 南通壹宸生物医药科技有限公司
<120> 一种免疫细胞因子及其制备与用途
<160> 120
<170> PatentIn version 3.5
<210> 1
<211> 1737
<212> DNA
<213> 人工序列
<400> 1
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacgacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccgga 360
ggcggaggtt ccggcggggg tgggagcggg caggtgaccc tgcgcgagtc cggccctgca 420
ctggtgaagc ccacccagac cctgaccctg acctgcacct tctccggctt ctccctgtcc 480
acctccggca tgtccgtggg ctggatccgg cagcctcccg gcaaggccct ggagtggctg 540
gctgacatct ggtgggacga caagaaggac tacaacccct ccctgaagtc ccgcctgacc 600
atctccaagg acacctccaa gaaccaggtg gtgctgaagg tgaccaacat ggaccccgcc 660
gacaccgcca cctactactg cgcccgctca atgattacca actggtactt cgacgtgtgg 720
ggagccggta ccaccgtgac cgtgtcttcc gcctccacca agggcccatc ggtcttcccc 780
ctggcaccct cctccaagag cacctctggg ggcacagcgg ccctgggctg cctggtcaag 840
gactacttcc ccgaaccggt gacggtgtcg tggaactcag gcgccctgac cagcggcgtg 900
cacaccttcc cggctgtcct acagtcctca ggactctact ccctcagcag cgtggtgact 960
gtgccctcta gcagcttggg cacccagacc tacatctgca acgtgaatca caagcccagc 1020
aacaccaagg tggacaagaa agttgaaccc aaatcttgcg acaaaactca cacatgccca 1080
ccgtgcccag cacctccagt cgccggaccg tcagtcttcc tcttccctcc aaaacccaag 1140
gacaccctca tgatctcccg gacccctgag gtcacatgcg tggtggtgga cgtgagccac 1200
gaagaccctg aggtcaagtt caactggtac gtggacggcg tggaggtgca taatgccaag 1260
acaaagccgc gggaggagca gtacaacagc acgtaccgtg tggtcagcgt cctcaccgtc 1320
ctgcaccagg actggctgaa tggcaaggag tacaagtgca aggtctccaa caaaggcctc 1380
ccaagctcca tcgagaaaac catctccaaa gccaaagggc agccccgaga accacaggtg 1440
tacaccctgc ctccatcccg ggatgagctg accaagaacc aggtcagcct gacctgcctg 1500
gtcaaaggct tctatcccag cgacatcgcc gtggagtggg agagcaatgg gcagccggag 1560
aacaactaca agaccacgcc tcccgtgctg gactccgacg gctccttctt cctctacagc 1620
aagctcaccg tggacaagag caggtggcag caggggaacg tcttctcatg ctccgtgatg 1680
catgaggctc tgcacaacca ctacacgcag aagagcctct ccctgtctcc gggtaaa 1737
<210> 2
<211> 579
<212> PRT
<213> 人工序列
<400> 2
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gln Val Thr Leu Arg Glu Ser Gly Pro Ala Leu Val Lys Pro
130 135 140
Thr Gln Thr Leu Thr Leu Thr Cys Thr Phe Ser Gly Phe Ser Leu Ser
145 150 155 160
Thr Ser Gly Met Ser Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Ala
165 170 175
Leu Glu Trp Leu Ala Asp Ile Trp Trp Asp Asp Lys Lys Asp Tyr Asn
180 185 190
Pro Ser Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Lys Asn
195 200 205
Gln Val Val Leu Lys Val Thr Asn Met Asp Pro Ala Asp Thr Ala Thr
210 215 220
Tyr Tyr Cys Ala Arg Ser Met Ile Thr Asn Trp Tyr Phe Asp Val Trp
225 230 235 240
Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
245 250 255
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
260 265 270
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
275 280 285
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
290 295 300
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
305 310 315 320
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
325 330 335
His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser
340 345 350
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala
355 360 365
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
370 375 380
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
385 390 395 400
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
405 410 415
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
420 425 430
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
435 440 445
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile
450 455 460
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
465 470 475 480
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
485 490 495
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
500 505 510
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
515 520 525
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
530 535 540
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
545 550 555 560
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
565 570 575
Pro Gly Lys
<210> 3
<211> 1029
<212> DNA
<213> 人工序列
<400> 3
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacgacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccgga 360
ggcggaggtt ccggcggggg tgggagcggg gacatccaga tgacccagtc cccctccacc 420
ctgtccgcct ccgtgggcga ccgcgtgacc atcacctgca agtgccagct gtccgtgggc 480
tacatgcact ggtaccagca gaagcccggc aaggccccca agctgctgat ctacgacacc 540
tccaagctgg cctccggcgt gccctcccgc ttctccggct ccggctccgg caccgagttc 600
accctgacca tctcctccct gcagcccgac gacttcgcca cctactactg cttccagggc 660
tccggctacc ccttcacctt cggcggcggc accaagctgg agatcaaacg aactgtggct 720
gcaccatctg tcttcatctt cccgccatct gatgagcagt tgaaatctgg aactgcctct 780
gtcgtgtgcc tgctgaataa cttctatccc agagaggcca aagtacagtg gaaggtggat 840
aacgccctcc aatcgggtaa ctcccaggag agtgtcacag agcaggacag caaggacagc 900
acctacagcc tcagcagcac cctgacgctg agcaaagcag actacgagaa acacaaagtc 960
tacgcctgcg aagtcaccca tcagggcctg tcctcgcccg tcacaaagag cttcaacagg 1020
ggagagtgt 1029
<210> 4
<211> 343
<212> PRT
<213> 人工序列
<400> 4
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser
130 135 140
Val Gly Asp Arg Val Thr Ile Thr Cys Lys Cys Gln Leu Ser Val Gly
145 150 155 160
Tyr Met His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
165 170 175
Ile Tyr Asp Thr Ser Lys Leu Ala Ser Gly Val Pro Ser Arg Phe Ser
180 185 190
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
195 200 205
Pro Asp Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Gly Tyr Pro
210 215 220
Phe Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala
225 230 235 240
Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser
245 250 255
Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu
260 265 270
Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser
275 280 285
Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu
290 295 300
Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val
305 310 315 320
Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys
325 330 335
Ser Phe Asn Arg Gly Glu Cys
340
<210> 5
<211> 1590
<212> DNA
<213> 人工序列
<400> 5
atcacctgcc cacctcccat gagcgtggag cacgccgaca tctgggtgaa gagctacagc 60
ctgtacagcc gcgagcgcta catctgcaac agcggcttca agcgcaaggc cggcaccagc 120
agcctgaccg agtgcgtgct gaacaaggcc accaacgtgg cccactggac cacccccagc 180
ctgaagtgca tccgcggcgg aggcggatcc ggaggcggag gttccggcgg gggtgggagc 240
gggcaggtga ccctgcgcga gtccggccct gcactggtga agcccaccca gaccctgacc 300
ctgacctgca ccttctccgg cttctccctg tccacctccg gcatgtccgt gggctggatc 360
cggcagcctc ccggcaaggc cctggagtgg ctggctgaca tctggtggga cgacaagaag 420
gactacaacc cctccctgaa gtcccgcctg accatctcca aggacacctc caagaaccag 480
gtggtgctga aggtgaccaa catggacccc gccgacaccg ccacctacta ctgcgcccgc 540
tcaatgatta ccaactggta cttcgacgtg tggggagccg gtaccaccgt gaccgtgtct 600
tccgcctcca ccaagggccc atcggtcttc cccctggcac cctcctccaa gagcacctct 660
gggggcacag cggccctggg ctgcctggtc aaggactact tccccgaacc ggtgacggtg 720
tcgtggaact caggcgccct gaccagcggc gtgcacacct tcccggctgt cctacagtcc 780
tcaggactct actccctcag cagcgtggtg actgtgccct ctagcagctt gggcacccag 840
acctacatct gcaacgtgaa tcacaagccc agcaacacca aggtggacaa gaaagttgaa 900
cccaaatctt gcgacaaaac tcacacatgc ccaccgtgcc cagcacctcc agtcgccgga 960
ccgtcagtct tcctcttccc tccaaaaccc aaggacaccc tcatgatctc ccggacccct 1020
gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 1080
tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 1140
agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 1200
gagtacaagt gcaaggtctc caacaaaggc ctcccaagct ccatcgagaa aaccatctcc 1260
aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcctccatc ccgggatgag 1320
ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1380
gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1440
ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 1500
cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1560
cagaagagcc tctccctgtc tccgggtaaa 1590
<210> 6
<211> 530
<212> PRT
<213> 人工序列
<400> 6
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val
1 5 10 15
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly
20 25 30
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn
35 40 45
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile
50 55 60
Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
65 70 75 80
Gly Gln Val Thr Leu Arg Glu Ser Gly Pro Ala Leu Val Lys Pro Thr
85 90 95
Gln Thr Leu Thr Leu Thr Cys Thr Phe Ser Gly Phe Ser Leu Ser Thr
100 105 110
Ser Gly Met Ser Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Ala Leu
115 120 125
Glu Trp Leu Ala Asp Ile Trp Trp Asp Asp Lys Lys Asp Tyr Asn Pro
130 135 140
Ser Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Lys Asn Gln
145 150 155 160
Val Val Leu Lys Val Thr Asn Met Asp Pro Ala Asp Thr Ala Thr Tyr
165 170 175
Tyr Cys Ala Arg Ser Met Ile Thr Asn Trp Tyr Phe Asp Val Trp Gly
180 185 190
Ala Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
195 200 205
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
210 215 220
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
225 230 235 240
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
245 250 255
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
260 265 270
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
275 280 285
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
290 295 300
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly
305 310 315 320
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
325 330 335
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
340 345 350
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
355 360 365
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
370 375 380
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
385 390 395 400
Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu
405 410 415
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
420 425 430
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
435 440 445
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
450 455 460
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
465 470 475 480
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
485 490 495
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
500 505 510
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
515 520 525
Gly Lys
530
<210> 7
<211> 882
<212> DNA
<213> 人工序列
<400> 7
atcacctgcc cacctcccat gagcgtggag cacgccgaca tctgggtgaa gagctacagc 60
ctgtacagcc gcgagcgcta catctgcaac agcggcttca agcgcaaggc cggcaccagc 120
agcctgaccg agtgcgtgct gaacaaggcc accaacgtgg cccactggac cacccccagc 180
ctgaagtgca tccgcggcgg aggcggatcc ggaggcggag gttccggcgg gggtgggagc 240
ggggacatcc agatgaccca gtccccctcc accctgtccg cctccgtggg cgaccgcgtg 300
accatcacct gcaagtgcca gctgtccgtg ggctacatgc actggtacca gcagaagccc 360
ggcaaggccc ccaagctgct gatctacgac acctccaagc tggcctccgg cgtgccctcc 420
cgcttctccg gctccggctc cggcaccgag ttcaccctga ccatctcctc cctgcagccc 480
gacgacttcg ccacctacta ctgcttccag ggctccggct accccttcac cttcggcggc 540
ggcaccaagc tggagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 600
tctgatgagc agttgaaatc tggaactgcc tctgtcgtgt gcctgctgaa taacttctat 660
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 720
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 780
ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 840
ctgtcctcgc ccgtcacaaa gagcttcaac aggggagagt gt 882
<210> 8
<211> 294
<212> PRT
<213> 人工序列
<400> 8
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val
1 5 10 15
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly
20 25 30
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn
35 40 45
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile
50 55 60
Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
65 70 75 80
Gly Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val
85 90 95
Gly Asp Arg Val Thr Ile Thr Cys Lys Cys Gln Leu Ser Val Gly Tyr
100 105 110
Met His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
115 120 125
Tyr Asp Thr Ser Lys Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly
130 135 140
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
145 150 155 160
Asp Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Gly Tyr Pro Phe
165 170 175
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala
180 185 190
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
195 200 205
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
210 215 220
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
225 230 235 240
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
245 250 255
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
260 265 270
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
275 280 285
Phe Asn Arg Gly Glu Cys
290
<210> 9
<211> 1737
<212> DNA
<213> 人工序列
<400> 9
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacgacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccgga 360
ggcggaggtt ccggcggggg tgggagcggg gaggtgcagc tggtggagtc tggaggaggc 420
ttggtccagc ctggggggtc cctgagactc tcctgtgcag cctctgggtt caatattaag 480
gacacttaca tccactgggt ccgccaggct ccagggaagg ggctggagtg ggtcgcacgt 540
atttatccta ccaatggtta cacacgctac gcagactccg tgaagggccg attcaccatc 600
tccgcagaca cttccaagaa cacggcgtat cttcaaatga acagcctgag agccgaggac 660
acggccgtgt attactgttc gagatggggc ggtgacggct tctatgccat ggactactgg 720
ggccaaggaa ccctggtcac cgtctcctca gcctccacca agggcccatc ggtcttcccc 780
ctggcaccct cctccaagag cacctctggg ggcacagcgg ccctgggctg cctggtcaag 840
gactacttcc ccgaaccggt gacggtgtcg tggaactcag gcgccctgac cagcggcgtg 900
cacaccttcc cggctgtcct acagtcctca ggactctact ccctcagcag cgtggtgact 960
gtgccctcta gcagcttggg cacccagacc tacatctgca acgtgaatca caagcccagc 1020
aacaccaagg tggacaagaa agttgagccc aaatcttgcg acaaaactca cacatgccca 1080
ccgtgcccag cacctccagt cgccggaccg tcagtcttcc tcttccctcc aaaacccaag 1140
gacaccctca tgatctcccg gacccctgag gtcacatgcg tggtggtgga cgtgagccac 1200
gaagaccctg aggtcaagtt caactggtac gtggacggcg tggaggtgca taatgccaag 1260
acaaagccgc gggaggagca gtacaacagc acgtaccgtg tggtcagcgt cctcaccgtc 1320
ctgcaccagg actggctgaa tggcaaggag tacaagtgca aggtctccaa caaaggcctc 1380
ccaagctcca tcgagaaaac catctccaaa gccaaagggc agccccgaga accacaggtg 1440
tacaccctgc ctccatcccg ggatgagctg accaagaacc aggtcagcct gacctgcctg 1500
gtcaaaggct tctatcccag cgacatcgcc gtggagtggg agagcaatgg gcagccggag 1560
aacaactaca agaccacgcc tcccgtgctg gactccgacg gctccttctt cctctacagc 1620
aagctcaccg tggacaagag caggtggcag caggggaacg tcttctcatg ctccgtgatg 1680
catgaggctc tgcacaacca ctacacgcag aagagcctct ccctgtctcc gggtaaa 1737
<210> 10
<211> 579
<212> PRT
<213> 人工序列
<400> 10
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile Lys
145 150 155 160
Asp Thr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala Asp
180 185 190
Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr
195 200 205
Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
210 215 220
Tyr Cys Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
245 250 255
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
260 265 270
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
275 280 285
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
290 295 300
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
305 310 315 320
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
325 330 335
His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser
340 345 350
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala
355 360 365
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
370 375 380
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
385 390 395 400
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
405 410 415
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
420 425 430
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
435 440 445
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile
450 455 460
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
465 470 475 480
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
485 490 495
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
500 505 510
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
515 520 525
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
530 535 540
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
545 550 555 560
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
565 570 575
Pro Gly Lys
<210> 11
<211> 885
<212> DNA
<213> 人工序列
<400> 11
atcacctgcc cacctcccat gagcgtggag cacgccgaca tctgggtgaa gagctacagc 60
ctgtacagcc gcgagcgcta catctgcaac agcggcttca agcgcaaggc cggcaccagc 120
agcctgaccg agtgcgtgct gaacaaggcc accaacgtgg cccactggac cacccccagc 180
ctgaagtgca tccgcggcgg aggcggatcc ggaggcggag gttccggcgg gggtgggagc 240
ggggacatcc agatgaccca gtctccatcc tccctgtctg catctgtagg agacagagtc 300
accatcactt gccgggcaag tcaggatgtg aataccgcgg tcgcatggta tcagcagaaa 360
ccagggaaag cccctaagct cctgatctat tctgcatcct tcttgtatag tggggtccca 420
tcaaggttca gtggcagtag atctgggaca gatttcactc tcaccatcag cagtctgcaa 480
cctgaagatt ttgcaactta ctactgtcaa cagcattaca ctacccctcc gacgttcggc 540
caaggtacca aggtggagat caaacgaact gtggctgcac catctgtctt catcttcccg 600
ccatctgatg agcagttgaa atctggaact gcctctgtcg tgtgcctgct gaataacttc 660
tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 720
caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 780
acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 840
ggcctgtcct cgcccgtcac aaagagcttc aacaggggag agtgt 885
<210> 12
<211> 295
<212> PRT
<213> 人工序列
<400> 12
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val
1 5 10 15
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly
20 25 30
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn
35 40 45
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile
50 55 60
Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
65 70 75 80
Gly Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val
85 90 95
Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Asn Thr
100 105 110
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
115 120 125
Ile Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser
130 135 140
Gly Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln
145 150 155 160
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Thr Thr Pro
165 170 175
Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala
180 185 190
Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser
195 200 205
Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu
210 215 220
Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser
225 230 235 240
Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu
245 250 255
Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val
260 265 270
Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys
275 280 285
Ser Phe Asn Arg Gly Glu Cys
290 295
<210> 13
<211> 1590
<212> DNA
<213> 人工序列
<400> 13
atcacctgcc cacctcccat gagcgtggag cacgccgaca tctgggtgaa gagctacagc 60
ctgtacagcc gcgagcgcta catctgcaac agcggcttca agcgcaaggc cggcaccagc 120
agcctgaccg agtgcgtgct gaacaaggcc accaacgtgg cccactggac cacccccagc 180
ctgaagtgca tccgcggcgg aggcggatcc ggaggcggag gttccggcgg gggtgggagc 240
ggggaggtgc agctggtgga gtctggagga ggcttggtcc agcctggggg gtccctgaga 300
ctctcctgtg cagcctctgg gttcaatatt aaggacactt acatccactg ggtccgccag 360
gctccaggga aggggctgga gtgggtcgca cgtatttatc ctaccaatgg ttacacacgc 420
tacgcagact ccgtgaaggg ccgattcacc atctccgcag acacttccaa gaacacggcg 480
tatcttcaaa tgaacagcct gagagccgag gacacggccg tgtattactg ttcgagatgg 540
ggcggtgacg gcttctatgc catggactac tggggccaag gaaccctggt caccgtctcc 600
tcagcctcca ccaagggccc atcggtcttc cccctggcac cctcctccaa gagcacctct 660
gggggcacag cggccctggg ctgcctggtc aaggactact tccccgaacc ggtgacggtg 720
tcgtggaact caggcgccct gaccagcggc gtgcacacct tcccggctgt cctacagtcc 780
tcaggactct actccctcag cagcgtggtg actgtgccct ctagcagctt gggcacccag 840
acctacatct gcaacgtgaa tcacaagccc agcaacacca aggtggacaa gaaagttgag 900
cccaaatctt gcgacaaaac tcacacatgc ccaccgtgcc cagcacctcc agtcgccgga 960
ccgtcagtct tcctcttccc tccaaaaccc aaggacaccc tcatgatctc ccggacccct 1020
gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 1080
tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 1140
agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 1200
gagtacaagt gcaaggtctc caacaaaggc ctcccaagct ccatcgagaa aaccatctcc 1260
aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcctccatc ccgggatgag 1320
ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1380
gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1440
ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 1500
cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1560
cagaagagcc tctccctgtc tccgggtaaa 1590
<210> 14
<211> 530
<212> PRT
<213> 人工序列
<400> 14
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val
1 5 10 15
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly
20 25 30
