CN110831669A - 神经退行性疾病病理的光遗传学诱导 - Google Patents

神经退行性疾病病理的光遗传学诱导 Download PDF

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CN110831669A
CN110831669A CN201880024360.1A CN201880024360A CN110831669A CN 110831669 A CN110831669 A CN 110831669A CN 201880024360 A CN201880024360 A CN 201880024360A CN 110831669 A CN110831669 A CN 110831669A
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C·J·唐纳利
J·R·曼恩
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Abstract

本公开涉及用于诱导神经退行性疾病病理的化合物、组合物和方法。在一个方面,本文公开了编码嵌合多肽的核苷酸序列,所述核苷酸序列包含:编码光诱导的寡聚化结构域的第一核苷酸序列和编码神经退行性疾病靶蛋白的第二核苷酸序列。本文公开了一种在细胞中诱导神经退行性疾病病理的方法,所述方法包括以下步骤:将编码嵌合多肽的表达载体导入细胞,所述表达载体包含:编码光诱导的寡聚化结构域的第一核苷酸序列和编码来自神经退行性疾病靶蛋白的低复杂性结构域的第二核苷酸序列,其中,第一核苷酸序列与启动子可操作地连接;表达嵌合多肽;和通过用蓝光刺激诱导嵌合多肽的寡聚化。

Description

神经退行性疾病病理的光遗传学诱导
相关申请的交叉引用
本申请要求于2017年3月7日提交的美国临时专利申请序列号62/468,065的权益,其公开内容通过引用明确并入本文。
技术领域
本公开涉及用于诱导神经退行性疾病病理的化合物、组合物和方法。
背景技术
世界正在衰老。到2050年,超过60岁的人口比例将从2000年的6.05亿增加到20亿。不幸的是,衰老是发展致命神经退行性疾病的最大风险因素。反过来,患有痴呆症(诸如阿尔茨海默氏病(AD)、路易体痴呆(LBD)、额颞痴呆(FTD))和运动障碍(诸如帕金森氏病(PD)和肌萎缩侧索硬化症(ALS))的患者人数将显著增加。目前,美国有近650万人患有这些疾病中的一种,并且相关费用是不可持续的。
在美国,目前AD、PD和ALS的经济负担估计为每年2410亿美元。AD和ALS/FTD患者每年可承担高达100,000美元至250,000美元的个人医疗费用。对于AD,估计到2050年美国将有1380万人被诊断出来,而2010年为470万人,而到2040年全球ALS病例数将增加约31%,目前对于这些疾病尚无有效治疗方法。尽管有多种基因突变导致这些神经退行性疾病,但没有已知的单一原因。然而,尽管存在这种多样性,但每种疾病中的几乎所有患者都表现出细胞内蛋白质聚集体形式的共同神经病理学标志。重现这些神经病理学的动物模型目前需要使用基因突变或严重过表达的蛋白质,这些通常不能模仿患者的病理学。需要的是用于在细胞系和动物模型中用于诱导神经退行性疾病病理的新的和改进的方法。
本文公开的化合物、组合物和方法解决了这些和其他需要。
发明内容
本文公开了用于在细胞或动物中诱导神经退行性疾病病理的化合物、组合物和方法。本发明人开发了用于在细胞和动物中诱导神经退行性疾病病理的新方法,而不需要基因突变或严重过表达的神经退行性疾病蛋白。
一方面,本文公开了编码嵌合多肽的核苷酸序列,所述核苷酸序列包含:编码光诱导的寡聚化结构域的第一核苷酸序列和编码来自神经退行性疾病靶蛋白的低复杂性结构域的第二核苷酸序列。
一方面,本文公开了编码嵌合多肽的表达载体,所述表达载体肽包含:编码光诱导的寡聚化结构域的第一核苷酸序列和编码来自神经退行性疾病靶蛋白的低复杂性结构域的第二核苷酸序列,其中,第一核苷酸序列与启动子可操作地连接。
一方面,本文公开了包含编码嵌合多肽的核苷酸序列的细胞,所述细胞包含:编码光诱导的寡聚化结构域的第一核苷酸序列和编码神经退行性疾病靶蛋白的第二核苷酸序列。
一方面,本文公开了一种嵌合多肽,所述嵌合多肽包含:光诱导的寡聚化结构域;和来自神经退行性疾病靶蛋白的低复杂性结构域。
一方面,本文公开了一种在细胞中诱导神经退行性疾病病理的方法,所述方法包括以下步骤:
将编码嵌合多肽的表达载体导入细胞,所述表达载体包含:
编码光诱导的寡聚化结构域的第一核苷酸序列和编码来自神经退行性疾病靶蛋白的低复杂性结构域的第二核苷酸序列,其中,第一核苷酸序列与启动子可操作地连接;
表达嵌合多肽;和
通过用蓝光刺激而诱导嵌合多肽的寡聚化。
另一方面,本文公开了筛选调节蛋白质聚集的试剂的方法,所述方法包括以下步骤:
将编码嵌合多肽的表达载体导入细胞,所述表达载体包含:
编码光诱导的寡聚化结构域的第一核苷酸序列和编码来自神经退行性疾病靶蛋白的低复杂性结构域的第二核苷酸序列,其中,第一核苷酸序列与启动子可操作地连接;
表达嵌合多肽;
将所述试剂引入包含细胞的培养基中;
通过用蓝光刺激而诱导嵌合多肽的寡聚化;和
确定所述试剂对蛋白质聚集的调节。
在一个实施方式中,光诱导的寡聚化结构域选自以下组成的组:CRYPHR、CRY2OLIG、NcVVD、NcVVDY50W、NcLOV、VfAU1、YtvA、EL222、RsLOV和AsLOV2。在一个实施方式中,光诱导的寡聚化结构域选自表2中的结构域列表。在一个实施方式中,光诱导的寡聚化结构域是NcVVDY50W。在一个实施方式中,光诱导的寡聚化结构域是CRY2OLIG。在一个实施方式中,光诱导的寡聚化结构域是CRYPHR。
在一个实施方式中,光诱导的寡聚化结构域选自以下组成的组:CRY2PHR结构域(例如,CRY2PHR、CRY2OLIG)或光氧电压感测(LOV)结构域(例如,NcVVD、NcVVDY50W、VfAU1、YtvA、EL222、RsLOV、AsLOV2)。
在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自以下组成的组:TDP-43、ɑ突触核蛋白、Tau、Fus、TIA1、SOD1、亨廷顿蛋白(Huntingtin)、Ataxin 2、hnRNPA1、hnRNPA2B1、EWS RNA结合蛋白1和TATA盒结合蛋白因子15。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自表3。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是TDP-43。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是ɑ突触核蛋白。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是Tau。
在一个实施方式中,所述细胞是哺乳动物细胞。在一个实施方式中,所述细胞是人类细胞。
在一个实施方式中,蓝光的波长在405nm和499nm之间。在一个实施方式中,蓝光的波长为约465nm。
附图说明
附图包含在本说明书中并构成其一部分,其示出了下面描述的几个方面。
图1显示了ALS的遗传原因和常见神经病理的实例。左图在Y轴上显示了引起ALS的基因数量的图表,X轴表示发现每个突变的年份。在图1中,图A显示ALS表现出极端的遗传异质性,特别是因为这些突变仅在约10%的ALS病例中发现。如表1所述,尽管存在ALS的这些遗传原因,但几乎所有患者在运动皮层和脊髓中都表现出相同的神经病理学。右图通过对来自ALS患者运动皮层的石蜡组织切片的H和E染色而显示了ALS神经病理学的实例。显示的是TDP-43的细胞质聚集体。TDP-43在正常细胞中主要是核,如*所示。在ALS中,如箭头所示,TDP-43不存在于细胞核中并且在细胞质中聚集。虽然以ALS为例,细胞质聚集神经病理学是许多神经退行性疾病的常见特征,参见表1。
图2A-2B描述了使用TDP-43和CRY2OLIG作为实例利用光产生含有LCD/IDR/朊病毒样结构域的神经病理学聚集蛋白的方法。开发了各种蛋白质排列和蓝光暴露范例以诱导含有LCD/IDR/朊病毒样结构域结构域的蛋白质和蛋白质片段的蛋白质聚集,促进核蛋白质的错误定位并重现神经退行性疾病的神经病理学。TDP-43主要是含有DR/IDD/朊病毒样结构域的核蛋白,并且作为实例,在ALS、FTD和某些AD患者中错误定位和聚集。设计DNA序列以产生编码CRY2OLIG蛋白的氨基酸序列,该蛋白在暴露于蓝光时成簇,产生融合蛋白,或是整个TDP-43蛋白(cry2-TDP43-mCh)或仅低复杂性结构域(LCD/IDD/朊病毒样结构域),这使得TDP-43易于聚集(Cry2-274-mCh)。作为对照,仅使用CRY2OLIG。将所有构建体与称为mCherry(mCh)的荧光蛋白融合以事活细胞中的蛋白质可视化。用蓝光刺激CRY2OLIG-mCh可逆地聚集,但用特定的蓝光刺激范例,CRY2OLIG-TDP-43-mCh或截短的CRY2OLIG-274-mCh形成不可逆的聚集体。图2A显示了在该工作中使用的CRY2OLIG-TDP-43布置和截短的CRY2OLIG-274布置的实例。图2B显示了所描述的技术的模型。
图3显示了使用NcVVD、NcVVDY50W或NcLOV感光体描述蛋白质的蓝光诱导的寡聚化和聚集的示意图。NcVVD或LOV结构域仅用蓝光刺激显示同源二聚化。开发了诱导寡聚化和聚集的光暴露范例。上图显示了当与感兴趣的蛋白质融合时,用蓝光(405nm-499nm)的单次急性刺激如何诱导LOV蛋白的同源二聚化的示意图。下图显示用蓝光进行的慢性刺激促进了含有朊病毒样结构域/LCD/IDD的NcVVD或LOV融合蛋白的同源寡聚化。
图4A-4E显示了低复杂性结构域蛋白的光诱导聚集。使用光刺激,含有低复杂性结构域(LCD)的光遗传学TDP-43片段经历渐进聚集。(图4A-4B)当通过活共聚焦显微镜监测时,TDP-43的C-末端片段(optoRRM2+LCD/optoLCD)在蓝光的短暂脉冲(8秒,10%激光功率,488nm)后快速寡聚化。这些寡聚物比单独的Cry2光感受器持续更长时间(约10分钟的拆解)。(图4C-4D)光遗传学LCD片段在短暂的光脉冲之后也继续聚集,随着时间的推移尺寸增大。(图4E)TDP-43LCD的持续蓝光刺激在细胞中形成细胞内聚集体。光漂白(FRAP)实验后的荧光恢复显示持久的轻LCD内含物不能从FRAP中恢复,表明这些不可溶。
图5A-5K显示了慢性蓝光刺激诱导了optoTDP43的错误定位和聚集,其概括了在患者CNS组织中看到的病理学特征。将表达optoTDP43-mCh的HEK293细胞暴露于488nm LED刺激或黑暗中长达36小时。(图5A-5C)代表性图像显示了optoTDP43(图5B)首先经历逐渐的细胞质错误定位,(图5C)其通过核/细胞质级分证实。(图5D)如通过同时进行的慢性蓝光暴露和高通量自动共聚焦显微镜所测量的,在optoTDP43聚集之后是错误定位,其随着暴露的增加而倾向增加。(图5E)进行在光漂白(FRAP)成像后的荧光恢复以评估optoTDP43结构的动力学。荧光恢复的缺乏表明光诱导的optoTDP43聚集体是非动态的固定颗粒,让人联想到聚集结构。(图5F)通过亚细胞分级评估optoTDP43结构的去垢剂溶解性,以确认光诱导的optoTDP43颗粒的聚集状态。(左泳道)非光遗传性TDP-43(TDP43-mCh)在使用和不使用光处理的情况下都没有显示出溶解度的变化,而在慢性的蓝光刺激下,optoTDP43(右泳道)显示了向不溶级分的急剧变化。除了增加外源性全长optoTDP43(上条带)的不溶性外,慢性蓝光暴露还导致募集异常的optoTDP43切割产物(中间条带)以及内源性全长TDP-43和与疾病相关的切割产物(底部条带),如在患者组织中观察到的细胞切割物的去污剂不溶、尿素可溶的级分。(图5G)为了证实将非光遗传性TDP-43物质直接募集到外源光诱导的optoTDP43内含物中,将带有EGFP标签的TDP-43与optoTDP43或仅Cry2光感受器对照共表达。在暴露于慢性蓝光刺激的细胞中,在optoTDP43内含物和EGFP-TDP43之间观察到强烈的共定位,从而确认optoTDP43内含物直接募集其他TDP-43物质的能力。这种募集似乎依赖于TDP43:TDP43的相互作用,因为在蓝光暴露后未观察到Cry2-mCh斑点的共定位。(图5H-5J)对光诱导的optoTDP43聚集体进行了免疫荧光分析,以确认在患者组织中看到的病理学标志。optoTDP43内含物似乎是(图5H)泛素化的,(图5I)超磷酸化的和(图5J)p62阳性的,所有这些均已在患者CNS中用TDP-43内含物观察到。(图5K)进行自动化的高通量共聚焦显微镜以评估光诱导的optoTDP43内含物的神经毒性。将表达TDP43-mCh或optoTDP43的人类ReN神经元暴露于慢性蓝光刺激下,并通过纵向成像同时监测其生存力。表达非光遗传性TDP43-mCh的神经元在暴露或不暴露于蓝光下均未显示存活率显著降低。但是,暴露于蓝光刺激的表达optoTDP43的神经元随时间的推移显示出明显降低的生存力,这表明optoTDP43内含物具有神经毒性。*=p<.05,**=p<.01
图6A-6E显示了CRY2OLIGα-突触核蛋白或α-突触核蛋白LOV的慢性刺激诱导成簇和聚集。测试了CRY2-asyn-mCh的慢性刺激以诱导α-突触核蛋白聚集。图6A显示了慢性刺激范例,图6B显示了随着时间的推移利用光的α-突触核蛋白成簇的代表性图像以及图6C中的成簇的量化。这些数据表明,该光遗传学系统可用于诱导易于聚集的多种神经退行性疾病蛋白(即含有朊病毒样结构域/LCD/IDD的蛋白)的成簇和聚集。图6D显示了与LOV(二聚化光感受器)融合的α-突触核蛋白形成α突触核蛋白的细胞内簇。图6E显示了光诱导的α-突触核蛋白LOV聚集体表现出突触核蛋白病的病理学特征,其包括129位丝氨酸的磷酸化和p62阳性。
图7A-7D显示了Cry2-Tau融合蛋白,该融合蛋白显示了各种Tau蛋白病的病理学标志物。(图7A-7C)将表达单独的Cry2光感受器或Cry2-Tau融合蛋白的HEK293细胞暴露于慢性蓝光刺激(16小时,488nm,10mW)。表达Cry2-Tau的细胞显示出与磷酸化Tau抗体AT8(图7A)和PHF1(图7B)以及病理构象依赖性Tau抗体MC1(图7C)共染色的原纤维样聚集体。(图7D)概述显示了在光诱导神经原纤维缠结形成之后与病理性Tau抗体共定位的各种光遗传性Tau构建体。
图8A-8E显示了LOV-Tau融合蛋白还显示了各种Tau蛋白病的病理学标志物并且是不可溶的。(图8A-图8B)将表达VVD-Tau或VfAU-Tau融合蛋白的HEK293细胞暴露于慢性蓝光刺激(16小时,488nm,10mW)。两种融合蛋白均与磷酸化Tau抗体AT8和PHF1以及病理构象依赖性Tau抗体MC1共染色。(图8C)表达VVD-Tau的分化的MAP2+人ReN神经元还显示出在与AT8共定位的慢性光处理后神经原纤维缠结的形成。(图8D)对光诱导的缠结进行在光漂白分析后的荧光恢复,并显示缺乏荧光恢复,其表明非动态固定的结构。(图8E)接下来进行尿素提取以在表达VVD-Tau的HEK293细胞中用光处理确认不溶性tau物质。暴露于慢性光下的细胞显示出增加水平的可溶性和不溶性150kDa tau物质,该物质存在于阿尔茨海默氏病和额颞痴呆患者组织中。
图9A-9B显示了基于蛋白质排列和光刺激范例组合的CRY2或VVD融合蛋白的聚集潜力。研究表明,Cry2或VVD光感受器刺激成簇和激活的能力取决于蛋白质排列以及光刺激范例。图9A显示了TDP-43-CRY2OLIG-mCh蛋白错误定位,但没有表现出像CRY2OLIG-TDP-43-mCh排列那样聚集的能力。类似地,图9B显示了mCh-aSyn-NvVVDY50W不具有聚集能力。该数据表明,蛋白质排列和光刺激范例对于诱导神经病理蛋白聚集非常重要,如在神经退行性疾病患者的CNS组织中观察到的。
图10A-10B显示了蓝光诱导的TDP-43聚集体或截短的LCD/IDR/朊病毒样结构域聚集体对细胞有毒性。图10A显示表达CRY2OLIG-TDP274-mCh的HEK细胞的急性刺激可以在1小时内诱导病理性聚集体的形成。随着时间的流逝,这些聚集体尺寸增长并且变得有毒。图10B是使用神经退行性疾病病理的诱导来鉴定可挽救毒性并预防或消除诱导的神经退行性疾病病理的形成的治疗性化合物的筛选管线的示意图。
具体实施方式
本文公开了用于在细胞或动物中诱导神经退行性疾病病理的化合物、组合物和方法。本发明人已经开发了用于在细胞和动物中诱导神经退行性疾病病理的新方法,而无需基因突变或严重过表达神经退行性疾病蛋白。
现在将详细参考本发明的实施方式,其实例在附图和实施例中示出。然而,本发明可以以许多不同的形式来实施,并且不应被解释为限于在此阐述的实施方式。
除非另有定义,否则本文中使用的所有技术和科学术语具有与本公开所属领域的普通技术人员通常理解的相同含义。本文所使用的术语“包含”及其变体与术语“包括”及其变体同义使用,并且是开放的非限制性术语。尽管本文已使用术语“包含”和“包括”来描述各种实施方式,但是可以使用术语“基本上由……组成”和“由……成”来代替“包含”和“包括”以提供更具体的实施方式,并且也被公开。
提供以下定义是为了完全理解本说明书中使用的术语。
术语
如本文所用,冠词“一”、“一个”和“该”表示“至少一个”,除非使用该冠词的上下文另外明确指出。
当涉及诸如量、百分比等的可测量值时,本文所使用的术语“约”意味着包含与可测量值相差±20%,±10%,±5%或±1%的变化。
如本文所用,术语“可以”、“可选地”和“可以可选地”可互换使用,并且意在包括其中发生状况的情况以及不发生状况的情况。
本文所用的术语“核酸”是指由核苷酸(例如脱氧核糖核苷酸或核糖核苷酸)组成的聚合物。
本文所用的术语“核糖核酸”和“RNA”是指由核糖核苷酸组成的聚合物。
本文所用的术语“脱氧核糖核酸”和“DNA”是指由脱氧核糖核苷酸组成的聚合物。
术语“寡核苷酸”表示长度为约2至多达约100个核苷酸的单链或双链核苷酸多聚体。合适的寡核苷酸可通过Beaucage和Carruthers,Tetrahedron Lett.,22:1859-1862(1981)所述的亚磷酰胺方法,或根据Matteucci等,J.Am.Chem.Soc.,103:3185(1981)三酯法制备,二者均通过引用或通过使用商业自动化寡核苷酸合成仪或VLSIPSTM技术的其他化学方法并入本文。当寡核苷酸被称为“双链”时,本领域技术人员应理解,一对寡核苷酸存在于通常与例如DNA相关的氢键结合的螺旋阵列中。除了双链寡核苷酸的100%互补形式外,本文所用的术语“双链”还意指包括这样的结构特征(如凸起和环)的那些形式,其在如Stryer,Biochemistry,第三版,(1988)这些生物化学文本中更充分地描述,将其出于所有目的通过引用并入本文。
术语“多核苷酸”、“核苷酸序列”和“核酸序列”在本文可互换使用,并且是指由核苷酸单体组成的单链或双链聚合物。
术语“多肽”是指由通过肽键连接的D-或L-氨基酸或D-和L-氨基酸的混合物的单链组成的化合物。
术语“互补的”是指探针分子与其靶标的相互作用表面的拓扑相容性或匹配在一起。因此,靶标及其探针可被描述为互补的,此外,接触表面特性彼此互补。
术语“杂交”是指将两条以上互补核酸链之间的非共价序列特异性相互作用的建立为单个杂交物的过程,在两条链的情况下被称为双链体。
术语“退火”是指其中单链核酸序列通过氢键与互补序列配对,形成双链核酸序列的过程,其包括互补链的重整(复性),所述互补链通过热分离(热变性)。
术语“解链”是指由于高温引起的双链核酸序列的变性,从而通过断开链之间的氢键将双链分离成两条单链。
术语“启动子”或“调控元件”是指位于转录起始上游或下游并且参与RNA聚合酶和其他蛋白质的识别和结合以起始转录的区域或序列决定簇。启动子不必是细菌来源的,例如,衍生自病毒或其他生物的启动子可用于本文所述的组合物、系统或方法中。术语“调节元件”旨在包括启动子、增强子、内部核糖体进入位点(IRES)和其他表达控制元件(例如转录终止信号,诸如聚腺苷酸化信号和poly-U序列)。这样的调控元件例如在以下文献中描述:Goeddel,Gene Expression Technology:Methods inEnzymology 185,AcademicPress,San Diego,Calif(1990)。调控元件包括在许多类型的宿主细胞中指导核苷酸序列组成性表达的那些和仅在某些宿主细胞中指导核苷酸序列表达的那些(例如组织特异性调控序列)。组织特异性启动子可以指导主要在所需的目标组织中的表达,诸如肌肉、神经元、骨骼、皮肤、血液、特定器官(例如肝脏、胰腺)或特定细胞类型(例如淋巴细胞)。调控元件也可以以时间依赖性的方式指导表达,诸如以细胞周期依赖性或发育阶段依赖性的方式,其也可以是或不是组织特异性或细胞类型特异性的。在某些实施方式中,载体包含一个或多个pol III启动子(例如1、2、3、4、5或更多个pol I启动子),一个或多个pol II启动子(例如1、2、3、4、5,或更多个pol II启动子),一个或多个pol I启动子(例如1、2、3、4、5或更多个pol I启动子)或其组合。pol III启动子的实例包括但不限于U6和H1启动子。pol II启动子的例子包括但不限于逆转录病毒劳斯肉瘤病毒(RSV)LTR启动子(可选地带有RSV增强子)、巨细胞病毒(CMV)启动子(可选地带有CMV增强子)[参见,例如,Boshart等,Cell,41:521-530(1985)]、SV40启动子、二氢叶酸还原酶启动子、β-肌动蛋白启动子、磷酸甘油激酶(PGK)启动子和EF1α启动子。术语“调控元件”还包括增强子元件,诸如WPRE;CMV增强子;HTLV-I的LTR中的R-U5′区段(Mol.Cell.Biol.,第8卷(1),第466-472页,1988);SV40增强子;和兔β-球蛋白的外显子2和3之间的内含子序列(Proc.Natl.Acad.Sci.USA.,第78卷(3),第1527-31页,1981)。本领域技术人员将认识到,表达载体的设计可以取决于诸如待转化的宿主细胞的选择,所需表达水平等因素。
术语“重组”是指人为操纵的核酸(例如,多核苷酸)或人为操纵的核酸(例如,多核苷酸)的拷贝或补体,或者如果涉及蛋白质(即“重组蛋白”),通过重组核酸(例如多核苷酸)编码的蛋白质。在实施方式中,包含可操作地连接至第二核酸(例如多核苷酸)的启动子的重组表达盒可以包括由于人为操纵(例如,通过以下描述的方法,Sambrook等,MolecularCloning—A Laboratory Manual,Cold Spring Harbor Laboratory,Cold SpringHarbor,N.Y.,(1989)或Current Protocols in Molecular Biology第1-3卷,John Wiley&Sons,Inc.(1994-1998))而与第二核酸(例如多核苷酸)是异源的启动子。在另一个实例中,重组表达盒可以包含以这样的方式组合的核酸(例如多核苷酸),使得在自然界中极不可能发现所述核酸(例如多核苷酸)。例如,人为操纵的限制性位点或质粒载体序列可以将启动子与第二核酸(例如多核苷酸)侧接或分离。本领域技术人员将认识到,可以以许多方式来操纵核酸(例如多核苷酸),并且不限于上述实例。
术语“表达盒”是指核酸构建体,当其被引入宿主细胞时,其分别导致RNA或多肽的转录和/或翻译。在实施方式中,包含可操作地连接至第二核酸(例如多核苷酸)的启动子的表达盒可以包括由于人为操纵(例如,通过以下描述的方法,Sambrook等,MolecularCloning—A Laboratory Manual,Cold Spring Harbor Laboratory,Cold SpringHarbor,N.Y.,(1989)或Current Protocols in Molecular Biology第1-3卷,John Wiley&Sons,Inc.(1994-1998))而与第二核酸(例如多核苷酸)是异源的启动子。在某些实施方式中,包含可操作地连接至第二核酸(例如多核苷酸)的终止子(或终止序列)的表达盒可以包括由于人为操纵而与第二核酸(例如多核苷酸)异源的终止子。在某些实施方式中,表达盒包含作为人为操纵结果的可操作地连接至第二核酸(例如多核苷酸)的启动子和可操作地连接至第二核酸(例如多核苷酸)的终止子。在某些实施方式中,表达盒包含内源性启动子。在某些实施方式中,表达盒包含内源性终止子。在某些实施方式中,表达盒包含合成(或非天然)启动子。在某些实施方式中,表达盒包含合成(或非天然)终止子。
在两个以上核酸或多肽序列的上下文中,术语“相同”或“同一性”百分数是指两个以上序列或亚序列或者具有指定百分比(即,在比较窗或指定区域进行比较和比对以获得最大对应性时,在指定区域具有约60%同一性,优选61%、62%、63%、64%、65%、66%、67%、68%、69%、70%、71%、72%、73%、74%、75%、76%、77%、78%、79%、80%、81%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%,94%、95%、96%、97%、98%、99%以上同一性)的氨基酸残基或核苷酸与使用具有以下描述的默认参数的BLAST或BLAST 2.0序列比较算法或通过手动比对和视觉检测的相同检查(例如,参见NCBI网站等)测量相同。然后,这样的序列被认为是“基本上相同的”。该定义也指的是或可以应用于测试序列的互补。该定义还包括具有缺失和/或添加的序列以及具有取代的序列。如下所述,优选算法可以考虑空位等。优选地,同一性存在于长度至少约10个氨基酸或20个核苷酸的区域上,或更优选地存在于长度为10个至50个氨基酸或20个至50个核苷酸的区域上。如本文所用,氨基酸序列同一性百分比(%)被定义为候选序列中与参考序列中的氨基酸相同的氨基酸的百分比,在比对序列并引入空位之后(如果必要的话),以实现最大序列同一性百分比。用于确定序列同一性百分比的比对可以以本领域技术范围内的多种方式来实现,例如,使用公开可用的计算机软件,诸如BLAST、BLAST-2、ALIGN、ALIGN-2或Megalign(DNASTAR)软件。可以通过已知方法确定用于测量比对的合适参数,包括在所比较的序列的全长上实现最大比对所需的任何算法。
为了进行序列比较,通常将一个序列用作参考序列,将测试序列与其进行比较。使用序列比较算法时,将测试序列和参考序列输入计算机,必要时指定子序列坐标,并指定序列算法程序参数。优选地,可以使用默认程序参数,或者可以指定替代参数。然后,序列比较算法根据程序参数计算测试序列相对于参考序列的序列同一性百分比。
适于确定序列同一性和序列相似性百分比的算法的一个实例是BLAST和BLAST2.0算法,这些算法分别在Altschul等(1977)Nuc.Acids Res.25:3389-3402,和Altschul等(1990)J.Mol.Biol.215:403-410中描述。可通过国家生物技术信息中心(http://www.ncbi.nlm.nih.gov/)公开获得进行BLAST分析的软件。该算法涉及首先通过识别查询序列中长度为W的短单词来识别高分序列对(HSP),这些短单词在与数据库序列中相同长度的单词比对时匹配或满足某些正值阈值得分T。T被称为邻近单词分数阈值(Altschul等(1990)J.Mol.Biol.215:403-410)。这些最初的邻近单词命中充当启动搜索以查找包含它们的较长HSP的种子。单词命中沿着每个序列在两个方向上延伸,直到可以增加累积比对得分为止。对于核苷酸序列,使用参数M(一对匹配残基的奖励分数;始终>0)和N(错配残基的罚分;始终<0)来计算累积分数。对于氨基酸序列,使用得分矩阵来计算累积分数。在以下情况下,将停止单词命中在每个方向上的扩展:累积比对分数比其最大实现值减少数量X;由于一个或多个负得分残基比对的累积,累积得分变为零以下;或到达任一序列的末尾。BLAST算法参数W、T和X确定比对的灵敏度和速度。BLASTN程序(对于核苷酸序列)默认使用字长(W)为11,期望(E)为10,M=5,N=-4以及两条链的比较。对于氨基酸序列,BLASTP程序默认使用字长为3和期望值(E)为10,以及BLOSUM62评分矩阵(参见Henikoff和Henikoff(1989)Proc.Natl.Acad.Sci.USA 89:10915)比对(B)为50,期望(E)为10,M=5,N=-4,以及两条链的比较。
BLAST算法还对两个序列之间的相似性进行统计分析(参见,例如,Karlin和Altschul(1993)Proc.Natl.Acad.Sci.USA 90:5873-5787)。BLAST算法提供的一种相似性度量是最小总和概率(P(N)),其提供了偶然发生两个核苷酸或氨基酸序列匹配的概率的指示。例如,如果在测试核酸与参考核酸的比较中最小的总和概率小于约0.2,更优选小于约0.01,则认为该核酸与参考序列相似。
短语“经密码子优化”是指用于转化各种宿主的核酸分子的基因或编码区,是指多核酸分子的基因或编码区中密码子的变化,以反映选定生物体的典型密码子用法,而不改变DNA编码的多肽。这样的优化包括用一种或多种在该所选生物体的基因中更频繁使用的密码子替换至少一个或多个,或一个或大量的密码子。
当核酸与另一核酸序列处于功能关系时,核酸是“可操作地连接的”。例如,如果前序列或分泌前导序列的DNA表达为参与多肽分泌的前蛋白,则所述前序列或分泌前导序列可操作地连接至该多肽的DNA;如果启动子或增强子影响编码序列的转录,则所述启动子或增强子可操作地连接至编码序列;或者如果核糖体结合位点被定位以便于翻译,则所述核糖体结合位点可操作地连接至编码序列。通常,“可操作地连接的”是指被连接的DNA序列彼此靠近,并且在分泌前导序列的情况下,是连续的并且处于阅读阶段。然而,可操作地连接的核酸(例如增强子和编码序列)不必是连续的。通过在方便的限制性位点连接来完成连接。如果不存在这样的位点,则根据常规实践使用合成的寡核苷酸连接子或接头。在实施方式中,当启动子能够影响(例如相对于没有启动子的情况下进行调节)来自所述编码序列的蛋白质的表达时(即,所述编码序列在启动子的转录控制下),所述启动子与编码序列可操作地连接。
如本文所用的术语“变体”或“衍生物”是指衍生自具有一个或多个氨基酸取代、插入和/或缺失的亲本蛋白质的氨基酸序列的氨基酸序列。
嵌合构建体
一方面,本文公开了编码嵌合多肽的核苷酸序列,所述核苷酸序列包含:编码光诱导的寡聚化结构域的第一核苷酸序列和编码来自神经退行性疾病靶蛋白的低复杂性结构域的第二核苷酸序列。
一方面,本文公开了编码嵌合多肽的表达载体,所述表达载体包含:编码光诱导的寡聚化结构域的第一核苷酸序列和编码来自神经退行性疾病靶蛋白的低复杂性结构域的第二核苷酸序列,其中,第一核苷酸序列与启动子可操作地连接。
在某些实施方式中,编码嵌合多肽的表达载体包含在质粒或病毒或病毒载体中。质粒或病毒载体可以是能够进行染色体外复制的,或者可选地,可以整合到宿主基因组中。如本文所用,用于表达载体(例如质粒或病毒载体)的术语“整合的”是指将表达载体或其一部分引入(物理插入或连接)到宿主细胞的染色体DNA中。如本文所用,“病毒载体”是指含有遗传物质的病毒样颗粒,其可以被引入真核细胞而不会对真核细胞造成实质的致病作用。可以使用多种病毒或病毒载体进行转导,但应与将病毒或病毒载体转导的细胞类型兼容(例如低毒性,进入细胞的能力)。除其他外,合适的病毒和病毒载体包括腺病毒、慢病毒、逆转录病毒。在某些实施方式中,编码嵌合多肽的表达载体是裸DNA或包含在纳米颗粒(例如脂质体囊泡、多孔硅纳米颗粒、金-DNA缀合物颗粒、聚乙烯亚胺聚合物颗粒、阳离子肽等)中。
在某些实施方式中,本公开的表达载体能够在细胞中诱导神经退行性疾病病理(例如,诱导蛋白质的聚集),而基本上不改变参与神经退行性疾病病理的蛋白质的表达水平。例如但不限于,表达载体可以诱导来自神经退行性疾病靶蛋白的具有低复杂性结构域的蛋白质的聚集,而基本上不增加或降低包含相同低复杂性结构域的内源性靶蛋白的表达水平。这样,与不包含编码嵌合多肽的核苷酸序列的相同细胞类型的细胞相比,包含本文公开的编码嵌合多肽的核苷酸序列的细胞可以具有基本上未改变的表达水平的包含低复杂性结构域的内源性神经退行性疾病靶蛋白。如本文所用,术语“基本上未改变的表达水平”是指表达水平的变化,如果有的话,达到未知或不怀疑会引起细胞中的神经退行性疾病病理或与之相关的程度。
在某些实施方式中,本文公开的表达载体能够使用来自神经退行性疾病靶蛋白的低复杂性结构域的野生型形式诱导细胞中的神经退行性疾病病理(例如,诱导蛋白质的聚集)。因此,在某些实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域不包括不同于野生型序列并且已知或怀疑引起细胞中的神经退行性疾病病理或与其相关的突变。例如但不限于,表达载体可以包含来自野生型TDP-43蛋白的低复杂性结构域,其不包含已知引起或与ALS相关的突变,诸如Q331K。
一方面,本文公开了包含编码嵌合多肽的核苷酸序列的细胞,所述细胞包含:编码光诱导的寡聚化结构域的第一核苷酸序列和编码神经退行性疾病靶蛋白的第二核苷酸序列.
在某些实施方式中,所述细胞是可以受到神经退行性疾病影响的细胞。例如,所述细胞可以是神经胶质细胞或神经元细胞。
一方面,本文公开了嵌合多肽,所述嵌合多肽包含:光诱导的寡聚化结构域;和来自神经退行性疾病靶蛋白的低复杂性结构域。
在一个实施方式中,光诱导的寡聚化结构域选自以下组成的组:CRYPHR、CRY2OLIG、NcVVD、NcVVDY50W和NcLOV。在一个实施方式中,光诱导的寡聚化结构域选自以下组成的组:CRYPHR、CRY2OLIG、NcVVD、NcVVDY50W、NcLOV、VfAU1、YtvA、EL222、RsLOV和AsLOV2。在一个实施方式中,光诱导的寡聚化结构域选自表2中的结构域列表。在一个实施方式中,光诱导的寡聚化结构域选自以下的变体:CRYPHR、CRY2OLIG、NcVVD、NcVVDY50W、NcLOV、VfAU1、YtvA、EL222、RsLOV或AsLOV2。在一个实施方式中,光诱导的寡聚化结构域选自以下的片段:CRYPHR、CRY2OLIG、NcVVD、NcVVDY50W、NcLOV、VfAU1、YtvA、EL222、RsLOV或AsLOV2。
在一个实施方式中,光诱导的寡聚化结构域是NcVVDY50W。在一个实施方式中,光诱导的寡聚化结构域是CRY2OLIG。在一个实施方式中,光诱导的寡聚化结构域是CRYPHR。在一个实施方式中,光诱导的寡聚化结构域包含来自VVD蛋白的LOV结构域。在一个实施方式中,光诱导的寡聚化结构域包含来自LOV蛋白的LOV结构域。在一个实施方式中,光诱导的寡聚化结构域包含PHR结构域。在一个实施方式中,光诱导的寡聚化结构域包含来自CRY2蛋白的PHR结构域。在一个实施方式中,光诱导的寡聚化结构域是VfAU1。在一个实施方式中,光诱导的寡聚化结构域是YtvA。在一个实施方式中,光诱导的寡聚化结构域是EL222。在一个实施方式中,光诱导的寡聚化结构域是RsLOV。在一个实施方式中,光诱导的寡聚化结构域是AsLOV2。
在一个实施方式中,光诱导的寡聚化结构域与CRYPHR具有至少90%同一性。在一个实施方式中,光诱导的寡聚化结构域与NcVVD具有至少90%同一性。在一个实施方式中,光诱导的寡聚化结构域与NcVVDY50W具有至少90%同一性。在一个实施方式中,光诱导的寡聚化结构域与NcLOV具有至少90%同一性。在一个实施方式中,光诱导的寡聚化结构域与CRY2OLIG具有至少90%同一性。在一个实施方式中,光诱导的寡聚化结构域与VfAU1具有至少90%同一性。在一个实施方式中,光诱导的寡聚化结构域与YtvA具有至少90%同一性。在一个实施方式中,光诱导的寡聚化结构域与EL222具有至少90%同一性。在一个实施方式中,光诱导的寡聚化结构域与RsLOV具有至少90%同一性。在一个实施方式中,光诱导的寡聚化结构域与AsLOV2具有至少90%同一性。
在某些实施方式中,第一核苷酸序列可以包含编码选自以下组成的组的光诱导的寡聚化结构域的核苷酸序列:CRYPHR、CRY2OLIG、NcVVD、NcVVDY50W、NcLOV和VfAU1LOV。
在某些实施方式中,第一核苷酸序列可以包含编码与SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:92、SEQ ID NO:93、SEQ ID NO:99、SEQ ID NO:100、SEQ ID NO:101或SEQ ID NO:102具有至少70%同一性的氨基酸序列的核苷酸序列。在某些实施方式中,第一核苷酸序列可以编码与SEQ ID NO:1、SEQ ID NO:2、SEQID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:92、SEQ ID NO:93、SEQ ID NO:99、SEQ IDNO:100、SEQ ID NO:101或SEQ ID NO:102具有至少75%同一性、至少80%同一性、至少85%同一性、至少90%同一性、至少95%同一性或至少99%同一性的氨基酸序列。在某些实施方式中,第一核苷酸序列可以包含SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:92、SEQ ID NO:93、SEQ ID NO:99、SEQ ID NO:100、SEQ ID NO:101或SEQ ID NO:102。在某些实施方式中,第一核苷酸序列可以包含SEQ ID NO:94。核苷酸序列可以是编码本文公开的氨基酸序列的野生型核酸序列的核苷酸序列。在某些实施方式中,核苷酸序列是从野生型序列修饰的,但是由于遗传密码的简并性,仍可以编码相同的氨基酸序列。在某些实施方式中,核苷酸序列是本文公开的序列之一的变体(或编码变体蛋白序列)。在某些实施方式中,核苷酸序列是本文核酸之一的片段,或编码本文公开的氨基酸之一的片段。在某些实施方式中,核苷酸序列是经密码子优化的(例如,以改善表达)。
在一个实施方式中,光诱导的寡聚化结构域选自以下组成的组:CRY2PHR结构域(例如,CRY2PHR、CRY2OLIG)或光氧电压感测(LOV)结构域(例如,NcVVD、NcVVDY50W、VfAU1、YtvA、EL222、RsLOV、AsLOV2)。
在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自以下组成的组:TDP-43、ɑ突触核蛋白、Tau、Fus、TIA1、SOD1、亨廷顿蛋白、Ataxin 2和hnRNPA2B1。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自以下组成的组:TDP-43、ɑ突触核蛋白、Tau、Fus、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA1和hnRNPA2B1。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自以下组成的组:TDP-43、ɑ突触核蛋白、Tau、Fus、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA1、hnRNPA2B1、EWS RNA结合蛋白1和TATA盒结合蛋白因子15。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自以下的变体:TDP-43、ɑ突触核蛋白、Tau、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA1、hnRNPA2B1、EWS RNA结合蛋白1或TATA盒结合蛋白因子15。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自以下的片段TDP-43、ɑ突触核蛋白、Tau、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA1、hnRNPA2B1、EWS RNA结合蛋白1或TATA盒结合蛋白因子15。在一个实施方式中,TDP-43、ɑ突触核蛋白、Tau、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA1、hnRNPA2B1、EWS RNA结合蛋白1或TATA盒结合蛋白因子15的片段包含每种神经退行性疾病靶蛋白之内的低复杂性结构域(或其片段)。
在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自表3。在一个实施方式中,低复杂性结构域来自在神经退行性疾病中聚集的任何神经退行性疾病靶蛋白。
在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自以下组成的组:与TDP-43、ɑ突触核蛋白、Tau、Fus、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA1、hnRNPA2B1、EWS RNA结合蛋白1和TATA盒结合蛋白因子15具有至少90%同一性的氨基酸序列。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自与选自表3的来自神经退行性疾病靶蛋白的低复杂性结构域具有至少90%同一性的氨基酸序列。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自以下组成的组的直系同源物:TDP-43、ɑ突触核蛋白、Tau、Fus、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA1、hnRNPA2B1、EWS RNA结合蛋白1和TATA盒结合蛋白因子15。
在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自以下组成的组:与TDP-43、ɑ突触核蛋白、Tau、Fus、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA1、hnRNPA2B1、EWS RNA结合蛋白1和TATA盒结合蛋白因子15(或其片段)具有至少60%(例如,至少60%、至少70%、至少80%、至少90%、至少95%)同一性的氨基酸序列。
在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是TDP-43。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是ɑ突触核蛋白。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是Tau。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是Fus。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是TIA1。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是SOD1。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是亨廷顿蛋白。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是Ataxin2。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是hnRNPA1。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是hnRNPA2B1。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是EWS RNA结合蛋白1。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是TATA盒结合蛋白因子15。
在一个实施方式中,VVD光诱导的寡聚化结构域与TDP-43的低复杂性结构域融合。在一个实施方式中,VVD光诱导的寡聚化与全长TDP-43(包含低复杂性结构域)融合。在一个实施方式中,光诱导的寡聚化结构域与来自在神经退行性疾病中聚集的任何神经退行性疾病靶蛋白的低复杂性结构域融合。
在一个实施方式中,光诱导的寡聚化结构域与TDP-43的低复杂性结构域融合,其中TDP-43的低复杂性结构域序列包含SEQ ID NO:95、SEQ ID NO:96、SEQ ID NO:9或SEQ IDNO:98(或其片段)。
在一个实施方式中,编码嵌合多肽的核苷酸序列可以进一步包含编码报告基因蛋白(诸如荧光蛋白,以允许通过荧光将蛋白质聚集体可视化)的第三核苷酸序列。在一个实施方式中,荧光蛋白是mCherry(mCh)。在某些实施方式中,荧光蛋白是GFP或YFP。在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其包含拟南芥隐花色素2蛋白的PHR结构域(例如,CRYPHR)。在某些实施方式中,光诱导的寡聚化结构域可以包含如在SEQID NO:1中公开的野生型CRYPHR氨基酸序列,或者可选地,可包含如在SEQ ID NO:2中公开的突变的CRYPHR氨基酸序列。在某些实施方式中,突变的CRYPHR氨基酸序列可以包含E490G突变,与野生型CRYPHR氨基酸序列相比,其可增加蓝光刺激时的成簇效率。在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其中,光诱导的寡聚化结构域包含与SEQ ID NO:1或SEQ ID NO:2具有至少70%同一性的多肽序列。在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其中,光诱导的寡聚化结构域包含与SEQ IDNO:1或SEQ ID NO:2具有至少75%同一性、至少80%同一性、至少85%同一性、至少90%同一性、至少95%同一性或至少99%同一性的多肽序列。在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其包含SEQ ID NO:1或SEQ ID NO:2的多肽序列。
在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其包含来自链孢霉活蛋白的光氧电压感测结构域(LOV)(例如,LOV、NcVVD、NcVVDY50W、NcLOV、VfAU1、YtvA、EL222、RsLOV和/或AsLOV2)。在某些实施方式中、光诱导的寡聚化结构域可以包含如在SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:92、SEQ ID NO:93、SEQ ID NO:99、SEQ ID NO:100、SEQ ID NO:101或SEQ ID NO:102中公开的野生型LOV氨基酸序列,或者可选地,可以包含例如在SEQ ID NO:5中公开的突变的LOV氨基酸序列。在某些实施方式中,突变的LOV氨基酸序列可以包含Y50W突变,与野生型LOV氨基酸序列相比,其可以降低从二聚状态的耗散率。在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其中,光诱导的寡聚化结构域包含与SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:92、SEQ ID NO:93、SEQ ID NO:99、SEQ ID NO:100、SEQ ID NO:101或SEQ ID NO:102具有至少70%同一性的多肽序列。在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其中,光诱导的寡聚化结构域包含与SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:92、SEQ ID NO:93、SEQ ID NO:99、SEQ ID NO:100、SEQ ID NO:101或SEQ ID NO:102具有至少75%同一性、至少80%同一性、至少85%同一性、至少90%同一性、至少95%同一性或至少99%同一性的多肽序列。在某些实施方式中、第一核苷酸序列可以编码光诱导的寡聚化结构域,其包含SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:92、SEQ ID NO:93、SEQID NO:99、SEQ ID NO:100、SEQ ID NO:101或SEQ ID NO:102的多肽序列。
在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其包含拟南芥隐花色素2蛋白的PHR结构域(例如,CRYPHR),并且第二核苷酸序列可以编码来自神经退行性疾病靶蛋白的低复杂性结构域。在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其包含拟南芥隐花色素2蛋白的PHR结构域(例如,CRYPHR),并且第二核苷酸序列可以编码来自神经退行性疾病靶蛋白的低复杂性结构域,其包含TDP-43。在某些实施方式中,第二核苷酸序列可以编码来自神经退行性疾病靶蛋白的低复杂性结构域,其包含全长TDP-43(例如,SEQ ID NO:6或SEQ ID NO:7)。在某些实施方式中,第二核苷酸序列可以编码来自神经退行性疾病靶蛋白的低复杂性结构域,其包含截短的TDP-43(例如,SEQID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12或SEQ ID NO:13)。在某些实施方式中,截短的TDP-43包含全长TDP-43氨基酸序列的氨基酸105-414、191-414或274-414或者由全长TDP-43氨基酸序列的氨基酸105-414、191-414或274-414组成。因此,在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其包含CRYPHR,并且第二核苷酸序列可以编码来自神经退行性疾病靶蛋白的低复杂性结构域,其包含全长或截短的TDP-43,其中,第一核苷酸序列和第二核苷酸序列编码与SEQ ID NO:6、SEQ ID NO:7、SEQID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12或SEQ ID NO:13具有至少75%同一性、至少80%同一性、至少85%同一性、至少90%同一性,至少95%同一性或至少99%同一性的嵌合多肽序列。在某些实施方式中,第一核苷酸序列和第二核苷酸序列编码根据SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ IDNO:11、SEQ ID NO:12或SEQ ID NO:13的嵌合多肽序列。在某些实施方式中,选择SEQ IDNO:6。在某些实施方式中,选择SEQ ID NO:11。
在某些实施方式中,包含第一核苷酸序列和第二核苷酸序列的编码嵌合多肽的核苷酸序列可以进一步包含编码报告基因蛋白或其片段的第三核苷酸序列(例如,荧光蛋白,诸如mCherry,也被称为mCH)。因此,在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其包含CRYPHR,第二核苷酸序列可以编码来自神经退行性疾病靶蛋白的低复杂性结构域,其包含全长或截短的TDP-43,并且第三核苷酸序列可以编码mCherry蛋白,其中,第一、第二和第三核苷酸序列编码与SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24或SEQ ID NO:25具有至少75%同一性、至少80%同一性、至少85%同一性、至少90%同一性、至少95%同一性或至少99%同一性的嵌合多肽序列。在某些实施方式中,第一、第二和第三核苷酸序列编码根据SEQ ID NO:14、SEQ ID NO:15、SEQID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQID NO:22、SEQ ID NO:23、SEQ ID NO:24或SEQ ID NO:25的嵌合多肽序列。在某些实施方式中,选择SEQ ID NO:14。在某些实施方式中,选择SEQ ID NO:23。
在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其包含LOV光感受器结构域(例如,NcVVD、NcVVDY50W、NcLOV、VfAU1、YtvA、EL222、RsLOV和AsLOV2),并且第二核苷酸序列可以编码来自神经退行性疾病靶蛋白的低复杂性结构域。在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其包含LOV光感受器结构域(例如,NcVVD、NcVVDY50W、NcLOV、VfAU1、YtvA、EL222、RsLOV和AsLOV2),并且第二核苷酸序列可以编码来自神经退行性疾病靶蛋白的低复杂性结构域,其包含TDP-43。在某些实施方式中,第二核苷酸序列可以编码来自神经退行性疾病靶蛋白的低复杂性结构域,其包含全长TDP-43(例如,SEQ ID NO:2或SEQ ID NO:27)。在某些实施方式中,第二核苷酸序列可以编码来自神经退行性疾病靶蛋白的低复杂性结构域,其包含截短的TDP-43(例如,SEQ ID NO:28、SEQID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32或SEQ ID NO:33)。在某些实施方式中,截短的TDP-43由全长TDP-43氨基酸序列的氨基酸105-414、191-414或274-414组成。因此,在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其包含NcVVDY50W,并且第二核苷酸序列可以编码来自神经退行性疾病靶蛋白的低复杂性结构域,其包含全长或截短的TDP-43,其中,第一核苷酸序列和第二核苷酸序列编码与SEQ ID NO:26、SEQ ID NO:27、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ IDNO:32或SEQ ID NO:33具有至少75%同一性、至少80%同一性、至少85%同一性、至少90%同一性、至少95%同一性或至少99%同一性的嵌合多肽序列。在某些实施方式中,第一核苷酸序列和第二核苷酸序列编码根据SEQ ID NO:26、SEQ ID NO:27、SEQ ID NO:28、SEQ IDNO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32或SEQ ID NO:33的嵌合多肽序列。
在某些实施方式中,包含第一核苷酸序列和第二核苷酸序列的编码嵌合多肽的核苷酸序列可以进一步包含编码报告基因蛋白或其片段的第三核苷酸序列(例如,荧光蛋白,诸如mCherry)。因此,在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其包含NcVVDY50W,第二核苷酸序列可以编码来自神经退行性疾病靶蛋白的低复杂性结构域,其包含全长或截短的TDP-43,并且第三核苷酸序列可以编码mCherry蛋白,其中,第一、第二和第三核苷酸序列编码与SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ IDNO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40或SEQ ID NO:41具有至少75%同一性、至少80%同一性、至少85%同一性、至少90%同一性、至少95%同一性或至少99%同一性的嵌合多肽序列。在某些实施方式中,第一、第二和第三核苷酸序列编码根据SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37、SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40或SEQ ID NO:41的嵌合多肽序列。在某些实施方式中,选择SEQ ID NO:34。在某些实施方式中,选择SEQ ID NO:41。
在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其包含拟南芥隐花色素2蛋白的PHR结构域(例如,CRY2OLIG),并且第二核苷酸序列可以编码来自神经退行性疾病靶蛋白的低复杂性结构域,其包含α-突触核蛋白。因此,在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其包含CRY2OLIG,第二核苷酸序列可以编码来自神经退行性疾病靶蛋白的低复杂性结构域,其包含α-突触核蛋白,其中,第一核苷酸序列和第二核苷酸序列编码与SEQ ID NO:42或SEQ ID NO:43具有至少75%同一性、至少80%同一性、至少85%同一性、至少90%同一性、至少95%同一性或至少99%同一性的嵌合多肽序列。在某些实施方式中,第一核苷酸序列和第二核苷酸序列编码根据SEQ ID NO:42或SEQ ID NO:43的嵌合多肽序列。
在某些实施方式中,包含第一核苷酸序列和第二核苷酸序列的编码嵌合多肽的核苷酸序列可以进一步包含编码报告基因蛋白或其片段的第三核苷酸序列(例如,荧光蛋白,诸如mCherry)。因此,在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其包含CRY2OLIG,第二核苷酸序列可以编码来自神经退行性疾病靶蛋白的低复杂性结构域,其包含α-突触核蛋白,并且第三核苷酸序列可以编码mCherry蛋白,其中,第一、第二和第三核苷酸序列编码与SEQ ID NO:44、SEQ ID NO:45或SEQ ID NO:46具有至少75%同一性、至少80%同一性、至少85%同一性、至少90%同一性、至少95%同一性或至少99%同一性的嵌合多肽序列。在某些实施方式中,第一、第二和第三核苷酸序列编码根据SEQ ID NO:44、SEQ ID NO:45或SEQ ID NO:46的嵌合多肽序列。在某些实施方式中,选择SEQ ID NO:44。
在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其包含LOV光感受器结构域(例如,NcVVD、NcVVDY50W、NcLOV、VfAU1、YtvA、EL222、RsLOV和AsLOV2),并且第二核苷酸序列可以编码来自神经退行性疾病靶蛋白的低复杂性结构域,其包含α-突触核蛋白。因此,在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其包含NcVVDY50W,并且第二核苷酸序列可以编码来自神经退行性疾病靶蛋白的低复杂性结构域,其包含α-突触核蛋白,其中,第一核苷酸序列和第二核苷酸序列编码与SEQ ID NO:47或SEQ ID NO:48具有至少75%同一性、至少80%同一性、至少85%同一性、至少90%同一性、至少95%同一性或至少99%同一性的嵌合多肽序列。在某些实施方式中,第一核苷酸序列和第二核苷酸序列编码根据SEQ ID NO:47或SEQ ID NO:48的嵌合多肽序列。
在某些实施方式中,包含第一核苷酸序列和第二核苷酸序列的编码嵌合多肽的核苷酸序列可以进一步包含编码报告基因蛋白或其片段的第三核苷酸序列(例如,荧光蛋白,诸如mCherry)。因此,在某些实施方式中,第一核苷酸序列可以编码光诱导的寡聚化结构域,其包含NcVVDY50W,第二核苷酸序列可以编码来自神经退行性疾病靶蛋白的低复杂性结构域,其包含α-突触核蛋白,并且第三核苷酸序列可以编码mCherry蛋白,其中,第一、第二和第三核苷酸序列编码与SEQ ID NO:49、SEQ ID NO:50或SEQ ID NO:51具有至少75%同一性、至少80%同一性、至少85%同一性、至少90%同一性、至少95%同一性或至少99%同一性的嵌合多肽序列。在某些实施方式中,第一、第二和第三核苷酸序列编码根据SEQ ID NO:49、SEQ ID NO:50或SEQ ID NO:51的嵌合多肽序列。在某些实施方式中,选择SEQ ID NO:51。
在某些实施方式中,第一核苷酸序列位于第二核苷酸序列的上游。在某些实施方式中,第一核苷酸序列位于第二核苷酸序列的下游。
在某些实施方式中,当本文公开的序列在蛋白质起始处含有甲硫氨酸时,则还公开了不含甲硫氨酸的蛋白质。在某些实施方式中,在本文公开的序列在蛋白质起始处不包含甲硫氨酸的情况下,则还公开了在蛋白质起始处具有甲硫氨酸的蛋白质。
在某些实施方式中,编码嵌合多肽的核苷酸序列包含选自以下的序列:SEQ IDNO:52、SEQ ID NO:53、SEQ ID NO:54、SEQ ID NO:55、SEQ ID NO:56、SEQ ID NO:57、SEQ IDNO:58、SEQ ID NO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63、SEQ IDNO:64、SEQ ID NO:65、SEQ ID NO:66、SEQ ID NO:67、SEQ ID NO:68、SEQ ID NO:69、SEQ IDNO:70、SEQ ID NO:61、SEQ ID NO:62、SEQ ID NO:63、SEQ ID NO:64、SEQ ID NO:65、SEQ IDNO:66、SEQ ID NO:67、SEQ ID NO:68、SEQ ID NO:69、SEQ ID NO:70、SEQ ID NO:71、SEQ IDNO:72、SEQ ID NO:73、SEQ ID NO:74、SEQ ID NO:75、SEQ ID NO:76、SEQ ID NO:77、SEQ IDNO:78、SEQ ID NO:79、SEQ ID NO:80、SEQ ID NO:81、SEQ ID NO:82、SEQ ID NO:83、SEQ IDNO:84、SEQ ID NO:85、SEQ ID NO:86、SEQ ID NO:87、SEQ ID NO:88、SEQ ID NO:89、SEQ IDNO:90或SEQ ID NO:91。
方法
一方面,本文公开了一种在细胞中诱导神经退行性疾病病理的方法,所述方法包括以下步骤:
将编码嵌合多肽的表达载体导入细胞,所述表达载体包含:
编码光诱导的寡聚化结构域的第一核苷酸序列和编码来自神经退行性疾病靶蛋白的低复杂性结构域的第二核苷酸序列,其中,第一核苷酸序列与启动子可操作地连接;
表达嵌合多肽;和
通过用蓝光刺激而诱导嵌合多肽的寡聚化。
另一方面,本文公开了筛选调节蛋白质聚集的试剂的方法,所述方法包括以下步骤:
将编码嵌合多肽的表达载体导入细胞,所述表达载体包含:
编码光诱导的寡聚化结构域的第一核苷酸序列和编码来自神经退行性疾病靶蛋白的低复杂性结构域的第二核苷酸序列,其中,第一核苷酸序列与启动子可操作地连接;
表达嵌合多肽;
将所述试剂引入包含细胞的培养基中;
通过用蓝光刺激而诱导嵌合多肽的寡聚化;和
确定试剂对蛋白质聚集的调节。
在一个实施方式中,光诱导的寡聚化结构域选自以下组成的组:CRY2PHR结构域(例如,CRY2PHR、CRY2OLIG)或光氧电压感测(LOV)结构域(例如,NcVVD、NcVVDY50W、VfAU1、YtvA、EL222、RsLOV、AsLOV2)。
在一个实施方式中,光诱导的寡聚化结构域选自以下组成的组:CRYPHR、CRY2OLIG、NcVVD、NcVVDY50W和NcLOV。在一个实施方式中,光诱导的寡聚化结构域选自以下组成的组:CRYPHR、CRY2OLIG、NcVVD、NcVVDY50W、NcLOV、VfAU1、YtvA、EL222、RsLOV和AsLOV2。在一个实施方式中,光诱导的寡聚化结构域选自表2中的结构域的列表。在一个实施方式中,光诱导的寡聚化结构域选自以下的变体:CRYPHR、CRY2OLIG、NcVVD、NcVVDY50W、NcLOV、VfAU1、YtvA、EL222、RsLOV或AsLOV2。在一个实施方式中,光诱导的寡聚化结构域选自以下的片段:CRYPHR、CRY2OLIG、NcVVD、NcVVDY50W、NcLOV、VfAU1、YtvA、EL222、RsLOV或AsLOV2。
在一个实施方式中,光诱导的寡聚化结构域是NcVVDY50W。在一个实施方式中,光诱导的寡聚化结构域是CRY2OLIG。在一个实施方式中,光诱导的寡聚化结构域是CRYPHR。在一个实施方式中,光诱导的寡聚化结构域包含来自VVD蛋白的LOV结构域。在一个实施方式中,光诱导的寡聚化结构域包含来自LOV蛋白的LOV结构域。在一个实施方式中,光诱导的寡聚化结构域包含PHR结构域。在一个实施方式中,光诱导的寡聚化结构域包含来自CRY2蛋白的PHR结构域。在一个实施方式中,光诱导的寡聚化结构域是VfAU1。在一个实施方式中,光诱导的寡聚化结构域是YtvA。在一个实施方式中,光诱导的寡聚化结构域是EL222。在一个实施方式中,光诱导的寡聚化结构域是RsLOV。在一个实施方式中,光诱导的寡聚化结构域是AsLOV2.