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn
35 40 45
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile
50 55 60
Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
65 70 75 80
Gly Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
85 90 95
Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile Lys Asp
100 105 110
Thr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
115 120 125
Val Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala Asp Ser
130 135 140
Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala
145 150 155 160
Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr
165 170 175
Cys Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly
180 185 190
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
195 200 205
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
210 215 220
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
225 230 235 240
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
245 250 255
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
260 265 270
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
275 280 285
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
290 295 300
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly
305 310 315 320
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
325 330 335
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
340 345 350
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
355 360 365
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
370 375 380
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
385 390 395 400
Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu
405 410 415
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
420 425 430
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
435 440 445
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
450 455 460
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
465 470 475 480
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
485 490 495
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
500 505 510
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
515 520 525
Gly Lys
530
<210> 15
<211> 1032
<212> DNA
<213> 人工序列
<400> 15
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacgacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccgga 360
ggcggaggtt ccggcggggg tgggagcggg gacatccaga tgacccagtc tccatcctcc 420
ctgtctgcat ctgtaggaga cagagtcacc atcacttgcc gggcaagtca ggatgtgaat 480
accgcggtcg catggtatca gcagaaacca gggaaagccc ctaagctcct gatctattct 540
gcatccttct tgtatagtgg ggtcccatca aggttcagtg gcagtagatc tgggacagat 600
ttcactctca ccatcagcag tctgcaacct gaagattttg caacttacta ctgtcaacag 660
cattacacta cccctccgac gttcggccaa ggtaccaagg tggagatcaa acgaactgtg 720
gctgcaccat ctgtcttcat cttcccgcca tctgatgagc agttgaaatc tggaactgcc 780
tctgtcgtgt gcctgctgaa taacttctat cccagagagg ccaaagtaca gtggaaggtg 840
gataacgccc tccaatcggg taactcccag gagagtgtca cagagcagga cagcaaggac 900
agcacctaca gcctcagcag caccctgacg ctgagcaaag cagactacga gaaacacaaa 960
gtctacgcct gcgaagtcac ccatcagggc ctgtcctcgc ccgtcacaaa gagcttcaac 1020
aggggagagt gt 1032
<210> 16
<211> 344
<212> PRT
<213> 人工序列
<400> 16
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser
130 135 140
Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Asn
145 150 155 160
Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu
165 170 175
Leu Ile Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe
180 185 190
Ser Gly Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu
195 200 205
Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Thr Thr
210 215 220
Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val
225 230 235 240
Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys
245 250 255
Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg
260 265 270
Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn
275 280 285
Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser
290 295 300
Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys
305 310 315 320
Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr
325 330 335
Lys Ser Phe Asn Arg Gly Glu Cys
340
<210> 17
<211> 642
<212> DNA
<213> 人工序列
<400> 17
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca ggatgtgaat accgcggtcg catggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctattct gcatccttct tgtatagtgg ggtcccatca 180
aggttcagtg gcagtagatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240
gaagattttg caacttacta ctgtcaacag cattacacta cccctccgac gttcggccaa 300
ggtaccaagg tggagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 360
tctgatgagc agttgaaatc tggaactgcc tctgtcgtgt gcctgctgaa taacttctat 420
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540
ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 600
ctgtcctcgc ccgtcacaaa gagcttcaac aggggagagt gt 642
<210> 18
<211> 450
<212> PRT
<213> 人工序列
<400> 18
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile Lys Asp Thr
20 25 30
Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly Lys
450
<210> 19
<211> 642
<212> DNA
<213> 人工序列
<400> 19
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60
atcacttgcc gggcaagtca ggatgtgaat accgcggtcg catggtatca gcagaaacca 120
gggaaagccc ctaagctcct gatctattct gcatccttct tgtatagtgg ggtcccatca 180
aggttcagtg gcagtagatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240
gaagattttg caacttacta ctgtcaacag cattacacta cccctccgac gttcggccaa 300
ggtaccaagg tggagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 360
tctgatgagc agttgaaatc tggaactgcc tctgtcgtgt gcctgctgaa taacttctat 420
cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480
gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540
ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc 600
ctgtcctcgc ccgtcacaaa gagcttcaac aggggagagt gt 642
<210> 20
<211> 214
<212> PRT
<213> 人工序列
<400> 20
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Asn Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Thr Thr Pro Pro
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 21
<211> 1737
<212> DNA
<213> 人工序列
<400> 21
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacgacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccgga 360
ggcggaggtt ccggcggggg tgggagcggg caggtgcagc tgcaggagag cggccccggc 420
ctggtgaagc ccagcgagac cctgagcctg acctgcaccg tgagcggcgg cagcgtgagc 480
agcggcgact actactggac ctggatccgc cagagccccg gcaagggcct ggagtggatc 540
ggccacatct actacagcgg caacaccaac tacaacccca gcctgaagag ccgcctgacc 600
atcagcatcg acaccagcaa gacccagttc agcctgaagc tgagcagcgt gaccgccgcc 660
gacaccgcca tctactactg cgtgcgcgac cgcgtgaccg gcgccttcga catctggggc 720
cagggcacca tggtgactgt gtctagcgcc tccaccaagg gcccatcggt cttccccctg 780
gcaccctcct ccaagagcac ctctgggggc acagcggccc tgggctgcct ggtcaaggac 840
tacttccccg aaccggtgac ggtgtcgtgg aactcaggcg ccctgaccag cggcgtgcac 900
accttcccgg ctgtcctaca gtcctcagga ctctactccc tcagcagcgt ggtgactgtg 960
ccctctagca gcttgggcac ccagacctac atctgcaacg tgaatcacaa gcccagcaac 1020
accaaggtgg acaagaaagt tgaacccaaa tcttgcgaca aaactcacac atgcccaccg 1080
tgcccagcac ctgaactcct ggggggaccg tcagtcttcc tcttcccccc aaaacccaag 1140
gacaccctca tgatctcccg gacccctgag gtcacatgcg tggtggtgga cgtgagccac 1200
gaagaccctg aggtcaagtt caactggtac gtggacggcg tggaggtgca taatgccaag 1260
acaaagccgc gggaggagca gtacaacagc acgtaccgtg tggtcagcgt cctcaccgtc 1320
ctgcaccagg actggctgaa tggcaaggag tacaagtgca aggtctccaa caaagccctc 1380
ccagccccca tagagaaaac catctccaaa gccaaagggc agccccgaga accacaggtg 1440
tacaccctgc ccccatcccg ggaggagatg accaagaacc aggtcagcct gacctgcctg 1500
gtcaaaggct tctatcccag cgacatcgcc gtggagtggg agagcaatgg gcagccggag 1560
aacaactaca agaccacgcc tcccgtgctg gactccgacg gctccttctt cctctacagc 1620
aagctcaccg tggacaagag caggtggcag caggggaacg tcttctcatg ctccgtgatg 1680
catgaggctc tgcacaacca ctacacgcag aagagcctct ccctgtctcc gggtaaa 1737
<210> 22
<211> 579
<212> PRT
<213> 人工序列
<400> 22
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro
130 135 140
Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser
145 150 155 160
Ser Gly Asp Tyr Tyr Trp Thr Trp Ile Arg Gln Ser Pro Gly Lys Gly
165 170 175
Leu Glu Trp Ile Gly His Ile Tyr Tyr Ser Gly Asn Thr Asn Tyr Asn
180 185 190
Pro Ser Leu Lys Ser Arg Leu Thr Ile Ser Ile Asp Thr Ser Lys Thr
195 200 205
Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Ile
210 215 220
Tyr Tyr Cys Val Arg Asp Arg Val Thr Gly Ala Phe Asp Ile Trp Gly
225 230 235 240
Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
245 250 255
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
260 265 270
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
275 280 285
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
290 295 300
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
305 310 315 320
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
325 330 335
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
340 345 350
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
355 360 365
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
370 375 380
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
385 390 395 400
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
405 410 415
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
420 425 430
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
435 440 445
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
450 455 460
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
465 470 475 480
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
485 490 495
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
500 505 510
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
515 520 525
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
530 535 540
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
545 550 555 560
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
565 570 575
Pro Gly Lys
<210> 23
<211> 885
<212> DNA
<213> 人工序列
<400> 23
atcacctgcc cacctcccat gagcgtggag cacgccgaca tctgggtgaa gagctacagc 60
ctgtacagcc gcgagcgcta catctgcaac agcggcttca agcgcaaggc cggcaccagc 120
agcctgaccg agtgcgtgct gaacaaggcc accaacgtgg cccactggac cacccccagc 180
ctgaagtgca tccgcggcgg aggcggatcc ggaggcggag gttccggcgg gggtgggagc 240
ggggacatcc agatgaccca gagccccagc agcctgagcg ccagcgtggg cgaccgcgtg 300
accatcacct gccaggccag ccaggacatc agcaactacc tgaactggta ccagcagaag 360
cccggcaagg cccccaagct gctgatctac gacgccagca acctggagac cggcgtgccc 420
agccgcttca gcggcagcgg cagcggcacc gacttcacct tcaccatcag cagcctgcag 480
cccgaggaca tcgccaccta cttctgccag cacttcgacc acctgcccct ggccttcggc 540
ggcggcacca aggtggagat caagcgcaca gtggcagccc ccagcgtctt catttttccc 600
ccttccgatg aacagctgaa gtccggcact gcttctgtgg tctgtctgct gaacaatttc 660
tatcccagag aggccaaggt gcagtggaaa gtggacaacg ctctgcagtc cggcaacagc 720
caggagagtg tgaccgaaca ggatagtaag gacagcacat attctctgtc tagtaccctg 780
acactgagta aggcagatta cgagaagcac aaagtgtatg cctgcgaagt cactcatcag 840
ggactgtcaa gccccgtgac caagagcttc aaccggggcg agtgt 885
<210> 24
<211> 295
<212> PRT
<213> 人工序列
<400> 24
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val
1 5 10 15
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly
20 25 30
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn
35 40 45
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile
50 55 60
Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
65 70 75 80
Gly Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val
85 90 95
Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn
100 105 110
Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
115 120 125
Ile Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser
130 135 140
Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln
145 150 155 160
Pro Glu Asp Ile Ala Thr Tyr Phe Cys Gln His Phe Asp His Leu Pro
165 170 175
Leu Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala
180 185 190
Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser
195 200 205
Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu
210 215 220
Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser
225 230 235 240
Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu
245 250 255
Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val
260 265 270
Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys
275 280 285
Ser Phe Asn Arg Gly Glu Cys
290 295
<210> 25
<211> 1590
<212> DNA
<213> 人工序列
<400> 25
atcacctgcc cacctcccat gagcgtggag cacgccgaca tctgggtgaa gagctacagc 60
ctgtacagcc gcgagcgcta catctgcaac agcggcttca agcgcaaggc cggcaccagc 120
agcctgaccg agtgcgtgct gaacaaggcc accaacgtgg cccactggac cacccccagc 180
ctgaagtgca tccgcggcgg aggcggatcc ggaggcggag gttccggcgg gggtgggagc 240
gggcaggtgc agctgcagga gagcggcccc ggcctggtga agcccagcga gaccctgagc 300
ctgacctgca ccgtgagcgg cggcagcgtg agcagcggcg actactactg gacctggatc 360
cgccagagcc ccggcaaggg cctggagtgg atcggccaca tctactacag cggcaacacc 420
aactacaacc ccagcctgaa gagccgcctg accatcagca tcgacaccag caagacccag 480
ttcagcctga agctgagcag cgtgaccgcc gccgacaccg ccatctacta ctgcgtgcgc 540
gaccgcgtga ccggcgcctt cgacatctgg ggccagggca ccatggtgac tgtgtctagc 600
gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 660
ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 720
tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 780
ggactctact ccctcagcag cgtggtgact gtgccctcta gcagcttggg cacccagacc 840
tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgaaccc 900
aaatcttgcg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 960
ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 1020
gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 1080
tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 1140
agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 1200
gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatagagaa aaccatctcc 1260
aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggaggag 1320
atgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1380
gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1440
ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 1500
cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1560
cagaagagcc tctccctgtc tccgggtaaa 1590
<210> 26
<211> 530
<212> PRT
<213> 人工序列
<400> 26
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val
1 5 10 15
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly
20 25 30
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn
35 40 45
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile
50 55 60
Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
65 70 75 80
Gly Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser
85 90 95
Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser
100 105 110
Gly Asp Tyr Tyr Trp Thr Trp Ile Arg Gln Ser Pro Gly Lys Gly Leu
115 120 125
Glu Trp Ile Gly His Ile Tyr Tyr Ser Gly Asn Thr Asn Tyr Asn Pro
130 135 140
Ser Leu Lys Ser Arg Leu Thr Ile Ser Ile Asp Thr Ser Lys Thr Gln
145 150 155 160
Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Ile Tyr
165 170 175
Tyr Cys Val Arg Asp Arg Val Thr Gly Ala Phe Asp Ile Trp Gly Gln
180 185 190
Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
195 200 205
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
210 215 220
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
225 230 235 240
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
245 250 255
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
260 265 270
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
275 280 285
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
290 295 300
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
305 310 315 320
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
325 330 335
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
340 345 350
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
355 360 365
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
370 375 380
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
385 390 395 400
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
405 410 415
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
420 425 430
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
435 440 445
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
450 455 460
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
465 470 475 480
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
485 490 495
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
500 505 510
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
515 520 525
Gly Lys
530
<210> 27
<211> 1032
<212> DNA
<213> 人工序列
<400> 27
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacgacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccgga 360
ggcggaggtt ccggcggggg tgggagcggg gacatccaga tgacccagag ccccagcagc 420
ctgagcgcca gcgtgggcga ccgcgtgacc atcacctgcc aggccagcca ggacatcagc 480
aactacctga actggtacca gcagaagccc ggcaaggccc ccaagctgct gatctacgac 540
gccagcaacc tggagaccgg cgtgcccagc cgcttcagcg gcagcggcag cggcaccgac 600
ttcaccttca ccatcagcag cctgcagccc gaggacatcg ccacctactt ctgccagcac 660
ttcgaccacc tgcccctggc cttcggcggc ggcaccaagg tggagatcaa gcgcacagtg 720
gcagccccca gcgtcttcat ttttccccct tccgatgaac agctgaagtc cggcactgct 780
tctgtggtct gtctgctgaa caatttctat cccagagagg ccaaggtgca gtggaaagtg 840
gacaacgctc tgcagtccgg caacagccag gagagtgtga ccgaacagga tagtaaggac 900
agcacatatt ctctgtctag taccctgaca ctgagtaagg cagattacga gaagcacaaa 960
gtgtatgcct gcgaagtcac tcatcaggga ctgtcaagcc ccgtgaccaa gagcttcaac 1020
cggggcgagt gt 1032
<210> 28
<211> 344
<212> PRT
<213> 人工序列
<400> 28
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser
130 135 140
Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser
145 150 155 160
Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu
165 170 175
Leu Ile Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe
180 185 190
Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu
195 200 205
Gln Pro Glu Asp Ile Ala Thr Tyr Phe Cys Gln His Phe Asp His Leu
210 215 220
Pro Leu Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val
225 230 235 240
Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys
245 250 255
Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg
260 265 270
Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn
275 280 285
Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser
290 295 300
Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys
305 310 315 320
Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr
325 330 335
Lys Ser Phe Asn Arg Gly Glu Cys
340
<210> 29
<211> 1347
<212> DNA
<213> 人工序列
<400> 29
caggtgcagc tgcaggagag cggccccggc ctggtgaagc ccagcgagac cctgagcctg 60
acctgcaccg tgagcggcgg cagcgtgagc agcggcgact actactggac ctggatccgc 120
cagagccccg gcaagggcct ggagtggatc ggccacatct actacagcgg caacaccaac 180
tacaacccca gcctgaagag ccgcctgacc atcagcatcg acaccagcaa gacccagttc 240
agcctgaagc tgagcagcgt gaccgccgcc gacaccgcca tctactactg cgtgcgcgac 300
cgcgtgaccg gcgccttcga catctggggc cagggcacca tggtgactgt gtctagcgcc 360
tccaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420
acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480
aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540
ctctactccc tcagcagcgt ggtgactgtg ccctctagca gcttgggcac ccagacctac 600
atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgaacccaaa 660
tcttgcgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720
tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780
gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 840
gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900
acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960
tacaagtgca aggtctccaa caaagccctc ccagccccca tagagaaaac catctccaaa 1020
gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggaggagatg 1080
accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140
gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200
gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260
caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320
aagagcctct ccctgtctcc gggtaaa 1347
<210> 30
<211> 449
<212> PRT
<213> 人工序列
<400> 30
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser Gly
20 25 30
Asp Tyr Tyr Trp Thr Trp Ile Arg Gln Ser Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly His Ile Tyr Tyr Ser Gly Asn Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Leu Thr Ile Ser Ile Asp Thr Ser Lys Thr Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Ile Tyr Tyr
85 90 95
Cys Val Arg Asp Arg Val Thr Gly Ala Phe Asp Ile Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
260 265 270
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
275 280 285
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
340 345 350
Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr
355 360 365
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
370 375 380
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
385 390 395 400
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
405 410 415
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
420 425 430
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
Lys
<210> 31
<211> 1344
<212> DNA
<213> 人工序列
<400> 31
caggtgcagc tgcaggagag cggccccggc ctggtgaagc ccagcgagac cctgagcctg 60
acctgcaccg tgagcggcgg cagcgtgagc agcggcgact actactggac ctggatccgc 120
cagagccccg gcaagggcct ggagtggatc ggccacatct actacagcgg caacaccaac 180
tacaacccca gcctgaagag ccgcctgacc atcagcatcg acaccagcaa gacccagttc 240
agcctgaagc tgagcagcgt gaccgccgcc gacaccgcca tctactactg cgtgcgcgac 300
cgcgtgaccg gcgccttcga catctggggc cagggcacca tggtgactgt gtctagcgcc 360
tccaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420
acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480
aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540
ctctactccc tcagcagcgt ggtgactgtg ccctctagca gcttgggcac ccagacctac 600
atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgaacccaaa 660
tcttgcgaca aaactcacac atgcccaccg tgcccagcac ctccagtcgc cggaccgtca 720
gtcttcctct tccctccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 780
acatgcgtgg tggtggacgt gagccacgaa gaccctgagg tcaagttcaa ctggtacgtg 840
gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 900
taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 960
aagtgcaagg tctccaacaa aggcctccca agctccatcg agaaaaccat ctccaaagcc 1020
aaagggcagc cccgagaacc acaggtgtac accctgcctc catcccggga tgagctgacc 1080
aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1140
gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1200
tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1260
gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1320
agcctctccc tgtctccggg taaa 1344
<210> 32
<211> 448
<212> PRT
<213> 人工序列
<400> 32
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser Gly
20 25 30
Asp Tyr Tyr Trp Thr Trp Ile Arg Gln Ser Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly His Ile Tyr Tyr Ser Gly Asn Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Leu Thr Ile Ser Ile Asp Thr Ser Lys Thr Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Ile Tyr Tyr
85 90 95
Cys Val Arg Asp Arg Val Thr Gly Ala Phe Asp Ile Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro
260 265 270
Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440 445
<210> 33
<211> 642
<212> DNA
<213> 人工序列
<400> 33
gacatccaga tgacccagag ccccagcagc ctgagcgcca gcgtgggcga ccgcgtgacc 60
atcacctgcc aggccagcca ggacatcagc aactacctga actggtacca gcagaagccc 120
ggcaaggccc ccaagctgct gatctacgac gccagcaacc tggagaccgg cgtgcccagc 180
cgcttcagcg gcagcggcag cggcaccgac ttcaccttca ccatcagcag cctgcagccc 240
gaggacatcg ccacctactt ctgccagcac ttcgaccacc tgcccctggc cttcggcggc 300
ggcaccaagg tggagatcaa gcgcacagtg gcagccccca gcgtcttcat ttttccccct 360
tccgatgaac agctgaagtc cggcactgct tctgtggtct gtctgctgaa caatttctat 420
cccagagagg ccaaggtgca gtggaaagtg gacaacgctc tgcagtccgg caacagccag 480
gagagtgtga ccgaacagga tagtaaggac agcacatatt ctctgtctag taccctgaca 540
ctgagtaagg cagattacga gaagcacaaa gtgtatgcct gcgaagtcac tcatcaggga 600
ctgtcaagcc ccgtgaccaa gagcttcaac cggggcgagt gt 642
<210> 34
<211> 214
<212> PRT
<213> 人工序列
<400> 34
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Phe Cys Gln His Phe Asp His Leu Pro Leu
85 90 95
Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 35
<211> 1341
<212> DNA
<213> 人工序列
<400> 35
gaggtgcagc tggtggagag cggaggtgga ctagtacagc ctggtggcag cctacgactg 60
agttgcgccg ccagcggctt caccttcagc gacagctgga tccactgggt gcgccaggcc 120
cccggcaagg gcctggagtg ggtggcctgg atcagcccct acggcggcag cacctactac 180
gccgacagcg tgaagggccg cttcaccatc agcgccgaca ccagcaagaa caccgcctac 240
ctgcagatga acagcctgcg cgccgaggac accgccgtgt actactgcgc ccgccgccac 300
tggcccggcg gcttcgacta ctggggccag ggcaccctgg tgaccgtgag cagcgcctcc 360
accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca 420
gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 480
tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 540
tactccctca gcagcgtggt gactgtgccc tctagcagct tgggcaccca gacctacatc 600
tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga acccaaatct 660
tgcgacaaaa ctcacacatg cccaccgtgc ccagcacctc cagtcgccgg accgtcagtc 720
ttcctcttcc ctccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 780
tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 840
ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 900
cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 960
tgcaaggtct ccaacaaagg cctcccaagc tccatcgaga aaaccatctc caaagccaaa 1020
gggcagcccc gagaaccaca ggtgtacacc ctgcctccat cccgggatga gctgaccaag 1080
aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag 1140
tgggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1200
gacggctcct tcttcctcta cagcaagctc accgtggaca agagcaggtg gcagcagggg 1260
aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagagc 1320
ctctccctgt ctccgggtaa a 1341
<210> 36
<211> 447
<212> PRT
<213> 人工序列
<400> 36
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Ser
20 25 30
Trp Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Trp Ile Ser Pro Tyr Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg His Trp Pro Gly Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr
210 215 220
His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu
260 265 270
Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440 445
<210> 37
<211> 642
<212> DNA
<213> 人工序列
<400> 37
gacatccaga tgacccagag ccccagcagc ctgagcgcca gcgtgggcga ccgcgtgacc 60
atcacctgcc gcgccagcca ggacgtgagc accgccgtgg cctggtacca gcagaagccc 120
ggcaaggccc ccaagctgct gatctacagc gccagcttcc tgtacagcgg cgtgcccagc 180
cgcttcagcg gcagcggcag cggcaccgac ttcaccctga ccatcagcag cctgcagccc 240
gaggacttcg ccacctacta ctgccagcag tacctgtacc accccgccac cttcggccag 300
ggcaccaagg tggagatcaa gcgcacagtg gcagccccca gcgtcttcat ttttccccct 360
tccgatgaac agctgaagtc cggcactgct tctgtggtct gtctgctgaa caatttctat 420
cccagagagg ccaaggtgca gtggaaagtg gacaacgctc tgcagtccgg caacagccag 480
gagagtgtga ccgaacagga tagtaaggac agcacatatt ctctgtctag taccctgaca 540
ctgagtaagg cagattacga gaagcacaaa gtgtatgcct gcgaagtcac tcatcaggga 600
ctgtcaagcc ccgtgaccaa gagcttcaac cggggcgagt gt 642
<210> 38
<211> 214
<212> PRT
<213> 人工序列
<400> 38
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Ser Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Leu Tyr His Pro Ala
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 39
<211> 1734
<212> DNA
<213> 人工序列
<400> 39
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacgacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccgga 360
ggcggaggtt ccggcggggg tgggagcggg caggtgcagc tgcaggagag cggccccggc 420
ctggtgaagc ccagcgagac cctgagcctg acctgcaccg tgagcggcgg cagcgtgagc 480
agcggcgact actactggac ctggatccgc cagagccccg gcaagggcct ggagtggatc 540
ggccacatct actacagcgg caacaccaac tacaacccca gcctgaagag ccgcctgacc 600
atcagcatcg acaccagcaa gacccagttc agcctgaagc tgagcagcgt gaccgccgcc 660
gacaccgcca tctactactg cgtgcgcgac cgcgtgaccg gcgccttcga catctggggc 720
cagggcacca tggtgactgt gtctagcgcc tccaccaagg gcccatcggt cttccccctg 780
gcaccctcct ccaagagcac ctctgggggc acagcggccc tgggctgcct ggtcaaggac 840
tacttccccg aaccggtgac ggtgtcgtgg aactcaggcg ccctgaccag cggcgtgcac 900
accttcccgg ctgtcctaca gtcctcagga ctctactccc tcagcagcgt ggtgactgtg 960
ccctctagca gcttgggcac ccagacctac atctgcaacg tgaatcacaa gcccagcaac 1020
accaaggtgg acaagaaagt tgaacccaaa tcttgcgaca aaactcacac atgcccaccg 1080
tgcccagcac ctccagtcgc cggaccgtca gtcttcctct tccctccaaa acccaaggac 1140
accctcatga tctcccggac ccctgaggtc acatgcgtgg tggtggacgt gagccacgaa 1200
gaccctgagg tcaagttcaa ctggtacgtg gacggcgtgg aggtgcataa tgccaagaca 1260
aagccgcggg aggagcagta caacagcacg taccgtgtgg tcagcgtcct caccgtcctg 1320
caccaggact ggctgaatgg caaggagtac aagtgcaagg tctccaacaa aggcctccca 1380
agctccatcg agaaaaccat ctccaaagcc aaagggcagc cccgagaacc acaggtgtac 1440
accctgcctc catcccggga tgagctgacc aagaaccagg tcagcctgac ctgcctggtc 1500
aaaggcttct atcccagcga catcgccgtg gagtgggaga gcaatgggca gccggagaac 1560
aactacaaga ccacgcctcc cgtgctggac tccgacggct ccttcttcct ctacagcaag 1620
ctcaccgtgg acaagagcag gtggcagcag gggaacgtct tctcatgctc cgtgatgcat 1680
gaggctctgc acaaccacta cacgcagaag agcctctccc tgtctccggg taaa 1734
<210> 40
<211> 578
<212> PRT
<213> 人工序列
<400> 40
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro
130 135 140
Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser
145 150 155 160
Ser Gly Asp Tyr Tyr Trp Thr Trp Ile Arg Gln Ser Pro Gly Lys Gly
165 170 175
Leu Glu Trp Ile Gly His Ile Tyr Tyr Ser Gly Asn Thr Asn Tyr Asn
180 185 190
Pro Ser Leu Lys Ser Arg Leu Thr Ile Ser Ile Asp Thr Ser Lys Thr
195 200 205
Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Ile
210 215 220
Tyr Tyr Cys Val Arg Asp Arg Val Thr Gly Ala Phe Asp Ile Trp Gly
225 230 235 240
Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
245 250 255
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
260 265 270
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
275 280 285
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
290 295 300
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
305 310 315 320
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
325 330 335
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
340 345 350
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly
355 360 365
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
370 375 380
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
385 390 395 400
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
405 410 415
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
420 425 430
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
435 440 445
Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu
450 455 460
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
465 470 475 480
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
485 490 495
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
500 505 510
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
515 520 525
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
530 535 540
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
545 550 555 560
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
565 570 575
Gly Lys
<210> 41
<211> 1569
<212> DNA
<213> 人工序列
<400> 41
atcacctgcc cacctcccat gagcgtggag cacgccgaca tctgggtgaa gagctacagc 60
ctgtacagcc gcgagcgcta catctgcaac agcggcttca agcgcaaggc cggcaccagc 120
agcctgaccg agtgcgtgct gaacaaggcc accaacgtgg cccactggac cacccccagc 180
ctgaagtgca tccgcggcgg aggcggatcc ggaggcggag gttccggcgg gggtgggagc 240
gggcaggtgc agctggtgga gagtggaggt ggcgtggtac agcccggccg cagcctgcgc 300
ctggactgca aggccagcgg catcaccttc agcaacagcg gcatgcactg ggtgcgccag 360
gcccccggca agggcctgga gtgggtggcc gtgatctggt acgacggcag caagcgctac 420
tacgccgaca gcgtgaaggg ccgcttcacc atcagccgcg acaacagcaa gaacaccctg 480
ttcctgcaga tgaacagcct gcgcgccgag gacaccgccg tgtactactg cgccaccaac 540
gacgactact ggggccaggg caccctggtg accgtgagca gcgcctccac caagggccca 600
tcggtcttcc ccctggcacc ctcctccaag agcacctctg ggggcacagc ggccctgggc 660
tgcctggtca aggactactt ccccgaaccg gtgacggtgt cgtggaactc aggcgccctg 720
accagcggcg tgcacacctt cccggctgtc ctacagtcct caggactcta ctccctcagc 780
agcgtggtga ctgtgccctc tagcagcttg ggcacccaga cctacatctg caacgtgaat 840
cacaagccca gcaacaccaa ggtggacaag aaagttgaac ccaaatcttg cgacaaaact 900
cacacatgcc caccgtgccc agcacctcca gtcgccggac cgtcagtctt cctcttccct 960
ccaaaaccca aggacaccct catgatctcc cggacccctg aggtcacatg cgtggtggtg 1020
gacgtgagcc acgaagaccc tgaggtcaag ttcaactggt acgtggacgg cgtggaggtg 1080
cataatgcca agacaaagcc gcgggaggag cagtacaaca gcacgtaccg tgtggtcagc 1140
gtcctcaccg tcctgcacca ggactggctg aatggcaagg agtacaagtg caaggtctcc 1200
aacaaaggcc tcccaagctc catcgagaaa accatctcca aagccaaagg gcagccccga 1260
gaaccacagg tgtacaccct gcctccatcc cgggatgagc tgaccaagaa ccaggtcagc 1320
ctgacctgcc tggtcaaagg cttctatccc agcgacatcg ccgtggagtg ggagagcaat 1380
gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc 1440
ttcctctaca gcaagctcac cgtggacaag agcaggtggc agcaggggaa cgtcttctca 1500
tgctccgtga tgcatgaggc tctgcacaac cactacacgc agaagagcct ctccctgtct 1560
ccgggtaaa 1569
<210> 42
<211> 523
<212> PRT
<213> 人工序列
<400> 42
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val
1 5 10 15
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly
20 25 30
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn
35 40 45
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile
50 55 60
Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
65 70 75 80
Gly Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly
85 90 95
Arg Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn
100 105 110
Ser Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
115 120 125
Val Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala Asp Ser
130 135 140
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
145 150 155 160
Phe Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr
165 170 175
Cys Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
180 185 190
Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser
195 200 205
Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys
210 215 220
Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu
225 230 235 240
Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu
245 250 255
Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr
260 265 270
Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val
275 280 285
Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro
290 295 300
Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro
305 310 315 320
Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr
325 330 335
Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn
340 345 350
Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg
355 360 365
Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val
370 375 380
Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser
385 390 395 400
Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys
405 410 415
Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp
420 425 430
Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
435 440 445
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
450 455 460
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe
465 470 475 480
Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly
485 490 495
Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr
500 505 510
Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
515 520
<210> 43
<211> 1587
<212> DNA
<213> 人工序列
<400> 43
atcacctgcc cacctcccat gagcgtggag cacgccgaca tctgggtgaa gagctacagc 60
ctgtacagcc gcgagcgcta catctgcaac agcggcttca agcgcaaggc cggcaccagc 120
agcctgaccg agtgcgtgct gaacaaggcc accaacgtgg cccactggac cacccccagc 180
ctgaagtgca tccgcggcgg aggcggatcc ggaggcggag gttccggcgg gggtgggagc 240
gggcaggtgc agctgcagga gagcggcccc ggcctggtga agcccagcga gaccctgagc 300
ctgacctgca ccgtgagcgg cggcagcgtg agcagcggcg actactactg gacctggatc 360
cgccagagcc ccggcaaggg cctggagtgg atcggccaca tctactacag cggcaacacc 420
aactacaacc ccagcctgaa gagccgcctg accatcagca tcgacaccag caagacccag 480
ttcagcctga agctgagcag cgtgaccgcc gccgacaccg ccatctacta ctgcgtgcgc 540
gaccgcgtga ccggcgcctt cgacatctgg ggccagggca ccatggtgac tgtgtctagc 600
gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 660
ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 720
tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 780
ggactctact ccctcagcag cgtggtgact gtgccctcta gcagcttggg cacccagacc 840
tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgaaccc 900
aaatcttgcg acaaaactca cacatgccca ccgtgcccag cacctccagt cgccggaccg 960
tcagtcttcc tcttccctcc aaaacccaag gacaccctca tgatctcccg gacccctgag 1020
gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 1080
gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 1140
acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 1200
tacaagtgca aggtctccaa caaaggcctc ccaagctcca tcgagaaaac catctccaaa 1260
gccaaagggc agccccgaga accacaggtg tacaccctgc ctccatcccg ggatgagctg 1320
accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1380
gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1440
gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1500
caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1560
aagagcctct ccctgtctcc gggtaaa 1587
<210> 44
<211> 529
<212> PRT
<213> 人工序列
<400> 44
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val
1 5 10 15
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly
20 25 30
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn
35 40 45
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile
50 55 60
Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
65 70 75 80
Gly Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser
85 90 95
Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser
100 105 110
Gly Asp Tyr Tyr Trp Thr Trp Ile Arg Gln Ser Pro Gly Lys Gly Leu
115 120 125
Glu Trp Ile Gly His Ile Tyr Tyr Ser Gly Asn Thr Asn Tyr Asn Pro
130 135 140
Ser Leu Lys Ser Arg Leu Thr Ile Ser Ile Asp Thr Ser Lys Thr Gln
145 150 155 160
Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Ile Tyr
165 170 175
Tyr Cys Val Arg Asp Arg Val Thr Gly Ala Phe Asp Ile Trp Gly Gln
180 185 190
Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
195 200 205
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
210 215 220
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
225 230 235 240
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
245 250 255
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
260 265 270
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
275 280 285
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
290 295 300
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
305 310 315 320
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
325 330 335
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
340 345 350
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
355 360 365
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
370 375 380
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
385 390 395 400
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys
405 410 415
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
420 425 430
Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr
435 440 445
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
450 455 460
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
465 470 475 480
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
485 490 495
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
500 505 510
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
515 520 525
Lys
<210> 45
<211> 1731
<212> DNA
<213> 人工序列
<400> 45
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacgacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccgga 360
ggcggaggtt ccggcggggg tgggagcggg gaggtgcagc tggtggagag cggaggtgga 420
ctagtacagc ctggtggcag cctacgactg agttgcgccg ccagcggctt caccttcagc 480
gacagctgga tccactgggt gcgccaggcc cccggcaagg gcctggagtg ggtggcctgg 540
atcagcccct acggcggcag cacctactac gccgacagcg tgaagggccg cttcaccatc 600
agcgccgaca ccagcaagaa caccgcctac ctgcagatga acagcctgcg cgccgaggac 660
accgccgtgt actactgcgc ccgccgccac tggcccggcg gcttcgacta ctggggccag 720
ggcaccctgg tgaccgtgag cagcgcctcc accaagggcc catcggtctt ccccctggca 780
ccctcctcca agagcacctc tgggggcaca gcggccctgg gctgcctggt caaggactac 840
ttccccgaac cggtgacggt gtcgtggaac tcaggcgccc tgaccagcgg cgtgcacacc 900
ttcccggctg tcctacagtc ctcaggactc tactccctca gcagcgtggt gactgtgccc 960
tctagcagct tgggcaccca gacctacatc tgcaacgtga atcacaagcc cagcaacacc 1020
aaggtggaca agaaagttga acccaaatct tgcgacaaaa ctcacacatg cccaccgtgc 1080
ccagcacctc cagtcgccgg accgtcagtc ttcctcttcc ctccaaaacc caaggacacc 1140
ctcatgatct cccggacccc tgaggtcaca tgcgtggtgg tggacgtgag ccacgaagac 1200
cctgaggtca agttcaactg gtacgtggac ggcgtggagg tgcataatgc caagacaaag 1260
ccgcgggagg agcagtacaa cagcacgtac cgtgtggtca gcgtcctcac cgtcctgcac 1320
caggactggc tgaatggcaa ggagtacaag tgcaaggtct ccaacaaagg cctcccaagc 1380
tccatcgaga aaaccatctc caaagccaaa gggcagcccc gagaaccaca ggtgtacacc 1440
ctgcctccat cccgggatga gctgaccaag aaccaggtca gcctgacctg cctggtcaaa 1500
ggcttctatc ccagcgacat cgccgtggag tgggagagca atgggcagcc ggagaacaac 1560
tacaagacca cgcctcccgt gctggactcc gacggctcct tcttcctcta cagcaagctc 1620
accgtggaca agagcaggtg gcagcagggg aacgtcttct catgctccgt gatgcatgag 1680
gctctgcaca accactacac gcagaagagc ctctccctgt ctccgggtaa a 1731
<210> 46
<211> 577
<212> PRT
<213> 人工序列
<400> 46
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
145 150 155 160
Asp Ser Trp Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Trp Ile Ser Pro Tyr Gly Gly Ser Thr Tyr Tyr Ala Asp
180 185 190
Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr
195 200 205
Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
210 215 220
Tyr Cys Ala Arg Arg His Trp Pro Gly Gly Phe Asp Tyr Trp Gly Gln
225 230 235 240
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
245 250 255
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
260 265 270
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
275 280 285
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
290 295 300
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
305 310 315 320
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
325 330 335
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
340 345 350
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
355 360 365
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
370 375 380
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
385 390 395 400
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
405 410 415
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
420 425 430
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
435 440 445
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys
450 455 460
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
465 470 475 480
Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr
485 490 495
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
500 505 510
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
515 520 525
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
530 535 540
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
545 550 555 560
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
565 570 575
Lys
<210> 47
<211> 885
<212> DNA
<213> 人工序列
<400> 47
atcacctgcc cacctcccat gagcgtggag cacgccgaca tctgggtgaa gagctacagc 60
ctgtacagcc gcgagcgcta catctgcaac agcggcttca agcgcaaggc cggcaccagc 120
agcctgaccg agtgcgtgct gaacaaggcc accaacgtgg cccactggac cacccccagc 180
ctgaagtgca tccgcggcgg aggcggatcc ggaggcggag gttccggcgg gggtgggagc 240
ggggacatcc agatgaccca gagccccagc agcctgagcg ccagcgtggg cgaccgcgtg 300
accatcacct gccgcgccag ccaggacgtg agcaccgccg tggcctggta ccagcagaag 360
cccggcaagg cccccaagct gctgatctac agcgccagct tcctgtacag cggcgtgccc 420
agccgcttca gcggcagcgg cagcggcacc gacttcaccc tgaccatcag cagcctgcag 480
cccgaggact tcgccaccta ctactgccag cagtacctgt accaccccgc caccttcggc 540
cagggcacca aggtggagat caagcgcaca gtggcagccc ccagcgtctt catttttccc 600
ccttccgatg aacagctgaa gtccggcact gcttctgtgg tctgtctgct gaacaatttc 660
tatcccagag aggccaaggt gcagtggaaa gtggacaacg ctctgcagtc cggcaacagc 720
caggagagtg tgaccgaaca ggatagtaag gacagcacat attctctgtc tagtaccctg 780
acactgagta aggcagatta cgagaagcac aaagtgtatg cctgcgaagt cactcatcag 840
ggactgtcaa gccccgtgac caagagcttc aaccggggcg agtgt 885
<210> 48
<211> 295
<212> PRT
<213> 人工序列
<400> 48
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val
1 5 10 15
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly
20 25 30
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn
35 40 45
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile
50 55 60
Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
65 70 75 80
Gly Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val
85 90 95
Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Ser Thr
100 105 110
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
115 120 125
Ile Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser
130 135 140
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln
145 150 155 160
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Leu Tyr His Pro
165 170 175
Ala Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala
180 185 190
Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser
195 200 205
Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu
210 215 220
Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser
225 230 235 240
Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu
245 250 255
Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val
260 265 270
Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys
275 280 285
Ser Phe Asn Arg Gly Glu Cys
290 295
<210> 49
<211> 1584
<212> DNA
<213> 人工序列
<400> 49
atcacctgcc cacctcccat gagcgtggag cacgccgaca tctgggtgaa gagctacagc 60
ctgtacagcc gcgagcgcta catctgcaac agcggcttca agcgcaaggc cggcaccagc 120
agcctgaccg agtgcgtgct gaacaaggcc accaacgtgg cccactggac cacccccagc 180
ctgaagtgca tccgcggcgg aggcggatcc ggaggcggag gttccggcgg gggtgggagc 240
ggggaggtgc agctggtgga gagcggaggt ggactagtac agcctggtgg cagcctacga 300
ctgagttgcg ccgccagcgg cttcaccttc agcgacagct ggatccactg ggtgcgccag 360
gcccccggca agggcctgga gtgggtggcc tggatcagcc cctacggcgg cagcacctac 420
tacgccgaca gcgtgaaggg ccgcttcacc atcagcgccg acaccagcaa gaacaccgcc 480
tacctgcaga tgaacagcct gcgcgccgag gacaccgccg tgtactactg cgcccgccgc 540
cactggcccg gcggcttcga ctactggggc cagggcaccc tggtgaccgt gagcagcgcc 600
tccaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 660
acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 720
aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 780
ctctactccc tcagcagcgt ggtgactgtg ccctctagca gcttgggcac ccagacctac 840
atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgaacccaaa 900
tcttgcgaca aaactcacac atgcccaccg tgcccagcac ctccagtcgc cggaccgtca 960
gtcttcctct tccctccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 1020
acatgcgtgg tggtggacgt gagccacgaa gaccctgagg tcaagttcaa ctggtacgtg 1080
gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 1140
taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 1200
aagtgcaagg tctccaacaa aggcctccca agctccatcg agaaaaccat ctccaaagcc 1260
aaagggcagc cccgagaacc acaggtgtac accctgcctc catcccggga tgagctgacc 1320
aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1380
gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1440
tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1500
gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1560
agcctctccc tgtctccggg taaa 1584
<210> 50
<211> 528
<212> PRT
<213> 人工序列
<400> 50
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val
1 5 10 15
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly
20 25 30
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn
35 40 45
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile
50 55 60
Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
65 70 75 80
Gly Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
85 90 95
Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp
100 105 110
Ser Trp Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
115 120 125
Val Ala Trp Ile Ser Pro Tyr Gly Gly Ser Thr Tyr Tyr Ala Asp Ser
130 135 140
Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala
145 150 155 160
Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr
165 170 175
Cys Ala Arg Arg His Trp Pro Gly Gly Phe Asp Tyr Trp Gly Gln Gly
180 185 190
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
195 200 205
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
210 215 220
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
225 230 235 240
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
245 250 255
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
260 265 270
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
275 280 285
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
290 295 300
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser
305 310 315 320
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
325 330 335
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro
340 345 350
Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
355 360 365
Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val
370 375 380
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
385 390 395 400
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
405 410 415
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
420 425 430
Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys
435 440 445
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
450 455 460
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
465 470 475 480
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
485 490 495
Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
500 505 510
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
515 520 525
<210> 51
<211> 1032
<212> DNA
<213> 人工序列
<400> 51
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacgacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccgga 360
ggcggaggtt ccggcggggg tgggagcggg gacatccaga tgacccagag ccccagcagc 420
ctgagcgcca gcgtgggcga ccgcgtgacc atcacctgcc gcgccagcca ggacgtgagc 480
accgccgtgg cctggtacca gcagaagccc ggcaaggccc ccaagctgct gatctacagc 540
gccagcttcc tgtacagcgg cgtgcccagc cgcttcagcg gcagcggcag cggcaccgac 600
ttcaccctga ccatcagcag cctgcagccc gaggacttcg ccacctacta ctgccagcag 660
tacctgtacc accccgccac cttcggccag ggcaccaagg tggagatcaa gcgcacagtg 720
gcagccccca gcgtcttcat ttttccccct tccgatgaac agctgaagtc cggcactgct 780
tctgtggtct gtctgctgaa caatttctat cccagagagg ccaaggtgca gtggaaagtg 840
gacaacgctc tgcagtccgg caacagccag gagagtgtga ccgaacagga tagtaaggac 900
agcacatatt ctctgtctag taccctgaca ctgagtaagg cagattacga gaagcacaaa 960
gtgtatgcct gcgaagtcac tcatcaggga ctgtcaagcc ccgtgaccaa gagcttcaac 1020
cggggcgagt gt 1032
<210> 52
<211> 344
<212> PRT
<213> 人工序列
<400> 52
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser
130 135 140
Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Ser
145 150 155 160
Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu
165 170 175
Leu Ile Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe
180 185 190
Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu
195 200 205
Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Leu Tyr His
210 215 220
Pro Ala Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val
225 230 235 240
Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys
245 250 255
Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg
260 265 270
Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn
275 280 285
Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser
290 295 300
Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys
305 310 315 320
Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr
325 330 335
Lys Ser Phe Asn Arg Gly Glu Cys
340
<210> 53
<211> 1350
<212> DNA
<213> 人工序列
<400> 53
caggtgaccc tgcgcgagtc cggccctgca ctggtgaagc ccacccagac cctgaccctg 60
acctgcacct tctccggctt ctccctgtcc acctccggca tgtccgtggg ctggatccgg 120
cagcctcccg gcaaggccct ggagtggctg gctgacatct ggtgggacga caagaaggac 180
tacaacccct ccctgaagtc ccgcctgacc atctccaagg acacctccaa gaaccaggtg 240
gtgctgaagg tgaccaacat ggaccccgcc gacaccgcca cctactactg cgcccgctca 300
atgattacca actggtactt cgacgtgtgg ggagccggta ccaccgtgac cgtgtcttcc 360
gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420
ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480
tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540
ggactctact ccctcagcag cgtggtgact gtgccctcta gcagcttggg cacccagacc 600
tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgaaccc 660
aaatcttgcg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 720
ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 780
gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840
tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 900
agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960
gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1020
aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag 1080
ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1140
gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1200
ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 1260
cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1320
cagaagagcc tctccctgtc tccgggtaaa 1350
<210> 54
<211> 450
<212> PRT
<213> 人工序列
<400> 54
Gln Val Thr Leu Arg Glu Ser Gly Pro Ala Leu Val Lys Pro Thr Gln
1 5 10 15
Thr Leu Thr Leu Thr Cys Thr Phe Ser Gly Phe Ser Leu Ser Thr Ser
20 25 30
Gly Met Ser Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Ala Leu Glu
35 40 45
Trp Leu Ala Asp Ile Trp Trp Asp Asp Lys Lys Asp Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Lys Asn Gln Val
65 70 75 80
Val Leu Lys Val Thr Asn Met Asp Pro Ala Asp Thr Ala Thr Tyr Tyr
85 90 95
Cys Ala Arg Ser Met Ile Thr Asn Trp Tyr Phe Asp Val Trp Gly Ala
100 105 110
Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly Lys
450
<210> 55
<211> 639
<212> DNA
<213> 人工序列
<400> 55
gacatccaga tgacccagtc cccctccacc ctgtccgcct ccgtgggcga ccgcgtgacc 60
atcacctgca agtgccagct gtccgtgggc tacatgcact ggtaccagca gaagcccggc 120
aaggccccca agctgctgat ctacgacacc tccaagctgg cctccggcgt gccctcccgc 180
ttctccggct ccggctccgg caccgagttc accctgacca tctcctccct gcagcccgac 240
gacttcgcca cctactactg cttccagggc tccggctacc ccttcacctt cggcggcggc 300
accaagctgg agatcaaacg aactgtggct gcaccatctg tcttcatctt cccgccatct 360
gatgagcagt tgaaatctgg aactgcctct gtcgtgtgcc tgctgaataa cttctatccc 420
agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 480
agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 540
agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 600
tcctcgcccg tcacaaagag cttcaacagg ggagagtgt 639
<210> 56
<211> 213
<212> PRT
<213> 人工序列
<400> 56
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Cys Gln Leu Ser Val Gly Tyr Met
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr
35 40 45
Asp Thr Ser Lys Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Asp
65 70 75 80
Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Gly Tyr Pro Phe Thr
85 90 95
Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala Pro
100 105 110
Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr
115 120 125
Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys
130 135 140
Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu
145 150 155 160
Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala
180 185 190
Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe
195 200 205
Asn Arg Gly Glu Cys
210
<210> 57
<211> 1032
<212> DNA
<213> 人工序列
<400> 57
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacgacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccgga 360
ggcggaggtt ccggcggggg tgggagcggg gagatcgtgc tgacccagag ccccgccacc 420
ctgagcctga gccccggcga gcgcgccacc ctgagctgcc gcgccagcca gagcgtgagc 480
agctacctgg cctggtacca gcagaagcca ggacaggctc cacgactgct aatctatgac 540
gccagcaacc gcgccaccgg catccccgcc cgcttcagcg gcagcggcag cggcaccgac 600
ttcaccctga ccatcagcag cctggagccc gaggacttcg ccgtgtacta ctgccagcag 660
agcagcaact ggccccgcac cttcggccag ggcaccaagg tggagatcaa gcgcacagtg 720
gcagccccca gcgtcttcat ttttccccct tccgatgaac agctgaagtc cggcactgct 780
tctgtggtct gtctgctgaa caatttctat cccagagagg ccaaggtgca gtggaaagtg 840
gacaacgctc tgcagtccgg caacagccag gagagtgtga ccgaacagga tagtaaggac 900
agcacatatt ctctgtctag taccctgaca ctgagtaagg cagattacga gaagcacaaa 960
gtgtatgcct gcgaagtcac tcatcaggga ctgtcaagcc ccgtgaccaa gagcttcaac 1020
cggggcgagt gt 1032
<210> 58
<211> 344
<212> PRT
<213> 人工序列
<400> 58
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser
130 135 140
Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser
145 150 155 160
Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu
165 170 175
Leu Ile Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe
180 185 190
Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu
195 200 205
Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Ser Asn Trp
210 215 220
Pro Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val
225 230 235 240
Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys
245 250 255
Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg
260 265 270
Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn
275 280 285
Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser
290 295 300
Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys
305 310 315 320
Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr
325 330 335
Lys Ser Phe Asn Arg Gly Glu Cys
340
<210> 59
<211> 1740
<212> DNA
<213> 人工序列
<400> 59
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacgacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccgga 360
ggcggaggtt ccggcggggg tgggagcggg gaagtacagc tgcttgagag tggaggaggt 420
ttggtacagc ccggcggatc cctccgcctg tcctgtgcgg ctagtggctt tacattctca 480
tcctatatca tgatgtgggt aagacaggcc ccaggaaagg gcctggagtg ggttagttct 540
atctacccct caggcgggat taccttctac gcagatactg tgaagggcag gtttaccata 600
tcccgagaca acagtaagaa taccctttac cttcaaatga actcccttcg ggccgaggac 660
actgcggtgt actattgcgc tcgcattaag cttggcaccg tgacaaccgt gaactattgg 720
ggtcaaggca cgctggtgac tgtctcttcc gcctccacca agggcccatc ggtcttcccc 780
ctggcaccct cctccaagag cacctctggg ggcacagcgg ccctgggctg cctggtcaag 840
gactacttcc ccgaaccggt gacggtgtcg tggaactcag gcgccctgac cagcggcgtg 900
cacaccttcc cggctgtcct acagtcctca ggactctact ccctcagcag cgtggtgact 960
gtgccctcta gcagcttggg cacccagacc tacatctgca acgtgaatca caagcccagc 1020
aacaccaagg tggacaagaa agttgaaccc aaatcttgcg acaaaactca cacatgccca 1080
ccgtgcccag cacctgaact cctgggggga ccgtcagtct tcctcttccc cccaaaaccc 1140
aaggacaccc tcatgatctc ccggacccct gaggtcacat gcgtggtggt ggacgtgagc 1200
cacgaagacc ctgaggtcaa gttcaactgg tacgtggacg gcgtggaggt gcataatgcc 1260
aagacaaagc cgcgggagga gcagtacaac agcacgtacc gtgtggtcag cgtcctcacc 1320
gtcctgcacc aggactggct gaatggcaag gagtacaagt gcaaggtctc caacaaagcc 1380
ctcccagccc ccatagagaa aaccatctcc aaagccaaag ggcagccccg agaaccacag 1440
gtgtacaccc tgcccccatc ccgggatgag ctgaccaaga accaggtcag cctgacctgc 1500
ctggtcaaag gcttctatcc cagcgacatc gccgtggagt gggagagcaa tgggcagccg 1560
gagaacaact acaagaccac gcctcccgtg ctggactccg acggctcctt cttcctctac 1620
agcaagctca ccgtggacaa gagcaggtgg cagcagggga acgtcttctc atgctccgtg 1680
atgcatgagg ctctgcacaa ccactacacg cagaagagcc tctccctgtc tccgggtaaa 1740
<210> 60
<211> 580
<212> PRT
<213> 人工序列
<400> 60
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
145 150 155 160
Ser Tyr Ile Met Met Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ser Ser Ile Tyr Pro Ser Gly Gly Ile Thr Phe Tyr Ala Asp
180 185 190
Thr Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
195 200 205
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
210 215 220
Tyr Cys Ala Arg Ile Lys Leu Gly Thr Val Thr Thr Val Asn Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
245 250 255
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
260 265 270
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
275 280 285
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
290 295 300
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
305 310 315 320
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
325 330 335
His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser
340 345 350
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu
355 360 365
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
370 375 380
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
385 390 395 400
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
405 410 415
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
420 425 430
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
435 440 445
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
450 455 460
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
465 470 475 480
Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val
485 490 495
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
500 505 510
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
515 520 525
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
530 535 540
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
545 550 555 560
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
565 570 575
Ser Pro Gly Lys
580
<210> 61
<211> 891
<212> DNA
<213> 人工序列
<400> 61
atcacctgcc cacctcccat gagcgtggag cacgccgaca tctgggtgaa gagctacagc 60
ctgtacagcc gcgagcgcta catctgcaac agcggcttca agcgcaaggc cggcaccagc 120
agcctgaccg agtgcgtgct gaacaaggcc accaacgtgg cccactggac cacccccagc 180
ctgaagtgca tccgcggcgg aggcggatcc ggaggcggag gttccggcgg gggtgggagc 240
gggcaatccg cactgactca accagccagc gttagcggct cccctggtca atctatcacc 300
atcagctgta ccgggaccag ctcagacgtt ggcggttaca actacgtcag ctggtaccag 360
cagcacccgg gtaaagctcc aaagctgatg atttatgatg tgtctaatcg accttctggt 420
gtatctaacc gattttcagg ctctaaaagt ggaaatactg cttccctcac gatctcaggg 480
ctgcaagccg aagacgaagc cgattattat tgttctagct atacatccag cagcacccgc 540
gtgtttggaa cgggaaccaa ggtcacggtt ctgggacagc ccaaagccaa tcctaccgtc 600
actctgttcc cacccagtag tgaggagctg caggcaaata aggctaccct ggtctgtctt 660
atatccgatt tctatcccgg ggcagtcaca gtcgcttgga aggcagatgg ctctccagtg 720
aaggccggcg tcgaaacaac taaaccttcc aagcagtcta ataacaagta cgctgcttct 780
tcttaccttt cacttactcc tgaacaatgg aagagccaca ggagttactc ttgtcaggta 840