在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自以下组成的组:TDP-43、ɑ突触核蛋白、Tau、Fus、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA1和hnRNPA2B1。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自以下组成的组:TDP-43、ɑ突触核蛋白、Tau、Fus、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA1、hnRNPA2B1、EWS RNA结合蛋白1和TATA盒结合蛋白因子15。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自以下的变体:TDP-43、ɑ突触核蛋白、Tau、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA1、hnRNPA2B1、EWS RNA结合蛋白1或TATA盒结合蛋白因子15。在一个实施方式中、来自神经退行性疾病靶蛋白的低复杂性结构域选自以下的片段:TDP-43、ɑ突触核蛋白、Tau、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA1、hnRNPA2B1、EWSRNA结合蛋白1或TATA盒结合蛋白因子15。在一个实施方式中,TDP-43、ɑ突触核蛋白、Tau、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA1、hnRNPA2B1、EWS RNA结合蛋白1或TATA盒结合蛋白因子15的片段包含在每个神经退行性疾病靶蛋白内的低复杂性结构域。
在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自表3。在一个实施方式中,低复杂性结构域来自在神经退行性疾病中聚集的任何神经退行性疾病靶蛋白。
在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自与TDP-43、ɑ突触核蛋白、Tau、Fus、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA1、hnRNPA2B1、EWSRNA结合蛋白1和TATA盒结合蛋白因子15具有至少90%同一性的氨基酸序列。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自与选自表3的来自神经退行性疾病靶蛋白的低复杂性结构域具有至少90%同一性的氨基酸序列。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自以下组成的组的直系同源物:TDP-43、ɑ突触核蛋白、Tau、Fus、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA1、hnRNPA2B1、EWS RNA结合蛋白1和TATA盒结合蛋白因子15。
在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域选自以下组成的组:与TDP-43、ɑ突触核蛋白、Tau、Fus、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA1、hnRNPA2B1、EWS RNA结合蛋白1和TATA盒结合蛋白因子15(或其片段)至少60%(例如、至少60%、至少70%、至少80%、至少90%、至少95%)同一性的氨基酸序列。
在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是TDP-43。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是ɑ突触核蛋白。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是Tau。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是Fus。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是TIA1。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是SOD1。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是亨廷顿蛋白。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是Ataxin2。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是hnRNPA1。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是hnRNPA2B1。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是EWS RNA结合蛋白1。在一个实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域是TATA盒结合蛋白因子15。
在一个实施方式中,所述细胞是哺乳动物细胞。在一个实施方式中,所述细胞是人类细胞。在一个实施方式中,所述细胞选自以下组成的组:酵母、昆虫、禽类、鱼类、蠕虫、两栖动物、非洲爪蟾、细菌、藻类和哺乳动物细胞。在一个实施方式中,本文公开了一种非人类转基因生物体,其中该生物体是昆虫、鱼类、鸟类、蠕虫、两栖动物、非洲爪蟾或非人类哺乳动物。
诱导神经退行性疾病病理是指引起神经退行性疾病病理或与不进行所选择的动作相比增加神经退行性疾病病理的表型、症状或严重性的动作。
神经退行性疾病病理可以包括一系列已知或怀疑与任何一种或多种神经退行性疾病相关的病理。这样的病理的实例包括但不限于细胞质中的蛋白质聚集,核蛋白向例如细胞质的错误定位、泛素的表达增加、细胞变性和/或死亡、细胞外淀粉样β(Aβ)聚集和/或Tau蛋白的细胞内和/或细胞质聚集。在某些实施方式中,蛋白聚集体可以与p62蛋白共定位,可以被过度磷酸化,可以包括包含来自神经退行性疾病靶蛋白的低复杂性结构域的内源性蛋白(例如,内源性TDP-43)或其组合。
泛素化增加或泛素表达增加可以是神经退行性疾病的表型特征。泛素具有多种细胞作用,其包括在蛋白酶体中“标记”蛋白(例如,通过共价键连接)以进行降解的。通常将细胞中泛素表达的增加与对照进行比较。在某些实施方式中,与对照相比,具有增加的泛素的细胞具有至少50%的增加的泛素表达。在某些实施方式中,与对照相比,具有增加的泛素的细胞具有至少60%、至少70%、至少80%、至少90%、至少95%、至少98%或至少99%的增加的泛素表达。
可以在转录水平,翻译水平或其组合中确定细胞中泛素表达,并且可以通过用于测量基因或多肽表达水平的多种方法来测量。在某些实施方式中,可以在基因转录水平上测量泛素表达。例如但不限于,泛素mRNA转录物的水平可以通过以下确定:辐射吸收率(例如,在260nm、280nm或230nm处的紫外线吸收),荧光染料或标签发射(例如,溴化乙锭嵌入)的定量,从mRNA转录物产生的cDNA的定量聚合酶链反应(qPCR),southern印迹分析,基因表达微阵列或其他合适方法。mRNA转录物水平的增加可用于推断或估计多肽表达水平的增加。在某些实施方式中,可以在翻译后水平上测量泛素表达。例如但不限于,泛素多肽的水平可以通过以下确定:辐射吸收(例如紫外线)、双辛可宁酸(BCA)测定、布拉德福德测定、缩二脲测试、Lowry法、考马斯亮蓝染色、功能或酶测定、免疫检测法和/或Western印迹分析或其他合适的方法。
如本文所用,涉及将表达载体引入细胞中的术语“引入”、“导入”及其语法变体是指适合于将表达载体转移至细胞中的任何方法。该术语包括但不限于例如缀合、转化/转染(例如,二价阳离子暴露、热休克、电穿孔)、核显微注射、用磷酸钙多核苷酸沉淀物温育、用多核苷酸包覆的微粒高速轰击(例如,通过基因枪)、脂质体转染、阳离子聚合物络合(例如,DEAE-葡聚糖、聚乙烯亚胺)、树状聚合物络合、细胞膜的机械变形(例如,细胞挤压)、超声穿孔、光学转染、刺染(impalefection)、流体动力学多核苷酸递送、农杆菌介导的转化、转导(例如,用病毒或病毒载体转导)、天然或人工感受态、原生质体融合、磁转染、核转染或其组合。可以将引入的表达载体或来自其的多核苷酸遗传整合或在染色体外存在。
在本公开的方法中可以使用一定范围的蓝光波长。在一个实施方式中,蓝光的波长为约400nm至约500nm。在一个实施方式中,蓝光的波长为约405nm至约499nm。在一个实施方式中,蓝光的波长为约420nm至约490nm。在一个实施方式中,蓝光的波长为约450nm至约490nm。在一个实施方式中,蓝光的波长为约460nm至约495nm。在一个实施方式中,蓝光的波长为约488nm。在一个实施方式中,蓝光的波长为约475nm。在一个实施方式中,蓝光的波长为约465nm。
在一个实施方式中,蓝光的波长为约405nm、约410nm、约415nm、约420nm、约425nm、约430nm、约435nm、约440nm、约445nm、约450nm、约455nm、约460nm、约465nm、约470nm、约475nm、约480nm、约485nm、约490nm、约495nm或约500nm。
所述方法可以包括各种程度的蓝光刺激。在某些实施方式中,刺激是急性的或可选地慢性的。急性刺激是指用约0.2秒至约60秒的蓝光脉冲进行刺激,其中蓝光的波长可以是本文公开的任何蓝光波长。在某些实施方式中,急性刺激包括约0.5秒至约30秒、约1秒至约20秒或约5秒的蓝光脉冲。蓝光可以由针对所公开的波长过滤的蓝光源或广谱光源提供。
在某些实施方式中,急性刺激可导致光诱导的寡聚化结构域(例如,细胞质朊病毒样结构域/LCD/IDD蛋白片段)的暂时聚集。在某些实施方式中,暂时聚集包括通过本文公开的方法可观察到小于约二十分钟或可选地小于约十五分钟、小于约十分钟或约五分钟以下的蛋白质聚集。在某些实施方式中,急性刺激在二十分钟以上的时间不会导致细胞质朊病毒样结构域/LCD/IDD蛋白片段的聚集。
在某些实施方式中,急性刺激可以导致光诱导的寡聚化结构域的聚集,其持续时间比与来自神经退行性疾病靶蛋白的低复杂性结构域融合的光诱导的寡聚化结构域的聚集持续时间短。在某些实施方式中,急性刺激可导致与来自神经退行性疾病靶蛋白的低复杂性结构域融合的光诱导的寡聚结构域的聚集,其持续时间短于具有已知引起或与神经退行性疾病有关的氨基酸突变(例如,TDP-43Q331K)的相同蛋白质的聚集。
慢性刺激是通过在约0.1mW/cm2至8mW/cm2暴露在波长约400nm至约500nm的蓝光中持续约1分钟以上的时间(例如,至少1分钟、至少5分钟、至少10分钟、至少30分钟、至少60分钟、至少2小时、至少4小时、至少8小时、至少12小时、至少24小时、至少36小时以上)(在400nm至500nm波长内)。
在某些实施方式中,本文公开的方法可以诱导细胞中的神经退行性疾病病理(例如,蛋白质的聚集),而基本上不改变参与神经退行性疾病病理的蛋白质的表达水平。例如但不限于,所述方法可以诱导包含TDP-43的嵌合多肽的聚集(其可以包括内源TDP-43的聚集),而基本上不增加或降低内源性TDP-43的表达水平。在某些或其他实施方式中,所述方法可以使用来自神经退行性疾病靶蛋白的低复杂性结构域的野生型形式在细胞中诱导神经退行性疾病病理。因此,在某些实施方式中,来自神经退行性疾病靶蛋白的低复杂性结构域不包括不同于野生型序列并且已知或怀疑引起细胞中的神经退行性疾病病理或与诱导神经退行性疾病病理相关的突变。例如但不限于,所述方法可以诱导包含野生型TDP-43蛋白或其片段的嵌合多肽的聚集,所述嵌合多肽不包含已知引起ALS或与ALS相关的突变,诸如Q331K。
实施例
下面列出以下实施例以说明根据所公开主题的化合物、组合物、方法和结果。这些实施例并不旨在包括本文公开的主题的所有方面,而是用于说明代表性的方法和结果。这些实施例并不旨在排除本领域技术人员显而易见的本发明的等同物和变化形式。
实施例1.神经退行性疾病病理的光遗传性诱导
世界正在老化。到2050年,60岁以上的人口比例将从2000年的6.05亿增加到20亿,翻了一番。不幸的是,衰老是发展致命性神经退行性疾病的最大风险因素。反过来,患有痴呆症(诸如阿尔茨海默氏病(AD)、路易体痴呆(LBD)、额颞痴呆(FTD)和运动障碍(诸如帕金森氏病(PD)和肌萎缩侧索硬化症(ALS))的人数将大大增加。在美国,目前有近650万人患有这些疾病中的一种,其相关费用难以承受。在美国,目前AD、PD和ALS的经济负担估计为每年2,410亿美元。AD和ALS/FTD患者每年可能要承担100,000美元至250,000美元的个人医疗费用。对于AD,据估计,到2050年,美国将诊断出1380万个体,高于2010年的470万,而到2040年,全世界ALS病例的数量将上升约31%。此外,对于这些疾病目前尚无有效的治疗方法。
二十年的遗传分析发现了许多与神经退行性疾病相关的突变。但是,仅在AD、LBD、FTD、PD和ALS患者中发现了这些(表1)。
表1.常见的神经退行性疾病、病理学和遗传成分贡献的列表。
表1描述了神经退行性疾病的选择、主要症状、中枢神经系统(CNS)的受影响区域、在患者CNS中观察到的聚集神经病理学、表现出这种病理学的患者百分率以及具有某些疾病遗传成分的患者百分率(家庭中已知或未知的突变)。阿尔茨海默氏病(AD)的特征是由于海马体和内嗅皮层的变性而导致记忆力损害和混乱。只有1-3%的患者具有诱因基因突变;但是,所有患者在受影响的组织中均表现出共同的聚集病理。其特征在于细胞外淀粉样β(Aβ)聚集以及Tau蛋白的细胞内和细胞质聚集。额颞痴呆(FTD)的特征在于额叶和颞叶逐渐退化,尽管20-25%的患者可以携带所述疾病的遗传原因,但80-75%的患者没有家族史。但是,所有患者均表现出某种形式的细胞质蛋白聚集,其包括TDP-43(占病例的45%),Tau(占病例的45%)或FUS(占病例的5%)蛋白。帕金森氏病(PD)的特征在于黑质中的多巴胺能神经元逐渐退化,虽然只有10%的患者有已知的遗传原因,但几乎所有患者(99%)都显示出α-突触核蛋白的细胞质聚集。肌萎缩侧索硬化症(ALS)的特征在于脊髓运动皮层中运动神经元快速退化,导致患者麻痹和死亡。只有10%的ALS患者有该病的家族史,而近90%的病例是偶发性的。迄今为止,已经在各种基因中鉴定出近35个致病性基因突变(参见图1),但是尽管具有这种遗传多样性,几乎所有ALS患者都表现出相同的神经病理学。将近97%的ALS患者在受影响的区域中显示出主要是核TDP-43蛋白的细胞质错误定位。SOD1或FUS基因突变的患者也显示出这些蛋白的细胞质聚集,但是这种情况仅分别发生在2%和1%的所有ALS病例中。
总之,该表突出表明许多神经退行性疾病的主要统一因素是神经病理学的标志。这些神经病理学主要以细胞内蛋白质聚集体的形式发生,并且在大多数情况下,无论任何已知的遗传原因如何,这些细胞内蛋白质聚集体均会形成。而且,这些神经病理学主要在每种疾病中受影响最大的区域和细胞类型中形成。
有趣的是,尽管缺乏公知的遗传或环境原因,但对于每种疾病,这些都是患者普遍的神经病理学特征。因此,尽管没有已知的遗传原因,绝大多数患者(取决于疾病的所有患者的90-100%)在中枢神经系统中表现出相同的病理。这些病理学标志以中枢神经系统中不溶性蛋白质块或聚集体的形式表现出来(表1,图1)。
迄今为止,不可能精确地模拟人类神经病理学的模型神经退行性疾病聚集。对于每种神经退行性疾病,细胞内蛋白质聚集体中都有一个主要成分,其中包含蛋白结构域,当处于较高的局部浓度时,这些蛋白结构域易于使这些蛋白质聚集(也称为:朊病毒样结构域、低复杂性结构域、内在无序结构域、内在无序区域)。因此,目前对这些神经退行性疾病聚集体进行建模的方法依赖于体外或体内过表达这些易于发生聚集的蛋白质,这些蛋白质包含神经退行性疾病聚集体,因为在某些模型中高细胞浓度可以形成聚集体。除此之外或作为另选,对这些疾病进行建模的另一种方法是表达包含神经退行性疾病聚集体的蛋白质的突变形式。这些突变是在很小的患者子集中发现的,通常会增强蛋白质聚集的能力。不幸的是,这些方法都无法概括患者的细胞环境,因为绝大多数患者没有携带任何致病突变,也没有完全过表达聚集体的成分。事实上,尽管这些蛋白完全过表达,但许多模型仍未表现出人类神经病理学。患者生物学和模型系统之间的这种脱节极大地导致了当前神经退行性疾病模型缺乏可翻译性。
在该实施例中描述了新颖的方法,其在空间和时间上诱导蛋白质聚集体,而不会简单地过表达聚集体易感基因或表达这些基因的突变形式。因此,该方法更好地概括了人类疾病状况。在这里,已经采取了一种创新的方法来利用光遗传学的力量(用光控制蛋白质的功能)来解决这一具有挑战性的生物学问题。已经构建了可以诱导神经退行性疾病病理的一系列新的DNA排列,如仅当细胞暴露于特定的光刺激下才在患者中观察到的。此方法用于创建体外和体内模型系统,以模拟在患者中观察到的神经病理,并仅在细胞暴露于特定的光波长后才诱导这种病理。这种新方法可以改变神经退行性疾病的建模,并且与突变转基因的表达不同,可以用于生成适用于绝大多数患者并且在时间和空间上均可诱导的各种疾病模型。
已经开发出一系列DNA排列,其包括响应于蓝光暴露分别成簇或均二聚化的PHR结构域(CRY2OLIG或CRY2PHR)或光氧电压感测(LOV)结构域(NcVVD、NcVVDY50W、Vfau1、YtvA、EL222、RsLOV、AsLOV2)(表2)和编码包含低复杂性域(LCD)并包含神经退行性疾病蛋白聚集体的蛋白的基因的DNA序列(表3)。
表2.在暴露于蓝光的细胞中,通过光遗传学诱导神经退行性病理的光感受器/光诱导的寡聚化结构域的列表。
Figure BDA0002228112600000321
表2列出了在蓝光暴露下,用于光遗传学诱导细胞中神经退行性病理的光感受器列表。在拟南芥植物中发现的隐花色素2蛋白的PHR结构域的变异将是所使用的一个光感受器家族(在本文件中分别命名为CRY2PHR和CRY2OLIG)。当暴露于单个蓝光脉冲(在405nm-499nm范围内)时,CRY2蛋白的PHR结构域及其变体具有成簇/同源寡聚能力约5分钟。CRY2PHR是在拟南芥中发现的内源性蛋白质序列。虽然CRY2OLIG是内源性氨基酸序列,但具有E490G突变,并且在蓝光刺激下显示出稍高的成簇效率。CRY2PHR和CRY2OLIG的自结合通过相同的机制起作用,并且需要细胞内FAD+。已经产生了包括神经病理蛋白聚集体的CRY2OLIG和靶蛋白的各种排列,以显示出对CRY2OLIG的光诱导的成簇特性的调节,以诱导主要是胞质蛋白和主要是核蛋白的神经退行性疾病病理。如在患者神经病理中观察到的,这包括诱导核蛋白的细胞质错误定位。另外,这些蛋白结构域已被用于诱导这些神经退行性蛋白的截短形式的固有无序结构域/朊病毒样结构域/低复杂性结构域的聚集。
Vivid(VVD)是在链孢霉生物体中产生的蛋白质,并且是一种响应于蓝光(在405nm-499nm范围内)而同源二聚化的光感受器。光氧电压感测(LOV)结构域在许多生物中都很常见,但在该生物中此结构域很小。NcLOV只是VVD蛋白的LOV结构域,但在其他物种中都是保守的。NcVVD包含N端VVD蛋白和VVD LOV结构域的小片段。然而,来自NcVVD蛋白序列的NcVVDY50W被Y50W变化所改变,其促进了较慢的从二聚状态消散的能力。在此显示,当融合至含有LCD的蛋白质时,LOV结构域的持续二聚化用慢性光诱导了寡聚化(图6、8)。尽管没有报道LOV结构域形成寡聚体,但是本文已经开发了光刺激范例以诱导这些光感受器和特定靶神经退行性疾病蛋白质的特定蛋白质排列的蛋白质聚集。本文使用的其他LOV结构域还包括VfAU1、YtvA、EL222、RsLOV和AsLOV2。
表3.靶标神经退行性疾病蛋白。
Figure BDA0002228112600000331
缩写:ALS,肌萎缩侧索硬化症;FTD,额颞痴呆;PD,帕金森氏病;AD,阿尔茨海默氏病;CTE,慢性外伤性脑病;LBD,路易体痴呆
表3列出了产生概括神经退行性疾病病理的蛋白质排列的靶标神经退行性疾病蛋白质的列表。本文公开了与神经退行性疾病蛋白(如表3中所列的那些)融合的表2中的光感受器的新排列,其响应于这些各种蓝光暴露范例以概括神经退行性疾病病理。该技术还用于聚集包含患者的神经病理学聚集体的这些成分的截短形式的朊病毒样结构域/LCD/IDD。在该实施例中,已经对与TDP-43、α-突触核蛋白和Tau蛋白融合的CRY2OLIG和LOV进行了研究。在另一实施例中,靶标神经退行性疾病蛋白可以是亨廷顿蛋白基因/蛋白(登录号NM_002111;NP_002102.4)。然而,由于创建的光处理范例,因此开发了一种可以应用于具有二聚或低聚能力的任何光感受器的方法。该方法的主要目的是在特定时间段内控制神经退行性疾病蛋白的局部浓度,迫使包含LCD并聚集在神经退行性疾病中的蛋白的分子内拥挤。由于蛋白质的性质,每种神经退行性疾病蛋白质和光感受器排列都可能需要特定的光刺激参数。例如将其定位在胞质中的胞质蛋白或核蛋白的截短形式通常(但不总是)需要短暂的刺激范式,而主要是核蛋白是慢性刺激,因为在翻译过程中需要将蛋白捕获在胞质中(例如TDP-43,FUS)。刺激范例的细节在下面讨论。
然后,光暴露迫使这些独特的融合蛋白排列紧密接近,并采用慢性或反复的光刺激,可以得到全长蛋白或仅LCD的神经退行性疾病聚集体病理。神经退行性疾病聚集体的这种时间和空间控制是新颖的,因为它不需要仅与每种疾病的一小部分患者相关的过表达或突变(表1)。这些蛋白质被迫相互作用,并形成人类患者中发生的疾病病理,而不是用这些倾向聚集的蛋白质填充细胞。
除了蛋白质聚集以外,该系统还可以创建光诱导的病理学,其模仿患者中发现的关键病理学特征,从而使其与过表达系统相比具有独特性。将包含LCD的TDP-43蛋白与CRY2OLIG光感受器结构域结合,该结构域在暴露于蓝光时会成簇,并在持续的光处理下变得不溶并聚集。产生了具有全长和部分LCD序列的融合蛋白以概括人类神经退行性疾病的病理学,其包括发生在ALS和FTD患者中的核蛋白的细胞质错误定位。该系统可以通过使活的HEK细胞暴露于各种蓝光刺激范例中来诱导神经退行性疾病蛋白聚集体(图4-5)。另外,产生了ALS、FTD和AD的生化标志(图7),这表明尽管添加了这些标签,但是如患者CNS中所观察到的,细胞对光诱导的聚集体响应。值得注意的是,TDP-43神经病理学是待模拟的更复杂的神经病理学之一,因为它是主要的核蛋白,但发现在患者中细胞质错误定位。以这种DNA排列和光刺激系统为例,获得了胞质TDP-43聚集体,如在ALS、FTD和AD患者中观察到的,它们也被泛素化、切割和过磷酸化。TDP-43病理也可在AD和慢性创伤性脑病(CTE)中发现,从而突显了这项工作的潜在疾病相关性。另外,开发了蛋白质排列和光刺激范例以诱导α-突触核蛋白的聚集(图6),其在诊断为帕金森氏病和路易体痴呆的患者的CNS中发现。还开发了使用Cry-PHR和LOV光感受器(图7)和持续的蓝光刺激来诱导Tau蛋白的细胞内聚集的方法。这些tau缠结是HEK细胞中AD、FTD和CTE的病理标志。这些还表现出在患者中观察到的Tau蛋白病的病理学特征,包括使用针对病理学tau内含物开发的特异性抗体的过度磷酸化(图7-8)。最后,表明该方法可用于接种聚集体,因为使用该方法形成的TDP-43的聚集体募集内源性TDP-43以接种致病性神经病理学(图5F、5G)。
还开发了一种新的方法来迫使与包含LCD的蛋白融合的LOV结构域蛋白的寡聚和聚集。包括NcVVDY50W在内的LOV域仅在蓝光刺激下显示二聚化。使用慢性蓝光刺激范例(在图3和图6-8中描述),诱导了与LOV序列融合的含LCD蛋白质的寡聚和最终聚集。该氨基酸序列明显小于CRY2的PHR结构域,并可以充当CRY2PHR的替代物,因为它不太可能干扰内源性靶蛋白的功能。
在某些实施方式中,构建DNA排列,其编码与LCD片段或表3中列出的全长神经退行性疾病蛋白(或90%相似性)融合的PHR结构域(CRY2PHR或CRY2OLIG)或LOV光感受器蛋白(NcVVD、NcVVDY50W、Vfau1、YtvA、EL222、RsLOV、AsLOV2)(或90%相似性)。在某些实施方式中,本文公开了采用蓝光暴露处理范例来诱发这些神经变性疾病病理的方法。在其他实施方式中,所得蛋白质聚集体和细胞生存力用作神经退行性疾病药物筛选的读数(图10)。通过使用药理或遗传学缓解神经退行性疾病的病理学形成或驻留时间的系统可鉴定用于治疗特定神经退行性疾病的新型化合物。还公开了以下实施方式:
1.新型模型系统的产生:将这些光感受器序列插入各种体外和体内系统的基因组中,这些系统可以作为研究神经退行性疾病的新模型。体外用途的某些实例包括人类和啮齿动物细胞系、诱导性多能干细胞(iPSC)或酵母。体内用途的某些实例包括无脊椎动物:果蝇(Drosophila melanogaster)(果蝇)、秀丽隐杆线虫(Caenorhabditis elegans)(蛔虫)或斑马鱼(Danio rerio,zebrafish)。体内用途的其他实例包括脊椎动物:小鼠、大鼠或非人灵长类。
2.具有经编辑基因组的这些化合物、方法和系统(诸如iPSC)用于高通量药物筛选系统。为此,通过用光刺激细胞来诱导神经退行性疾病病理。然后检查存在化合物库时的细胞活力以及蛋白质聚集体/病理的形成和驻留时间。另外,测定还涉及在光诱导后采用体内模型的存活和神经病理学。
序列
光感受器工具的氨基酸序列
拟南芥隐花色素2蛋白质的光解酶同源区(PHR)结构域的氨基酸序列:
SEQ ID NO:1.隐花色素2PHR结构域;Cry2PHR:MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTREAQIMIGAA
SEQ ID NO:2.具有E490G取代的隐花色素2PHR结构域;Cry2Olig:(E490G粗体)
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAA
包含来自链孢霉(链孢霉)活蛋白的光氧电压感测结构域(LOV)的氨基酸序列:
SEQ ID NO:3.仅VVD LOV结构域:
MTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMR KAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETE
SEQ ID NO:4.NcVivid(NcVVD):
HTLYAPGGYDIMGYLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLG RNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQ CETE
SEQ ID NO:5.NcVivid Y50W取代;NcVVDY50W:(Y50W粗体)
HTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLG RNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQ CETE
产生的TDP-43蛋白质排列:
1.Cry2olig融合蛋白氨基酸序列:
A)全长TDP-43蛋白无报告基因
SEQ ID NO:6.Cry2olig-TDP-43:
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARGMSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM
SEQ ID NO:7.TDP-43-Cry2olig:
MSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM LEATMKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAA
B)截短的TDP-43蛋白无报告基因
SEQ ID NO:8.TDP-43(AA274-414)-Cry2olig:
MGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMLEATMKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAA
SEQ ID NO:9.TDP-43(AA191-414)-Cry2olig:
MRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMLEATMKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAA
SEQ ID NO:10.TDP-43(AA105-414)-Cry2olig:
MDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM
LEATMKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAA
SEQ ID NO:11.Cry2olig-TDP-43(AA274-414):
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARGGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM
SEQ ID NO:12.Cry2olig-TDP-43(AA191-414):
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARGRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM
SEQ ID NO:13.Cry2olig-TDP-43(AA105-414):
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARGDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM
C)全长TDP-43蛋白+mCherry报告基因
SEQ ID NO:14.Cry2olig-TDP-43-mCherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARG
MSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMSRDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK
SEQ ID NO:15.TDP-43-Cry2olig-mCherry:
MSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMLEATMKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK
SEQ ID NO:16.mCherry-TDP-43-Cry2olig:
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKMSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMLEATMKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAA
D)截短的TDP-43蛋白+mCherry报告基因
SEQ ID NO:17.TDP-43(AA274-414)-Cry2olig-mCherry:
MGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMLEATMKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK
SEQ ID NO:18.TDP-43(AA191-414)-Cry2olig-mCherry:
MRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMLEATMKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK
SEQ ID NO:19.TDP-43(AA105-414)-Cry2olig-mCherry:
MDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMLEATMKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK
SEQ ID NO:20.mCherry-Cry2olig-TDP-43(AA274-414):
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARGGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM
SEQ ID NO:21.mCherry-Cry2olig-TDP-43(AA191-414):
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARGRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM
SEQ ID NO:22.mCherry-Cry2olig-TDP-43(AA105-414):
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKMKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARGDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM
SEQ ID NO:23.Cry2olig-TDP-43(AA274-414)-mCherry:
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARGGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMSRDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK
SEQ ID NO:24.Cry2olig-TDP-43(AA191-414)-mCherry:
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARGRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMSRDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK
SEQ ID NO:25.Cry2olig-TDP-43(AA105-414)-mCherry:
MDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMLEATMKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAASRDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK
2.NcVVDY50W融合蛋白氨基酸序列:
A)全长TDP-43蛋白无报告基因
SEQ ID NO:26.NcVVDY50W-TDP-43
MHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEAMSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM
SEQ ID NO:27.TDP-43-NcVVDY50W
MSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMFRAQRHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETE
B)截短的TDP-43蛋白无报告基因
SEQ ID NO:28.TDP-43(AA105-414)-NcVVDY50W
MDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMFRAQRHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETE
SEQ ID NO:29.TDP-43(AA191-414)-NcVVDY50W
MRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMFRAQRHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETE
SEQ ID NO:30.TDP-43(AA274-414)-NcVVDY50W
MGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMFRAQRHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETE
SEQ ID NO:31.NcVVDY50W-TDP-43(AA105-414)
MHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEADLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM
SEQ ID NO:32.NcVVDY50W-TDP-43(AA191-414)
MHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEARKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM
SEQ ID NO:33.NcVVDY50W-TDP-43(AA274-414)
HTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEAGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM
C)全长TDP-43蛋白+mCherry报告基因
SEQ ID NO:34.NcVVDY50W-TDP-43-mCherry
MHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEAMSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMFAPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK
SEQ ID NO:35.mCherry-TDP-43-NcVVDY50W
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSGLKMSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMFRAQRHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETE
D)截短的TDP-43蛋白+mCherry报告基因
SEQ ID NO:36.mCherry-TDP-43(AA105-414)-NcVVDY50W
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSGLKDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMFRAQRHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETE
SEQ ID NO:37.mCherry-TDP-43(AA191-414)-NcVVDY50W
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSGLKRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMFRAQRHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETE
SEQ ID NO:38.mCherry-TDP-43(AA274-414)-NcVVDY50W
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSGLKGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMFRAQRHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETE
SEQ ID NO:39.NcVVDY50W-TDP-43(AA105-414)-mCherry
MHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEADLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMFAPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK
SEQ ID NO:40.NcVVDY50W-TDP-43(AA191-414)-mCherry
MHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEARKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMFAPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK
SEQ ID NO:41.NcVVDY50W-TDP-43(AA274-414)-mCherry
MHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEAGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMFAPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK
产生的ɑ突触核蛋白蛋白质排列:
1.Cry2olig融合蛋白氨基酸序列:
A)全长ɑ突触核蛋白(asyn)蛋白无报告基因
SEQ ID NO:42.Cry2olig-asyn
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAMDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDPDNEAYEMPSEEGYQDYEPEA
SEQ ID NO:43.Asyn-Cry2
MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDPDNEAYEMPSEEGYQDYEPEADPPVATMKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAA
B)全长ɑ突触核蛋白(asyn)蛋白+mCherry报告基因
SEQ ID NO:44.Cry2olig-asyn-mCherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAMDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDPDNEAYEMPSEEGYQDYEPEADPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK
SEQ ID NO:45.Cry2olig-mCherry-Asyn
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKMDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDPDNEAYEMPSEEGYQDYEPEA
SEQ ID NO:46.Asyn-Cry2-mCherry
MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDPDNEAYEMPSEEGYQDYEPEADPPVATMKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK
1.NcVVD融合蛋白氨基酸序列:
A)全长ɑ突触核蛋白(asyn)蛋白无报告基因
SEQ ID NO:47.Asyn-NcVVDY50W
MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDPDNEAYEMPSEEGYQDYEPEAFHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETE
SEQ ID NO:48.NcVVDY50W-Asyn
MHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEAMDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDPDNEAYEMPSEEGYQDYEPEA
B)全长ɑ突触核蛋白(asyn)蛋白+mCherry报告基因
SEQ ID NO:49.mCherry-Asyn-NcVVDY50W
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYSKMDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDPDNEAYEMPSEEGYQDYEPEAFHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETE
SEQ ID NO:50.mCherry-NcVVDY50W-Asyn
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSGLRSRAQRHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEALEFCSRRYRGPMDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDPDNEAYEMPSEEGYQDYEPEA
SEQ ID NO:51.NcVVDY50W-Asyn-mCherry
MHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEAMDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDPDNEAYEMPSEEGYQDYEPEAFAPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK
SEQ ID NO:52.ɑ突触核蛋白-mCherry-NcVVD(野生型)
MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDPDNEAYEMPSEEGYQDYEPEALLPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSGLRSRAQASNSAVDGTAGPMHTLYAPGGYDIMGYLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGY2SNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEGIHRI*
SEQ ID NO:53.mCherry-ɑ突触核蛋白-NcVVD(野生型)
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSGLRSRAQMDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDPDNEAYEMPSEEGYQDYEPEASNSAVDGTAGPMHTLYAPGGYDIMGYLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEGIHRI*
SEQ ID NO:54.mCherry-NcVVD(野生型)-ɑ突触核蛋白
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSGLRSRAQASNSAVDGTAGPMHTLYAPGGYDIMGYLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEGMDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTKEQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDPDNEAYEMPSEEGYQDYEPEAHRI*
Tau
SEQ ID NO:55.mCherry-Tau
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSGLRSRAQASNSAVDGTAGPMAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLGIHRI*
SEQ ID NO:56.mCherry-VfAU-Tau
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSGLRSRAQASNSAVDGTAGPMPDYSLVKALQMAQQNFVITDASLPDNPIVYASRGFLTLTGYSLDQILGRNCRFLQGPETDPRAVDKIRNAITKGVDTSVCLLNYRQDGTTFWNLFFVAGLRDSKGNIVNYVGVQSKVSEDYAKLLVNEQNIEYKGVRTSNMLRRKPGGIHRIMAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLITDHNQPYHICRGFTCFKKPPTPPPEPET*
SEQ ID NO:57.mCherry-(y50w)-Tau
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSGLRSRAQASNSAVDGTAGPMHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEGMAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLHRI*
SEQ ID NO:58.mCherry-Tau-NcVVD(y50w)
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSGLTMAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLRRAQRHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEALEFCSRRYRGPGIHRI*
SEQ ID NO:59.mCherry-NcVVD(y50w)-Tau
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSGLRSRAQRHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEALAMAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLRCSRRYRGPGIHRI*
SEQ ID NO:60.Tau-mCherry-NcVVD(y50w)
MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLALPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSGLRSRAQRHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEALEFCSRRYRGPGIHRI*
SEQ ID NO:61.Cry-mCherry-Tau
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSRMAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLGDSRS*
SEQ ID NO:62.Tau-mCherry
MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLFATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSGLRSRAQASNSAVDGTAGPGSTGSR*
SEQ ID NO:63.Tau-Cry2olig-mCherry
MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLALPDSDLEATMKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK*
SEQ ID NO:64.Cry2Olig-Tau-mCherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAPMAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLGDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK*
SEQ ID NO:65.Cry-mCherry-Tau
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSRMAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLGDSRS*
SEQ ID NO:66.mCherry-Tau-NcVVD(y50w)
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSGLTMAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLRRAQRHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEALEFCSRRYRGPGIHRI*
SEQ ID NO:67.mCherry-NcVVD(y50w)-Tau
MVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYKSGLRSRAQRHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETEALAMAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLRCSRRYRGPGIHRI*
SEQ ID NO:68.Cry-Tau
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAQMAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLATLDHNQPYHICRGFTCFKKPPTPPPEPET*
SEQ ID NO:69.NcVVD(y50w)-Tau
MHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEMAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLHRI*
SEQ ID NO:70.Tau-Cry
MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLMKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAATLDHNQPYHICRGFTCFKKPPTPPPEPET*
SEQ ID NO:71.Tau-VfAU
MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLPDYSLVKALQMAQQNFVITDASLPDNPIVYASRGFLTLTGYSLDQILGRNCRFLQGPETDPRAVDKIRNAITKGVDTSVCLLNYRQDGTTFWNLFFVAGLRDSKGNIVNYVGVQSKVSEDYAKLLVNEQNIEYKGVRTSNMLRRKPGLQSTVPRARDPPDLDN*
SEQ ID NO:72.Tau-NcVVD(y50w)
MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETELQSTVPRARDPPDLDN*
SEQ ID NO:73.Tau-NcVVD(野生型)
MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLHTLYAPGGYDIMGWLIQIMNRPNPQVELGPVDTSCALILCDLKQKDTPIVYASEAFLYMTGYSNAEVLGRNCRFLQSPDGMVKPKSTRKYVDSNTINTMRKAIDRNAEVQVEVVNFKKNGQRFVNFLTMIPVRDETGEYRYSMGFQCETELQSTVPRARDPPDLDN*
SEQ ID NO:74.VfAU-Tau
MPDYSLVKALQMAQQNFVITDASLPDNPIVYASRGFLTLTGYSLDQILGRNCRFLQGPETDPRAVDKIRNAITKGVDTSVCLLNYRQDGTTFWNLFFVAGLRDSKGNIVNYVGVQSKVSEDYAKLLVNEQNIEYKGVRTSNMLRRKPGSLMAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGLSNSAVDGTAGPGSTGSR*
SEQ ID NO:75.Cry-TDP(F147L)-mCherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARGMSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGLGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMSRDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK*
SEQ ID NO:76.Cry-TDP(F229L)-mCherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAARGMSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRALAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMSRDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK*
SEQ ID NO:77.Cry-TDP(S409,410A)-mCherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAQMSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKAAGWGMWDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK*
SEQ ID NO:78.Cry-TDP(S409,410D)-mCherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAQMSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKDDGWGMWDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK*
SEQ ID NO:79.Cry-TDP(A321V)-mCherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAQMSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPVMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGWDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK*
SEQ ID NO:80.Cry-TDP(m337V)-mCherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAQMSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMVGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGWDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK*
SEQ ID NO:81.Cry-TDP(LCD,A321V)-mCherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAQGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPVMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMRDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK*
SEQ ID NO:82.Cry-TDP(LCD,M337V)-mCherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAQGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMVGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMRDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK*
SEQ ID NO:83.Cry-TDP(LCD,S409,410A)-mCherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAQGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKAAGWGMRDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK*
SEQ ID NO:84.Cry-TDP(LCD,S409,410D)-mCherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAPGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKDDGWGMTRDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK*
SEQ ID NO:85.Cry-TDP(5FL)-mcherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAQMSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGLGLVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVLVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRALALVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGMWDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK*
SEQ ID NO:86.Cry-TDP(RRM1)-mCherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAQDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK*
SEQ ID NO:87.Cry-TDP(RRM2)-mCherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAQRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPRDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK*
SEQ ID NO:88.Cry-TDP(RRM1+2)-mCherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAQDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPRDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK*
SEQ ID NO:89.Cry-TDP(dLCD)-mCherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAQMSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSRDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK*
产生的FUS蛋白排列:
1.Cry2olig融合蛋白氨基酸序列:
A)全长FUS蛋白无报告基因
SEQ ID NO:90.Cry2Olig-FUS
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAQCRATMYPYDVPDYAMASNDYTQQATQSYGAYPTQPGQGYSQQSSQPYGQQSYSGYSQSTDTSGYGQSSYSSYGQSQNTGYGTQSTPQGYGSTGGYGSSQSSQSSYGQQSSYPGYGQQPAPSSTSGSYGSSSQSSSYGQPQSGSYSQQPSYGGQQQSYGQQQSYNPPQGYGQQNQYNSSSGGGGGGGGGGNYGQDQSSMSSGGGSGGGYGNQDQSGGGGSGGYGQQDRGGRGRGGSGGGGGGGGGGYNRSSGGYEPRGRGGGRGGRGGMGGSDRGGFNKFGGPRDQGSRHDSEQDNSDNNTIFVQGLGENVTIESVADYFKQIGIIKTNKKTGQPMINLYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNPIKVSFATRRADFNRGGGNGRGGRGRGGPMGRGGYGGGGSGGGGRGGFPSGGGGGGGQQRAGDWKCPNPTCENMNFSWRNECNQCKAPKPDGPGGGPGGSHMGGNYGDDRRGGRGGYDRGGYRGRGGDRGGFRGGRGGGDRGGFGPGKMDSRGEHRQDRRERPY
B)全长FUS蛋白+mCherry报告基因
SEQ ID NO:91.Cry2Olig-FUS-mCherry
MKMDKKTIVWFRRDLRIEDNPALAAAAHEGSVFPVFIWCPEEEGQFYPGRASRWWMKQSLAHLSQSLKALGSDLTLIKTHNTISAILDCIRVTGATKVVFNHLYDPVSLVRDHTVKEKLVERGISVQSYNGDLLYEPWEIYCEKGKPFTSFNSYWKKCLDMSIESVMLPPPWRLMPITAAAEAIWACSIEELGLENEAEKPSNALLTRAWSPGWSNADKLLNEFIEKQLIDYAKNSKKVVGNSTSLLSPYLHFGEISVRHVFQCARMKQIIWARDKNSEGEESADLFLRGIGLREYSRYICFNFPFTHEQSLLSHLRFFPWDADVDKFKAWRQGRTGYPLVDAGMRELWATGWMHNRIRVIVSSFAVKFLLLPWKWGMKYFWDTLLDADLECDILGWQYISGSIPDGHELDRLDNPALQGAKYDPEGEYIRQWLPELARLPTEWIHHPWDAPLTVLKASGVELGTNYAKPIVDIDTARELLAKAISRTRGAQIMIGAAAQCRATMYPYDVPDYAMASNDYTQQATQSYGAYPTQPGQGYSQQSSQPYGQQSYSGYSQSTDTSGYGQSSYSSYGQSQNTGYGTQSTPQGYGSTGGYGSSQSSQSSYGQQSSYPGYGQQPAPSSTSGSYGSSSQSSSYGQPQSGSYSQQPSYGGQQQSYGQQQSYNPPQGYGQQNQYNSSSGGGGGGGGGGNYGQDQSSMSSGGGSGGGYGNQDQSGGGGSGGYGQQDRGGRGRGGSGGGGGGGGGGYNRSSGGYEPRGRGGGRGGRGGMGGSDRGGFNKFGGPRDQGSRHDSEQDNSDNNTIFVQGLGENVTIESVADYFKQIGIIKTNKKTGQPMINLYTDRETGKLKGEATVSFDDPPSAKAAIDWFDGKEFSGNPIKVSFATRRADFNRGGGNGRGGRGRGGPMGRGGYGGGGSGGGGRGGFPSGGGGGGGQQRAGDWKCPNPTCENMNFSWRNECNQCKAPKPDGPGGGPGGSHMGGNYGDDRRGGRGGYDRGGYRGRGGDRGGFRGGRGGGDRGGFGPGKMDSRGEHRQDRRERPYWDPPVATMVSKGEEDNMAIIKEFMRFKVHMEGSVNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPFAWDILSPQFMYGSKAYVKHPADIPDYLKLSFPEGFKWERVMNFEDGGVVTVTQDSSLQDGEFIYKVKLRGTNFPSDGPVMQKKTMGWEASSERMYPEDGALKGEIKQRLKLKDGGHYDAEVKTTYKAKKPVQLPGAYNVNIKLDITSHNEDYTIVEQYERAEGRHSTGGMDELYK
无隔藻(黄绿藻)(Conferva frigida)Aureochrome1蛋白(基因是AUREO1)的氨基酸序列:
SEQ ID NO:92.VfAU1(A8QW55):
MNGLTPPLMFCSRSDDPSSTSNINLDDVFADVFFNSNGELLDIDEIDDFGDNTCPKSSMSVDDDASSQVFQGHLFGNALSSIALSDSGDLSTGIYESQGNASRGKSLRTKSSGSISSELTEAQKVERRERNREHAKRSRVRKKFLLESLQQSVNELNHENNCLKESIREHLGPRGDSLIAQCSPEADTLLTDNPSKANRILEDPDYSLVKALQMAQQNFV ITDASLPDNPIVYASRGFLTLTGYSLDQILGRNCRFLQGPETDPRAVDKIRNAITKGVDTSVCLLNYRQDGTTFWN LFFVAGLRDSKGNIVNYVGVQSKVSEDYAK LLVNEQNIEYKGVRTSNMLRRK
SEQ ID NO:93.VfAU1-LOV结构域:
PDYSLVKALQMAQQNFVITDASLPDNPIVYASRGFLTLTGYSLDQILGRNCRFLQGPETDPRAVDKIRNAITKGVDTSVCLLNYRQDGTTFWNLFFVAGLRDSKGNIVNYVGVQSKVSEDYAKLLVNEQNIEYKGVRTSNMLRRK
SEQ ID NO:94.VfAU1–DNA序列-VfAU1-LOV结构域(无起始密码子):
Cctgactacagtctcgtgaaggctctgcaaatggcacaacagaattttgtcattacagacgcctccctcccagacaaccctatcgtctacgccagtagagggtttctgacactgacaggctattctctcgaccagatcctgggcaggaactgcaggtttctgcaagggccagaaacagacccaagagctgtggataagatcaggaatgccatcaccaaaggcgttgataccagtgtctgtctgctgaattatagacaggatggcacaaccttctggaatctcttcttcgtggctggactcagagattctaagggcaatattgtcaactacgtcggagtgcagtcaaaggtgagcgaagattatgccaagctgctggtcaacgagcagaacattgagtacaaaggtgtgcgcaccagtaacatgctgcgcagaaag
SEQ ID NO:95.TDP-43(TAR DNA-结合蛋白-43)
MSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM
SEQ ID NO:96.TDP-43(氨基酸105-414)
MDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM
SEQ ID NO:97.TDP-43(氨基酸191-414)
MRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM
SEQ ID NO:98.TDP-43(氨基酸274-414)
MGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM
SEQ ID NO:99.AsLOV2
GEFLATTLERIEKNFVITDP RLPDNPIIFASDSFLQLTEY SREEILGRNCRFLQGPETDRATVRKIRDAIDNQTEVTVQL INYTKSGKKFWNLFHLQPMR DQKGDVQYFIGVQLDGTEHVRDAAEREGVMLIKKTAENIDEAAKELPDANLRPEDLWANH G
SEQ ID NO:100.EL222
MLDMGQDRPI DGSGAPGADD TRVEVQPPAQ WVLDLIEASP IASVVSDPRLADNPLIAINQAFTDLTGYSE EECVGRNCRF LAGSGTEPWL TDKIRQGVRE HKPVLVEILNYKKDGTPFRNAVLVAPIYDD DDELLYFLGS QVEVDDDQPN MGMARRERAA EMLKTLSPRQLEVTTLVASGLRNKEVAARL GLSEKTVKMH RGLVMEKLNL KTSADLVRIA VEAGI
SEQ ID NO:101.Ytva
MASFQSFGIP GQLEVIKKAL DHVRVGVVIT DPALEDNPIV YVNQGFVQMTGYETEEILGKNCRFLQGKHT DPAEVDNIRT ALQNKEPVTV QIQNYKKDGT MFWNELNIDPMEIEDKTYFVGIQNDITKQK
EYEKLLEDSL TEITALSTPI VPIRNGISAL PLVGNLTEER FNSIVCTLTNILSTSKDDYLIIDLSGLAQV NEQTADQIFK LSHLLKLTGT ELIITGIKPE LAMKMNKLDANFSSLKTYSNVKDAVKVLPI
M
SEQ ID NO:102.RsLOV
MDQKQFEKIRAVFDRSGVALTLVDMSLPEQPVVLANPPFLRMTGYTEGQILGFNCRFLQRGDENAQARAD
IRDALKLGRELQVVLRNYRANDEPFDNLLFLHPVGGRPDAPDYFLGSQFELGRSGNSEEAAAAGHAGALT
GELARIGTVAARLEMDSRRHLAQAAAALVRAWERRG
除非另外定义,否则本文使用的所有科技术语具有与所公开发明所属领域的技术人员通常理解的含义相同的含义。本文引用的出版物和引用它们的材料通过引用明确地并入本文。
本领域技术人员将理解,可以对本发明的优选实施方式进行许多改变和修改,并且可以在不脱离本发明的精神的情况下进行这些改变和修改。因此,所附权利要求旨在覆盖落入本发明的真实精神和范围内的所有这些等同变化。
序列表
<110> 匹兹堡大学 联邦高等教育系统
<120> 神经退行性疾病病理的光遗传学诱导
<130> 10504-011WO1
<160> 102
<170> PatentIn version 3.5
<210> 1
<400> 1
000
<210> 2
<211> 498
<212> PRT
<213> 拟南芥(Arabidopsis)
<400> 2
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala
<210> 3
<211> 119
<212> PRT
<213> 链孢霉(Neurospora)
<400> 3
Met Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr
1 5 10 15
Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser
20 25 30
Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp
35 40 45
Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr
50 55 60
Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val
65 70 75 80
Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu
85 90 95
Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met
100 105 110
Gly Phe Gln Cys Glu Thr Glu
115
<210> 4
<211> 150
<212> PRT
<213> 链孢霉(Neurospora)
<400> 4
His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Tyr Leu Ile
1 5 10 15
Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val Asp
20 25 30
Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr Pro
35 40 45
Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser Asn
50 55 60
Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp Gly
65 70 75 80
Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr Ile
85 90 95
Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val Glu
100 105 110
Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu Thr
115 120 125
Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met Gly
130 135 140
Phe Gln Cys Glu Thr Glu
145 150
<210> 5
<211> 150
<212> PRT
<213> 链孢霉(Neurospora)
<400> 5
His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Trp Leu Ile
1 5 10 15
Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val Asp
20 25 30
Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr Pro
35 40 45
Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser Asn
50 55 60
Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp Gly
65 70 75 80
Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr Ile
85 90 95
Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val Glu
100 105 110
Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu Thr
115 120 125
Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met Gly
130 135 140
Phe Gln Cys Glu Thr Glu
145 150
<210> 6
<211> 915
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 6
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Arg Gly Met Ser Glu Tyr Ile Arg Val Thr Glu Asp Glu
500 505 510
Asn Asp Glu Pro Ile Glu Ile Pro Ser Glu Asp Asp Gly Thr Val Leu
515 520 525
Leu Ser Thr Val Thr Ala Gln Phe Pro Gly Ala Cys Gly Leu Arg Tyr
530 535 540
Arg Asn Pro Val Ser Gln Cys Met Arg Gly Val Arg Leu Val Glu Gly
545 550 555 560
Ile Leu His Ala Pro Asp Ala Gly Trp Gly Asn Leu Val Tyr Val Val
565 570 575
Asn Tyr Pro Lys Asp Asn Lys Arg Lys Met Asp Glu Thr Asp Ala Ser
580 585 590
Ser Ala Val Lys Val Lys Arg Ala Val Gln Lys Thr Ser Asp Leu Ile
595 600 605
Val Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp Leu Lys Glu Tyr
610 615 620
Phe Ser Thr Phe Gly Glu Val Leu Met Val Gln Val Lys Lys Asp Leu
625 630 635 640
Lys Thr Gly His Ser Lys Gly Phe Gly Phe Val Arg Phe Thr Glu Tyr
645 650 655
Glu Thr Gln Val Lys Val Met Ser Gln Arg His Met Ile Asp Gly Arg
660 665 670
Trp Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser Gln Asp Glu Pro
675 680 685
Leu Arg Ser Arg Lys Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr
690 695 700
Glu Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp
705 710 715 720
Val Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala
725 730 735
Asp Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys
740 745 750
Gly Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn
755 760 765
Arg Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe
770 775 780
Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu
785 790 795 800
Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala
805 810 815
Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln
820 825 830
Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser
835 840 845
Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro
850 855 860
Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser
865 870 875 880
Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser
885 890 895
Gly Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly
900 905 910
Trp Gly Met
915
<210> 7
<211> 916
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 7
Met Ser Glu Tyr Ile Arg Val Thr Glu Asp Glu Asn Asp Glu Pro Ile
1 5 10 15
Glu Ile Pro Ser Glu Asp Asp Gly Thr Val Leu Leu Ser Thr Val Thr
20 25 30
Ala Gln Phe Pro Gly Ala Cys Gly Leu Arg Tyr Arg Asn Pro Val Ser
35 40 45
Gln Cys Met Arg Gly Val Arg Leu Val Glu Gly Ile Leu His Ala Pro
50 55 60
Asp Ala Gly Trp Gly Asn Leu Val Tyr Val Val Asn Tyr Pro Lys Asp
65 70 75 80
Asn Lys Arg Lys Met Asp Glu Thr Asp Ala Ser Ser Ala Val Lys Val
85 90 95
Lys Arg Ala Val Gln Lys Thr Ser Asp Leu Ile Val Leu Gly Leu Pro
100 105 110
Trp Lys Thr Thr Glu Gln Asp Leu Lys Glu Tyr Phe Ser Thr Phe Gly
115 120 125
Glu Val Leu Met Val Gln Val Lys Lys Asp Leu Lys Thr Gly His Ser
130 135 140
Lys Gly Phe Gly Phe Val Arg Phe Thr Glu Tyr Glu Thr Gln Val Lys
145 150 155 160
Val Met Ser Gln Arg His Met Ile Asp Gly Arg Trp Cys Asp Cys Lys
165 170 175
Leu Pro Asn Ser Lys Gln Ser Gln Asp Glu Pro Leu Arg Ser Arg Lys
180 185 190
Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr Glu Asp Glu Leu Arg
195 200 205
Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val Phe Ile Pro Lys
210 215 220
Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala Asp Asp Gln Ile Ala
225 230 235 240
Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly Ile Ser Val His
245 250 255
Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg Gln Leu Glu Arg
260 265 270
Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn Gln Gly Gly
275 280 285
Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn Asn Gln Gly
290 295 300
Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser Ile Asn Pro
305 310 315 320
Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser Trp Gly Met
325 330 335
Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro Ser Gly Asn
340 345 350
Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln Ala Phe Gly
355 360 365
Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala Ala Ile Gly
370 375 380
Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe Asn Gly Gly
385 390 395 400
Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly Met Leu Glu
405 410 415
Ala Thr Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp
420 425 430
Leu Arg Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly
435 440 445
Ser Val Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe
450 455 460
Tyr Pro Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His
465 470 475 480
Leu Ser Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys
485 490 495
Thr His Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly
500 505 510
Ala Thr Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val
515 520 525
Arg Asp His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val
530 535 540
Gln Ser Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys
545 550 555 560
Glu Lys Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys
565 570 575
Leu Asp Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu
580 585 590
Met Pro Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu
595 600 605
Glu Leu Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu
610 615 620
Thr Arg Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn
625 630 635 640
Glu Phe Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys
645 650 655
Val Val Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly
660 665 670
Glu Ile Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile
675 680 685
Ile Trp Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu
690 695 700
Phe Leu Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe
705 710 715 720
Asn Phe Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe
725 730 735
Phe Pro Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly
740 745 750
Arg Thr Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala
755 760 765
Thr Gly Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala
770 775 780
Val Lys Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp
785 790 795 800
Asp Thr Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln
805 810 815
Tyr Ile Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp
820 825 830
Asn Pro Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile
835 840 845
Arg Gln Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His
850 855 860
His Pro Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu
865 870 875 880
Leu Gly Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg
885 890 895
Glu Leu Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met
900 905 910
Ile Gly Ala Ala
915
<210> 8
<211> 644
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 8
Met Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn Gln Gly Gly
1 5 10 15
Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn Asn Gln Gly
20 25 30
Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser Ile Asn Pro
35 40 45
Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser Trp Gly Met
50 55 60
Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro Ser Gly Asn
65 70 75 80
Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln Ala Phe Gly
85 90 95
Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala Ala Ile Gly
100 105 110
Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe Asn Gly Gly
115 120 125
Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly Met Leu Glu
130 135 140
Ala Thr Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp
145 150 155 160
Leu Arg Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly
165 170 175
Ser Val Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe
180 185 190
Tyr Pro Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His
195 200 205
Leu Ser Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys
210 215 220
Thr His Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly
225 230 235 240
Ala Thr Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val
245 250 255
Arg Asp His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val
260 265 270
Gln Ser Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys
275 280 285
Glu Lys Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys
290 295 300
Leu Asp Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu
305 310 315 320
Met Pro Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu
325 330 335
Glu Leu Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu
340 345 350
Thr Arg Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn
355 360 365
Glu Phe Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys
370 375 380
Val Val Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly
385 390 395 400
Glu Ile Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile
405 410 415
Ile Trp Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu
420 425 430
Phe Leu Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe
435 440 445
Asn Phe Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe
450 455 460
Phe Pro Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly
465 470 475 480
Arg Thr Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala
485 490 495
Thr Gly Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala
500 505 510
Val Lys Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp
515 520 525
Asp Thr Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln
530 535 540
Tyr Ile Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp
545 550 555 560
Asn Pro Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile
565 570 575
Arg Gln Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His
580 585 590
His Pro Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu
595 600 605
Leu Gly Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg
610 615 620
Glu Leu Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met
625 630 635 640
Ile Gly Ala Ala
<210> 9
<211> 727
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 9
Met Arg Lys Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr Glu Asp
1 5 10 15
Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val Phe
20 25 30
Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala Asp Asp
35 40 45
Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly Ile
50 55 60
Ser Val His Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg Gln
65 70 75 80
Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn
85 90 95
Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn
100 105 110
Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser
115 120 125
Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser
130 135 140
Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro
145 150 155 160
Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln
165 170 175
Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala
180 185 190
Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe
195 200 205
Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly
210 215 220
Met Leu Glu Ala Thr Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe
225 230 235 240
Arg Arg Asp Leu Arg Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala
245 250 255
His Glu Gly Ser Val Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu
260 265 270
Gly Gln Phe Tyr Pro Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser
275 280 285
Leu Ala His Leu Ser Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr
290 295 300
Leu Ile Lys Thr His Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg
305 310 315 320
Val Thr Gly Ala Thr Lys Val Val Phe Asn His Leu Tyr Asp Pro Val
325 330 335
Ser Leu Val Arg Asp His Thr Val Lys Glu Lys Leu Val Glu Arg Gly
340 345 350
Ile Ser Val Gln Ser Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu
355 360 365
Ile Tyr Cys Glu Lys Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp
370 375 380
Lys Lys Cys Leu Asp Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro
385 390 395 400
Trp Arg Leu Met Pro Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys
405 410 415
Ser Ile Glu Glu Leu Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn
420 425 430
Ala Leu Leu Thr Arg Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys
435 440 445
Leu Leu Asn Glu Phe Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn
450 455 460
Ser Lys Lys Val Val Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu
465 470 475 480
His Phe Gly Glu Ile Ser Val Arg His Val Phe Gln Cys Ala Arg Met
485 490 495
Lys Gln Ile Ile Trp Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser
500 505 510
Ala Asp Leu Phe Leu Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr
515 520 525
Ile Cys Phe Asn Phe Pro Phe Thr His Glu Gln Ser Leu Leu Ser His
530 535 540
Leu Arg Phe Phe Pro Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp
545 550 555 560
Arg Gln Gly Arg Thr Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu
565 570 575
Leu Trp Ala Thr Gly Trp Met His Asn Arg Ile Arg Val Ile Val Ser
580 585 590
Ser Phe Ala Val Lys Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys
595 600 605
Tyr Phe Trp Asp Thr Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu
610 615 620
Gly Trp Gln Tyr Ile Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp
625 630 635 640
Arg Leu Asp Asn Pro Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly
645 650 655
Glu Tyr Ile Arg Gln Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu
660 665 670
Trp Ile His His Pro Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser
675 680 685
Gly Val Glu Leu Gly Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp
690 695 700
Thr Ala Arg Glu Leu Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala
705 710 715 720
Gln Ile Met Ile Gly Ala Ala
725
<210> 10
<211> 813
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 10
Met Asp Leu Ile Val Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp
1 5 10 15
Leu Lys Glu Tyr Phe Ser Thr Phe Gly Glu Val Leu Met Val Gln Val
20 25 30
Lys Lys Asp Leu Lys Thr Gly His Ser Lys Gly Phe Gly Phe Val Arg
35 40 45
Phe Thr Glu Tyr Glu Thr Gln Val Lys Val Met Ser Gln Arg His Met
50 55 60
Ile Asp Gly Arg Trp Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser
65 70 75 80
Gln Asp Glu Pro Leu Arg Ser Arg Lys Val Phe Val Gly Arg Cys Thr
85 90 95
Glu Asp Met Thr Glu Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly
100 105 110
Asp Val Met Asp Val Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe
115 120 125
Val Thr Phe Ala Asp Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp
130 135 140
Leu Ile Ile Lys Gly Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys
145 150 155 160
His Asn Ser Asn Arg Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn
165 170 175
Pro Gly Gly Phe Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly
180 185 190
Gly Ala Gly Leu Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met
195 200 205
Asn Phe Gly Ala Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln
210 215 220
Ala Ala Leu Gln Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln
225 230 235 240
Gln Asn Gln Ser Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met
245 250 255
Gln Arg Glu Pro Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser
260 265 270
Gly Ser Asn Ser Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala
275 280 285
Gly Ser Gly Ser Gly Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser
290 295 300
Lys Ser Ser Gly Trp Gly Met Leu Glu Ala Thr Met Lys Met Asp Lys
305 310 315 320
Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg Ile Glu Asp Asn Pro
325 330 335
Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val Phe Pro Val Phe Ile
340 345 350
Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro Gly Arg Ala Ser Arg
355 360 365
Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser Gln Ser Leu Lys Ala
370 375 380
Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His Asn Thr Ile Ser Ala
385 390 395 400
Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr Lys Val Val Phe Asn
405 410 415
His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp His Thr Val Lys Glu
420 425 430
Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser Tyr Asn Gly Asp Leu
435 440 445
Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys Gly Lys Pro Phe Thr
450 455 460
Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp Met Ser Ile Glu Ser
465 470 475 480
Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro Ile Thr Ala Ala Ala
485 490 495
Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu Gly Leu Glu Asn Glu
500 505 510
Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg Ala Trp Ser Pro Gly
515 520 525
Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe Ile Glu Lys Gln Leu
530 535 540
Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val Gly Asn Ser Thr Ser
545 550 555 560
Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile Ser Val Arg His Val
565 570 575
Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp Ala Arg Asp Lys Asn
580 585 590
Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu Arg Gly Ile Gly Leu
595 600 605
Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe Pro Phe Thr His Glu
610 615 620
Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro Trp Asp Ala Asp Val
625 630 635 640
Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr Gly Tyr Pro Leu Val
645 650 655
Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly Trp Met His Asn Arg
660 665 670
Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys Phe Leu Leu Leu Pro
675 680 685
Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr Leu Leu Asp Ala Asp
690 695 700
Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile Ser Gly Ser Ile Pro
705 710 715 720
Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro Ala Leu Gln Gly Ala
725 730 735
Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln Trp Leu Pro Glu Leu
740 745 750
Ala Arg Leu Pro Thr Glu Trp Ile His His Pro Trp Asp Ala Pro Leu
755 760 765
Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly Thr Asn Tyr Ala Lys
770 775 780
Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu Leu Ala Lys Ala Ile
785 790 795 800
Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly Ala Ala
805 810
<210> 11
<211> 642
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 11
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Arg Gly Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly
500 505 510
Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly
515 520 525
Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe
530 535 540
Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser
545 550 555 560
Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly
565 570 575
Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn
580 585 590
Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly
595 600 605
Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly
610 615 620
Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp
625 630 635 640
Gly Met
<210> 12
<211> 725
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 12
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Arg Gly Arg Lys Val Phe Val Gly Arg Cys Thr Glu Asp
500 505 510
Met Thr Glu Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val
515 520 525
Met Asp Val Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val Thr
530 535 540
Phe Ala Asp Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile
545 550 555 560
Ile Lys Gly Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys His Asn
565 570 575
Ser Asn Arg Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro Gly
580 585 590
Gly Phe Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala
595 600 605
Gly Leu Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe
610 615 620
Gly Ala Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala
625 630 635 640
Leu Gln Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn
645 650 655
Gln Ser Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg
660 665 670
Glu Pro Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser
675 680 685
Asn Ser Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser
690 695 700
Gly Ser Gly Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser
705 710 715 720
Ser Gly Trp Gly Met
725
<210> 13
<211> 811
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 13
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Arg Gly Asp Leu Ile Val Leu Gly Leu Pro Trp Lys Thr
500 505 510
Thr Glu Gln Asp Leu Lys Glu Tyr Phe Ser Thr Phe Gly Glu Val Leu
515 520 525
Met Val Gln Val Lys Lys Asp Leu Lys Thr Gly His Ser Lys Gly Phe
530 535 540
Gly Phe Val Arg Phe Thr Glu Tyr Glu Thr Gln Val Lys Val Met Ser
545 550 555 560
Gln Arg His Met Ile Asp Gly Arg Trp Cys Asp Cys Lys Leu Pro Asn
565 570 575
Ser Lys Gln Ser Gln Asp Glu Pro Leu Arg Ser Arg Lys Val Phe Val
580 585 590
Gly Arg Cys Thr Glu Asp Met Thr Glu Asp Glu Leu Arg Glu Phe Phe
595 600 605
Ser Gln Tyr Gly Asp Val Met Asp Val Phe Ile Pro Lys Pro Phe Arg
610 615 620
Ala Phe Ala Phe Val Thr Phe Ala Asp Asp Gln Ile Ala Gln Ser Leu
625 630 635 640
Cys Gly Glu Asp Leu Ile Ile Lys Gly Ile Ser Val His Ile Ser Asn
645 650 655
Ala Glu Pro Lys His Asn Ser Asn Arg Gln Leu Glu Arg Ser Gly Arg
660 665 670
Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn Gln Gly Gly Phe Gly Asn
675 680 685
Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn Asn Gln Gly Ser Asn Met
690 695 700
Gly Gly Gly Met Asn Phe Gly Ala Phe Ser Ile Asn Pro Ala Met Met
705 710 715 720
Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser Trp Gly Met Met Gly Met
725 730 735
Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro Ser Gly Asn Asn Gln Asn
740 745 750
Gln Gly Asn Met Gln Arg Glu Pro Asn Gln Ala Phe Gly Ser Gly Asn
755 760 765
Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala Ala Ile Gly Trp Gly Ser
770 775 780
Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe Asn Gly Gly Phe Gly Ser
785 790 795 800
Ser Met Asp Ser Lys Ser Ser Gly Trp Gly Met
805 810
<210> 14
<211> 1159
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 14
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Arg Gly Met Ser Glu Tyr Ile Arg Val Thr Glu Asp Glu
500 505 510
Asn Asp Glu Pro Ile Glu Ile Pro Ser Glu Asp Asp Gly Thr Val Leu
515 520 525
Leu Ser Thr Val Thr Ala Gln Phe Pro Gly Ala Cys Gly Leu Arg Tyr
530 535 540
Arg Asn Pro Val Ser Gln Cys Met Arg Gly Val Arg Leu Val Glu Gly
545 550 555 560
Ile Leu His Ala Pro Asp Ala Gly Trp Gly Asn Leu Val Tyr Val Val
565 570 575
Asn Tyr Pro Lys Asp Asn Lys Arg Lys Met Asp Glu Thr Asp Ala Ser
580 585 590
Ser Ala Val Lys Val Lys Arg Ala Val Gln Lys Thr Ser Asp Leu Ile
595 600 605
Val Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp Leu Lys Glu Tyr
610 615 620
Phe Ser Thr Phe Gly Glu Val Leu Met Val Gln Val Lys Lys Asp Leu
625 630 635 640
Lys Thr Gly His Ser Lys Gly Phe Gly Phe Val Arg Phe Thr Glu Tyr
645 650 655
Glu Thr Gln Val Lys Val Met Ser Gln Arg His Met Ile Asp Gly Arg
660 665 670
Trp Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser Gln Asp Glu Pro
675 680 685
Leu Arg Ser Arg Lys Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr
690 695 700
Glu Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp
705 710 715 720
Val Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala
725 730 735
Asp Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys
740 745 750
Gly Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn
755 760 765
Arg Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe
770 775 780
Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu
785 790 795 800
Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala
805 810 815
Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln
820 825 830
Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser
835 840 845
Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro
850 855 860
Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser
865 870 875 880
Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser
885 890 895
Gly Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly
900 905 910
Trp Gly Met Ser Arg Asp Pro Pro Val Ala Thr Met Val Ser Lys Gly
915 920 925
Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val
930 935 940
His Met Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu
945 950 955 960
Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val
965 970 975
Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln
980 985 990
Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro
995 1000 1005
Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg
1010 1015 1020
Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp
1025 1030 1035
Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg
1040 1045 1050
Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr
1055 1060 1065
Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
1070 1075 1080
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly
1085 1090 1095
Gly His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys
1100 1105 1110
Pro Val Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp
1115 1120 1125
Ile Thr Ser His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu
1130 1135 1140
Arg Ala Glu Gly Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr
1145 1150 1155
Lys
<210> 15
<211> 1160
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 15
Met Ser Glu Tyr Ile Arg Val Thr Glu Asp Glu Asn Asp Glu Pro Ile
1 5 10 15
Glu Ile Pro Ser Glu Asp Asp Gly Thr Val Leu Leu Ser Thr Val Thr
20 25 30
Ala Gln Phe Pro Gly Ala Cys Gly Leu Arg Tyr Arg Asn Pro Val Ser
35 40 45
Gln Cys Met Arg Gly Val Arg Leu Val Glu Gly Ile Leu His Ala Pro
50 55 60
Asp Ala Gly Trp Gly Asn Leu Val Tyr Val Val Asn Tyr Pro Lys Asp
65 70 75 80
Asn Lys Arg Lys Met Asp Glu Thr Asp Ala Ser Ser Ala Val Lys Val
85 90 95
Lys Arg Ala Val Gln Lys Thr Ser Asp Leu Ile Val Leu Gly Leu Pro
100 105 110
Trp Lys Thr Thr Glu Gln Asp Leu Lys Glu Tyr Phe Ser Thr Phe Gly
115 120 125
Glu Val Leu Met Val Gln Val Lys Lys Asp Leu Lys Thr Gly His Ser
130 135 140
Lys Gly Phe Gly Phe Val Arg Phe Thr Glu Tyr Glu Thr Gln Val Lys
145 150 155 160
Val Met Ser Gln Arg His Met Ile Asp Gly Arg Trp Cys Asp Cys Lys
165 170 175
Leu Pro Asn Ser Lys Gln Ser Gln Asp Glu Pro Leu Arg Ser Arg Lys
180 185 190
Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr Glu Asp Glu Leu Arg
195 200 205
Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val Phe Ile Pro Lys
210 215 220
Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala Asp Asp Gln Ile Ala
225 230 235 240
Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly Ile Ser Val His
245 250 255
Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg Gln Leu Glu Arg
260 265 270
Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn Gln Gly Gly
275 280 285
Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn Asn Gln Gly
290 295 300
Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser Ile Asn Pro
305 310 315 320
Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser Trp Gly Met
325 330 335
Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro Ser Gly Asn
340 345 350
Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln Ala Phe Gly
355 360 365
Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala Ala Ile Gly
370 375 380
Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe Asn Gly Gly
385 390 395 400
Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly Met Leu Glu
405 410 415
Ala Thr Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp
420 425 430
Leu Arg Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly
435 440 445
Ser Val Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe
450 455 460
Tyr Pro Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His
465 470 475 480
Leu Ser Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys
485 490 495
Thr His Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly
500 505 510
Ala Thr Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val
515 520 525
Arg Asp His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val
530 535 540
Gln Ser Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys
545 550 555 560
Glu Lys Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys
565 570 575
Leu Asp Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu
580 585 590
Met Pro Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu
595 600 605
Glu Leu Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu
610 615 620
Thr Arg Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn
625 630 635 640
Glu Phe Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys
645 650 655
Val Val Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly
660 665 670
Glu Ile Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile
675 680 685
Ile Trp Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu
690 695 700
Phe Leu Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe
705 710 715 720
Asn Phe Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe
725 730 735
Phe Pro Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly
740 745 750
Arg Thr Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala
755 760 765
Thr Gly Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala
770 775 780
Val Lys Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp
785 790 795 800
Asp Thr Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln
805 810 815
Tyr Ile Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp
820 825 830
Asn Pro Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile
835 840 845
Arg Gln Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His
850 855 860
His Pro Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu
865 870 875 880
Leu Gly Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg
885 890 895
Glu Leu Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met
900 905 910
Ile Gly Ala Ala Ala Arg Asp Pro Pro Val Ala Thr Met Val Ser Lys
915 920 925
Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys
930 935 940
Val His Met Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly
945 950 955 960
Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys
965 970 975
Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro
980 985 990
Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile
995 1000 1005
Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu
1010 1015 1020
Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln
1025 1030 1035
Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu
1040 1045 1050
Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
1055 1060 1065
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp
1070 1075 1080
Gly Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp
1085 1090 1095
Gly Gly His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys
1100 1105 1110
Lys Pro Val Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu
1115 1120 1125
Asp Ile Thr Ser His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr
1130 1135 1140
Glu Arg Ala Glu Gly Arg His Ser Thr Gly Gly Met Asp Glu Leu
1145 1150 1155
Tyr Lys
1160
<210> 16
<211> 1152
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 16
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Met Ser Glu Tyr
225 230 235 240
Ile Arg Val Thr Glu Asp Glu Asn Asp Glu Pro Ile Glu Ile Pro Ser
245 250 255
Glu Asp Asp Gly Thr Val Leu Leu Ser Thr Val Thr Ala Gln Phe Pro
260 265 270
Gly Ala Cys Gly Leu Arg Tyr Arg Asn Pro Val Ser Gln Cys Met Arg
275 280 285
Gly Val Arg Leu Val Glu Gly Ile Leu His Ala Pro Asp Ala Gly Trp
290 295 300
Gly Asn Leu Val Tyr Val Val Asn Tyr Pro Lys Asp Asn Lys Arg Lys
305 310 315 320
Met Asp Glu Thr Asp Ala Ser Ser Ala Val Lys Val Lys Arg Ala Val
325 330 335
Gln Lys Thr Ser Asp Leu Ile Val Leu Gly Leu Pro Trp Lys Thr Thr
340 345 350
Glu Gln Asp Leu Lys Glu Tyr Phe Ser Thr Phe Gly Glu Val Leu Met
355 360 365
Val Gln Val Lys Lys Asp Leu Lys Thr Gly His Ser Lys Gly Phe Gly
370 375 380
Phe Val Arg Phe Thr Glu Tyr Glu Thr Gln Val Lys Val Met Ser Gln
385 390 395 400
Arg His Met Ile Asp Gly Arg Trp Cys Asp Cys Lys Leu Pro Asn Ser
405 410 415
Lys Gln Ser Gln Asp Glu Pro Leu Arg Ser Arg Lys Val Phe Val Gly
420 425 430
Arg Cys Thr Glu Asp Met Thr Glu Asp Glu Leu Arg Glu Phe Phe Ser
435 440 445
Gln Tyr Gly Asp Val Met Asp Val Phe Ile Pro Lys Pro Phe Arg Ala
450 455 460
Phe Ala Phe Val Thr Phe Ala Asp Asp Gln Ile Ala Gln Ser Leu Cys
465 470 475 480
Gly Glu Asp Leu Ile Ile Lys Gly Ile Ser Val His Ile Ser Asn Ala
485 490 495
Glu Pro Lys His Asn Ser Asn Arg Gln Leu Glu Arg Ser Gly Arg Phe
500 505 510
Gly Gly Asn Pro Gly Gly Phe Gly Asn Gln Gly Gly Phe Gly Asn Ser
515 520 525
Arg Gly Gly Gly Ala Gly Leu Gly Asn Asn Gln Gly Ser Asn Met Gly
530 535 540
Gly Gly Met Asn Phe Gly Ala Phe Ser Ile Asn Pro Ala Met Met Ala
545 550 555 560
Ala Ala Gln Ala Ala Leu Gln Ser Ser Trp Gly Met Met Gly Met Leu
565 570 575