acccacgagg ggtccactgt ggagaaaacc gtcgctccca cagagtgttc t 891
<210> 62
<211> 297
<212> PRT
<213> 人工序列
<400> 62
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val
1 5 10 15
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly
20 25 30
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn
35 40 45
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile
50 55 60
Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
65 70 75 80
Gly Gln Ser Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly
85 90 95
Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly
100 105 110
Tyr Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys
115 120 125
Leu Met Ile Tyr Asp Val Ser Asn Arg Pro Ser Gly Val Ser Asn Arg
130 135 140
Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly
145 150 155 160
Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Thr Ser
165 170 175
Ser Ser Thr Arg Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly
180 185 190
Gln Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Pro Ser Ser Glu
195 200 205
Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe
210 215 220
Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val
225 230 235 240
Lys Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys
245 250 255
Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser
260 265 270
His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu
275 280 285
Lys Thr Val Ala Pro Thr Glu Cys Ser
290 295
<210> 63
<211> 1593
<212> DNA
<213> 人工序列
<400> 63
atcacctgcc cacctcccat gagcgtggag cacgccgaca tctgggtgaa gagctacagc 60
ctgtacagcc gcgagcgcta catctgcaac agcggcttca agcgcaaggc cggcaccagc 120
agcctgaccg agtgcgtgct gaacaaggcc accaacgtgg cccactggac cacccccagc 180
ctgaagtgca tccgcggcgg aggcggatcc ggaggcggag gttccggcgg gggtgggagc 240
ggggaagtac agctgcttga gagtggagga ggtttggtac agcccggcgg atccctccgc 300
ctgtcctgtg cggctagtgg ctttacattc tcatcctata tcatgatgtg ggtaagacag 360
gccccaggaa agggcctgga gtgggttagt tctatctacc cctcaggcgg gattaccttc 420
tacgcagata ctgtgaaggg caggtttacc atatcccgag acaacagtaa gaataccctt 480
taccttcaaa tgaactccct tcgggccgag gacactgcgg tgtactattg cgctcgcatt 540
aagcttggca ccgtgacaac cgtgaactat tggggtcaag gcacgctggt gactgtctct 600
tccgcctcca ccaagggccc atcggtcttc cccctggcac cctcctccaa gagcacctct 660
gggggcacag cggccctggg ctgcctggtc aaggactact tccccgaacc ggtgacggtg 720
tcgtggaact caggcgccct gaccagcggc gtgcacacct tcccggctgt cctacagtcc 780
tcaggactct actccctcag cagcgtggtg actgtgccct ctagcagctt gggcacccag 840
acctacatct gcaacgtgaa tcacaagccc agcaacacca aggtggacaa gaaagttgaa 900
cccaaatctt gcgacaaaac tcacacatgc ccaccgtgcc cagcacctga actcctgggg 960
ggaccgtcag tcttcctctt ccccccaaaa cccaaggaca ccctcatgat ctcccggacc 1020
cctgaggtca catgcgtggt ggtggacgtg agccacgaag accctgaggt caagttcaac 1080
tggtacgtgg acggcgtgga ggtgcataat gccaagacaa agccgcggga ggagcagtac 1140
aacagcacgt accgtgtggt cagcgtcctc accgtcctgc accaggactg gctgaatggc 1200
aaggagtaca agtgcaaggt ctccaacaaa gccctcccag cccccataga gaaaaccatc 1260
tccaaagcca aagggcagcc ccgagaacca caggtgtaca ccctgccccc atcccgggat 1320
gagctgacca agaaccaggt cagcctgacc tgcctggtca aaggcttcta tcccagcgac 1380
atcgccgtgg agtgggagag caatgggcag ccggagaaca actacaagac cacgcctccc 1440
gtgctggact ccgacggctc cttcttcctc tacagcaagc tcaccgtgga caagagcagg 1500
tggcagcagg ggaacgtctt ctcatgctcc gtgatgcatg aggctctgca caaccactac 1560
acgcagaaga gcctctccct gtctccgggt aaa 1593
<210> 64
<211> 531
<212> PRT
<213> 人工序列
<400> 64
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val
1 5 10 15
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly
20 25 30
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn
35 40 45
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile
50 55 60
Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
65 70 75 80
Gly Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
85 90 95
Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser
100 105 110
Tyr Ile Met Met Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
115 120 125
Val Ser Ser Ile Tyr Pro Ser Gly Gly Ile Thr Phe Tyr Ala Asp Thr
130 135 140
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
145 150 155 160
Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr
165 170 175
Cys Ala Arg Ile Lys Leu Gly Thr Val Thr Thr Val Asn Tyr Trp Gly
180 185 190
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
195 200 205
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
210 215 220
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
225 230 235 240
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
245 250 255
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
260 265 270
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
275 280 285
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
290 295 300
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
305 310 315 320
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
325 330 335
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
340 345 350
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
355 360 365
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
370 375 380
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
385 390 395 400
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
405 410 415
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
420 425 430
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
435 440 445
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
450 455 460
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
465 470 475 480
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
485 490 495
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
500 505 510
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
515 520 525
Pro Gly Lys
530
<210> 65
<211> 1038
<212> DNA
<213> 人工序列
<400> 65
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacgacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccgga 360
ggcggaggtt ccggcggggg tgggagcggg caatccgcac tgactcaacc agccagcgtt 420
agcggctccc ctggtcaatc tatcaccatc agctgtaccg ggaccagctc agacgttggc 480
ggttacaact acgtcagctg gtaccagcag cacccgggta aagctccaaa gctgatgatt 540
tatgatgtgt ctaatcgacc ttctggtgta tctaaccgat tttcaggctc taaaagtgga 600
aatactgctt ccctcacgat ctcagggctg caagccgaag acgaagccga ttattattgt 660
tctagctata catccagcag cacccgcgtg tttggaacgg gaaccaaggt cacggttctg 720
ggacagccca aagccaatcc taccgtcact ctgttcccac ccagtagtga ggagctgcag 780
gcaaataagg ctaccctggt ctgtcttata tccgatttct atcccggggc agtcacagtc 840
gcttggaagg cagatggctc tccagtgaag gccggcgtcg aaacaactaa accttccaag 900
cagtctaata acaagtacgc tgcttcttct tacctttcac ttactcctga acaatggaag 960
agccacagga gttactcttg tcaggtaacc cacgaggggt ccactgtgga gaaaaccgtc 1020
gctcccacag agtgttct 1038
<210> 66
<211> 346
<212> PRT
<213> 人工序列
<400> 66
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gln Ser Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro
130 135 140
Gly Gln Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly
145 150 155 160
Gly Tyr Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro
165 170 175
Lys Leu Met Ile Tyr Asp Val Ser Asn Arg Pro Ser Gly Val Ser Asn
180 185 190
Arg Phe Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser
195 200 205
Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Thr
210 215 220
Ser Ser Ser Thr Arg Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu
225 230 235 240
Gly Gln Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Pro Ser Ser
245 250 255
Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp
260 265 270
Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro
275 280 285
Val Lys Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn
290 295 300
Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys
305 310 315 320
Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val
325 330 335
Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
340 345
<210> 67
<211> 1740
<212> DNA
<213> 人工序列
<400> 67
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacgacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccgga 360
ggcggaggtt ccggcggggg tgggagcggg caggtgaccc tgcgcgagtc cggccctgca 420
ctggtgaagc ccacccagac cctgaccctg acctgcacct tctccggctt ctccctgtcc 480
acctccggca tgtccgtggg ctggatccgg cagcctcccg gcaaggccct ggagtggctg 540
gctgacatct ggtgggacga caagaaggac tacaacccct ccctgaagtc ccgcctgacc 600
atctccaagg acacctccaa gaaccaggtg gtgctgaagg tgaccaacat ggaccccgcc 660
gacaccgcca cctactactg cgcccgctca atgattacca actggtactt cgacgtgtgg 720
ggagccggta ccaccgtgac cgtgtcttcc gcctccacca agggcccatc ggtcttcccc 780
ctggcaccct cctccaagag cacctctggg ggcacagcgg ccctgggctg cctggtcaag 840
gactacttcc ccgaaccggt gacggtgtcg tggaactcag gcgccctgac cagcggcgtg 900
cacaccttcc cggctgtcct acagtcctca ggactctact ccctcagcag cgtggtgact 960
gtgccctcta gcagcttggg cacccagacc tacatctgca acgtgaatca caagcccagc 1020
aacaccaagg tggacaagaa agttgaaccc aaatcttgcg acaaaactca cacatgccca 1080
ccgtgcccag cacctgaact cctgggggga ccgtcagtct tcctcttccc cccaaaaccc 1140
aaggacaccc tcatgatctc ccggacccct gaggtcacat gcgtggtggt ggacgtgagc 1200
cacgaagacc ctgaggtcaa gttcaactgg tacgtggacg gcgtggaggt gcataatgcc 1260
aagacaaagc cgcgggagga gcagtacaac agcacgtacc gtgtggtcag cgtcctcacc 1320
gtcctgcacc aggactggct gaatggcaag gagtacaagt gcaaggtctc caacaaagcc 1380
ctcccagccc ccatagagaa aaccatctcc aaagccaaag ggcagccccg agaaccacag 1440
gtgtacaccc tgcccccatc ccgggaggag atgaccaaga accaggtcag cctgacctgc 1500
ctggtcaaag gcttctatcc cagcgacatc gccgtggagt gggagagcaa tgggcagccg 1560
gagaacaact acaagaccac gcctcccgtg ctggactccg acggctcctt cttcctctac 1620
agcaagctca ccgtggacaa gagcaggtgg cagcagggga acgtcttctc atgctccgtg 1680
atgcatgagg ctctgcacaa ccactacacg cagaagagcc tctccctgtc tccgggtaaa 1740
<210> 68
<211> 563
<212> PRT
<213> 人工序列
<400> 68
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gln Val Thr Leu Arg Glu Ser Gly Pro Ala Leu Val Lys Pro
130 135 140
Thr Gln Thr Leu Thr Leu Thr Cys Thr Phe Ser Gly Phe Ser Leu Ser
145 150 155 160
Thr Ser Gly Met Ser Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Ala
165 170 175
Leu Glu Trp Leu Ala Asp Ile Trp Trp Asp Asp Lys Lys Asp Tyr Asn
180 185 190
Pro Ser Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Lys Asn
195 200 205
Gln Val Val Leu Lys Val Thr Asn Met Asp Pro Ala Asp Thr Ala Thr
210 215 220
Tyr Tyr Cys Ala Arg Ser Met Ile Thr Asn Trp Tyr Phe Asp Val Trp
225 230 235 240
Gly Ala Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
245 250 255
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
260 265 270
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
275 280 285
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
290 295 300
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
305 310 315 320
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
325 330 335
His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser
340 345 350
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu
355 360 365
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
370 375 380
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
385 390 395 400
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
405 410 415
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
420 425 430
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
435 440 445
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
450 455 460
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
465 470 475 480
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
485 490 495
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
500 505 510
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
515 520 525
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
530 535 540
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
545 550 555 560
Met His Glu
<210> 69
<211> 1593
<212> DNA
<213> 人工序列
<400> 69
atcacctgcc cacctcccat gagcgtggag cacgccgaca tctgggtgaa gagctacagc 60
ctgtacagcc gcgagcgcta catctgcaac agcggcttca agcgcaaggc cggcaccagc 120
agcctgaccg agtgcgtgct gaacaaggcc accaacgtgg cccactggac cacccccagc 180
ctgaagtgca tccgcggcgg aggcggatcc ggaggcggag gttccggcgg gggtgggagc 240
gggcaggtga ccctgcgcga gtccggccct gcactggtga agcccaccca gaccctgacc 300
ctgacctgca ccttctccgg cttctccctg tccacctccg gcatgtccgt gggctggatc 360
cggcagcctc ccggcaaggc cctggagtgg ctggctgaca tctggtggga cgacaagaag 420
gactacaacc cctccctgaa gtcccgcctg accatctcca aggacacctc caagaaccag 480
gtggtgctga aggtgaccaa catggacccc gccgacaccg ccacctacta ctgcgcccgc 540
tcaatgatta ccaactggta cttcgacgtg tggggagccg gtaccaccgt gaccgtgtct 600
tccgcctcca ccaagggccc atcggtcttc cccctggcac cctcctccaa gagcacctct 660
gggggcacag cggccctggg ctgcctggtc aaggactact tccccgaacc ggtgacggtg 720
tcgtggaact caggcgccct gaccagcggc gtgcacacct tcccggctgt cctacagtcc 780
tcaggactct actccctcag cagcgtggtg actgtgccct ctagcagctt gggcacccag 840
acctacatct gcaacgtgaa tcacaagccc agcaacacca aggtggacaa gaaagttgaa 900
cccaaatctt gcgacaaaac tcacacatgc ccaccgtgcc cagcacctga actcctgggg 960
ggaccgtcag tcttcctctt ccccccaaaa cccaaggaca ccctcatgat ctcccggacc 1020
cctgaggtca catgcgtggt ggtggacgtg agccacgaag accctgaggt caagttcaac 1080
tggtacgtgg acggcgtgga ggtgcataat gccaagacaa agccgcggga ggagcagtac 1140
aacagcacgt accgtgtggt cagcgtcctc accgtcctgc accaggactg gctgaatggc 1200
aaggagtaca agtgcaaggt ctccaacaaa gccctcccag cccccataga gaaaaccatc 1260
tccaaagcca aagggcagcc ccgagaacca caggtgtaca ccctgccccc atcccgggag 1320
gagatgacca agaaccaggt cagcctgacc tgcctggtca aaggcttcta tcccagcgac 1380
atcgccgtgg agtgggagag caatgggcag ccggagaaca actacaagac cacgcctccc 1440
gtgctggact ccgacggctc cttcttcctc tacagcaagc tcaccgtgga caagagcagg 1500
tggcagcagg ggaacgtctt ctcatgctcc gtgatgcatg aggctctgca caaccactac 1560
acgcagaaga gcctctccct gtctccgggt aaa 1593
<210> 70
<211> 531
<212> PRT
<213> 人工序列
<400> 70
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val
1 5 10 15
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly
20 25 30
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn
35 40 45
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile
50 55 60
Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
65 70 75 80
Gly Gln Val Thr Leu Arg Glu Ser Gly Pro Ala Leu Val Lys Pro Thr
85 90 95
Gln Thr Leu Thr Leu Thr Cys Thr Phe Ser Gly Phe Ser Leu Ser Thr
100 105 110
Ser Gly Met Ser Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Ala Leu
115 120 125
Glu Trp Leu Ala Asp Ile Trp Trp Asp Asp Lys Lys Asp Tyr Asn Pro
130 135 140
Ser Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Lys Asn Gln
145 150 155 160
Val Val Leu Lys Val Thr Asn Met Asp Pro Ala Asp Thr Ala Thr Tyr
165 170 175
Tyr Cys Ala Arg Ser Met Ile Thr Asn Trp Tyr Phe Asp Val Trp Gly
180 185 190
Ala Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
195 200 205
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
210 215 220
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
225 230 235 240
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
245 250 255
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
260 265 270
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
275 280 285
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
290 295 300
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
305 310 315 320
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
325 330 335
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
340 345 350
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
355 360 365
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
370 375 380
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
385 390 395 400
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
405 410 415
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
420 425 430
Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
435 440 445
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
450 455 460
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
465 470 475 480
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
485 490 495
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
500 505 510
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
515 520 525
Pro Gly Lys
530
<210> 71
<211> 342
<212> DNA
<213> 人工序列
<400> 71
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacgacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gc 342
<210> 72
<211> 114
<212> PRT
<213> 人工序列
<400> 72
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser
<210> 73
<211> 195
<212> DNA
<213> 人工序列
<400> 73
atcacctgcc cacctcccat gagcgtggag cacgccgaca tctgggtgaa gagctacagc 60
ctgtacagcc gcgagcgcta catctgcaac agcggcttca agcgcaaggc cggcaccagc 120
agcctgaccg agtgcgtgct gaacaaggcc accaacgtgg cccactggac cacccccagc 180
ctgaagtgca tccgc 195
<210> 74
<211> 65
<212> PRT
<213> 人工序列
<400> 74
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val
1 5 10 15
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly
20 25 30
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn
35 40 45
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile
50 55 60
Arg
65
<210> 75
<211> 1326
<212> DNA
<213> 人工序列
<400> 75
caggtgcagc tggtggagag tggaggtggc gtggtacagc ccggccgcag cctgcgcctg 60
gactgcaagg ccagcggcat caccttcagc aacagcggca tgcactgggt gcgccaggcc 120
cccggcaagg gcctggagtg ggtggccgtg atctggtacg acggcagcaa gcgctactac 180
gccgacagcg tgaagggccg cttcaccatc agccgcgaca acagcaagaa caccctgttc 240
ctgcagatga acagcctgcg cgccgaggac accgccgtgt actactgcgc caccaacgac 300
gactactggg gccagggcac cctggtgacc gtgagcagcg cctccaccaa gggcccatcg 360
gtcttccccc tggcaccctc ctccaagagc acctctgggg gcacagcggc cctgggctgc 420
ctggtcaagg actacttccc cgaaccggtg acggtgtcgt ggaactcagg cgccctgacc 480
agcggcgtgc acaccttccc ggctgtccta cagtcctcag gactctactc cctcagcagc 540
gtggtgactg tgccctctag cagcttgggc acccagacct acatctgcaa cgtgaatcac 600
aagcccagca acaccaaggt ggacaagaaa gttgaaccca aatcttgcga caaaactcac 660
acatgcccac cgtgcccagc acctccagtc gccggaccgt cagtcttcct cttccctcca 720
aaacccaagg acaccctcat gatctcccgg acccctgagg tcacatgcgt ggtggtggac 780
gtgagccacg aagaccctga ggtcaagttc aactggtacg tggacggcgt ggaggtgcat 840
aatgccaaga caaagccgcg ggaggagcag tacaacagca cgtaccgtgt ggtcagcgtc 900
ctcaccgtcc tgcaccagga ctggctgaat ggcaaggagt acaagtgcaa ggtctccaac 960
aaaggcctcc caagctccat cgagaaaacc atctccaaag ccaaagggca gccccgagaa 1020
ccacaggtgt acaccctgcc tccatcccgg gatgagctga ccaagaacca ggtcagcctg 1080
acctgcctgg tcaaaggctt ctatcccagc gacatcgccg tggagtggga gagcaatggg 1140
cagccggaga acaactacaa gaccacgcct cccgtgctgg actccgacgg ctccttcttc 1200
ctctacagca agctcaccgt ggacaagagc aggtggcagc aggggaacgt cttctcatgc 1260
tccgtgatgc atgaggctct gcacaaccac tacacgcaga agagcctctc cctgtctccg 1320
ggtaaa 1326
<210> 76
<211> 442
<212> PRT
<213> 人工序列
<400> 76
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser
115 120 125
Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
130 135 140
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
145 150 155 160
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr
165 170 175
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln
180 185 190
Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp
195 200 205
Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro
210 215 220
Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro
225 230 235 240
Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys
245 250 255
Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp
260 265 270
Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu
275 280 285
Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu
290 295 300
His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn
305 310 315 320
Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly
325 330 335
Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu
340 345 350
Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr
355 360 365
Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn
370 375 380
Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe
385 390 395 400
Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn
405 410 415
Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr
420 425 430
Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440
<210> 77
<211> 642
<212> DNA
<213> 人工序列
<400> 77
gagatcgtgc tgacccagag ccccgccacc ctgagcctga gccccggcga gcgcgccacc 60
ctgagctgcc gcgccagcca gagcgtgagc agctacctgg cctggtacca gcagaagcca 120
ggacaggctc cacgactgct aatctatgac gccagcaacc gcgccaccgg catccccgcc 180
cgcttcagcg gcagcggcag cggcaccgac ttcaccctga ccatcagcag cctggagccc 240
gaggacttcg ccgtgtacta ctgccagcag agcagcaact ggccccgcac cttcggccag 300
ggcaccaagg tggagatcaa gcgcacagtg gcagccccca gcgtcttcat ttttccccct 360
tccgatgaac agctgaagtc cggcactgct tctgtggtct gtctgctgaa caatttctat 420
cccagagagg ccaaggtgca gtggaaagtg gacaacgctc tgcagtccgg caacagccag 480
gagagtgtga ccgaacagga tagtaaggac agcacatatt ctctgtctag taccctgaca 540
ctgagtaagg cagattacga gaagcacaaa gtgtatgcct gcgaagtcac tcatcaggga 600
ctgtcaagcc ccgtgaccaa gagcttcaac cggggcgagt gt 642
<210> 78
<211> 214
<212> PRT
<213> 人工序列
<400> 78
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Ser Asn Trp Pro Arg
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 79
<211> 1350
<212> DNA
<213> 人工序列
<400> 79
gaagtacagc tgcttgagag tggaggaggt ttggtacagc ccggcggatc cctccgcctg 60
tcctgtgcgg ctagtggctt tacattctca tcctatatca tgatgtgggt aagacaggcc 120
ccaggaaagg gcctggagtg ggttagttct atctacccct caggcgggat taccttctac 180
gcagatactg tgaagggcag gtttaccata tcccgagaca acagtaagaa taccctttac 240
cttcaaatga actcccttcg ggccgaggac actgcggtgt actattgcgc tcgcattaag 300
cttggcaccg tgacaaccgt gaactattgg ggtcaaggca cgctggtgac tgtctcttcc 360
gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420
ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480
tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540
ggactctact ccctcagcag cgtggtgact gtgccctcta gcagcttggg cacccagacc 600
tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgaaccc 660
aaatcttgcg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 720
ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 780
gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840
tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac 900
agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960
gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatagagaa aaccatctcc 1020
aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag 1080
ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1140
gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg 1200
ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 1260
cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1320
cagaagagcc tctccctgtc tccgggtaaa 1350
<210> 80
<211> 450
<212> PRT
<213> 人工序列
<400> 80
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr
20 25 30
Ile Met Met Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ser Ile Tyr Pro Ser Gly Gly Ile Thr Phe Tyr Ala Asp Thr Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ile Lys Leu Gly Thr Val Thr Thr Val Asn Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly Lys
450
<210> 81
<211> 648
<212> DNA
<213> 人工序列
<400> 81
caatccgcac tgactcaacc agccagcgtt agcggctccc ctggtcaatc tatcaccatc 60
agctgtaccg ggaccagctc agacgttggc ggttacaact acgtcagctg gtaccagcag 120
cacccgggta aagctccaaa gctgatgatt tatgatgtgt ctaatcgacc ttctggtgta 180
tctaaccgat tttcaggctc taaaagtgga aatactgctt ccctcacgat ctcagggctg 240
caagccgaag acgaagccga ttattattgt tctagctata catccagcag cacccgcgtg 300
tttggaacgg gaaccaaggt cacggttctg ggacagccca aagccaatcc taccgtcact 360
ctgttcccac ccagtagtga ggagctgcag gcaaataagg ctaccctggt ctgtcttata 420
tccgatttct atcccggggc agtcacagtc gcttggaagg cagatggctc tccagtgaag 480
gccggcgtcg aaacaactaa accttccaag cagtctaata acaagtacgc tgcttcttct 540
tacctttcac ttactcctga acaatggaag agccacagga gttactcttg tcaggtaacc 600
cacgaggggt ccactgtgga gaaaaccgtc gctcccacag agtgttct 648
<210> 82
<211> 216
<212> PRT
<213> 人工序列
<400> 82
Gln Ser Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln
1 5 10 15
Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr
20 25 30
Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu
35 40 45
Met Ile Tyr Asp Val Ser Asn Arg Pro Ser Gly Val Ser Asn Arg Phe
50 55 60
Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu
65 70 75 80
Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Thr Ser Ser
85 90 95
Ser Thr Arg Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Gln
100 105 110
Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Pro Ser Ser Glu Glu
115 120 125
Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr
130 135 140
Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys
145 150 155 160
Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr
165 170 175
Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His
180 185 190
Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys
195 200 205
Thr Val Ala Pro Thr Glu Cys Ser
210 215
<210> 83
<211> 1716
<212> DNA
<213> 人工序列
<400> 83
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacgacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccgga 360
ggcggaggtt ccggcggggg tgggagcggg caggtgcagc tggtggagag tggaggtggc 420
gtggtacagc ccggccgcag cctgcgcctg gactgcaagg ccagcggcat caccttcagc 480
aacagcggca tgcactgggt gcgccaggcc cccggcaagg gcctggagtg ggtggccgtg 540
atctggtacg acggcagcaa gcgctactac gccgacagcg tgaagggccg cttcaccatc 600
agccgcgaca acagcaagaa caccctgttc ctgcagatga acagcctgcg cgccgaggac 660
accgccgtgt actactgcgc caccaacgac gactactggg gccagggcac cctggtgacc 720
gtgagcagcg cctccaccaa gggcccatcg gtcttccccc tggcaccctc ctccaagagc 780
acctctgggg gcacagcggc cctgggctgc ctggtcaagg actacttccc cgaaccggtg 840
acggtgtcgt ggaactcagg cgccctgacc agcggcgtgc acaccttccc ggctgtccta 900
cagtcctcag gactctactc cctcagcagc gtggtgactg tgccctctag cagcttgggc 960
acccagacct acatctgcaa cgtgaatcac aagcccagca acaccaaggt ggacaagaaa 1020
gttgaaccca aatcttgcga caaaactcac acatgcccac cgtgcccagc acctccagtc 1080
gccggaccgt cagtcttcct cttccctcca aaacccaagg acaccctcat gatctcccgg 1140
acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 1200
aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggaggagcag 1260
tacaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 1320
ggcaaggagt acaagtgcaa ggtctccaac aaaggcctcc caagctccat cgagaaaacc 1380
atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc tccatcccgg 1440
gatgagctga ccaagaacca ggtcagcctg acctgcctgg tcaaaggctt ctatcccagc 1500
gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct 1560
cccgtgctgg actccgacgg ctccttcttc ctctacagca agctcaccgt ggacaagagc 1620
aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac 1680
tacacgcaga agagcctctc cctgtctccg ggtaaa 1716
<210> 84
<211> 572
<212> PRT
<213> 人工序列
<400> 84
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro
130 135 140
Gly Arg Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser
145 150 155 160
Asn Ser Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala Asp
180 185 190
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
195 200 205
Leu Phe Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
210 215 220
Tyr Cys Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr
225 230 235 240
Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro
245 250 255
Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val
260 265 270
Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala
275 280 285
Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly
290 295 300
Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly
305 310 315 320
Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys
325 330 335
Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys
340 345 350
Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu Phe
355 360 365
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val
370 375 380
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
385 390 395 400
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
405 410 415
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
420 425 430
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
435 440 445
Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala
450 455 460
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg
465 470 475 480
Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly
485 490 495
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
500 505 510
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
515 520 525
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
530 535 540
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
545 550 555 560
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
565 570
<210> 85
<211> 885
<212> DNA
<213> 人工序列
<400> 85
atcacctgcc cacctcccat gagcgtggag cacgccgaca tctgggtgaa gagctacagc 60
ctgtacagcc gcgagcgcta catctgcaac agcggcttca agcgcaaggc cggcaccagc 120
agcctgaccg agtgcgtgct gaacaaggcc accaacgtgg cccactggac cacccccagc 180
ctgaagtgca tccgcggcgg aggcggatcc ggaggcggag gttccggcgg gggtgggagc 240
ggggagatcg tgctgaccca gagccccgcc accctgagcc tgagccccgg cgagcgcgcc 300
accctgagct gccgcgccag ccagagcgtg agcagctacc tggcctggta ccagcagaag 360
ccaggacagg ctccacgact gctaatctat gacgccagca accgcgccac cggcatcccc 420
gcccgcttca gcggcagcgg cagcggcacc gacttcaccc tgaccatcag cagcctggag 480
cccgaggact tcgccgtgta ctactgccag cagagcagca actggccccg caccttcggc 540
cagggcacca aggtggagat caagcgcaca gtggcagccc ccagcgtctt catttttccc 600
ccttccgatg aacagctgaa gtccggcact gcttctgtgg tctgtctgct gaacaatttc 660
tatcccagag aggccaaggt gcagtggaaa gtggacaacg ctctgcagtc cggcaacagc 720
caggagagtg tgaccgaaca ggatagtaag gacagcacat attctctgtc tagtaccctg 780
acactgagta aggcagatta cgagaagcac aaagtgtatg cctgcgaagt cactcatcag 840
ggactgtcaa gccccgtgac caagagcttc aaccggggcg agtgt 885
<210> 86
<211> 295
<212> PRT
<213> 人工序列
<400> 86
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val
1 5 10 15
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly
20 25 30
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn
35 40 45
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile
50 55 60
Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
65 70 75 80
Gly Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro
85 90 95
Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser
100 105 110
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
115 120 125
Ile Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser
130 135 140
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu
145 150 155 160
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Ser Asn Trp Pro
165 170 175
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala
180 185 190
Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser
195 200 205
Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu
210 215 220
Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser
225 230 235 240
Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu
245 250 255
Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val
260 265 270
Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys
275 280 285
Ser Phe Asn Arg Gly Glu Cys
290 295
<210> 87
<211> 711
<212> DNA
<213> 人工序列
<400> 87
atcacgtgcc ctccccccat gtccgtggaa cacgcagaca tctgggtcaa gagctacagc 60
ttgtactcca gggagcggta catttgtaac tctggtttca agcgtaaagc cggcacgtcc 120
agcctgacgg agtgcgtgtt gaacaaggcc acgaatgtcg cccactggac aacccccagt 180
ctcaaatgca ttagagaccc tgccctggtt caccaaaggc cagcgccacc ctccacagta 240
acgacggcag gggtgacccc acagccagag agcctctccc cttctggaaa agagcccgca 300
gcttcatctc ccagctcaaa caacacagcg gccacaacag cagctattgt cccgggctcc 360
cagctgatgc cttcaaaatc accttccaca ggaaccacag agataagcag tcatgagtcc 420
tcccacggca ccccctctca gacaacagcc aagaactggg aactcacagc atccgcctcc 480
caccagccgc caggtgtgta tccacagggc cacagcgaca ccactgtggc tatctccacg 540
tccactgtcc tgctgtgtgg gctgagcgct gtgtctctcc tggcatgcta cctcaagtca 600
aggcaaactc ccccgctggc cagcgttgaa atggaagcca tggaggctct gccggtgact 660
tgggggacca gcagcagaga tgaagacttg gaaaactgct ctcaccacct a 711
<210> 88
<211> 237
<212> PRT
<213> 人工序列
<400> 88
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val
1 5 10 15
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly
20 25 30
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn
35 40 45
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile
50 55 60
Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val
65 70 75 80
Thr Thr Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly
85 90 95
Lys Glu Pro Ala Ala Ser Ser Pro Ser Ser Asn Asn Thr Ala Ala Thr
100 105 110
Thr Ala Ala Ile Val Pro Gly Ser Gln Leu Met Pro Ser Lys Ser Pro
115 120 125
Ser Thr Gly Thr Thr Glu Ile Ser Ser His Glu Ser Ser His Gly Thr
130 135 140
Pro Ser Gln Thr Thr Ala Lys Asn Trp Glu Leu Thr Ala Ser Ala Ser
145 150 155 160
His Gln Pro Pro Gly Val Tyr Pro Gln Gly His Ser Asp Thr Thr Val
165 170 175
Ala Ile Ser Thr Ser Thr Val Leu Leu Cys Gly Leu Ser Ala Val Ser
180 185 190
Leu Leu Ala Cys Tyr Leu Lys Ser Arg Gln Thr Pro Pro Leu Ala Ser
195 200 205
Val Glu Met Glu Ala Met Glu Ala Leu Pro Val Thr Trp Gly Thr Ser
210 215 220
Ser Arg Asp Glu Asp Leu Glu Asn Cys Ser His His Leu
225 230 235
<210> 89
<211> 1737
<212> DNA
<213> 人工序列
<400> 89
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacaacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccggt 360
cctctgggag tacgaggcgg gggtgggagc gggcaggtgc agctgcagga gagcggcccc 420
ggcctggtga agcccagcga gaccctgagc ctgacctgca ccgtgagcgg cggcagcgtg 480
agcagcggcg actactactg gacctggatt cgccagagcc ccggcaaggg cctggagtgg 540
atcggccaca tctactacag cggcaacacc aactacaacc ccagcctgaa gagccgcctg 600
accatcagca tcgacaccag caagacccag ttcagcctga agctgagcag cgtgaccgcc 660
gccgacaccg ccatctacta ctgcgtgcgc gaccgcgtga ccggcgcctt cgacatctgg 720
ggccagggca ccatggtgac tgtgtctagc gcctccacca agggcccatc ggtcttcccc 780
ctggcaccct cctccaagag cacctctggg ggcacagcgg ccctgggctg cctggtcaag 840
gactacttcc ccgaaccggt gacggtgtcg tggaactcag gcgccctgac cagcggcgtg 900
cacaccttcc cggctgtcct acagtcctca ggactctact ccctcagcag cgtggtgact 960
gtgccctcta gcagcttggg cacccagacc tacatctgca acgtgaatca caagcccagc 1020
aacaccaagg tggacaagaa agttgaaccc aaatcttgcg acaaaactca cacatgccca 1080
ccgtgcccag cacctccagt cgccggaccg tcagtcttcc tcttccctcc aaaacccaag 1140
gacaccctca tgatctcccg gacccctgag gtcacatgcg tggtggtgga cgtgagccac 1200
gaagaccctg aggtcaagtt caactggtac gtggacggcg tggaggtgca taatgccaag 1260
acaaagccgc gggaggagca gtacaacagc acgtaccgtg tggtcagcgt cctcaccgtc 1320
ctgcaccagg actggctgaa tggcaaggag tacaagtgca aggtctccaa caaaggcctc 1380
ccaagctcca tcgagaaaac catctccaaa gccaaagggc agccccgaga accacaggtg 1440
tacaccctgc ctccatcccg ggatgagctg accaagaacc aggtcagcct gacctgcctg 1500
gtcaaaggct tctatcccag cgacatcgcc gtggagtggg agagcaatgg gcagccggag 1560
aacaactaca agaccacgcc tcccgtgctg gactccgacg gctccttctt cctctacagc 1620
aagctcaccg tggacaagag caggtggcag caggggaacg tcttctcatg ctccgtgatg 1680
catgaggctc tgcacaacca ctacacgcag aagagcctct ccctgtctcc gggtaaa 1737
<210> 90
<211> 579
<212> PRT
<213> 人工序列
<400> 90
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg Gly Gly Gly
115 120 125
Gly Ser Gly Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys
130 135 140
Pro Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val
145 150 155 160
Ser Ser Gly Asp Tyr Tyr Trp Thr Trp Ile Arg Gln Ser Pro Gly Lys
165 170 175
Gly Leu Glu Trp Ile Gly His Ile Tyr Tyr Ser Gly Asn Thr Asn Tyr
180 185 190
Asn Pro Ser Leu Lys Ser Arg Leu Thr Ile Ser Ile Asp Thr Ser Lys
195 200 205
Thr Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala
210 215 220
Ile Tyr Tyr Cys Val Arg Asp Arg Val Thr Gly Ala Phe Asp Ile Trp
225 230 235 240
Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
245 250 255
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
260 265 270
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
275 280 285
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
290 295 300
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
305 310 315 320
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
325 330 335
His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser
340 345 350
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala
355 360 365
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
370 375 380
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
385 390 395 400
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
405 410 415
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
420 425 430
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
435 440 445
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile
450 455 460
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
465 470 475 480
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
485 490 495
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
500 505 510
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
515 520 525
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
530 535 540
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
545 550 555 560
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
565 570 575
Pro Gly Lys
<210> 91
<211> 1719
<212> DNA
<213> 人工序列
<400> 91
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacaacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccggt 360
cctctgggag tacgacaggt gcagctgcag gagagcggcc ccggcctggt gaagcccagc 420
gagaccctga gcctgacctg caccgtgagc ggcggcagcg tgagcagcgg cgactactac 480
tggacctgga ttcgccagag ccccggcaag ggcctggagt ggatcggcca catctactac 540
agcggcaaca ccaactacaa ccccagcctg aagagccgcc tgaccatcag catcgacacc 600
agcaagaccc agttcagcct gaagctgagc agcgtgaccg ccgccgacac cgccatctac 660
tactgcgtgc gcgaccgcgt gaccggcgcc ttcgacatct ggggccaggg caccatggtg 720
actgtgtcta gcgcctccac caagggccca tcggtcttcc ccctggcacc ctcctccaag 780
agcacctctg ggggcacagc ggccctgggc tgcctggtca aggactactt ccccgaaccg 840
gtgacggtgt cgtggaactc aggcgccctg accagcggcg tgcacacctt cccggctgtc 900
ctacagtcct caggactcta ctccctcagc agcgtggtga ctgtgccctc tagcagcttg 960
ggcacccaga cctacatctg caacgtgaat cacaagccca gcaacaccaa ggtggacaag 1020
aaagttgaac ccaaatcttg cgacaaaact cacacatgcc caccgtgccc agcacctcca 1080
gtcgccggac cgtcagtctt cctcttccct ccaaaaccca aggacaccct catgatctcc 1140
cggacccctg aggtcacatg cgtggtggtg gacgtgagcc acgaagaccc tgaggtcaag 1200
ttcaactggt acgtggacgg cgtggaggtg cataatgcca agacaaagcc gcgggaggag 1260
cagtacaaca gcacgtaccg tgtggtcagc gtcctcaccg tcctgcacca ggactggctg 1320
aatggcaagg agtacaagtg caaggtctcc aacaaaggcc tcccaagctc catcgagaaa 1380
accatctcca aagccaaagg gcagccccga gaaccacagg tgtacaccct gcctccatcc 1440
cgggatgagc tgaccaagaa ccaggtcagc ctgacctgcc tggtcaaagg cttctatccc 1500
agcgacatcg ccgtggagtg ggagagcaat gggcagccgg agaacaacta caagaccacg 1560
cctcccgtgc tggactccga cggctccttc ttcctctaca gcaagctcac cgtggacaag 1620
agcaggtggc agcaggggaa cgtcttctca tgctccgtga tgcatgaggc tctgcacaac 1680
cactacacgc agaagagcct ctccctgtct ccgggtaaa 1719
<210> 92
<211> 573
<212> PRT
<213> 人工序列
<400> 92
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg Gln Val Gln
115 120 125
Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu Thr Leu Ser
130 135 140
Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser Gly Asp Tyr Tyr
145 150 155 160
Trp Thr Trp Ile Arg Gln Ser Pro Gly Lys Gly Leu Glu Trp Ile Gly
165 170 175
His Ile Tyr Tyr Ser Gly Asn Thr Asn Tyr Asn Pro Ser Leu Lys Ser
180 185 190
Arg Leu Thr Ile Ser Ile Asp Thr Ser Lys Thr Gln Phe Ser Leu Lys
195 200 205
Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Ile Tyr Tyr Cys Val Arg
210 215 220
Asp Arg Val Thr Gly Ala Phe Asp Ile Trp Gly Gln Gly Thr Met Val
225 230 235 240
Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala
245 250 255
Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu
260 265 270
Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly
275 280 285
Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser
290 295 300
Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu
305 310 315 320
Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr
325 330 335
Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr
340 345 350
Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu
355 360 365
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
370 375 380
Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys
385 390 395 400
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
405 410 415
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
420 425 430
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
435 440 445
Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys
450 455 460
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
465 470 475 480
Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
485 490 495
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
500 505 510
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
515 520 525
Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
530 535 540
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
545 550 555 560
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
565 570
<210> 93
<211> 1737
<212> DNA
<213> 人工序列
<400> 93
caggtgcagc tgcaggagag cggccccggc ctggtgaagc ccagcgagac cctgagcctg 60
acctgcaccg tgagcggcgg cagcgtgagc agcggcgact actactggac ctggattcgc 120
cagagccccg gcaagggcct ggagtggatc ggccacatct actacagcgg caacaccaac 180
tacaacccca gcctgaagag ccgcctgacc atcagcatcg acaccagcaa gacccagttc 240
agcctgaagc tgagcagcgt gaccgccgcc gacaccgcca tctactactg cgtgcgcgac 300
cgcgtgaccg gcgccttcga catctggggc cagggcacca tggtgactgt gtctagcgcc 360
tccaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420
acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480
aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540