Ala Ser Gln Gln Asn Gln Ser Gly Pro Ser Gly Asn Asn Gln Asn Gln
580 585 590
Gly Asn Met Gln Arg Glu Pro Asn Gln Ala Phe Gly Ser Gly Asn Asn
595 600 605
Ser Tyr Ser Gly Ser Asn Ser Gly Ala Ala Ile Gly Trp Gly Ser Ala
610 615 620
Ser Asn Ala Gly Ser Gly Ser Gly Phe Asn Gly Gly Phe Gly Ser Ser
625 630 635 640
Met Asp Ser Lys Ser Ser Gly Trp Gly Met Leu Glu Ala Thr Met Lys
645 650 655
Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg Ile Glu
660 665 670
Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val Phe Pro
675 680 685
Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro Gly Arg
690 695 700
Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser Gln Ser
705 710 715 720
Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His Asn Thr
725 730 735
Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr Lys Val
740 745 750
Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp His Thr
755 760 765
Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser Tyr Asn
770 775 780
Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys Gly Lys
785 790 795 800
Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp Met Ser
805 810 815
Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro Ile Thr
820 825 830
Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu Gly Leu
835 840 845
Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg Ala Trp
850 855 860
Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe Ile Glu
865 870 875 880
Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val Gly Asn
885 890 895
Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile Ser Val
900 905 910
Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp Ala Arg
915 920 925
Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu Arg Gly
930 935 940
Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe Pro Phe
945 950 955 960
Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro Trp Asp
965 970 975
Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr Gly Tyr
980 985 990
Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly Trp Met
995 1000 1005
His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys Phe
1010 1015 1020
Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
1025 1030 1035
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr
1040 1045 1050
Ile Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp
1055 1060 1065
Asn Pro Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr
1070 1075 1080
Ile Arg Gln Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp
1085 1090 1095
Ile His His Pro Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser
1100 1105 1110
Gly Val Glu Leu Gly Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile
1115 1120 1125
Asp Thr Ala Arg Glu Leu Leu Ala Lys Ala Ile Ser Arg Thr Arg
1130 1135 1140
Gly Ala Gln Ile Met Ile Gly Ala Ala
1145 1150
<210> 17
<211> 888
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 17
Met Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn Gln Gly Gly
1 5 10 15
Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn Asn Gln Gly
20 25 30
Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser Ile Asn Pro
35 40 45
Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser Trp Gly Met
50 55 60
Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro Ser Gly Asn
65 70 75 80
Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln Ala Phe Gly
85 90 95
Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala Ala Ile Gly
100 105 110
Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe Asn Gly Gly
115 120 125
Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly Met Leu Glu
130 135 140
Ala Thr Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp
145 150 155 160
Leu Arg Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly
165 170 175
Ser Val Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe
180 185 190
Tyr Pro Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His
195 200 205
Leu Ser Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys
210 215 220
Thr His Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly
225 230 235 240
Ala Thr Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val
245 250 255
Arg Asp His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val
260 265 270
Gln Ser Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys
275 280 285
Glu Lys Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys
290 295 300
Leu Asp Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu
305 310 315 320
Met Pro Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu
325 330 335
Glu Leu Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu
340 345 350
Thr Arg Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn
355 360 365
Glu Phe Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys
370 375 380
Val Val Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly
385 390 395 400
Glu Ile Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile
405 410 415
Ile Trp Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu
420 425 430
Phe Leu Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe
435 440 445
Asn Phe Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe
450 455 460
Phe Pro Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly
465 470 475 480
Arg Thr Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala
485 490 495
Thr Gly Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala
500 505 510
Val Lys Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp
515 520 525
Asp Thr Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln
530 535 540
Tyr Ile Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp
545 550 555 560
Asn Pro Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile
565 570 575
Arg Gln Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His
580 585 590
His Pro Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu
595 600 605
Leu Gly Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg
610 615 620
Glu Leu Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met
625 630 635 640
Ile Gly Ala Ala Ala Arg Asp Pro Pro Val Ala Thr Met Val Ser Lys
645 650 655
Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys
660 665 670
Val His Met Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly
675 680 685
Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys
690 695 700
Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro
705 710 715 720
Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile
725 730 735
Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg
740 745 750
Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser
755 760 765
Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr
770 775 780
Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp
785 790 795 800
Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys Gly
805 810 815
Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His Tyr Asp Ala
820 825 830
Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln Leu Pro Gly
835 840 845
Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser His Asn Glu Asp
850 855 860
Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr
865 870 875 880
Gly Gly Met Asp Glu Leu Tyr Lys
885
<210> 18
<211> 971
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 18
Met Arg Lys Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr Glu Asp
1 5 10 15
Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val Phe
20 25 30
Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala Asp Asp
35 40 45
Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly Ile
50 55 60
Ser Val His Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg Gln
65 70 75 80
Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn
85 90 95
Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn
100 105 110
Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser
115 120 125
Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser
130 135 140
Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro
145 150 155 160
Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln
165 170 175
Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala
180 185 190
Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe
195 200 205
Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly
210 215 220
Met Leu Glu Ala Thr Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe
225 230 235 240
Arg Arg Asp Leu Arg Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala
245 250 255
His Glu Gly Ser Val Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu
260 265 270
Gly Gln Phe Tyr Pro Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser
275 280 285
Leu Ala His Leu Ser Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr
290 295 300
Leu Ile Lys Thr His Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg
305 310 315 320
Val Thr Gly Ala Thr Lys Val Val Phe Asn His Leu Tyr Asp Pro Val
325 330 335
Ser Leu Val Arg Asp His Thr Val Lys Glu Lys Leu Val Glu Arg Gly
340 345 350
Ile Ser Val Gln Ser Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu
355 360 365
Ile Tyr Cys Glu Lys Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp
370 375 380
Lys Lys Cys Leu Asp Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro
385 390 395 400
Trp Arg Leu Met Pro Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys
405 410 415
Ser Ile Glu Glu Leu Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn
420 425 430
Ala Leu Leu Thr Arg Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys
435 440 445
Leu Leu Asn Glu Phe Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn
450 455 460
Ser Lys Lys Val Val Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu
465 470 475 480
His Phe Gly Glu Ile Ser Val Arg His Val Phe Gln Cys Ala Arg Met
485 490 495
Lys Gln Ile Ile Trp Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser
500 505 510
Ala Asp Leu Phe Leu Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr
515 520 525
Ile Cys Phe Asn Phe Pro Phe Thr His Glu Gln Ser Leu Leu Ser His
530 535 540
Leu Arg Phe Phe Pro Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp
545 550 555 560
Arg Gln Gly Arg Thr Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu
565 570 575
Leu Trp Ala Thr Gly Trp Met His Asn Arg Ile Arg Val Ile Val Ser
580 585 590
Ser Phe Ala Val Lys Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys
595 600 605
Tyr Phe Trp Asp Thr Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu
610 615 620
Gly Trp Gln Tyr Ile Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp
625 630 635 640
Arg Leu Asp Asn Pro Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly
645 650 655
Glu Tyr Ile Arg Gln Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu
660 665 670
Trp Ile His His Pro Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser
675 680 685
Gly Val Glu Leu Gly Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp
690 695 700
Thr Ala Arg Glu Leu Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala
705 710 715 720
Gln Ile Met Ile Gly Ala Ala Ala Arg Asp Pro Pro Val Ala Thr Met
725 730 735
Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met
740 745 750
Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe Glu
755 760 765
Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala
770 775 780
Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile
785 790 795 800
Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro
805 810 815
Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys
820 825 830
Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr
835 840 845
Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu
850 855 860
Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr
865 870 875 880
Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala
885 890 895
Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His
900 905 910
Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln
915 920 925
Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser His
930 935 940
Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly Arg
945 950 955 960
His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys
965 970
<210> 19
<211> 1057
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 19
Met Asp Leu Ile Val Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp
1 5 10 15
Leu Lys Glu Tyr Phe Ser Thr Phe Gly Glu Val Leu Met Val Gln Val
20 25 30
Lys Lys Asp Leu Lys Thr Gly His Ser Lys Gly Phe Gly Phe Val Arg
35 40 45
Phe Thr Glu Tyr Glu Thr Gln Val Lys Val Met Ser Gln Arg His Met
50 55 60
Ile Asp Gly Arg Trp Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser
65 70 75 80
Gln Asp Glu Pro Leu Arg Ser Arg Lys Val Phe Val Gly Arg Cys Thr
85 90 95
Glu Asp Met Thr Glu Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly
100 105 110
Asp Val Met Asp Val Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe
115 120 125
Val Thr Phe Ala Asp Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp
130 135 140
Leu Ile Ile Lys Gly Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys
145 150 155 160
His Asn Ser Asn Arg Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn
165 170 175
Pro Gly Gly Phe Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly
180 185 190
Gly Ala Gly Leu Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met
195 200 205
Asn Phe Gly Ala Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln
210 215 220
Ala Ala Leu Gln Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln
225 230 235 240
Gln Asn Gln Ser Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met
245 250 255
Gln Arg Glu Pro Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser
260 265 270
Gly Ser Asn Ser Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala
275 280 285
Gly Ser Gly Ser Gly Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser
290 295 300
Lys Ser Ser Gly Trp Gly Met Leu Glu Ala Thr Met Lys Met Asp Lys
305 310 315 320
Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg Ile Glu Asp Asn Pro
325 330 335
Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val Phe Pro Val Phe Ile
340 345 350
Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro Gly Arg Ala Ser Arg
355 360 365
Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser Gln Ser Leu Lys Ala
370 375 380
Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His Asn Thr Ile Ser Ala
385 390 395 400
Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr Lys Val Val Phe Asn
405 410 415
His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp His Thr Val Lys Glu
420 425 430
Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser Tyr Asn Gly Asp Leu
435 440 445
Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys Gly Lys Pro Phe Thr
450 455 460
Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp Met Ser Ile Glu Ser
465 470 475 480
Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro Ile Thr Ala Ala Ala
485 490 495
Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu Gly Leu Glu Asn Glu
500 505 510
Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg Ala Trp Ser Pro Gly
515 520 525
Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe Ile Glu Lys Gln Leu
530 535 540
Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val Gly Asn Ser Thr Ser
545 550 555 560
Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile Ser Val Arg His Val
565 570 575
Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp Ala Arg Asp Lys Asn
580 585 590
Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu Arg Gly Ile Gly Leu
595 600 605
Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe Pro Phe Thr His Glu
610 615 620
Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro Trp Asp Ala Asp Val
625 630 635 640
Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr Gly Tyr Pro Leu Val
645 650 655
Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly Trp Met His Asn Arg
660 665 670
Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys Phe Leu Leu Leu Pro
675 680 685
Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr Leu Leu Asp Ala Asp
690 695 700
Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile Ser Gly Ser Ile Pro
705 710 715 720
Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro Ala Leu Gln Gly Ala
725 730 735
Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln Trp Leu Pro Glu Leu
740 745 750
Ala Arg Leu Pro Thr Glu Trp Ile His His Pro Trp Asp Ala Pro Leu
755 760 765
Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly Thr Asn Tyr Ala Lys
770 775 780
Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu Leu Ala Lys Ala Ile
785 790 795 800
Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly Ala Ala Ala Arg Asp
805 810 815
Pro Pro Val Ala Thr Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala
820 825 830
Ile Ile Lys Glu Phe Met Arg Phe Lys Val His Met Glu Gly Ser Val
835 840 845
Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr
850 855 860
Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu
865 870 875 880
Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys
885 890 895
Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser
900 905 910
Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly
915 920 925
Gly Val Val Thr Val Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe
930 935 940
Ile Tyr Lys Val Lys Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro
945 950 955 960
Val Met Gln Lys Lys Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met
965 970 975
Tyr Pro Glu Asp Gly Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys
980 985 990
Leu Lys Asp Gly Gly His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys
995 1000 1005
Ala Lys Lys Pro Val Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile
1010 1015 1020
Lys Leu Asp Ile Thr Ser His Asn Glu Asp Tyr Thr Ile Val Glu
1025 1030 1035
Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr Gly Gly Met Asp
1040 1045 1050
Glu Leu Tyr Lys
1055
<210> 20
<211> 878
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 20
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Met Lys Met Asp
225 230 235 240
Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg Ile Glu Asp Asn
245 250 255
Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val Phe Pro Val Phe
260 265 270
Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro Gly Arg Ala Ser
275 280 285
Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser Gln Ser Leu Lys
290 295 300
Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His Asn Thr Ile Ser
305 310 315 320
Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr Lys Val Val Phe
325 330 335
Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp His Thr Val Lys
340 345 350
Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser Tyr Asn Gly Asp
355 360 365
Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys Gly Lys Pro Phe
370 375 380
Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp Met Ser Ile Glu
385 390 395 400
Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro Ile Thr Ala Ala
405 410 415
Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu Gly Leu Glu Asn
420 425 430
Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg Ala Trp Ser Pro
435 440 445
Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe Ile Glu Lys Gln
450 455 460
Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val Gly Asn Ser Thr
465 470 475 480
Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile Ser Val Arg His
485 490 495
Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp Ala Arg Asp Lys
500 505 510
Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu Arg Gly Ile Gly
515 520 525
Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe Pro Phe Thr His
530 535 540
Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro Trp Asp Ala Asp
545 550 555 560
Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr Gly Tyr Pro Leu
565 570 575
Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly Trp Met His Asn
580 585 590
Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys Phe Leu Leu Leu
595 600 605
Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr Leu Leu Asp Ala
610 615 620
Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile Ser Gly Ser Ile
625 630 635 640
Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro Ala Leu Gln Gly
645 650 655
Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln Trp Leu Pro Glu
660 665 670
Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro Trp Asp Ala Pro
675 680 685
Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly Thr Asn Tyr Ala
690 695 700
Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu Leu Ala Lys Ala
705 710 715 720
Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly Ala Ala Ala Arg
725 730 735
Gly Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn Gln Gly Gly
740 745 750
Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn Asn Gln Gly
755 760 765
Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser Ile Asn Pro
770 775 780
Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser Trp Gly Met
785 790 795 800
Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro Ser Gly Asn
805 810 815
Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln Ala Phe Gly
820 825 830
Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala Ala Ile Gly
835 840 845
Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe Asn Gly Gly
850 855 860
Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly Met
865 870 875
<210> 21
<211> 961
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 21
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Met Lys Met Asp
225 230 235 240
Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg Ile Glu Asp Asn
245 250 255
Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val Phe Pro Val Phe
260 265 270
Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro Gly Arg Ala Ser
275 280 285
Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser Gln Ser Leu Lys
290 295 300
Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His Asn Thr Ile Ser
305 310 315 320
Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr Lys Val Val Phe
325 330 335
Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp His Thr Val Lys
340 345 350
Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser Tyr Asn Gly Asp
355 360 365
Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys Gly Lys Pro Phe
370 375 380
Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp Met Ser Ile Glu
385 390 395 400
Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro Ile Thr Ala Ala
405 410 415
Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu Gly Leu Glu Asn
420 425 430
Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg Ala Trp Ser Pro
435 440 445
Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe Ile Glu Lys Gln
450 455 460
Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val Gly Asn Ser Thr
465 470 475 480
Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile Ser Val Arg His
485 490 495
Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp Ala Arg Asp Lys
500 505 510
Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu Arg Gly Ile Gly
515 520 525
Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe Pro Phe Thr His
530 535 540
Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro Trp Asp Ala Asp
545 550 555 560
Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr Gly Tyr Pro Leu
565 570 575
Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly Trp Met His Asn
580 585 590
Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys Phe Leu Leu Leu
595 600 605
Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr Leu Leu Asp Ala
610 615 620
Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile Ser Gly Ser Ile
625 630 635 640
Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro Ala Leu Gln Gly
645 650 655
Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln Trp Leu Pro Glu
660 665 670
Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro Trp Asp Ala Pro
675 680 685
Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly Thr Asn Tyr Ala
690 695 700
Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu Leu Ala Lys Ala
705 710 715 720
Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly Ala Ala Ala Arg
725 730 735
Gly Arg Lys Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr Glu Asp
740 745 750
Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val Phe
755 760 765
Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala Asp Asp
770 775 780
Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly Ile
785 790 795 800
Ser Val His Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg Gln
805 810 815
Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn
820 825 830
Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn
835 840 845
Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser
850 855 860
Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser
865 870 875 880
Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro
885 890 895
Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln
900 905 910
Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala
915 920 925
Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe
930 935 940
Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly
945 950 955 960
Met
<210> 22
<211> 1047
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 22
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Met Lys Met Asp
225 230 235 240
Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg Ile Glu Asp Asn
245 250 255
Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val Phe Pro Val Phe
260 265 270
Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro Gly Arg Ala Ser
275 280 285
Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser Gln Ser Leu Lys
290 295 300
Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His Asn Thr Ile Ser
305 310 315 320
Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr Lys Val Val Phe
325 330 335
Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp His Thr Val Lys
340 345 350
Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser Tyr Asn Gly Asp
355 360 365
Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys Gly Lys Pro Phe
370 375 380
Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp Met Ser Ile Glu
385 390 395 400
Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro Ile Thr Ala Ala
405 410 415
Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu Gly Leu Glu Asn
420 425 430
Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg Ala Trp Ser Pro
435 440 445
Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe Ile Glu Lys Gln
450 455 460
Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val Gly Asn Ser Thr
465 470 475 480
Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile Ser Val Arg His
485 490 495
Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp Ala Arg Asp Lys
500 505 510
Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu Arg Gly Ile Gly
515 520 525
Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe Pro Phe Thr His
530 535 540
Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro Trp Asp Ala Asp
545 550 555 560
Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr Gly Tyr Pro Leu
565 570 575
Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly Trp Met His Asn
580 585 590
Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys Phe Leu Leu Leu
595 600 605
Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr Leu Leu Asp Ala
610 615 620
Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile Ser Gly Ser Ile
625 630 635 640
Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro Ala Leu Gln Gly
645 650 655
Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln Trp Leu Pro Glu
660 665 670
Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro Trp Asp Ala Pro
675 680 685
Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly Thr Asn Tyr Ala
690 695 700
Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu Leu Ala Lys Ala
705 710 715 720
Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly Ala Ala Ala Arg
725 730 735
Gly Asp Leu Ile Val Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp
740 745 750
Leu Lys Glu Tyr Phe Ser Thr Phe Gly Glu Val Leu Met Val Gln Val
755 760 765
Lys Lys Asp Leu Lys Thr Gly His Ser Lys Gly Phe Gly Phe Val Arg
770 775 780
Phe Thr Glu Tyr Glu Thr Gln Val Lys Val Met Ser Gln Arg His Met
785 790 795 800
Ile Asp Gly Arg Trp Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser
805 810 815
Gln Asp Glu Pro Leu Arg Ser Arg Lys Val Phe Val Gly Arg Cys Thr
820 825 830
Glu Asp Met Thr Glu Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly
835 840 845
Asp Val Met Asp Val Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe
850 855 860
Val Thr Phe Ala Asp Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp
865 870 875 880
Leu Ile Ile Lys Gly Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys
885 890 895
His Asn Ser Asn Arg Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn
900 905 910
Pro Gly Gly Phe Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly
915 920 925
Gly Ala Gly Leu Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met
930 935 940
Asn Phe Gly Ala Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln
945 950 955 960
Ala Ala Leu Gln Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln
965 970 975
Gln Asn Gln Ser Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met
980 985 990
Gln Arg Glu Pro Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser
995 1000 1005
Gly Ser Asn Ser Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn
1010 1015 1020
Ala Gly Ser Gly Ser Gly Phe Asn Gly Gly Phe Gly Ser Ser Met
1025 1030 1035
Asp Ser Lys Ser Ser Gly Trp Gly Met
1040 1045
<210> 23
<211> 886
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 23
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Arg Gly Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly
500 505 510
Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly
515 520 525
Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe
530 535 540
Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser
545 550 555 560
Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly
565 570 575
Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn
580 585 590
Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly
595 600 605
Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly
610 615 620
Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp
625 630 635 640
Gly Met Ser Arg Asp Pro Pro Val Ala Thr Met Val Ser Lys Gly Glu
645 650 655
Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val His
660 665 670
Met Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly
675 680 685
Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr
690 695 700
Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe
705 710 715 720
Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp
725 730 735
Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met
740 745 750
Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser Ser Leu
755 760 765
Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr Asn Phe
770 775 780
Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp Glu Ala
785 790 795 800
Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys Gly Glu Ile
805 810 815
Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His Tyr Asp Ala Glu Val
820 825 830
Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln Leu Pro Gly Ala Tyr
835 840 845
Asn Val Asn Ile Lys Leu Asp Ile Thr Ser His Asn Glu Asp Tyr Thr
850 855 860
Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr Gly Gly
865 870 875 880
Met Asp Glu Leu Tyr Lys
885
<210> 24
<211> 969
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 24
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Arg Gly Arg Lys Val Phe Val Gly Arg Cys Thr Glu Asp
500 505 510
Met Thr Glu Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val
515 520 525
Met Asp Val Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val Thr
530 535 540
Phe Ala Asp Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile
545 550 555 560
Ile Lys Gly Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys His Asn
565 570 575
Ser Asn Arg Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro Gly
580 585 590
Gly Phe Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala
595 600 605
Gly Leu Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe
610 615 620
Gly Ala Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala
625 630 635 640
Leu Gln Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn
645 650 655
Gln Ser Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg
660 665 670
Glu Pro Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser
675 680 685
Asn Ser Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser
690 695 700
Gly Ser Gly Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser
705 710 715 720
Ser Gly Trp Gly Met Ser Arg Asp Pro Pro Val Ala Thr Met Val Ser
725 730 735
Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe
740 745 750
Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu
755 760 765
Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu
770 775 780
Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser
785 790 795 800
Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp
805 810 815
Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu
820 825 830
Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp
835 840 845
Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly
850 855 860
Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly
865 870 875 880
Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys
885 890 895
Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His Tyr Asp
900 905 910
Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln Leu Pro
915 920 925
Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser His Asn Glu
930 935 940
Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly Arg His Ser
945 950 955 960
Thr Gly Gly Met Asp Glu Leu Tyr Lys
965
<210> 25
<211> 1057
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 25
Met Asp Leu Ile Val Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp
1 5 10 15
Leu Lys Glu Tyr Phe Ser Thr Phe Gly Glu Val Leu Met Val Gln Val
20 25 30
Lys Lys Asp Leu Lys Thr Gly His Ser Lys Gly Phe Gly Phe Val Arg
35 40 45
Phe Thr Glu Tyr Glu Thr Gln Val Lys Val Met Ser Gln Arg His Met
50 55 60
Ile Asp Gly Arg Trp Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser
65 70 75 80
Gln Asp Glu Pro Leu Arg Ser Arg Lys Val Phe Val Gly Arg Cys Thr
85 90 95
Glu Asp Met Thr Glu Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly
100 105 110
Asp Val Met Asp Val Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe
115 120 125
Val Thr Phe Ala Asp Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp
130 135 140
Leu Ile Ile Lys Gly Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys
145 150 155 160
His Asn Ser Asn Arg Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn
165 170 175
Pro Gly Gly Phe Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly
180 185 190
Gly Ala Gly Leu Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met
195 200 205
Asn Phe Gly Ala Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln
210 215 220
Ala Ala Leu Gln Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln
225 230 235 240
Gln Asn Gln Ser Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met
245 250 255
Gln Arg Glu Pro Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser
260 265 270
Gly Ser Asn Ser Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala
275 280 285
Gly Ser Gly Ser Gly Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser
290 295 300
Lys Ser Ser Gly Trp Gly Met Leu Glu Ala Thr Met Lys Met Asp Lys
305 310 315 320
Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg Ile Glu Asp Asn Pro
325 330 335
Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val Phe Pro Val Phe Ile
340 345 350
Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro Gly Arg Ala Ser Arg
355 360 365
Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser Gln Ser Leu Lys Ala
370 375 380
Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His Asn Thr Ile Ser Ala
385 390 395 400
Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr Lys Val Val Phe Asn
405 410 415
His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp His Thr Val Lys Glu
420 425 430
Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser Tyr Asn Gly Asp Leu
435 440 445
Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys Gly Lys Pro Phe Thr
450 455 460
Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp Met Ser Ile Glu Ser
465 470 475 480
Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro Ile Thr Ala Ala Ala
485 490 495
Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu Gly Leu Glu Asn Glu
500 505 510
Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg Ala Trp Ser Pro Gly
515 520 525
Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe Ile Glu Lys Gln Leu
530 535 540
Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val Gly Asn Ser Thr Ser
545 550 555 560
Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile Ser Val Arg His Val
565 570 575
Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp Ala Arg Asp Lys Asn
580 585 590
Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu Arg Gly Ile Gly Leu
595 600 605
Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe Pro Phe Thr His Glu
610 615 620
Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro Trp Asp Ala Asp Val
625 630 635 640
Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr Gly Tyr Pro Leu Val
645 650 655
Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly Trp Met His Asn Arg
660 665 670
Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys Phe Leu Leu Leu Pro
675 680 685
Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr Leu Leu Asp Ala Asp
690 695 700
Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile Ser Gly Ser Ile Pro
705 710 715 720
Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro Ala Leu Gln Gly Ala
725 730 735
Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln Trp Leu Pro Glu Leu
740 745 750
Ala Arg Leu Pro Thr Glu Trp Ile His His Pro Trp Asp Ala Pro Leu
755 760 765
Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly Thr Asn Tyr Ala Lys
770 775 780
Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu Leu Ala Lys Ala Ile
785 790 795 800
Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly Ala Ala Ser Arg Asp
805 810 815
Pro Pro Val Ala Thr Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala
820 825 830
Ile Ile Lys Glu Phe Met Arg Phe Lys Val His Met Glu Gly Ser Val
835 840 845
Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr
850 855 860
Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu
865 870 875 880
Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys
885 890 895
Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser
900 905 910
Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly
915 920 925
Gly Val Val Thr Val Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe
930 935 940
Ile Tyr Lys Val Lys Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro
945 950 955 960
Val Met Gln Lys Lys Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met
965 970 975
Tyr Pro Glu Asp Gly Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys
980 985 990
Leu Lys Asp Gly Gly His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys
995 1000 1005
Ala Lys Lys Pro Val Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile
1010 1015 1020
Lys Leu Asp Ile Thr Ser His Asn Glu Asp Tyr Thr Ile Val Glu
1025 1030 1035
Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr Gly Gly Met Asp
1040 1045 1050
Glu Leu Tyr Lys
1055
<210> 26
<211> 566
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 26
Met His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Trp Leu
1 5 10 15
Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val
20 25 30
Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr
35 40 45
Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser
50 55 60
Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp
65 70 75 80
Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr
85 90 95
Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val
100 105 110
Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu
115 120 125
Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met
130 135 140
Gly Phe Gln Cys Glu Thr Glu Ala Met Ser Glu Tyr Ile Arg Val Thr
145 150 155 160
Glu Asp Glu Asn Asp Glu Pro Ile Glu Ile Pro Ser Glu Asp Asp Gly
165 170 175
Thr Val Leu Leu Ser Thr Val Thr Ala Gln Phe Pro Gly Ala Cys Gly
180 185 190
Leu Arg Tyr Arg Asn Pro Val Ser Gln Cys Met Arg Gly Val Arg Leu
195 200 205
Val Glu Gly Ile Leu His Ala Pro Asp Ala Gly Trp Gly Asn Leu Val
210 215 220
Tyr Val Val Asn Tyr Pro Lys Asp Asn Lys Arg Lys Met Asp Glu Thr
225 230 235 240
Asp Ala Ser Ser Ala Val Lys Val Lys Arg Ala Val Gln Lys Thr Ser
245 250 255
Asp Leu Ile Val Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp Leu
260 265 270
Lys Glu Tyr Phe Ser Thr Phe Gly Glu Val Leu Met Val Gln Val Lys
275 280 285
Lys Asp Leu Lys Thr Gly His Ser Lys Gly Phe Gly Phe Val Arg Phe
290 295 300
Thr Glu Tyr Glu Thr Gln Val Lys Val Met Ser Gln Arg His Met Ile
305 310 315 320
Asp Gly Arg Trp Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser Gln
325 330 335
Asp Glu Pro Leu Arg Ser Arg Lys Val Phe Val Gly Arg Cys Thr Glu
340 345 350
Asp Met Thr Glu Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp
355 360 365
Val Met Asp Val Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val
370 375 380
Thr Phe Ala Asp Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu
385 390 395 400
Ile Ile Lys Gly Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys His
405 410 415
Asn Ser Asn Arg Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro
420 425 430
Gly Gly Phe Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly
435 440 445
Ala Gly Leu Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn
450 455 460
Phe Gly Ala Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala
465 470 475 480
Ala Leu Gln Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln
485 490 495
Asn Gln Ser Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln
500 505 510
Arg Glu Pro Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly
515 520 525
Ser Asn Ser Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly
530 535 540
Ser Gly Ser Gly Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys
545 550 555 560
Ser Ser Gly Trp Gly Met
565
<210> 27
<211> 569
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 27
Met Ser Glu Tyr Ile Arg Val Thr Glu Asp Glu Asn Asp Glu Pro Ile
1 5 10 15
Glu Ile Pro Ser Glu Asp Asp Gly Thr Val Leu Leu Ser Thr Val Thr
20 25 30
Ala Gln Phe Pro Gly Ala Cys Gly Leu Arg Tyr Arg Asn Pro Val Ser
35 40 45
Gln Cys Met Arg Gly Val Arg Leu Val Glu Gly Ile Leu His Ala Pro
50 55 60
Asp Ala Gly Trp Gly Asn Leu Val Tyr Val Val Asn Tyr Pro Lys Asp
65 70 75 80
Asn Lys Arg Lys Met Asp Glu Thr Asp Ala Ser Ser Ala Val Lys Val
85 90 95
Lys Arg Ala Val Gln Lys Thr Ser Asp Leu Ile Val Leu Gly Leu Pro
100 105 110
Trp Lys Thr Thr Glu Gln Asp Leu Lys Glu Tyr Phe Ser Thr Phe Gly
115 120 125
Glu Val Leu Met Val Gln Val Lys Lys Asp Leu Lys Thr Gly His Ser
130 135 140
Lys Gly Phe Gly Phe Val Arg Phe Thr Glu Tyr Glu Thr Gln Val Lys
145 150 155 160
Val Met Ser Gln Arg His Met Ile Asp Gly Arg Trp Cys Asp Cys Lys
165 170 175
Leu Pro Asn Ser Lys Gln Ser Gln Asp Glu Pro Leu Arg Ser Arg Lys
180 185 190
Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr Glu Asp Glu Leu Arg
195 200 205
Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val Phe Ile Pro Lys
210 215 220
Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala Asp Asp Gln Ile Ala
225 230 235 240
Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly Ile Ser Val His
245 250 255
Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg Gln Leu Glu Arg
260 265 270
Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn Gln Gly Gly
275 280 285
Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn Asn Gln Gly
290 295 300
Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser Ile Asn Pro
305 310 315 320
Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser Trp Gly Met
325 330 335
Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro Ser Gly Asn
340 345 350
Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln Ala Phe Gly
355 360 365
Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala Ala Ile Gly
370 375 380
Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe Asn Gly Gly
385 390 395 400
Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly Met Phe Arg
405 410 415
Ala Gln Arg His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly
420 425 430
Trp Leu Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly
435 440 445
Pro Val Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys
450 455 460
Asp Thr Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly
465 470 475 480
Tyr Ser Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser
485 490 495
Pro Asp Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser
500 505 510
Asn Thr Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val
515 520 525
Gln Val Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn
530 535 540
Phe Leu Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr
545 550 555 560
Ser Met Gly Phe Gln Cys Glu Thr Glu
565
<210> 28
<211> 466
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 28
Met Asp Leu Ile Val Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp
1 5 10 15
Leu Lys Glu Tyr Phe Ser Thr Phe Gly Glu Val Leu Met Val Gln Val
20 25 30
Lys Lys Asp Leu Lys Thr Gly His Ser Lys Gly Phe Gly Phe Val Arg
35 40 45
Phe Thr Glu Tyr Glu Thr Gln Val Lys Val Met Ser Gln Arg His Met
50 55 60
Ile Asp Gly Arg Trp Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser
65 70 75 80
Gln Asp Glu Pro Leu Arg Ser Arg Lys Val Phe Val Gly Arg Cys Thr
85 90 95
Glu Asp Met Thr Glu Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly
100 105 110
Asp Val Met Asp Val Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe
115 120 125
Val Thr Phe Ala Asp Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp
130 135 140
Leu Ile Ile Lys Gly Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys
145 150 155 160
His Asn Ser Asn Arg Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn
165 170 175
Pro Gly Gly Phe Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly
180 185 190
Gly Ala Gly Leu Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met
195 200 205
Asn Phe Gly Ala Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln
210 215 220
Ala Ala Leu Gln Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln
225 230 235 240
Gln Asn Gln Ser Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met
245 250 255
Gln Arg Glu Pro Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser
260 265 270
Gly Ser Asn Ser Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala
275 280 285
Gly Ser Gly Ser Gly Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser
290 295 300
Lys Ser Ser Gly Trp Gly Met Phe Arg Ala Gln Arg His Thr Leu Tyr
305 310 315 320
Ala Pro Gly Gly Tyr Asp Ile Met Gly Trp Leu Ile Gln Ile Met Asn
325 330 335
Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val Asp Thr Ser Cys Ala
340 345 350
Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr Pro Ile Val Tyr Ala
355 360 365
Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser Asn Ala Glu Val Leu
370 375 380
Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp Gly Met Val Lys Pro
385 390 395 400
Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr Ile Asn Thr Met Arg
405 410 415
Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val Glu Val Val Asn Phe
420 425 430
Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu Thr Met Ile Pro Val
435 440 445
Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met Gly Phe Gln Cys Glu
450 455 460
Thr Glu
465
<210> 29
<211> 380
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 29
Met Arg Lys Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr Glu Asp
1 5 10 15
Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val Phe
20 25 30
Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala Asp Asp
35 40 45
Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly Ile
50 55 60
Ser Val His Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg Gln
65 70 75 80
Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn
85 90 95
Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn
100 105 110
Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser
115 120 125
Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser
130 135 140
Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro
145 150 155 160
Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln
165 170 175
Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala
180 185 190
Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe
195 200 205
Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly
210 215 220
Met Phe Arg Ala Gln Arg His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp
225 230 235 240
Ile Met Gly Trp Leu Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val
245 250 255
Glu Leu Gly Pro Val Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu
260 265 270
Lys Gln Lys Asp Thr Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr
275 280 285
Met Thr Gly Tyr Ser Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe
290 295 300
Leu Gln Ser Pro Asp Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr
305 310 315 320
Val Asp Ser Asn Thr Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn
325 330 335
Ala Glu Val Gln Val Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg
340 345 350
Phe Val Asn Phe Leu Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu
355 360 365
Tyr Arg Tyr Ser Met Gly Phe Gln Cys Glu Thr Glu
370 375 380
<210> 30
<211> 297
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 30
Met Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn Gln Gly Gly
1 5 10 15
Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn Asn Gln Gly
20 25 30
Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser Ile Asn Pro
35 40 45
Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser Trp Gly Met
50 55 60
Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro Ser Gly Asn
65 70 75 80
Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln Ala Phe Gly
85 90 95
Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala Ala Ile Gly
100 105 110
Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe Asn Gly Gly
115 120 125
Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly Met Phe Arg
130 135 140
Ala Gln Arg His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly
145 150 155 160
Trp Leu Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly
165 170 175
Pro Val Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys
180 185 190
Asp Thr Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly
195 200 205
Tyr Ser Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser
210 215 220
Pro Asp Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser
225 230 235 240
Asn Thr Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val
245 250 255
Gln Val Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn
260 265 270
Phe Leu Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr
275 280 285
Ser Met Gly Phe Gln Cys Glu Thr Glu
290 295
<210> 31
<211> 462
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 31
Met His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Trp Leu
1 5 10 15
Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val
20 25 30
Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr
35 40 45
Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser
50 55 60
Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp
65 70 75 80
Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr
85 90 95
Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val
100 105 110
Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu
115 120 125
Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met
130 135 140
Gly Phe Gln Cys Glu Thr Glu Ala Asp Leu Ile Val Leu Gly Leu Pro
145 150 155 160
Trp Lys Thr Thr Glu Gln Asp Leu Lys Glu Tyr Phe Ser Thr Phe Gly
165 170 175
Glu Val Leu Met Val Gln Val Lys Lys Asp Leu Lys Thr Gly His Ser
180 185 190
Lys Gly Phe Gly Phe Val Arg Phe Thr Glu Tyr Glu Thr Gln Val Lys
195 200 205
Val Met Ser Gln Arg His Met Ile Asp Gly Arg Trp Cys Asp Cys Lys
210 215 220
Leu Pro Asn Ser Lys Gln Ser Gln Asp Glu Pro Leu Arg Ser Arg Lys
225 230 235 240
Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr Glu Asp Glu Leu Arg
245 250 255
Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val Phe Ile Pro Lys
260 265 270
Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala Asp Asp Gln Ile Ala
275 280 285
Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly Ile Ser Val His
290 295 300
Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg Gln Leu Glu Arg
305 310 315 320
Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn Gln Gly Gly
325 330 335
Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn Asn Gln Gly
340 345 350
Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser Ile Asn Pro
355 360 365
Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser Trp Gly Met
370 375 380
Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro Ser Gly Asn
385 390 395 400
Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln Ala Phe Gly
405 410 415
Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala Ala Ile Gly
420 425 430
Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe Asn Gly Gly
435 440 445
Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly Met
450 455 460
<210> 32
<211> 376
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 32
Met His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Trp Leu
1 5 10 15
Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val
20 25 30
Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr
35 40 45
Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser
50 55 60
Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp
65 70 75 80
Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr
85 90 95
Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val
100 105 110
Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu
115 120 125
Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met
130 135 140
Gly Phe Gln Cys Glu Thr Glu Ala Arg Lys Val Phe Val Gly Arg Cys
145 150 155 160
Thr Glu Asp Met Thr Glu Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr
165 170 175
Gly Asp Val Met Asp Val Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala
180 185 190
Phe Val Thr Phe Ala Asp Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu
195 200 205
Asp Leu Ile Ile Lys Gly Ile Ser Val His Ile Ser Asn Ala Glu Pro
210 215 220
Lys His Asn Ser Asn Arg Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly
225 230 235 240
Asn Pro Gly Gly Phe Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly
245 250 255
Gly Gly Ala Gly Leu Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly
260 265 270
Met Asn Phe Gly Ala Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala
275 280 285
Gln Ala Ala Leu Gln Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser
290 295 300
Gln Gln Asn Gln Ser Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn
305 310 315 320
Met Gln Arg Glu Pro Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr
325 330 335
Ser Gly Ser Asn Ser Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn
340 345 350
Ala Gly Ser Gly Ser Gly Phe Asn Gly Gly Phe Gly Ser Ser Met Asp
355 360 365
Ser Lys Ser Ser Gly Trp Gly Met
370 375
<210> 33
<211> 292
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 33
His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Trp Leu Ile
1 5 10 15
Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val Asp
20 25 30
Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr Pro
35 40 45
Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser Asn
50 55 60
Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp Gly
65 70 75 80
Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr Ile
85 90 95
Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val Glu
100 105 110
Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu Thr
115 120 125
Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met Gly
130 135 140
Phe Gln Cys Glu Thr Glu Ala Gly Arg Phe Gly Gly Asn Pro Gly Gly
145 150 155 160
Phe Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly
165 170 175
Leu Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly
180 185 190
Ala Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu
195 200 205
Gln Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln
210 215 220
Ser Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu
225 230 235 240
Pro Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn
245 250 255
Ser Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly
260 265 270
Ser Gly Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser Ser
275 280 285
Gly Trp Gly Met
290
<210> 34
<211> 808
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 34
Met His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Trp Leu
1 5 10 15
Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val
20 25 30
Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr
35 40 45
Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser
50 55 60
Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp
65 70 75 80
Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr
85 90 95
Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val
100 105 110
Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu
115 120 125
Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met
130 135 140
Gly Phe Gln Cys Glu Thr Glu Ala Met Ser Glu Tyr Ile Arg Val Thr
145 150 155 160
Glu Asp Glu Asn Asp Glu Pro Ile Glu Ile Pro Ser Glu Asp Asp Gly
165 170 175
Thr Val Leu Leu Ser Thr Val Thr Ala Gln Phe Pro Gly Ala Cys Gly
180 185 190
Leu Arg Tyr Arg Asn Pro Val Ser Gln Cys Met Arg Gly Val Arg Leu
195 200 205
Val Glu Gly Ile Leu His Ala Pro Asp Ala Gly Trp Gly Asn Leu Val
210 215 220
Tyr Val Val Asn Tyr Pro Lys Asp Asn Lys Arg Lys Met Asp Glu Thr
225 230 235 240
Asp Ala Ser Ser Ala Val Lys Val Lys Arg Ala Val Gln Lys Thr Ser
245 250 255
Asp Leu Ile Val Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp Leu
260 265 270
Lys Glu Tyr Phe Ser Thr Phe Gly Glu Val Leu Met Val Gln Val Lys
275 280 285
Lys Asp Leu Lys Thr Gly His Ser Lys Gly Phe Gly Phe Val Arg Phe
290 295 300
Thr Glu Tyr Glu Thr Gln Val Lys Val Met Ser Gln Arg His Met Ile
305 310 315 320
Asp Gly Arg Trp Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser Gln
325 330 335
Asp Glu Pro Leu Arg Ser Arg Lys Val Phe Val Gly Arg Cys Thr Glu
340 345 350
Asp Met Thr Glu Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp
355 360 365
Val Met Asp Val Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val
370 375 380
Thr Phe Ala Asp Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu
385 390 395 400
Ile Ile Lys Gly Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys His
405 410 415
Asn Ser Asn Arg Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro
420 425 430
Gly Gly Phe Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly
435 440 445
Ala Gly Leu Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn
450 455 460
Phe Gly Ala Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala
465 470 475 480
Ala Leu Gln Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln
485 490 495
Asn Gln Ser Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln
500 505 510
Arg Glu Pro Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly
515 520 525
Ser Asn Ser Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly
530 535 540
Ser Gly Ser Gly Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys
545 550 555 560
Ser Ser Gly Trp Gly Met Phe Ala Pro Val Ala Thr Met Val Ser Lys
565 570 575
Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys
580 585 590
Val His Met Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly
595 600 605
Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys
610 615 620
Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro
625 630 635 640
Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile
645 650 655
Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg
660 665 670
Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser
675 680 685
Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr
690 695 700
Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp
705 710 715 720
Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys Gly
725 730 735
Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His Tyr Asp Ala
740 745 750
Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln Leu Pro Gly
755 760 765
Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser His Asn Glu Asp
770 775 780
Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr
785 790 795 800
Gly Gly Met Asp Glu Leu Tyr Lys
805
<210> 35
<211> 809
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 35
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Ser Gly Leu Lys
225 230 235 240
Met Ser Glu Tyr Ile Arg Val Thr Glu Asp Glu Asn Asp Glu Pro Ile
245 250 255
Glu Ile Pro Ser Glu Asp Asp Gly Thr Val Leu Leu Ser Thr Val Thr
260 265 270
Ala Gln Phe Pro Gly Ala Cys Gly Leu Arg Tyr Arg Asn Pro Val Ser
275 280 285
Gln Cys Met Arg Gly Val Arg Leu Val Glu Gly Ile Leu His Ala Pro
290 295 300
Asp Ala Gly Trp Gly Asn Leu Val Tyr Val Val Asn Tyr Pro Lys Asp
305 310 315 320
Asn Lys Arg Lys Met Asp Glu Thr Asp Ala Ser Ser Ala Val Lys Val
325 330 335
Lys Arg Ala Val Gln Lys Thr Ser Asp Leu Ile Val Leu Gly Leu Pro
340 345 350
Trp Lys Thr Thr Glu Gln Asp Leu Lys Glu Tyr Phe Ser Thr Phe Gly
355 360 365
Glu Val Leu Met Val Gln Val Lys Lys Asp Leu Lys Thr Gly His Ser
370 375 380
Lys Gly Phe Gly Phe Val Arg Phe Thr Glu Tyr Glu Thr Gln Val Lys
385 390 395 400
Val Met Ser Gln Arg His Met Ile Asp Gly Arg Trp Cys Asp Cys Lys
405 410 415
Leu Pro Asn Ser Lys Gln Ser Gln Asp Glu Pro Leu Arg Ser Arg Lys
420 425 430
Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr Glu Asp Glu Leu Arg
435 440 445
Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val Phe Ile Pro Lys
450 455 460
Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala Asp Asp Gln Ile Ala
465 470 475 480
Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly Ile Ser Val His
485 490 495
Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg Gln Leu Glu Arg
500 505 510
Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn Gln Gly Gly
515 520 525
Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn Asn Gln Gly
530 535 540
Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser Ile Asn Pro
545 550 555 560
Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser Trp Gly Met
565 570 575
Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro Ser Gly Asn
580 585 590
Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln Ala Phe Gly
595 600 605
Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala Ala Ile Gly
610 615 620
Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe Asn Gly Gly
625 630 635 640
Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly Met Phe Arg
645 650 655
Ala Gln Arg His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly
660 665 670
Trp Leu Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly
675 680 685
Pro Val Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys
690 695 700
Asp Thr Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly
705 710 715 720
Tyr Ser Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser
725 730 735
Pro Asp Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser
740 745 750
Asn Thr Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val
755 760 765
Gln Val Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn
770 775 780
Phe Leu Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr
785 790 795 800
Ser Met Gly Phe Gln Cys Glu Thr Glu
805
<210> 36
<211> 705
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 36
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Ser Gly Leu Lys
225 230 235 240
Asp Leu Ile Val Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp Leu
245 250 255
Lys Glu Tyr Phe Ser Thr Phe Gly Glu Val Leu Met Val Gln Val Lys
260 265 270
Lys Asp Leu Lys Thr Gly His Ser Lys Gly Phe Gly Phe Val Arg Phe
275 280 285
Thr Glu Tyr Glu Thr Gln Val Lys Val Met Ser Gln Arg His Met Ile
290 295 300
Asp Gly Arg Trp Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser Gln
305 310 315 320
Asp Glu Pro Leu Arg Ser Arg Lys Val Phe Val Gly Arg Cys Thr Glu
325 330 335
Asp Met Thr Glu Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp
340 345 350
Val Met Asp Val Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val
355 360 365
Thr Phe Ala Asp Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu
370 375 380
Ile Ile Lys Gly Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys His
385 390 395 400
Asn Ser Asn Arg Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro
405 410 415
Gly Gly Phe Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly
420 425 430
Ala Gly Leu Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn
435 440 445
Phe Gly Ala Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala
450 455 460
Ala Leu Gln Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln
465 470 475 480
Asn Gln Ser Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln
485 490 495
Arg Glu Pro Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly
500 505 510
Ser Asn Ser Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly
515 520 525
Ser Gly Ser Gly Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys
530 535 540
Ser Ser Gly Trp Gly Met Phe Arg Ala Gln Arg His Thr Leu Tyr Ala
545 550 555 560
Pro Gly Gly Tyr Asp Ile Met Gly Trp Leu Ile Gln Ile Met Asn Arg
565 570 575
Pro Asn Pro Gln Val Glu Leu Gly Pro Val Asp Thr Ser Cys Ala Leu
580 585 590
Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr Pro Ile Val Tyr Ala Ser
595 600 605
Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser Asn Ala Glu Val Leu Gly
610 615 620
Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp Gly Met Val Lys Pro Lys
625 630 635 640
Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr Ile Asn Thr Met Arg Lys
645 650 655
Ala Ile Asp Arg Asn Ala Glu Val Gln Val Glu Val Val Asn Phe Lys
660 665 670
Lys Asn Gly Gln Arg Phe Val Asn Phe Leu Thr Met Ile Pro Val Arg
675 680 685
Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met Gly Phe Gln Cys Glu Thr
690 695 700
Glu
705
<210> 37
<211> 619
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 37
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Ser Gly Leu Lys
225 230 235 240
Arg Lys Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr Glu Asp Glu
245 250 255
Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val Phe Ile
260 265 270
Pro Lys Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala Asp Asp Gln
275 280 285
Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly Ile Ser
290 295 300
Val His Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg Gln Leu
305 310 315 320
Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn Gln
325 330 335
Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn Asn
340 345 350
Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser Ile
355 360 365
Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser Trp
370 375 380
Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro Ser
385 390 395 400
Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln Ala
405 410 415
Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala Ala
420 425 430
Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe Asn
435 440 445
Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly Met
450 455 460
Phe Arg Ala Gln Arg His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile
465 470 475 480
Met Gly Trp Leu Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu
485 490 495
Leu Gly Pro Val Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys
500 505 510
Gln Lys Asp Thr Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met
515 520 525
Thr Gly Tyr Ser Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu
530 535 540
Gln Ser Pro Asp Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val
545 550 555 560
Asp Ser Asn Thr Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala
565 570 575
Glu Val Gln Val Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe
580 585 590
Val Asn Phe Leu Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr
595 600 605
Arg Tyr Ser Met Gly Phe Gln Cys Glu Thr Glu
610 615
<210> 38
<211> 536
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 38
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Ser Gly Leu Lys
225 230 235 240
Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn Gln Gly Gly Phe
245 250 255
Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn Asn Gln Gly Ser
260 265 270
Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser Ile Asn Pro Ala
275 280 285
Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser Trp Gly Met Met
290 295 300
Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro Ser Gly Asn Asn
305 310 315 320
Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln Ala Phe Gly Ser
325 330 335
Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala Ala Ile Gly Trp
340 345 350
Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe Asn Gly Gly Phe
355 360 365
Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly Met Phe Arg Ala
370 375 380
Gln Arg His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Trp
385 390 395 400
Leu Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro
405 410 415
Val Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp
420 425 430
Thr Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr
435 440 445
Ser Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro
450 455 460
Asp Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn
465 470 475 480
Thr Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln
485 490 495
Val Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe
500 505 510
Leu Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser
515 520 525
Met Gly Phe Gln Cys Glu Thr Glu
530 535
<210> 39
<211> 704
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 39
Met His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Trp Leu
1 5 10 15
Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val
20 25 30
Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr
35 40 45
Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser
50 55 60
Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp
65 70 75 80
Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr
85 90 95
Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val
100 105 110
Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu
115 120 125
Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met
130 135 140
Gly Phe Gln Cys Glu Thr Glu Ala Asp Leu Ile Val Leu Gly Leu Pro
145 150 155 160
Trp Lys Thr Thr Glu Gln Asp Leu Lys Glu Tyr Phe Ser Thr Phe Gly
165 170 175
Glu Val Leu Met Val Gln Val Lys Lys Asp Leu Lys Thr Gly His Ser
180 185 190
Lys Gly Phe Gly Phe Val Arg Phe Thr Glu Tyr Glu Thr Gln Val Lys
195 200 205
Val Met Ser Gln Arg His Met Ile Asp Gly Arg Trp Cys Asp Cys Lys
210 215 220
Leu Pro Asn Ser Lys Gln Ser Gln Asp Glu Pro Leu Arg Ser Arg Lys
225 230 235 240
Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr Glu Asp Glu Leu Arg
245 250 255
Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val Phe Ile Pro Lys
260 265 270
Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala Asp Asp Gln Ile Ala
275 280 285
Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly Ile Ser Val His
290 295 300
Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg Gln Leu Glu Arg
305 310 315 320
Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn Gln Gly Gly
325 330 335
Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn Asn Gln Gly
340 345 350
Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser Ile Asn Pro
355 360 365
Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser Trp Gly Met
370 375 380
Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro Ser Gly Asn
385 390 395 400
Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln Ala Phe Gly
405 410 415
Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala Ala Ile Gly
420 425 430
Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe Asn Gly Gly
435 440 445
Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly Met Phe Ala
450 455 460
Pro Val Ala Thr Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile
465 470 475 480
Ile Lys Glu Phe Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn
485 490 495
Gly His Glu Phe Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu
500 505 510
Gly Thr Gln Thr Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro
515 520 525
Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala
530 535 540
Tyr Val Lys His Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe
545 550 555 560
Pro Glu Gly Phe Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly
565 570 575
Val Val Thr Val Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile
580 585 590
Tyr Lys Val Lys Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val
595 600 605
Met Gln Lys Lys Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr
610 615 620
Pro Glu Asp Gly Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu
625 630 635 640
Lys Asp Gly Gly His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala
645 650 655
Lys Lys Pro Val Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu
660 665 670
Asp Ile Thr Ser His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu
675 680 685
Arg Ala Glu Gly Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys
690 695 700
<210> 40
<211> 618
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 40
Met His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Trp Leu
1 5 10 15
Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val
20 25 30
Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr
35 40 45
Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser
50 55 60
Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp
65 70 75 80
Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr
85 90 95
Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val
100 105 110
Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu
115 120 125
Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met
130 135 140
Gly Phe Gln Cys Glu Thr Glu Ala Arg Lys Val Phe Val Gly Arg Cys
145 150 155 160
Thr Glu Asp Met Thr Glu Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr
165 170 175
Gly Asp Val Met Asp Val Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala
180 185 190
Phe Val Thr Phe Ala Asp Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu
195 200 205
Asp Leu Ile Ile Lys Gly Ile Ser Val His Ile Ser Asn Ala Glu Pro
210 215 220
Lys His Asn Ser Asn Arg Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly
225 230 235 240
Asn Pro Gly Gly Phe Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly
245 250 255
Gly Gly Ala Gly Leu Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly
260 265 270
Met Asn Phe Gly Ala Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala
275 280 285
Gln Ala Ala Leu Gln Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser
290 295 300
Gln Gln Asn Gln Ser Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn
305 310 315 320
Met Gln Arg Glu Pro Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr
325 330 335
Ser Gly Ser Asn Ser Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn
340 345 350
Ala Gly Ser Gly Ser Gly Phe Asn Gly Gly Phe Gly Ser Ser Met Asp
355 360 365
Ser Lys Ser Ser Gly Trp Gly Met Phe Ala Pro Val Ala Thr Met Val
370 375 380
Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg
385 390 395 400
Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile
405 410 415
Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys
420 425 430
Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu
435 440 445
Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala
450 455 460
Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp
465 470 475 480
Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln
485 490 495
Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg
500 505 510
Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met
515 520 525
Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu
530 535 540
Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His Tyr
545 550 555 560
Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln Leu
565 570 575
Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser His Asn
580 585 590
Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly Arg His
595 600 605
Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys
610 615
<210> 41
<211> 535
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 41
Met His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Trp Leu
1 5 10 15
Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val
20 25 30
Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr
35 40 45
Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser
50 55 60
Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp
65 70 75 80
Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr
85 90 95
Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val
100 105 110
Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu
115 120 125
Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met
130 135 140
Gly Phe Gln Cys Glu Thr Glu Ala Gly Arg Phe Gly Gly Asn Pro Gly
145 150 155 160
Gly Phe Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala
165 170 175
Gly Leu Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe
180 185 190
Gly Ala Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala
195 200 205
Leu Gln Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn
210 215 220
Gln Ser Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg
225 230 235 240
Glu Pro Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser
245 250 255
Asn Ser Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser
260 265 270
Gly Ser Gly Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser
275 280 285
Ser Gly Trp Gly Met Phe Ala Pro Val Ala Thr Met Val Ser Lys Gly
290 295 300
Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val
305 310 315 320
His Met Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu
325 330 335
Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val
340 345 350
Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln
355 360 365
Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro
370 375 380
Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg Val
385 390 395 400
Met Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser Ser
405 410 415
Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr Asn
420 425 430
Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp Glu
435 440 445
Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys Gly Glu
450 455 460
Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His Tyr Asp Ala Glu
465 470 475 480
Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln Leu Pro Gly Ala
485 490 495
Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser His Asn Glu Asp Tyr
500 505 510
Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr Gly
515 520 525
Gly Met Asp Glu Leu Tyr Lys
530 535
<210> 42
<211> 639
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 42
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Met Asp Val Phe Met Lys Gly Leu Ser Lys Ala Lys Glu
500 505 510
Gly Val Val Ala Ala Ala Glu Lys Thr Lys Gln Gly Val Ala Glu Ala
515 520 525
Ala Gly Lys Thr Lys Glu Gly Val Leu Tyr Val Gly Ser Lys Thr Lys
530 535 540
Glu Gly Val Val His Gly Val Ala Thr Val Ala Glu Lys Thr Lys Glu
545 550 555 560
Gln Val Thr Asn Val Gly Gly Ala Val Val Thr Gly Val Thr Ala Val
565 570 575
Ala Gln Lys Thr Val Glu Gly Ala Gly Ser Ile Ala Ala Ala Thr Gly
580 585 590
Phe Val Lys Lys Asp Gln Leu Gly Lys Asn Glu Glu Gly Ala Pro Gln
595 600 605
Glu Gly Ile Leu Glu Asp Met Pro Val Asp Pro Asp Asn Glu Ala Tyr
610 615 620
Glu Met Pro Ser Glu Glu Gly Tyr Gln Asp Tyr Glu Pro Glu Ala
625 630 635
<210> 43
<211> 644
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 43
Met Asp Val Phe Met Lys Gly Leu Ser Lys Ala Lys Glu Gly Val Val
1 5 10 15
Ala Ala Ala Glu Lys Thr Lys Gln Gly Val Ala Glu Ala Ala Gly Lys
20 25 30
Thr Lys Glu Gly Val Leu Tyr Val Gly Ser Lys Thr Lys Glu Gly Val
35 40 45
Val His Gly Val Ala Thr Val Ala Glu Lys Thr Lys Glu Gln Val Thr
50 55 60
Asn Val Gly Gly Ala Val Val Thr Gly Val Thr Ala Val Ala Gln Lys
65 70 75 80
Thr Val Glu Gly Ala Gly Ser Ile Ala Ala Ala Thr Gly Phe Val Lys
85 90 95
Lys Asp Gln Leu Gly Lys Asn Glu Glu Gly Ala Pro Gln Glu Gly Ile
100 105 110
Leu Glu Asp Met Pro Val Asp Pro Asp Asn Glu Ala Tyr Glu Met Pro
115 120 125
Ser Glu Glu Gly Tyr Gln Asp Tyr Glu Pro Glu Ala Asp Pro Pro Val
130 135 140
Ala Thr Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp
145 150 155 160
Leu Arg Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly
165 170 175
Ser Val Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe
180 185 190
Tyr Pro Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His
195 200 205
Leu Ser Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys
210 215 220
Thr His Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly
225 230 235 240
Ala Thr Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val
245 250 255
Arg Asp His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val
260 265 270
Gln Ser Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys
275 280 285
Glu Lys Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys
290 295 300
Leu Asp Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu
305 310 315 320
Met Pro Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu
325 330 335
Glu Leu Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu
340 345 350
Thr Arg Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn
355 360 365
Glu Phe Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys
370 375 380
Val Val Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly
385 390 395 400
Glu Ile Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile
405 410 415
Ile Trp Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu
420 425 430
Phe Leu Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe
435 440 445
Asn Phe Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe
450 455 460
Phe Pro Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly
465 470 475 480
Arg Thr Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala
485 490 495
Thr Gly Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala
500 505 510
Val Lys Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp
515 520 525
Asp Thr Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln
530 535 540
Tyr Ile Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp
545 550 555 560
Asn Pro Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile
565 570 575
Arg Gln Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His
580 585 590
His Pro Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu
595 600 605
Leu Gly Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg
610 615 620
Glu Leu Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met
625 630 635 640
Ile Gly Ala Ala
<210> 44
<211> 881
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 44
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Met Asp Val Phe Met Lys Gly Leu Ser Lys Ala Lys Glu
500 505 510
Gly Val Val Ala Ala Ala Glu Lys Thr Lys Gln Gly Val Ala Glu Ala
515 520 525
Ala Gly Lys Thr Lys Glu Gly Val Leu Tyr Val Gly Ser Lys Thr Lys
530 535 540
Glu Gly Val Val His Gly Val Ala Thr Val Ala Glu Lys Thr Lys Glu
545 550 555 560
Gln Val Thr Asn Val Gly Gly Ala Val Val Thr Gly Val Thr Ala Val
565 570 575
Ala Gln Lys Thr Val Glu Gly Ala Gly Ser Ile Ala Ala Ala Thr Gly
580 585 590
Phe Val Lys Lys Asp Gln Leu Gly Lys Asn Glu Glu Gly Ala Pro Gln
595 600 605
Glu Gly Ile Leu Glu Asp Met Pro Val Asp Pro Asp Asn Glu Ala Tyr
610 615 620
Glu Met Pro Ser Glu Glu Gly Tyr Gln Asp Tyr Glu Pro Glu Ala Asp
625 630 635 640
Pro Pro Val Ala Thr Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala
645 650 655
Ile Ile Lys Glu Phe Met Arg Phe Lys Val His Met Glu Gly Ser Val
660 665 670
Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr
675 680 685
Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu
690 695 700
Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys
705 710 715 720
Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser
725 730 735
Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly
740 745 750
Gly Val Val Thr Val Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe
755 760 765
Ile Tyr Lys Val Lys Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro
770 775 780
Val Met Gln Lys Lys Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met
785 790 795 800
Tyr Pro Glu Asp Gly Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys
805 810 815
Leu Lys Asp Gly Gly His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys
820 825 830
Ala Lys Lys Pro Val Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys
835 840 845
Leu Asp Ile Thr Ser His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr
850 855 860
Glu Arg Ala Glu Gly Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr
865 870 875 880
Lys
<210> 45
<211> 882
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 45
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Arg Asp Pro Pro Val Ala Thr Met Val Ser Lys Gly Glu
500 505 510
Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val His
515 520 525
Met Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly
530 535 540
Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr
545 550 555 560
Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe
565 570 575
Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp
580 585 590
Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met
595 600 605
Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser Ser Leu
610 615 620
Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr Asn Phe
625 630 635 640
Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp Glu Ala
645 650 655
Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys Gly Glu Ile
660 665 670
Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His Tyr Asp Ala Glu Val
675 680 685
Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln Leu Pro Gly Ala Tyr
690 695 700
Asn Val Asn Ile Lys Leu Asp Ile Thr Ser His Asn Glu Asp Tyr Thr
705 710 715 720
Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr Gly Gly
725 730 735
Met Asp Glu Leu Tyr Lys Met Asp Val Phe Met Lys Gly Leu Ser Lys
740 745 750
Ala Lys Glu Gly Val Val Ala Ala Ala Glu Lys Thr Lys Gln Gly Val
755 760 765
Ala Glu Ala Ala Gly Lys Thr Lys Glu Gly Val Leu Tyr Val Gly Ser
770 775 780
Lys Thr Lys Glu Gly Val Val His Gly Val Ala Thr Val Ala Glu Lys
785 790 795 800
Thr Lys Glu Gln Val Thr Asn Val Gly Gly Ala Val Val Thr Gly Val
805 810 815
Thr Ala Val Ala Gln Lys Thr Val Glu Gly Ala Gly Ser Ile Ala Ala
820 825 830
Ala Thr Gly Phe Val Lys Lys Asp Gln Leu Gly Lys Asn Glu Glu Gly
835 840 845
Ala Pro Gln Glu Gly Ile Leu Glu Asp Met Pro Val Asp Pro Asp Asn
850 855 860
Glu Ala Tyr Glu Met Pro Ser Glu Glu Gly Tyr Gln Asp Tyr Glu Pro
865 870 875 880
Glu Ala
<210> 46
<211> 881
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 46
Met Asp Val Phe Met Lys Gly Leu Ser Lys Ala Lys Glu Gly Val Val
1 5 10 15
Ala Ala Ala Glu Lys Thr Lys Gln Gly Val Ala Glu Ala Ala Gly Lys
20 25 30
Thr Lys Glu Gly Val Leu Tyr Val Gly Ser Lys Thr Lys Glu Gly Val
35 40 45
Val His Gly Val Ala Thr Val Ala Glu Lys Thr Lys Glu Gln Val Thr
50 55 60
Asn Val Gly Gly Ala Val Val Thr Gly Val Thr Ala Val Ala Gln Lys
65 70 75 80
Thr Val Glu Gly Ala Gly Ser Ile Ala Ala Ala Thr Gly Phe Val Lys
85 90 95
Lys Asp Gln Leu Gly Lys Asn Glu Glu Gly Ala Pro Gln Glu Gly Ile
100 105 110
Leu Glu Asp Met Pro Val Asp Pro Asp Asn Glu Ala Tyr Glu Met Pro
115 120 125
Ser Glu Glu Gly Tyr Gln Asp Tyr Glu Pro Glu Ala Asp Pro Pro Val
130 135 140
Ala Thr Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp
145 150 155 160
Leu Arg Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly
165 170 175
Ser Val Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe
180 185 190
Tyr Pro Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His
195 200 205
Leu Ser Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys
210 215 220
Thr His Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly
225 230 235 240
Ala Thr Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val
245 250 255
Arg Asp His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val
260 265 270
Gln Ser Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys
275 280 285
Glu Lys Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys
290 295 300
Leu Asp Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu
305 310 315 320
Met Pro Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu
325 330 335
Glu Leu Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu
340 345 350
Thr Arg Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn
355 360 365
Glu Phe Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys
370 375 380
Val Val Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly
385 390 395 400
Glu Ile Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile
405 410 415
Ile Trp Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu
420 425 430
Phe Leu Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe
435 440 445
Asn Phe Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe
450 455 460
Phe Pro Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly
465 470 475 480
Arg Thr Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala
485 490 495
Thr Gly Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala
500 505 510
Val Lys Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp
515 520 525
Asp Thr Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln
530 535 540
Tyr Ile Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp
545 550 555 560
Asn Pro Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile
565 570 575
Arg Gln Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His
580 585 590
His Pro Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu
595 600 605
Leu Gly Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg
610 615 620
Glu Leu Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met
625 630 635 640
Ile Gly Ala Ala Ala Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala
645 650 655
Ile Ile Lys Glu Phe Met Arg Phe Lys Val His Met Glu Gly Ser Val
660 665 670
Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr
675 680 685
Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu
690 695 700
Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys
705 710 715 720
Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser
725 730 735
Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly
740 745 750
Gly Val Val Thr Val Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe
755 760 765
Ile Tyr Lys Val Lys Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro
770 775 780
Val Met Gln Lys Lys Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met
785 790 795 800
Tyr Pro Glu Asp Gly Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys
805 810 815
Leu Lys Asp Gly Gly His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys
820 825 830
Ala Lys Lys Pro Val Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys
835 840 845
Leu Asp Ile Thr Ser His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr
850 855 860
Glu Arg Ala Glu Gly Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr
865 870 875 880
Lys
<210> 47
<211> 291
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 47
Met Asp Val Phe Met Lys Gly Leu Ser Lys Ala Lys Glu Gly Val Val
1 5 10 15
Ala Ala Ala Glu Lys Thr Lys Gln Gly Val Ala Glu Ala Ala Gly Lys
20 25 30
Thr Lys Glu Gly Val Leu Tyr Val Gly Ser Lys Thr Lys Glu Gly Val
35 40 45
Val His Gly Val Ala Thr Val Ala Glu Lys Thr Lys Glu Gln Val Thr
50 55 60
Asn Val Gly Gly Ala Val Val Thr Gly Val Thr Ala Val Ala Gln Lys
65 70 75 80
Thr Val Glu Gly Ala Gly Ser Ile Ala Ala Ala Thr Gly Phe Val Lys
85 90 95
Lys Asp Gln Leu Gly Lys Asn Glu Glu Gly Ala Pro Gln Glu Gly Ile
100 105 110
Leu Glu Asp Met Pro Val Asp Pro Asp Asn Glu Ala Tyr Glu Met Pro
115 120 125
Ser Glu Glu Gly Tyr Gln Asp Tyr Glu Pro Glu Ala Phe His Thr Leu
130 135 140
Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Trp Leu Ile Gln Ile Met
145 150 155 160
Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val Asp Thr Ser Cys
165 170 175
Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr Pro Ile Val Tyr
180 185 190
Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser Asn Ala Glu Val
195 200 205
Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp Gly Met Val Lys
210 215 220
Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr Ile Asn Thr Met
225 230 235 240
Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val Glu Val Val Asn
245 250 255
Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu Thr Met Ile Pro
260 265 270
Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met Gly Phe Gln Cys
275 280 285
Glu Thr Glu
290
<210> 48
<211> 292
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 48
Met His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Trp Leu
1 5 10 15
Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val
20 25 30
Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr
35 40 45
Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser
50 55 60
Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp
65 70 75 80
Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr
85 90 95
Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val
100 105 110
Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu
115 120 125
Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met
130 135 140
Gly Phe Gln Cys Glu Thr Glu Ala Met Asp Val Phe Met Lys Gly Leu
145 150 155 160
Ser Lys Ala Lys Glu Gly Val Val Ala Ala Ala Glu Lys Thr Lys Gln
165 170 175
Gly Val Ala Glu Ala Ala Gly Lys Thr Lys Glu Gly Val Leu Tyr Val
180 185 190
Gly Ser Lys Thr Lys Glu Gly Val Val His Gly Val Ala Thr Val Ala
195 200 205
Glu Lys Thr Lys Glu Gln Val Thr Asn Val Gly Gly Ala Val Val Thr
210 215 220
Gly Val Thr Ala Val Ala Gln Lys Thr Val Glu Gly Ala Gly Ser Ile
225 230 235 240
Ala Ala Ala Thr Gly Phe Val Lys Lys Asp Gln Leu Gly Lys Asn Glu
245 250 255
Glu Gly Ala Pro Gln Glu Gly Ile Leu Glu Asp Met Pro Val Asp Pro
260 265 270
Asp Asn Glu Ala Tyr Glu Met Pro Ser Glu Glu Gly Tyr Gln Asp Tyr
275 280 285
Glu Pro Glu Ala
290
<210> 49
<211> 528
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 49
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Ser Lys Met Asp Val
225 230 235 240
Phe Met Lys Gly Leu Ser Lys Ala Lys Glu Gly Val Val Ala Ala Ala
245 250 255
Glu Lys Thr Lys Gln Gly Val Ala Glu Ala Ala Gly Lys Thr Lys Glu
260 265 270
Gly Val Leu Tyr Val Gly Ser Lys Thr Lys Glu Gly Val Val His Gly
275 280 285
Val Ala Thr Val Ala Glu Lys Thr Lys Glu Gln Val Thr Asn Val Gly
290 295 300
Gly Ala Val Val Thr Gly Val Thr Ala Val Ala Gln Lys Thr Val Glu
305 310 315 320
Gly Ala Gly Ser Ile Ala Ala Ala Thr Gly Phe Val Lys Lys Asp Gln
325 330 335
Leu Gly Lys Asn Glu Glu Gly Ala Pro Gln Glu Gly Ile Leu Glu Asp
340 345 350
Met Pro Val Asp Pro Asp Asn Glu Ala Tyr Glu Met Pro Ser Glu Glu
355 360 365
Gly Tyr Gln Asp Tyr Glu Pro Glu Ala Phe His Thr Leu Tyr Ala Pro
370 375 380
Gly Gly Tyr Asp Ile Met Gly Trp Leu Ile Gln Ile Met Asn Arg Pro
385 390 395 400
Asn Pro Gln Val Glu Leu Gly Pro Val Asp Thr Ser Cys Ala Leu Ile
405 410 415
Leu Cys Asp Leu Lys Gln Lys Asp Thr Pro Ile Val Tyr Ala Ser Glu
420 425 430
Ala Phe Leu Tyr Met Thr Gly Tyr Ser Asn Ala Glu Val Leu Gly Arg
435 440 445
Asn Cys Arg Phe Leu Gln Ser Pro Asp Gly Met Val Lys Pro Lys Ser
450 455 460
Thr Arg Lys Tyr Val Asp Ser Asn Thr Ile Asn Thr Met Arg Lys Ala
465 470 475 480
Ile Asp Arg Asn Ala Glu Val Gln Val Glu Val Val Asn Phe Lys Lys
485 490 495
Asn Gly Gln Arg Phe Val Asn Phe Leu Thr Met Ile Pro Val Arg Asp
500 505 510
Glu Thr Gly Glu Tyr Arg Tyr Ser Met Gly Phe Gln Cys Glu Thr Glu
515 520 525
<210> 50
<211> 547
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 50
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Ser Gly Leu Arg
225 230 235 240
Ser Arg Ala Gln Arg His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile
245 250 255
Met Gly Trp Leu Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu
260 265 270
Leu Gly Pro Val Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys
275 280 285
Gln Lys Asp Thr Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met
290 295 300
Thr Gly Tyr Ser Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu
305 310 315 320
Gln Ser Pro Asp Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val
325 330 335
Asp Ser Asn Thr Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala
340 345 350
Glu Val Gln Val Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe
355 360 365
Val Asn Phe Leu Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr
370 375 380
Arg Tyr Ser Met Gly Phe Gln Cys Glu Thr Glu Ala Leu Glu Phe Cys
385 390 395 400
Ser Arg Arg Tyr Arg Gly Pro Met Asp Val Phe Met Lys Gly Leu Ser
405 410 415
Lys Ala Lys Glu Gly Val Val Ala Ala Ala Glu Lys Thr Lys Gln Gly
420 425 430
Val Ala Glu Ala Ala Gly Lys Thr Lys Glu Gly Val Leu Tyr Val Gly
435 440 445
Ser Lys Thr Lys Glu Gly Val Val His Gly Val Ala Thr Val Ala Glu
450 455 460
Lys Thr Lys Glu Gln Val Thr Asn Val Gly Gly Ala Val Val Thr Gly
465 470 475 480
Val Thr Ala Val Ala Gln Lys Thr Val Glu Gly Ala Gly Ser Ile Ala
485 490 495
Ala Ala Thr Gly Phe Val Lys Lys Asp Gln Leu Gly Lys Asn Glu Glu
500 505 510
Gly Ala Pro Gln Glu Gly Ile Leu Glu Asp Met Pro Val Asp Pro Asp
515 520 525
Asn Glu Ala Tyr Glu Met Pro Ser Glu Glu Gly Tyr Gln Asp Tyr Glu
530 535 540
Pro Glu Ala
545
<210> 51
<211> 534
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 51
Met His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Trp Leu
1 5 10 15
Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val
20 25 30
Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr
35 40 45
Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser
50 55 60
Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp
65 70 75 80
Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr
85 90 95
Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val
100 105 110
Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu
115 120 125
Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met
130 135 140
Gly Phe Gln Cys Glu Thr Glu Ala Met Asp Val Phe Met Lys Gly Leu
145 150 155 160
Ser Lys Ala Lys Glu Gly Val Val Ala Ala Ala Glu Lys Thr Lys Gln
165 170 175
Gly Val Ala Glu Ala Ala Gly Lys Thr Lys Glu Gly Val Leu Tyr Val
180 185 190
Gly Ser Lys Thr Lys Glu Gly Val Val His Gly Val Ala Thr Val Ala
195 200 205
Glu Lys Thr Lys Glu Gln Val Thr Asn Val Gly Gly Ala Val Val Thr
210 215 220
Gly Val Thr Ala Val Ala Gln Lys Thr Val Glu Gly Ala Gly Ser Ile
225 230 235 240
Ala Ala Ala Thr Gly Phe Val Lys Lys Asp Gln Leu Gly Lys Asn Glu
245 250 255
Glu Gly Ala Pro Gln Glu Gly Ile Leu Glu Asp Met Pro Val Asp Pro
260 265 270
Asp Asn Glu Ala Tyr Glu Met Pro Ser Glu Glu Gly Tyr Gln Asp Tyr
275 280 285
Glu Pro Glu Ala Phe Ala Pro Val Ala Thr Met Val Ser Lys Gly Glu
290 295 300
Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val His
305 310 315 320
Met Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly
325 330 335
Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr
340 345 350
Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe
355 360 365
Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp
370 375 380
Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met
385 390 395 400
Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser Ser Leu
405 410 415
Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr Asn Phe
420 425 430
Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp Glu Ala
435 440 445
Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys Gly Glu Ile
450 455 460
Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His Tyr Asp Ala Glu Val
465 470 475 480
Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln Leu Pro Gly Ala Tyr
485 490 495
Asn Val Asn Ile Lys Leu Asp Ile Thr Ser His Asn Glu Asp Tyr Thr
500 505 510
Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr Gly Gly
515 520 525
Met Asp Glu Leu Tyr Lys
530
<210> 52
<211> 558
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 52
Met Asp Val Phe Met Lys Gly Leu Ser Lys Ala Lys Glu Gly Val Val
1 5 10 15
Ala Ala Ala Glu Lys Thr Lys Gln Gly Val Ala Glu Ala Ala Gly Lys
20 25 30
Thr Lys Glu Gly Val Leu Tyr Val Gly Ser Lys Thr Lys Glu Gly Val
35 40 45
Val His Gly Val Ala Thr Val Ala Glu Lys Thr Lys Glu Gln Val Thr
50 55 60
Asn Val Gly Gly Ala Val Val Thr Gly Val Thr Ala Val Ala Gln Lys
65 70 75 80
Thr Val Glu Gly Ala Gly Ser Ile Ala Ala Ala Thr Gly Phe Val Lys
85 90 95
Lys Asp Gln Leu Gly Lys Asn Glu Glu Gly Ala Pro Gln Glu Gly Ile
100 105 110
Leu Glu Asp Met Pro Val Asp Pro Asp Asn Glu Ala Tyr Glu Met Pro
115 120 125
Ser Glu Glu Gly Tyr Gln Asp Tyr Glu Pro Glu Ala Leu Leu Pro Val
130 135 140
Ala Thr Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys
145 150 155 160
Glu Phe Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His
165 170 175
Glu Phe Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr
180 185 190
Gln Thr Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala
195 200 205
Trp Asp Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val
210 215 220
Lys His Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu
225 230 235 240
Gly Phe Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val
245 250 255
Thr Val Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys
260 265 270
Val Lys Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln
275 280 285
Lys Lys Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu
290 295 300
Asp Gly Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp
305 310 315 320
Gly Gly His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys
325 330 335
Pro Val Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile
340 345 350
Thr Ser His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala
355 360 365
Glu Gly Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Ser Gly
370 375 380
Leu Arg Ser Arg Ala Gln Ala Ser Asn Ser Ala Val Asp Gly Thr Ala
385 390 395 400
Gly Pro Met His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly
405 410 415
Tyr Leu Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly
420 425 430
Pro Val Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys
435 440 445
Asp Thr Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly
450 455 460
Tyr Ser Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser
465 470 475 480
Pro Asp Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser
485 490 495
Asn Thr Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val
500 505 510
Gln Val Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn
515 520 525
Phe Leu Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr
530 535 540
Ser Met Gly Phe Gln Cys Glu Thr Glu Gly Ile His Arg Ile
545 550 555
<210> 53
<211> 551