ctctactccc tcagcagcgt ggtgactgtg ccctctagca gcttgggcac ccagacctac 600
atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgaacccaaa 660
tcttgcgaca aaactcacac atgcccaccg tgcccagcac ctccagtcgc cggaccgtca 720
gtcttcctct tccctccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 780
acatgcgtgg tggtggacgt gagccacgaa gaccctgagg tcaagttcaa ctggtacgtg 840
gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 900
taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 960
aagtgcaagg tctccaacaa aggcctccca agctccatcg agaaaaccat ctccaaagcc 1020
aaagggcagc cccgagaacc acaggtgtac accctgcctc catcccggga tgagctgacc 1080
aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1140
gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1200
tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1260
gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1320
agcctctccc tgtctccggg taaaggcgga ggcggatccg gtcctctggg agtacgaggc 1380
gggggtggga gcgggaactg ggtgaacgtg atcagcgacc tgaagaagat cgaggacctg 1440
atccagagca tgcacatcga cgccaccctg tacaccgaga gcgacgtgca ccccagctgc 1500
aaggtgaccg ccatgaagtg cttcctgctg gagctgcagg tgatcagcct ggagagcggc 1560
gacgccagca tccacgacac cgtggagaac ctgatcatcc tggccaacaa cagcctgagc 1620
agcaacggca acgtgaccga gagcggctgc aaggagtgcg aggagctgga ggagaagaac 1680
atcaaggagt tcctgcagag cttcgtgcac atcgtgcaga tgttcatcaa caccagc 1737
<210> 94
<211> 579
<212> PRT
<213> 人工序列
<400> 94
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser Gly
20 25 30
Asp Tyr Tyr Trp Thr Trp Ile Arg Gln Ser Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly His Ile Tyr Tyr Ser Gly Asn Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Leu Thr Ile Ser Ile Asp Thr Ser Lys Thr Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Ile Tyr Tyr
85 90 95
Cys Val Arg Asp Arg Val Thr Gly Ala Phe Asp Ile Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro
260 265 270
Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440 445
Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg Gly Gly Gly Gly Ser
450 455 460
Gly Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu
465 470 475 480
Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val
485 490 495
His Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu
500 505 510
Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val
515 520 525
Glu Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn
530 535 540
Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn
545 550 555 560
Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile
565 570 575
Asn Thr Ser
<210> 95
<211> 1722
<212> DNA
<213> 人工序列
<400> 95
caggtgcagc tgcaggagag cggccccggc ctggtgaagc ccagcgagac cctgagcctg 60
acctgcaccg tgagcggcgg cagcgtgagc agcggcgact actactggac ctggattcgc 120
cagagccccg gcaagggcct ggagtggatc ggccacatct actacagcgg caacaccaac 180
tacaacccca gcctgaagag ccgcctgacc atcagcatcg acaccagcaa gacccagttc 240
agcctgaagc tgagcagcgt gaccgccgcc gacaccgcca tctactactg cgtgcgcgac 300
cgcgtgaccg gcgccttcga catctggggc cagggcacca tggtgactgt gtctagcgcc 360
tccaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctgggggc 420
acagcggccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480
aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540
ctctactccc tcagcagcgt ggtgactgtg ccctctagca gcttgggcac ccagacctac 600
atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgaacccaaa 660
tcttgcgaca aaactcacac atgcccaccg tgcccagcac ctccagtcgc cggaccgtca 720
gtcttcctct tccctccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 780
acatgcgtgg tggtggacgt gagccacgaa gaccctgagg tcaagttcaa ctggtacgtg 840
gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 900
taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 960
aagtgcaagg tctccaacaa aggcctccca agctccatcg agaaaaccat ctccaaagcc 1020
aaagggcagc cccgagaacc acaggtgtac accctgcctc catcccggga tgagctgacc 1080
aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1140
gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1200
tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1260
gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1320
agcctctccc tgtctccggg taaaggtcct ctgggagtac gaggcggggg tgggagcggg 1380
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 1440
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 1500
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 1560
gacaccgtgg agaacctgat catcctggcc aacaacagcc tgagcagcaa cggcaacgtg 1620
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 1680
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gc 1722
<210> 96
<211> 574
<212> PRT
<213> 人工序列
<400> 96
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser Gly
20 25 30
Asp Tyr Tyr Trp Thr Trp Ile Arg Gln Ser Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly His Ile Tyr Tyr Ser Gly Asn Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Leu Thr Ile Ser Ile Asp Thr Ser Lys Thr Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Ile Tyr Tyr
85 90 95
Cys Val Arg Asp Arg Val Thr Gly Ala Phe Asp Ile Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro
260 265 270
Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440 445
Gly Pro Leu Gly Val Arg Gly Gly Gly Gly Ser Gly Asn Trp Val Asn
450 455 460
Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile Gln Ser Met His
465 470 475 480
Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His Pro Ser Cys Lys
485 490 495
Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln Val Ile Ser Leu
500 505 510
Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu Asn Leu Ile Ile
515 520 525
Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val Thr Glu Ser Gly
530 535 540
Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile Lys Glu Phe Leu
545 550 555 560
Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn Thr Ser
565 570
<210> 97
<211> 1740
<212> DNA
<213> 人工序列
<400> 97
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacaacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccggt 360
cctctgggag tacgaggcgg gggtgggagc ggggaggtgc agctggtgga gtctggagga 420
ggcttggtcc agcctggggg gtccctgaga ctctcctgtg cagcctctgg gttcaatatt 480
aaggacactt acatccactg ggtccgccag gctccaggga aggggctgga gtgggtcgca 540
cgtatttatc ctaccaatgg ttacacacgc tacgcagact ccgtgaaggg ccgattcacc 600
atctccgcag acacttccaa gaacacggcg tatcttcaaa tgaacagcct gagagccgag 660
gacacggccg tgtattactg ttcgagatgg ggcggtgacg gcttctatgc catggactac 720
tggggccaag gaaccctggt caccgtctcc tcagcctcca ccaagggccc atcggtcttc 780
cccctggcac cctcctccaa gagcacctct gggggcacag cggccctggg ctgcctggtc 840
aaggactact tccccgaacc ggtgacggtg tcgtggaact caggcgccct gaccagcggc 900
gtgcacacct tcccggctgt cctacagtcc tcaggactct actccctcag cagcgtggtg 960
actgtgccct ctagcagctt gggcacccag acctacatct gcaacgtgaa tcacaagccc 1020
agcaacacca aggtggacaa gaaagttgaa cccaaatctt gcgacaaaac tcacacatgc 1080
ccaccgtgcc cagcacctcc agtcgccgga ccgtcagtct tcctcttccc tccaaaaccc 1140
aaggacaccc tcatgatctc ccggacccct gaggtcacat gcgtggtggt ggacgtgagc 1200
cacgaagacc ctgaggtcaa gttcaactgg tacgtggacg gcgtggaggt gcataatgcc 1260
aagacaaagc cgcgggagga gcagtacaac agcacgtacc gtgtggtcag cgtcctcacc 1320
gtcctgcacc aggactggct gaatggcaag gagtacaagt gcaaggtctc caacaaaggc 1380
ctcccaagct ccatcgagaa aaccatctcc aaagccaaag ggcagccccg agaaccacag 1440
gtgtacaccc tgcctccatc ccgggatgag ctgaccaaga accaggtcag cctgacctgc 1500
ctggtcaaag gcttctatcc cagcgacatc gccgtggagt gggagagcaa tgggcagccg 1560
gagaacaact acaagaccac gcctcccgtg ctggactccg acggctcctt cttcctctac 1620
agcaagctca ccgtggacaa gagcaggtgg cagcagggga acgtcttctc atgctccgtg 1680
atgcatgagg ctctgcacaa ccactacacg cagaagagcc tctccctgtc tccgggtaaa 1740
<210> 98
<211> 580
<212> PRT
<213> 人工序列
<400> 98
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg Gly Gly Gly
115 120 125
Gly Ser Gly Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
130 135 140
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile
145 150 155 160
Lys Asp Thr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
165 170 175
Glu Trp Val Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala
180 185 190
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn
195 200 205
Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
210 215 220
Tyr Tyr Cys Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr
225 230 235 240
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly
245 250 255
Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly
260 265 270
Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
275 280 285
Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe
290 295 300
Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val
305 310 315 320
Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val
325 330 335
Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys
340 345 350
Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val
355 360 365
Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
370 375 380
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
385 390 395 400
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
405 410 415
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
420 425 430
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
435 440 445
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser
450 455 460
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
465 470 475 480
Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val
485 490 495
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
500 505 510
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
515 520 525
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
530 535 540
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
545 550 555 560
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
565 570 575
Ser Pro Gly Lys
580
<210> 99
<211> 1722
<212> DNA
<213> 人工序列
<400> 99
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacaacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccggt 360
cctctgggag tacgagaggt gcagctggtg gagtctggag gaggcttggt ccagcctggg 420
gggtccctga gactctcctg tgcagcctct gggttcaata ttaaggacac ttacatccac 480
tgggtccgcc aggctccagg gaaggggctg gagtgggtcg cacgtattta tcctaccaat 540
ggttacacac gctacgcaga ctccgtgaag ggccgattca ccatctccgc agacacttcc 600
aagaacacgg cgtatcttca aatgaacagc ctgagagccg aggacacggc cgtgtattac 660
tgttcgagat ggggcggtga cggcttctat gccatggact actggggcca aggaaccctg 720
gtcaccgtct cctcagcctc caccaagggc ccatcggtct tccccctggc accctcctcc 780
aagagcacct ctgggggcac agcggccctg ggctgcctgg tcaaggacta cttccccgaa 840
ccggtgacgg tgtcgtggaa ctcaggcgcc ctgaccagcg gcgtgcacac cttcccggct 900
gtcctacagt cctcaggact ctactccctc agcagcgtgg tgactgtgcc ctctagcagc 960
ttgggcaccc agacctacat ctgcaacgtg aatcacaagc ccagcaacac caaggtggac 1020
aagaaagttg aacccaaatc ttgcgacaaa actcacacat gcccaccgtg cccagcacct 1080
ccagtcgccg gaccgtcagt cttcctcttc cctccaaaac ccaaggacac cctcatgatc 1140
tcccggaccc ctgaggtcac atgcgtggtg gtggacgtga gccacgaaga ccctgaggtc 1200
aagttcaact ggtacgtgga cggcgtggag gtgcataatg ccaagacaaa gccgcgggag 1260
gagcagtaca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca ccaggactgg 1320
ctgaatggca aggagtacaa gtgcaaggtc tccaacaaag gcctcccaag ctccatcgag 1380
aaaaccatct ccaaagccaa agggcagccc cgagaaccac aggtgtacac cctgcctcca 1440
tcccgggatg agctgaccaa gaaccaggtc agcctgacct gcctggtcaa aggcttctat 1500
cccagcgaca tcgccgtgga gtgggagagc aatgggcagc cggagaacaa ctacaagacc 1560
acgcctcccg tgctggactc cgacggctcc ttcttcctct acagcaagct caccgtggac 1620
aagagcaggt ggcagcaggg gaacgtcttc tcatgctccg tgatgcatga ggctctgcac 1680
aaccactaca cgcagaagag cctctccctg tctccgggta aa 1722
<210> 100
<211> 574
<212> PRT
<213> 人工序列
<400> 100
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg Glu Val Gln
115 120 125
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg
130 135 140
Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile Lys Asp Thr Tyr Ile His
145 150 155 160
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
165 170 175
Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala Asp Ser Val Lys Gly Arg
180 185 190
Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr Leu Gln Met
195 200 205
Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ser Arg Trp
210 215 220
Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu
225 230 235 240
Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu
245 250 255
Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys
260 265 270
Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser
275 280 285
Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser
290 295 300
Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser
305 310 315 320
Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn
325 330 335
Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His
340 345 350
Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe
355 360 365
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro
370 375 380
Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val
385 390 395 400
Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
405 410 415
Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val
420 425 430
Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
435 440 445
Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser
450 455 460
Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
465 470 475 480
Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
485 490 495
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
500 505 510
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp
515 520 525
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp
530 535 540
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
545 550 555 560
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
565 570
<210> 101
<211> 1035
<212> DNA
<213> 人工序列
<400> 101
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacaacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccggt 360
cctctgggag tacgaggcgg gggtgggagc ggggacatcc agatgaccca gtctccatcc 420
tccctgtctg catctgtagg agacagagtc accatcactt gccgggcaag tcaggatgtg 480
aataccgcgg tcgcatggta tcagcagaaa ccagggaaag cccctaagct cctgatctat 540
tctgcatcct tcttgtatag tggggtccca tcaaggttca gtggcagtag atctgggaca 600
gatttcactc tcaccatcag cagtctgcaa cctgaagatt ttgcaactta ctactgtcaa 660
cagcattaca ctacccctcc gacgttcggc caaggtacca aggttgagat caaacgcaca 720
gtggcagccc ccagcgtctt catttttccc ccttccgatg aacagctgaa gtccggcact 780
gcttctgtgg tctgtctgct gaacaatttc tatcccagag aggccaaggt gcagtggaaa 840
gtggacaacg ctctgcagtc cggcaacagc caggagagtg tgaccgaaca ggatagtaag 900
gacagcacat attctctgtc tagtaccctg acactgagta aggcagatta cgagaagcac 960
aaagtgtatg cctgcgaagt cactcatcag ggactgtcaa gccccgtgac caagagcttc 1020
aaccggggcg agtgt 1035
<210> 102
<211> 345
<212> PRT
<213> 人工序列
<400> 102
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg Gly Gly Gly
115 120 125
Gly Ser Gly Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala
130 135 140
Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val
145 150 155 160
Asn Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys
165 170 175
Leu Leu Ile Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg
180 185 190
Phe Ser Gly Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser
195 200 205
Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Thr
210 215 220
Thr Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr
225 230 235 240
Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu
245 250 255
Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro
260 265 270
Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly
275 280 285
Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr
290 295 300
Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His
305 310 315 320
Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val
325 330 335
Thr Lys Ser Phe Asn Arg Gly Glu Cys
340 345
<210> 103
<211> 1017
<212> DNA
<213> 人工序列
<400> 103
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacaacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccggt 360
cctctgggag tacgagacat ccagatgacc cagtctccat cctccctgtc tgcatctgta 420
ggagacagag tcaccatcac ttgccgggca agtcaggatg tgaataccgc ggtcgcatgg 480
tatcagcaga aaccagggaa agcccctaag ctcctgatct attctgcatc cttcttgtat 540
agtggggtcc catcaaggtt cagtggcagt agatctggga cagatttcac tctcaccatc 600
agcagtctgc aacctgaaga ttttgcaact tactactgtc aacagcatta cactacccct 660
ccgacgttcg gccaaggtac caaggttgag atcaaacgca cagtggcagc ccccagcgtc 720
ttcatttttc ccccttccga tgaacagctg aagtccggca ctgcttctgt ggtctgtctg 780
ctgaacaatt tctatcccag agaggccaag gtgcagtgga aagtggacaa cgctctgcag 840
tccggcaaca gccaggagag tgtgaccgaa caggatagta aggacagcac atattctctg 900
tctagtaccc tgacactgag taaggcagat tacgagaagc acaaagtgta tgcctgcgaa 960
gtcactcatc agggactgtc aagccccgtg accaagagct tcaaccgggg cgagtgt 1017
<210> 104
<211> 339
<212> PRT
<213> 人工序列
<400> 104
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg Asp Ile Gln
115 120 125
Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val
130 135 140
Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Asn Thr Ala Val Ala Trp
145 150 155 160
Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ser Ala
165 170 175
Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Arg Ser
180 185 190
Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe
195 200 205
Ala Thr Tyr Tyr Cys Gln Gln His Tyr Thr Thr Pro Pro Thr Phe Gly
210 215 220
Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val
225 230 235 240
Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser
245 250 255
Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln
260 265 270
Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val
275 280 285
Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu
290 295 300
Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu
305 310 315 320
Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg
325 330 335
Gly Glu Cys
<210> 105
<211> 1737
<212> DNA
<213> 人工序列
<400> 105
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacaacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccgga 360
ggcggaggtt ccggcggggg tgggagcggg gaggtgcagc tggtggagtc tggaggaggc 420
ttggtccagc ctggggggtc cctgagactc tcctgtgcag cctctgggtt caatattaag 480
gacacttaca tccactgggt ccgccaggct ccagggaagg ggctggagtg ggtcgcacgt 540
atttatccta ccaatggtta cacacgctac gcagactccg tgaagggccg attcaccatc 600
tccgcagaca cttccaagaa cacggcgtat cttcaaatga acagcctgag agccgaggac 660
acggccgtgt attactgttc gagatggggc ggtgacggct tctatgccat ggactactgg 720
ggccaaggaa ccctggtcac cgtctcctca gcctccacca agggcccatc ggtcttcccc 780
ctggcaccct cctccaagag cacctctggg ggcacagcgg ccctgggctg cctggtcaag 840
gactacttcc ccgaaccggt gacggtgtcg tggaactcag gcgccctgac cagcggcgtg 900
cacaccttcc cggctgtcct acagtcctca ggactctact ccctcagcag cgtggtgact 960
gtgccctcta gcagcttggg cacccagacc tacatctgca acgtgaatca caagcccagc 1020
aacaccaagg tggacaagaa agttgaaccc aaatcttgcg acaaaactca cacatgccca 1080
ccgtgcccag cacctccagt cgccggaccg tcagtcttcc tcttccctcc aaaacccaag 1140
gacaccctca tgatctcccg gacccctgag gtcacatgcg tggtggtgga cgtgagccac 1200
gaagaccctg aggtcaagtt caactggtac gtggacggcg tggaggtgca taatgccaag 1260
acaaagccgc gggaggagca gtacaacagc acgtaccgtg tggtcagcgt cctcaccgtc 1320
ctgcaccagg actggctgaa tggcaaggag tacaagtgca aggtctccaa caaaggcctc 1380
ccaagctcca tcgagaaaac catctccaaa gccaaagggc agccccgaga accacaggtg 1440
tacaccctgc ctccatcccg ggatgagctg accaagaacc aggtcagcct gacctgcctg 1500
gtcaaaggct tctatcccag cgacatcgcc gtggagtggg agagcaatgg gcagccggag 1560
aacaactaca agaccacgcc tcccgtgctg gactccgacg gctccttctt cctctacagc 1620
aagctcaccg tggacaagag caggtggcag caggggaacg tcttctcatg ctccgtgatg 1680
catgaggctc tgcacaacca ctacacgcag aagagcctct ccctgtctcc gggtaaa 1737
<210> 106
<211> 579
<212> PRT
<213> 人工序列
<400> 106
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile Lys
145 150 155 160
Asp Thr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala Asp
180 185 190
Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr
195 200 205
Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
210 215 220
Tyr Cys Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
245 250 255
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
260 265 270
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
275 280 285
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
290 295 300
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
305 310 315 320
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
325 330 335
His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser
340 345 350
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala
355 360 365
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
370 375 380
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
385 390 395 400
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
405 410 415
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
420 425 430
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
435 440 445
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile
450 455 460
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
465 470 475 480
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
485 490 495
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
500 505 510
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
515 520 525
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
530 535 540
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
545 550 555 560
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
565 570 575
Pro Gly Lys
<210> 107
<211> 1032
<212> DNA
<213> 人工序列
<400> 107
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacaacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gcggcggagg cggatccgga 360
ggcggaggtt ccggcggggg tgggagcggg gacatccaga tgacccagtc tccatcctcc 420
ctgtctgcat ctgtaggaga cagagtcacc atcacttgcc gggcaagtca ggatgtgaat 480
accgcggtcg catggtatca gcagaaacca gggaaagccc ctaagctcct gatctattct 540
gcatccttct tgtatagtgg ggtcccatca aggttcagtg gcagtagatc tgggacagat 600
ttcactctca ccatcagcag tctgcaacct gaagattttg caacttacta ctgtcaacag 660
cattacacta cccctccgac gttcggccaa ggtaccaagg ttgagatcaa acgcacagtg 720
gcagccccca gcgtcttcat ttttccccct tccgatgaac agctgaagtc cggcactgct 780
tctgtggtct gtctgctgaa caatttctat cccagagagg ccaaggtgca gtggaaagtg 840
gacaacgctc tgcagtccgg caacagccag gagagtgtga ccgaacagga tagtaaggac 900
agcacatatt ctctgtctag taccctgaca ctgagtaagg cagattacga gaagcacaaa 960
gtgtatgcct gcgaagtcac tcatcaggga ctgtcaagcc ccgtgaccaa gagcttcaac 1020
cggggcgagt gt 1032
<210> 108
<211> 344
<212> PRT
<213> 人工序列
<400> 108
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser
130 135 140
Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Asn
145 150 155 160
Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu
165 170 175
Leu Ile Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe
180 185 190
Ser Gly Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu
195 200 205
Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Thr Thr
210 215 220
Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val
225 230 235 240
Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys
245 250 255
Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg
260 265 270
Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn
275 280 285
Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser
290 295 300
Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys
305 310 315 320
Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr
325 330 335
Lys Ser Phe Asn Arg Gly Glu Cys
340
<210> 109
<211> 1347
<212> DNA
<213> 人工序列
<400> 109
gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60
tcctgtgcag cctctgggtt caatattaag gacacttaca tccactgggt ccgccaggct 120
ccagggaagg ggctggagtg ggtcgcacgt atttatccta ccaatggtta cacacgctac 180
gcagactccg tgaagggccg attcaccatc tccgcagaca cttccaagaa cacggcgtat 240
cttcaaatga acagcctgag agccgaggac acggccgtgt attactgttc gagatggggc 300
ggtgacggct tctatgccat ggactactgg ggccaaggaa ccctggtcac cgtctcctca 360
gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420
ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480
tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540
ggactctact ccctcagcag cgtggtgact gtgccctcta gcagcttggg cacccagacc 600
tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgaaccc 660
aaatcttgcg acaaaactca cacatgccca ccgtgcccag cacctccagt cgccggaccg 720
tcagtcttcc tcttccctcc aaaacccaag gacaccctca tgatctcccg gacccctgag 780
gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 840
gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900
acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 960
tacaagtgca aggtctccaa caaaggcctc ccaagctcca tcgagaaaac catctccaaa 1020
gccaaagggc agccccgaga accacaggtg tacaccctgc ctccatcccg ggatgagctg 1080
accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140
gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200
gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag 1260
caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320
aagagcctct ccctgtctcc gggtaaa 1347
<210> 110
<211> 449
<212> PRT
<213> 人工序列
<400> 110
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile Lys Asp Thr
20 25 30
Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro
225 230 235 240
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
260 265 270
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
275 280 285
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
340 345 350
Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr
355 360 365
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
370 375 380
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
385 390 395 400
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
405 410 415
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
420 425 430
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
Lys
<210> 111
<211> 342
<212> DNA
<213> 人工序列
<400> 111
aactgggtga acgtgatcag cgacctgaag aagatcgagg acctgatcca gagcatgcac 60
atcgacgcca ccctgtacac cgagagcgac gtgcacccca gctgcaaggt gaccgccatg 120
aagtgcttcc tgctggagct gcaggtgatc agcctggaga gcggcgacgc cagcatccac 180
gacaccgtgg agaacctgat catcctggcc aacaacagcc tgagcagcaa cggcaacgtg 240
accgagagcg gctgcaagga gtgcgaggag ctggaggaga agaacatcaa ggagttcctg 300
cagagcttcg tgcacatcgt gcagatgttc atcaacacca gc 342
<210> 112
<211> 114
<212> PRT
<213> 人工序列
<400> 112
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser
<210> 113
<211> 578
<212> PRT
<213> 人工序列
<400> 113
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro
130 135 140
Ser Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser
145 150 155 160
Ser Gly Asp Tyr Tyr Trp Thr Trp Ile Arg Gln Ser Pro Gly Lys Gly
165 170 175
Leu Glu Trp Ile Gly His Ile Tyr Tyr Ser Gly Asn Thr Asn Tyr Asn
180 185 190
Pro Ser Leu Lys Ser Arg Leu Thr Ile Ser Ile Asp Thr Ser Lys Thr
195 200 205
Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Ile
210 215 220
Tyr Tyr Cys Val Arg Asp Arg Val Thr Gly Ala Phe Asp Ile Trp Gly
225 230 235 240
Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
245 250 255
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
260 265 270
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
275 280 285
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
290 295 300
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
305 310 315 320
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
325 330 335
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
340 345 350
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly
355 360 365
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
370 375 380
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
385 390 395 400
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
405 410 415
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
420 425 430
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
435 440 445
Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu
450 455 460
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
465 470 475 480
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
485 490 495
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
500 505 510
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
515 520 525
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
530 535 540
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
545 550 555 560
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
565 570 575
Gly Lys
<210> 114
<211> 578
<212> PRT
<213> 人工序列
<400> 114
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser Gly
20 25 30
Asp Tyr Tyr Trp Thr Trp Ile Arg Gln Ser Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly His Ile Tyr Tyr Ser Gly Asn Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Leu Thr Ile Ser Ile Asp Thr Ser Lys Thr Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Ile Tyr Tyr
85 90 95
Cys Val Arg Asp Arg Val Thr Gly Ala Phe Asp Ile Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro
260 265 270
Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
435 440 445
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
450 455 460
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
465 470 475 480
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
485 490 495
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
500 505 510
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
515 520 525
Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val
530 535 540
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
545 550 555 560
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
565 570 575
Thr Ser
<210> 115
<211> 344
<212> PRT
<213> 人工序列
<400> 115
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Phe Cys Gln His Phe Asp His Leu Pro Leu
85 90 95
Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
210 215 220
Gly Gly Gly Gly Ser Gly Asn Trp Val Asn Val Ile Ser Asp Leu Lys
225 230 235 240
Lys Ile Glu Asp Leu Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr
245 250 255
Thr Glu Ser Asp Val His Pro Ser Cys Lys Val Thr Ala Met Lys Cys
260 265 270
Phe Leu Leu Glu Leu Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Ser
275 280 285
Ile His Asp Thr Val Glu Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu
290 295 300
Ser Ser Asn Gly Asn Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu
305 310 315 320
Leu Glu Glu Lys Asn Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile
325 330 335
Val Gln Met Phe Ile Asn Thr Ser
340
<210> 116
<211> 308
<212> PRT
<213> 人工序列
<400> 116
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser Gly
20 25 30
Asp Tyr Tyr Trp Thr Trp Ile Arg Gln Ser Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly His Ile Tyr Tyr Ser Gly Asn Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Leu Thr Ile Ser Ile Asp Thr Ser Lys Thr Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Ile Tyr Tyr
85 90 95
Cys Val Arg Asp Arg Val Thr Gly Ala Phe Asp Ile Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
225 230 235 240
Gly Ser Gly Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp
245 250 255
Ile Trp Val Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys
260 265 270
Asn Ser Gly Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys
275 280 285
Val Leu Asn Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu
290 295 300
Lys Cys Ile Arg
305
<210> 117
<211> 357
<212> PRT
<213> 人工序列
<400> 117
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser Gly
20 25 30
Asp Tyr Tyr Trp Thr Trp Ile Arg Gln Ser Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly His Ile Tyr Tyr Ser Gly Asn Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Leu Thr Ile Ser Ile Asp Thr Ser Lys Thr Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Ile Tyr Tyr
85 90 95
Cys Val Arg Asp Arg Val Thr Gly Ala Phe Asp Ile Trp Gly Gln Gly
100 105 110
Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
225 230 235 240
Gly Ser Gly Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu
245 250 255
Asp Leu Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser
260 265 270
Asp Val His Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu
275 280 285
Glu Leu Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp
290 295 300
Thr Val Glu Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn
305 310 315 320
Gly Asn Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu
325 330 335
Lys Asn Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met
340 345 350
Phe Ile Asn Thr Ser
355
<210> 118
<211> 295
<212> PRT
<213> 人工序列
<400> 118
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Phe Cys Gln His Phe Asp His Leu Pro Leu
85 90 95
Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
210 215 220
Gly Gly Gly Gly Ser Gly Ile Thr Cys Pro Pro Pro Met Ser Val Glu
225 230 235 240
His Ala Asp Ile Trp Val Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg
245 250 255
Tyr Ile Cys Asn Ser Gly Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu
260 265 270
Thr Glu Cys Val Leu Asn Lys Ala Thr Asn Val Ala His Trp Thr Thr
275 280 285
Pro Ser Leu Lys Cys Ile Arg
290 295
<210> 119
<211> 580
<212> PRT
<213> 人工序列
<400> 119
Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile
1 5 10 15
Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His
20 25 30
Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln
35 40 45
Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu
50 55 60
Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn Val
65 70 75 80
Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile
85 90 95
Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn
100 105 110
Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
115 120 125
Ser Gly Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile Lys
145 150 155 160
Asp Thr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala Asp
180 185 190
Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr
195 200 205
Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
210 215 220
Tyr Cys Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
245 250 255
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
260 265 270
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
275 280 285
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
290 295 300
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
305 310 315 320
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
325 330 335
His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser
340 345 350
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu
355 360 365
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
370 375 380
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
385 390 395 400
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
405 410 415
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
420 425 430
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
435 440 445
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
450 455 460
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
465 470 475 480
Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val
485 490 495
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
500 505 510
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
515 520 525
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
530 535 540
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
545 550 555 560
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
565 570 575
Ser Pro Gly Lys
580
<210> 120
<211> 531
<212> PRT
<213> 人工序列
<400> 120
Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val
1 5 10 15
Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly
20 25 30
Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn
35 40 45
Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile
50 55 60
Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
65 70 75 80
Gly Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
85 90 95
Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile Lys Asp
100 105 110
Thr Tyr Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
115 120 125
Val Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr Ala Asp Ser
130 135 140
Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala
145 150 155 160
Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr
165 170 175
Cys Ser Arg Trp Gly Gly Asp Gly Phe Tyr Ala Met Asp Tyr Trp Gly
180 185 190
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
195 200 205
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
210 215 220
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
225 230 235 240
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
245 250 255
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
260 265 270
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
275 280 285
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
290 295 300
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
305 310 315 320
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
325 330 335
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
340 345 350
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
355 360 365
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
370 375 380
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
385 390 395 400
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
405 410 415
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
420 425 430
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
435 440 445
Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
450 455 460
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
465 470 475 480
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
485 490 495
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
500 505 510
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
515 520 525
Pro Gly Lys
530

Claims (15)

1.一种免疫细胞因子，其包括：
(A)白介素-15(IL-15)，其中所述IL-15由SEQ ID NO:72或SEQ ID NO:112的氨基酸序列组成；
(B)白介素-15受体a亚基(IL-15Ra)，其中所述IL-15Ra由SEQ ID NO:74或SEQ ID NO:88的氨基酸序列组成；
(C)靶向治疗相关细胞表面抗原的抗体，其中所述治疗相关细胞表面抗原为免疫监测点蛋白或肿瘤抗原；
其中，所述IL-15通过连接肽与所述抗体的重链可变区N端连接，所述IL-15Ra通过连接肽与所述抗体的轻链可变区N端连接；或者，所述IL-15通过连接肽与所述抗体的轻链可变区N端连接，所述IL-15Ra通过连接肽与所述抗体的重链可变区N端连接。
2.根据权利要求1所述的免疫细胞因子，其中所述治疗相关细胞表面抗原选自：表皮生长因子受体家族(EGFR、HER2、HER3、HER4)、PD-1、PD-L1、STEAP1、CTLA-4、4-1BB(CD137)、OX40、CD28、CD40、CD47、CD70、CD80、CD122、GTIR、A2AR、B7-H3(CD276)、B7-H4、IDO、KIR、Tim-3、NY-ESO-1、GPC3、CLL-1、BCMA、mucin家族(MUC1、MUC2、MUC3A、MUC3B、MUC4、MUC5AC、MUC5B、MUC6、MUC7、MUC8、MUC12、MUC13、MUC15、MUC16、MUC17、MUC19、MUC20)、CD19、CD20、CD22、CD30、CD33、CD52、化学趋化因子受体家族(CCR1、CCR2、CCR3、CCR4、CCR5、CCR6、CCR7、CCR8、CCR9、CCR10、CCL27、CCL28、CX3CR1、CXCR1、CXCR2、CXCR3、CXCR4、CXCR5、CXCR6)、PSMA、CEA、HDAC6、EpCAM、Mesothelin、TERT、TLR、TLR9、TLR4、CD33、GITR、Survivin、CD123、TIGIT、TIM-3、CD73、成纤维细胞生长因子受体(FGFR)、血管内皮生长因子受体(FLT1、KDR/Flk-1、VEGFR-
3)、肝细胞生长因子受体(HGFR)、神经生长因子受体(NGFR)、胰岛素样生长因子受体(IGFR)、血小板衍生生长因子受体(PDGFR)、激素受体(黑皮质素1受体(MC1R，MSHR)。
3.根据权利要求2所述的免疫细胞因子，其中所述治疗相关细胞表面抗原选自EGFR、HER2、PD-1、PD-L1、CLL-1、GPC-3、RSV F蛋白、CD19、CD20、CD22、CD30、CD33或CD52。
4.根据权利要求3所述的免疫细胞因子，其中所述靶向治疗相关细胞表面抗原的抗体为靶向EGFR的抗体，该抗体具有如SEQ ID NO:32所示的重链氨基酸序列中所含的HCDR1、HCDR2和HCDR3序列，以及如SEQ ID NO:34所示的轻链氨基酸序列中所含的LCDR1、LCDR2和LCDR3序列；或者具有如SEQ ID NO:32所示的重链氨基酸序列中所含的VH序列，以及如SEQID NO:34所示的轻链氨基酸序列中所含的VL序列。
5.根据权利要求3所述的免疫细胞因子，其中所述靶向治疗相关细胞表面抗原的抗体为靶向HER2的抗体，该抗体具有如SEQ ID NO:18所示的重链氨基酸序列中所含的HCDR1、HCDR2和HCDR3序列，以及如SEQ ID NO:20所示的轻链氨基酸序列中所含的LCDR1、LCDR2和LCDR3序列；或者具有如SEQ ID NO:18所示的重链氨基酸序列中所含的VH序列，以及如SEQID NO:20所示的轻链氨基酸序列中所含的VL序列。
6.根据权利要求3所述的免疫细胞因子，其中所述靶向治疗相关细胞表面抗原的抗体为靶向PD-1的抗体，该抗体具有如SEQ ID NO:76所示的重链氨基酸序列中所含的HCDR1、HCDR2和HCDR3序列，以及如SEQ ID NO:78所示的轻链氨基酸序列中所含的LCDR1、LCDR2和LCDR3序列；或者具有如SEQ ID NO:76所示的重链氨基酸序列中所含的VH序列，以及如SEQID NO:78所示的轻链氨基酸序列中所含的VL序列。
7.根据权利要求3所述的免疫细胞因子，其中所述靶向治疗相关细胞表面抗原的抗体为靶向PD-L1的抗体，该抗体具有SEQ ID NO:36所示的重链氨基酸序列中所含的HCDR1、HCDR2和HCDR3序列，以及如SEQ ID NO:38所示的轻链氨基酸序列中所含的LCDR1、LCDR2和LCDR3序列；或者具有SEQ ID NO:80所示的重链氨基酸序列中所含的HCDR1、HCDR2和HCDR3序列，以及如SEQ ID NO:82所示的轻链氨基酸序列中所含的LCDR1、LCDR2和LCDR3序列，或者具有SEQ ID NO:36所示的氨基酸序列中所含的VH序列，以及如SEQ ID NO:38所示的氨基酸序列中所含的VL序列；或者具有SEQ ID NO:80所示的重链氨基酸序列中所含的VH，以及如SEQ ID NO:82所示的轻链氨基酸序列中所含的VL序列。
8.根据权利要求3所述的免疫细胞因子，其中所述靶向治疗相关细胞表面抗原的抗体为靶向RSV病毒F蛋白的抗体，该抗体具有SEQ ID NO:54所示的重链氨基酸序列中所含的HCDR1、HCDR2和HCDR3序列，以及如SEQ ID NO:56所示的轻链氨基酸序列中所含的LCDR1、LCDR2和LCDR3序列；或者具有SEQ ID NO:54所示的重链氨基酸序列中所含的VH序列，以及如SEQ ID NO:56所示的轻链氨基酸序列中所含的VL序列。
9.根据权利要求1-8中任一项所述的免疫细胞因子，其中所述靶向治疗相关细胞表面抗原的抗体进一步含有Fc片段。
10.根据权利要求9所述的免疫细胞因子，其中所述Fc片段选自人IgG1、IgG2、IgG3或IgG4。
11.根据权利要求1-8中任一项所述的免疫细胞因子，其中所述连接肽独立地选自GGGGSGGGGSGGGGSG、GSPLGVRGS、GSPLGVR、PLGVR、GGGGSGPLGVRGGGGSG或GGGGSGPLGVR。
12.根据权利要求1-8中任一项所述的免疫细胞因子，其中所述免疫细胞因子包含分别具有如下氨基酸序列的重链和轻链：SEQ ID NO:2和SEQ ID NO:8；SEQ ID NO:6和SEQ IDNO:4；SEQ ID NO:68和SEQ ID NO:8；SEQ ID NO:70和SEQ ID NO:4；SEQ ID NO:10和SEQ IDNO:12；SEQ ID NO:14和SEQ ID NO:16；SEQ ID NO:22和SEQ ID NO:24；SEQ ID NO:26和SEQID NO:28；SEQ ID NO:40和SEQ ID NO:24；SEQ ID NO:44和SEQ ID NO:28；SEQ ID NO:46和SEQ ID NO:48；SEQ ID NO:42和SEQ ID NO:58；SEQ ID NO:84和SEQ ID NO:86；SEQ ID NO:60和SEQ ID NO:62；SEQ ID NO:64和SEQ ID NO:66；SEQ ID NO:115和SEQ ID NO:116；SEQID NO:117和SEQ ID NO:118；SEQ ID NO:119和SEQ ID NO:12；SEQ ID NO:120和SEQ IDNO:16；SEQ ID NO:90和SEQ ID NO:34；SEQ ID NO:92和SEQ ID NO:34；SEQ ID NO:94和SEQID NO:34；SEQ ID NO:96和SEQ ID NO:34；SEQ ID NO:98和SEQ ID NO:20；SEQ ID NO:100和SEQ ID NO:20；SEQ ID NO:110和SEQ ID NO:102；SEQ ID NO:110和SEQ ID NO:104；SEQID NO:98和SEQ ID NO:102；SEQ ID NO:98和SEQ ID NO:104；SEQ ID NO:100和SEQ ID NO:102；SEQ ID NO:100和SEQ ID NO:104；SEQ ID NO:106和SEQ ID NO:20；SEQ ID NO:110和SEQ ID NO:108；SEQ ID NO:106和SEQ ID NO:108；SEQ ID NO:113和SEQ ID NO:34；SEQ IDNO:114和SEQ ID NO:34。
13.一种核酸，编码如权利要求1-12中任一项所述的免疫细胞因子。
14.一种载体，其包含如权利要求13所述的核酸。
15.一种宿主细胞，其包含如权利要求14所述的载体。
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