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 53
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Ser Gly Leu Arg
225 230 235 240
Ser Arg Ala Gln Met Asp Val Phe Met Lys Gly Leu Ser Lys Ala Lys
245 250 255
Glu Gly Val Val Ala Ala Ala Glu Lys Thr Lys Gln Gly Val Ala Glu
260 265 270
Ala Ala Gly Lys Thr Lys Glu Gly Val Leu Tyr Val Gly Ser Lys Thr
275 280 285
Lys Glu Gly Val Val His Gly Val Ala Thr Val Ala Glu Lys Thr Lys
290 295 300
Glu Gln Val Thr Asn Val Gly Gly Ala Val Val Thr Gly Val Thr Ala
305 310 315 320
Val Ala Gln Lys Thr Val Glu Gly Ala Gly Ser Ile Ala Ala Ala Thr
325 330 335
Gly Phe Val Lys Lys Asp Gln Leu Gly Lys Asn Glu Glu Gly Ala Pro
340 345 350
Gln Glu Gly Ile Leu Glu Asp Met Pro Val Asp Pro Asp Asn Glu Ala
355 360 365
Tyr Glu Met Pro Ser Glu Glu Gly Tyr Gln Asp Tyr Glu Pro Glu Ala
370 375 380
Ser Asn Ser Ala Val Asp Gly Thr Ala Gly Pro Met His Thr Leu Tyr
385 390 395 400
Ala Pro Gly Gly Tyr Asp Ile Met Gly Tyr Leu Ile Gln Ile Met Asn
405 410 415
Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val Asp Thr Ser Cys Ala
420 425 430
Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr Pro Ile Val Tyr Ala
435 440 445
Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser Asn Ala Glu Val Leu
450 455 460
Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp Gly Met Val Lys Pro
465 470 475 480
Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr Ile Asn Thr Met Arg
485 490 495
Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val Glu Val Val Asn Phe
500 505 510
Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu Thr Met Ile Pro Val
515 520 525
Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met Gly Phe Gln Cys Glu
530 535 540
Thr Glu Gly Ile His Arg Ile
545 550
<210> 54
<211> 551
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 54
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Ser Gly Leu Arg
225 230 235 240
Ser Arg Ala Gln Ala Ser Asn Ser Ala Val Asp Gly Thr Ala Gly Pro
245 250 255
Met His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Tyr Leu
260 265 270
Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val
275 280 285
Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr
290 295 300
Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser
305 310 315 320
Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp
325 330 335
Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr
340 345 350
Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val
355 360 365
Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu
370 375 380
Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met
385 390 395 400
Gly Phe Gln Cys Glu Thr Glu Gly Met Asp Val Phe Met Lys Gly Leu
405 410 415
Ser Lys Ala Lys Glu Gly Val Val Ala Ala Ala Glu Lys Thr Lys Gln
420 425 430
Gly Val Ala Glu Ala Ala Gly Lys Thr Lys Glu Gly Val Leu Tyr Val
435 440 445
Gly Ser Lys Thr Lys Glu Gly Val Val His Gly Val Ala Thr Val Ala
450 455 460
Glu Lys Thr Lys Glu Gln Val Thr Asn Val Gly Gly Ala Val Val Thr
465 470 475 480
Gly Val Thr Ala Val Ala Gln Lys Thr Val Glu Gly Ala Gly Ser Ile
485 490 495
Ala Ala Ala Thr Gly Phe Val Lys Lys Asp Gln Leu Gly Lys Asn Glu
500 505 510
Glu Gly Ala Pro Gln Glu Gly Ile Leu Glu Asp Met Pro Val Asp Pro
515 520 525
Asp Asn Glu Ala Tyr Glu Met Pro Ser Glu Glu Gly Tyr Gln Asp Tyr
530 535 540
Glu Pro Glu Ala His Arg Ile
545 550
<210> 55
<211> 702
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 55
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Ser Gly Leu Arg
225 230 235 240
Ser Arg Ala Gln Ala Ser Asn Ser Ala Val Asp Gly Thr Ala Gly Pro
245 250 255
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
260 265 270
Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His
275 280 285
Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu
290 295 300
Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser
305 310 315 320
Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val
325 330 335
Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu
340 345 350
Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro
355 360 365
Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln Ala Arg Met Val
370 375 380
Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly
385 390 395 400
Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro
405 410 415
Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro
420 425 430
Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly
435 440 445
Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser
450 455 460
Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys
465 470 475 480
Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys
485 490 495
Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val
500 505 510
Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly
515 520 525
Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln
530 535 540
Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly
545 550 555 560
Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser
565 570 575
Lys Cys Gly Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln
580 585 590
Val Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser
595 600 605
Lys Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn
610 615 620
Lys Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala
625 630 635 640
Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser
645 650 655
Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser
660 665 670
Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val
675 680 685
Ser Ala Ser Leu Ala Lys Gln Gly Leu Gly Ile His Arg Ile
690 695 700
<210> 56
<211> 879
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 56
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Ser Gly Leu Arg
225 230 235 240
Ser Arg Ala Gln Ala Ser Asn Ser Ala Val Asp Gly Thr Ala Gly Pro
245 250 255
Met Pro Asp Tyr Ser Leu Val Lys Ala Leu Gln Met Ala Gln Gln Asn
260 265 270
Phe Val Ile Thr Asp Ala Ser Leu Pro Asp Asn Pro Ile Val Tyr Ala
275 280 285
Ser Arg Gly Phe Leu Thr Leu Thr Gly Tyr Ser Leu Asp Gln Ile Leu
290 295 300
Gly Arg Asn Cys Arg Phe Leu Gln Gly Pro Glu Thr Asp Pro Arg Ala
305 310 315 320
Val Asp Lys Ile Arg Asn Ala Ile Thr Lys Gly Val Asp Thr Ser Val
325 330 335
Cys Leu Leu Asn Tyr Arg Gln Asp Gly Thr Thr Phe Trp Asn Leu Phe
340 345 350
Phe Val Ala Gly Leu Arg Asp Ser Lys Gly Asn Ile Val Asn Tyr Val
355 360 365
Gly Val Gln Ser Lys Val Ser Glu Asp Tyr Ala Lys Leu Leu Val Asn
370 375 380
Glu Gln Asn Ile Glu Tyr Lys Gly Val Arg Thr Ser Asn Met Leu Arg
385 390 395 400
Arg Lys Pro Gly Gly Ile His Arg Ile Met Ala Glu Pro Arg Gln Glu
405 410 415
Phe Glu Val Met Glu Asp His Ala Gly Thr Tyr Gly Leu Gly Asp Arg
420 425 430
Lys Asp Gln Gly Gly Tyr Thr Met His Gln Asp Gln Glu Gly Asp Thr
435 440 445
Asp Ala Gly Leu Lys Glu Ser Pro Leu Gln Thr Pro Thr Glu Asp Gly
450 455 460
Ser Glu Glu Pro Gly Ser Glu Thr Ser Asp Ala Lys Ser Thr Pro Thr
465 470 475 480
Ala Glu Asp Val Thr Ala Pro Leu Val Asp Glu Gly Ala Pro Gly Lys
485 490 495
Gln Ala Ala Ala Gln Pro His Thr Glu Ile Pro Glu Gly Thr Thr Ala
500 505 510
Glu Glu Ala Gly Ile Gly Asp Thr Pro Ser Leu Glu Asp Glu Ala Ala
515 520 525
Gly His Val Thr Gln Ala Arg Met Val Ser Lys Ser Lys Asp Gly Thr
530 535 540
Gly Ser Asp Asp Lys Lys Ala Lys Gly Ala Asp Gly Lys Thr Lys Ile
545 550 555 560
Ala Thr Pro Arg Gly Ala Ala Pro Pro Gly Gln Lys Gly Gln Ala Asn
565 570 575
Ala Thr Arg Ile Pro Ala Lys Thr Pro Pro Ala Pro Lys Thr Pro Pro
580 585 590
Ser Ser Gly Glu Pro Pro Lys Ser Gly Asp Arg Ser Gly Tyr Ser Ser
595 600 605
Pro Gly Ser Pro Gly Thr Pro Gly Ser Arg Ser Arg Thr Pro Ser Leu
610 615 620
Pro Thr Pro Pro Thr Arg Glu Pro Lys Lys Val Ala Val Val Arg Thr
625 630 635 640
Pro Pro Lys Ser Pro Ser Ser Ala Lys Ser Arg Leu Gln Thr Ala Pro
645 650 655
Val Pro Met Pro Asp Leu Lys Asn Val Lys Ser Lys Ile Gly Ser Thr
660 665 670
Glu Asn Leu Lys His Gln Pro Gly Gly Gly Lys Val Gln Ile Ile Asn
675 680 685
Lys Lys Leu Asp Leu Ser Asn Val Gln Ser Lys Cys Gly Ser Lys Asp
690 695 700
Asn Ile Lys His Val Pro Gly Gly Gly Ser Val Gln Ile Val Tyr Lys
705 710 715 720
Pro Val Asp Leu Ser Lys Val Thr Ser Lys Cys Gly Ser Leu Gly Asn
725 730 735
Ile His His Lys Pro Gly Gly Gly Gln Val Glu Val Lys Ser Glu Lys
740 745 750
Leu Asp Phe Lys Asp Arg Val Gln Ser Lys Ile Gly Ser Leu Asp Asn
755 760 765
Ile Thr His Val Pro Gly Gly Gly Asn Lys Lys Ile Glu Thr His Lys
770 775 780
Leu Thr Phe Arg Glu Asn Ala Lys Ala Lys Thr Asp His Gly Ala Glu
785 790 795 800
Ile Val Tyr Lys Ser Pro Val Val Ser Gly Asp Thr Ser Pro Arg His
805 810 815
Leu Ser Asn Val Ser Ser Thr Gly Ser Ile Asp Met Val Asp Ser Pro
820 825 830
Gln Leu Ala Thr Leu Ala Asp Glu Val Ser Ala Ser Leu Ala Lys Gln
835 840 845
Gly Leu Ile Thr Asp His Asn Gln Pro Tyr His Ile Cys Arg Gly Phe
850 855 860
Thr Cys Phe Lys Lys Pro Pro Thr Pro Pro Pro Glu Pro Glu Thr
865 870 875
<210> 57
<211> 852
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 57
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Ser Gly Leu Arg
225 230 235 240
Ser Arg Ala Gln Ala Ser Asn Ser Ala Val Asp Gly Thr Ala Gly Pro
245 250 255
Met His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Trp Leu
260 265 270
Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val
275 280 285
Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr
290 295 300
Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser
305 310 315 320
Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp
325 330 335
Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr
340 345 350
Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val
355 360 365
Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu
370 375 380
Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met
385 390 395 400
Gly Phe Gln Cys Glu Thr Glu Gly Met Ala Glu Pro Arg Gln Glu Phe
405 410 415
Glu Val Met Glu Asp His Ala Gly Thr Tyr Gly Leu Gly Asp Arg Lys
420 425 430
Asp Gln Gly Gly Tyr Thr Met His Gln Asp Gln Glu Gly Asp Thr Asp
435 440 445
Ala Gly Leu Lys Glu Ser Pro Leu Gln Thr Pro Thr Glu Asp Gly Ser
450 455 460
Glu Glu Pro Gly Ser Glu Thr Ser Asp Ala Lys Ser Thr Pro Thr Ala
465 470 475 480
Glu Asp Val Thr Ala Pro Leu Val Asp Glu Gly Ala Pro Gly Lys Gln
485 490 495
Ala Ala Ala Gln Pro His Thr Glu Ile Pro Glu Gly Thr Thr Ala Glu
500 505 510
Glu Ala Gly Ile Gly Asp Thr Pro Ser Leu Glu Asp Glu Ala Ala Gly
515 520 525
His Val Thr Gln Ala Arg Met Val Ser Lys Ser Lys Asp Gly Thr Gly
530 535 540
Ser Asp Asp Lys Lys Ala Lys Gly Ala Asp Gly Lys Thr Lys Ile Ala
545 550 555 560
Thr Pro Arg Gly Ala Ala Pro Pro Gly Gln Lys Gly Gln Ala Asn Ala
565 570 575
Thr Arg Ile Pro Ala Lys Thr Pro Pro Ala Pro Lys Thr Pro Pro Ser
580 585 590
Ser Gly Glu Pro Pro Lys Ser Gly Asp Arg Ser Gly Tyr Ser Ser Pro
595 600 605
Gly Ser Pro Gly Thr Pro Gly Ser Arg Ser Arg Thr Pro Ser Leu Pro
610 615 620
Thr Pro Pro Thr Arg Glu Pro Lys Lys Val Ala Val Val Arg Thr Pro
625 630 635 640
Pro Lys Ser Pro Ser Ser Ala Lys Ser Arg Leu Gln Thr Ala Pro Val
645 650 655
Pro Met Pro Asp Leu Lys Asn Val Lys Ser Lys Ile Gly Ser Thr Glu
660 665 670
Asn Leu Lys His Gln Pro Gly Gly Gly Lys Val Gln Ile Ile Asn Lys
675 680 685
Lys Leu Asp Leu Ser Asn Val Gln Ser Lys Cys Gly Ser Lys Asp Asn
690 695 700
Ile Lys His Val Pro Gly Gly Gly Ser Val Gln Ile Val Tyr Lys Pro
705 710 715 720
Val Asp Leu Ser Lys Val Thr Ser Lys Cys Gly Ser Leu Gly Asn Ile
725 730 735
His His Lys Pro Gly Gly Gly Gln Val Glu Val Lys Ser Glu Lys Leu
740 745 750
Asp Phe Lys Asp Arg Val Gln Ser Lys Ile Gly Ser Leu Asp Asn Ile
755 760 765
Thr His Val Pro Gly Gly Gly Asn Lys Lys Ile Glu Thr His Lys Leu
770 775 780
Thr Phe Arg Glu Asn Ala Lys Ala Lys Thr Asp His Gly Ala Glu Ile
785 790 795 800
Val Tyr Lys Ser Pro Val Val Ser Gly Asp Thr Ser Pro Arg His Leu
805 810 815
Ser Asn Val Ser Ser Thr Gly Ser Ile Asp Met Val Asp Ser Pro Gln
820 825 830
Leu Ala Thr Leu Ala Asp Glu Val Ser Ala Ser Leu Ala Lys Gln Gly
835 840 845
Leu His Arg Ile
850
<210> 58
<211> 853
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 58
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Ser Gly Leu Thr
225 230 235 240
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
245 250 255
Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His
260 265 270
Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu
275 280 285
Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser
290 295 300
Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val
305 310 315 320
Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu
325 330 335
Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro
340 345 350
Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln Ala Arg Met Val
355 360 365
Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly
370 375 380
Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro
385 390 395 400
Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro
405 410 415
Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly
420 425 430
Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser
435 440 445
Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys
450 455 460
Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys
465 470 475 480
Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val
485 490 495
Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly
500 505 510
Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln
515 520 525
Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly
530 535 540
Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser
545 550 555 560
Lys Cys Gly Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln
565 570 575
Val Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser
580 585 590
Lys Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn
595 600 605
Lys Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala
610 615 620
Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser
625 630 635 640
Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser
645 650 655
Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val
660 665 670
Ser Ala Ser Leu Ala Lys Gln Gly Leu Arg Arg Ala Gln Arg His Thr
675 680 685
Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Trp Leu Ile Gln Ile
690 695 700
Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val Asp Thr Ser
705 710 715 720
Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr Pro Ile Val
725 730 735
Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser Asn Ala Glu
740 745 750
Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp Gly Met Val
755 760 765
Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr Ile Asn Thr
770 775 780
Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val Glu Val Val
785 790 795 800
Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu Thr Met Ile
805 810 815
Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met Gly Phe Gln
820 825 830
Cys Glu Thr Glu Ala Leu Glu Phe Cys Ser Arg Arg Tyr Arg Gly Pro
835 840 845
Gly Ile His Arg Ile
850
<210> 59
<211> 853
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 59
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Ser Gly Leu Arg
225 230 235 240
Ser Arg Ala Gln Arg His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile
245 250 255
Met Gly Trp Leu Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu
260 265 270
Leu Gly Pro Val Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys
275 280 285
Gln Lys Asp Thr Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met
290 295 300
Thr Gly Tyr Ser Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu
305 310 315 320
Gln Ser Pro Asp Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val
325 330 335
Asp Ser Asn Thr Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala
340 345 350
Glu Val Gln Val Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe
355 360 365
Val Asn Phe Leu Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr
370 375 380
Arg Tyr Ser Met Gly Phe Gln Cys Glu Thr Glu Ala Leu Ala Met Ala
385 390 395 400
Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly Thr Tyr
405 410 415
Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His Gln Asp
420 425 430
Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu Gln Thr
435 440 445
Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser Asp Ala
450 455 460
Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val Asp Glu
465 470 475 480
Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu Ile Pro
485 490 495
Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro Ser Leu
500 505 510
Glu Asp Glu Ala Ala Gly His Val Thr Gln Ala Arg Met Val Ser Lys
515 520 525
Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly Ala Asp
530 535 540
Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro Gly Gln
545 550 555 560
Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro Pro Ala
565 570 575
Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly Asp Arg
580 585 590
Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser Arg Ser
595 600 605
Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys Lys Val
610 615 620
Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys Ser Arg
625 630 635 640
Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val Lys Ser
645 650 655
Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly Gly Lys
660 665 670
Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln Ser Lys
675 680 685
Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly Ser Val
690 695 700
Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser Lys Cys
705 710 715 720
Gly Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln Val Glu
725 730 735
Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser Lys Ile
740 745 750
Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn Lys Lys
755 760 765
Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala Lys Thr
770 775 780
Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser Gly Asp
785 790 795 800
Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser Ile Asp
805 810 815
Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val Ser Ala
820 825 830
Ser Leu Ala Lys Gln Gly Leu Arg Cys Ser Arg Arg Tyr Arg Gly Pro
835 840 845
Gly Ile His Arg Ile
850
<210> 60
<211> 859
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 60
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
1 5 10 15
Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His
20 25 30
Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu
35 40 45
Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser
50 55 60
Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val
65 70 75 80
Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu
85 90 95
Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro
100 105 110
Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln Ala Arg Met Val
115 120 125
Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly
130 135 140
Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro
145 150 155 160
Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro
165 170 175
Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly
180 185 190
Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser
195 200 205
Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys
210 215 220
Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys
225 230 235 240
Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val
245 250 255
Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly
260 265 270
Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln
275 280 285
Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly
290 295 300
Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser
305 310 315 320
Lys Cys Gly Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln
325 330 335
Val Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser
340 345 350
Lys Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn
355 360 365
Lys Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala
370 375 380
Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser
385 390 395 400
Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser
405 410 415
Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val
420 425 430
Ser Ala Ser Leu Ala Lys Gln Gly Leu Ala Leu Pro Val Ala Thr Met
435 440 445
Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met
450 455 460
Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe Glu
465 470 475 480
Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala
485 490 495
Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile
500 505 510
Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro
515 520 525
Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys
530 535 540
Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr
545 550 555 560
Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu
565 570 575
Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr
580 585 590
Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala
595 600 605
Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His
610 615 620
Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln
625 630 635 640
Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser His
645 650 655
Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly Arg
660 665 670
His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Ser Gly Leu Arg Ser
675 680 685
Arg Ala Gln Arg His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met
690 695 700
Gly Trp Leu Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu
705 710 715 720
Gly Pro Val Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln
725 730 735
Lys Asp Thr Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr
740 745 750
Gly Tyr Ser Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln
755 760 765
Ser Pro Asp Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp
770 775 780
Ser Asn Thr Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu
785 790 795 800
Val Gln Val Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val
805 810 815
Asn Phe Leu Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg
820 825 830
Tyr Ser Met Gly Phe Gln Cys Glu Thr Glu Ala Leu Glu Phe Cys Ser
835 840 845
Arg Arg Tyr Arg Gly Pro Gly Ile His Arg Ile
850 855
<210> 61
<211> 1190
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 61
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Arg Asp Pro Pro Val Ala Thr Met Val Ser Lys Gly Glu
500 505 510
Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val His
515 520 525
Met Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly
530 535 540
Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr
545 550 555 560
Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe
565 570 575
Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp
580 585 590
Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met
595 600 605
Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser Ser Leu
610 615 620
Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr Asn Phe
625 630 635 640
Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp Glu Ala
645 650 655
Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys Gly Glu Ile
660 665 670
Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His Tyr Asp Ala Glu Val
675 680 685
Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln Leu Pro Gly Ala Tyr
690 695 700
Asn Val Asn Ile Lys Leu Asp Ile Thr Ser His Asn Glu Asp Tyr Thr
705 710 715 720
Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr Gly Gly
725 730 735
Met Asp Glu Leu Tyr Lys Ser Arg Met Ala Glu Pro Arg Gln Glu Phe
740 745 750
Glu Val Met Glu Asp His Ala Gly Thr Tyr Gly Leu Gly Asp Arg Lys
755 760 765
Asp Gln Gly Gly Tyr Thr Met His Gln Asp Gln Glu Gly Asp Thr Asp
770 775 780
Ala Gly Leu Lys Glu Ser Pro Leu Gln Thr Pro Thr Glu Asp Gly Ser
785 790 795 800
Glu Glu Pro Gly Ser Glu Thr Ser Asp Ala Lys Ser Thr Pro Thr Ala
805 810 815
Glu Asp Val Thr Ala Pro Leu Val Asp Glu Gly Ala Pro Gly Lys Gln
820 825 830
Ala Ala Ala Gln Pro His Thr Glu Ile Pro Glu Gly Thr Thr Ala Glu
835 840 845
Glu Ala Gly Ile Gly Asp Thr Pro Ser Leu Glu Asp Glu Ala Ala Gly
850 855 860
His Val Thr Gln Ala Arg Met Val Ser Lys Ser Lys Asp Gly Thr Gly
865 870 875 880
Ser Asp Asp Lys Lys Ala Lys Gly Ala Asp Gly Lys Thr Lys Ile Ala
885 890 895
Thr Pro Arg Gly Ala Ala Pro Pro Gly Gln Lys Gly Gln Ala Asn Ala
900 905 910
Thr Arg Ile Pro Ala Lys Thr Pro Pro Ala Pro Lys Thr Pro Pro Ser
915 920 925
Ser Gly Glu Pro Pro Lys Ser Gly Asp Arg Ser Gly Tyr Ser Ser Pro
930 935 940
Gly Ser Pro Gly Thr Pro Gly Ser Arg Ser Arg Thr Pro Ser Leu Pro
945 950 955 960
Thr Pro Pro Thr Arg Glu Pro Lys Lys Val Ala Val Val Arg Thr Pro
965 970 975
Pro Lys Ser Pro Ser Ser Ala Lys Ser Arg Leu Gln Thr Ala Pro Val
980 985 990
Pro Met Pro Asp Leu Lys Asn Val Lys Ser Lys Ile Gly Ser Thr Glu
995 1000 1005
Asn Leu Lys His Gln Pro Gly Gly Gly Lys Val Gln Ile Ile Asn
1010 1015 1020
Lys Lys Leu Asp Leu Ser Asn Val Gln Ser Lys Cys Gly Ser Lys
1025 1030 1035
Asp Asn Ile Lys His Val Pro Gly Gly Gly Ser Val Gln Ile Val
1040 1045 1050
Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser Lys Cys Gly Ser
1055 1060 1065
Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln Val Glu Val
1070 1075 1080
Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser Lys Ile
1085 1090 1095
Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn Lys
1100 1105 1110
Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala
1115 1120 1125
Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val
1130 1135 1140
Ser Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr
1145 1150 1155
Gly Ser Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala
1160 1165 1170
Asp Glu Val Ser Ala Ser Leu Ala Lys Gln Gly Leu Gly Asp Ser
1175 1180 1185
Arg Ser
1190
<210> 62
<211> 706
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 62
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
1 5 10 15
Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His
20 25 30
Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu
35 40 45
Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser
50 55 60
Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val
65 70 75 80
Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu
85 90 95
Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro
100 105 110
Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln Ala Arg Met Val
115 120 125
Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly
130 135 140
Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro
145 150 155 160
Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro
165 170 175
Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly
180 185 190
Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser
195 200 205
Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys
210 215 220
Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys
225 230 235 240
Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val
245 250 255
Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly
260 265 270
Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln
275 280 285
Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly
290 295 300
Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser
305 310 315 320
Lys Cys Gly Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln
325 330 335
Val Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser
340 345 350
Lys Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn
355 360 365
Lys Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala
370 375 380
Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser
385 390 395 400
Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser
405 410 415
Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val
420 425 430
Ser Ala Ser Leu Ala Lys Gln Gly Leu Phe Ala Thr Met Val Ser Lys
435 440 445
Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys
450 455 460
Val His Met Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly
465 470 475 480
Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys
485 490 495
Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro
500 505 510
Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile
515 520 525
Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg
530 535 540
Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser
545 550 555 560
Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr
565 570 575
Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp
580 585 590
Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys Gly
595 600 605
Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His Tyr Asp Ala
610 615 620
Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln Leu Pro Gly
625 630 635 640
Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser His Asn Glu Asp
645 650 655
Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr
660 665 670
Gly Gly Met Asp Glu Leu Tyr Lys Ser Gly Leu Arg Ser Arg Ala Gln
675 680 685
Ala Ser Asn Ser Ala Val Asp Gly Thr Ala Gly Pro Gly Ser Thr Gly
690 695 700
Ser Arg
705
<210> 63
<211> 1193
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 63
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
1 5 10 15
Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His
20 25 30
Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu
35 40 45
Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser
50 55 60
Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val
65 70 75 80
Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu
85 90 95
Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro
100 105 110
Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln Ala Arg Met Val
115 120 125
Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly
130 135 140
Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro
145 150 155 160
Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro
165 170 175
Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly
180 185 190
Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser
195 200 205
Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys
210 215 220
Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys
225 230 235 240
Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val
245 250 255
Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly
260 265 270
Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln
275 280 285
Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly
290 295 300
Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser
305 310 315 320
Lys Cys Gly Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln
325 330 335
Val Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser
340 345 350
Lys Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn
355 360 365
Lys Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala
370 375 380
Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser
385 390 395 400
Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser
405 410 415
Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val
420 425 430
Ser Ala Ser Leu Ala Lys Gln Gly Leu Ala Leu Pro Asp Ser Asp Leu
435 440 445
Glu Ala Thr Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg
450 455 460
Asp Leu Arg Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu
465 470 475 480
Gly Ser Val Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln
485 490 495
Phe Tyr Pro Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala
500 505 510
His Leu Ser Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile
515 520 525
Lys Thr His Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr
530 535 540
Gly Ala Thr Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu
545 550 555 560
Val Arg Asp His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser
565 570 575
Val Gln Ser Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr
580 585 590
Cys Glu Lys Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys
595 600 605
Cys Leu Asp Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg
610 615 620
Leu Met Pro Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile
625 630 635 640
Glu Glu Leu Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu
645 650 655
Leu Thr Arg Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu
660 665 670
Asn Glu Phe Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys
675 680 685
Lys Val Val Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe
690 695 700
Gly Glu Ile Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln
705 710 715 720
Ile Ile Trp Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp
725 730 735
Leu Phe Leu Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys
740 745 750
Phe Asn Phe Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg
755 760 765
Phe Phe Pro Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln
770 775 780
Gly Arg Thr Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp
785 790 795 800
Ala Thr Gly Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe
805 810 815
Ala Val Lys Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe
820 825 830
Trp Asp Thr Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp
835 840 845
Gln Tyr Ile Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu
850 855 860
Asp Asn Pro Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr
865 870 875 880
Ile Arg Gln Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile
885 890 895
His His Pro Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val
900 905 910
Glu Leu Gly Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala
915 920 925
Arg Glu Leu Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile
930 935 940
Met Ile Gly Ala Ala Ala Arg Asp Pro Pro Val Ala Thr Met Val Ser
945 950 955 960
Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe
965 970 975
Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu
980 985 990
Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu
995 1000 1005
Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu
1010 1015 1020
Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro
1025 1030 1035
Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
1040 1045 1050
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr
1055 1060 1065
Val Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys
1070 1075 1080
Val Lys Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met
1085 1090 1095
Gln Lys Lys Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr
1100 1105 1110
Pro Glu Asp Gly Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys
1115 1120 1125
Leu Lys Asp Gly Gly His Tyr Asp Ala Glu Val Lys Thr Thr Tyr
1130 1135 1140
Lys Ala Lys Lys Pro Val Gln Leu Pro Gly Ala Tyr Asn Val Asn
1145 1150 1155
Ile Lys Leu Asp Ile Thr Ser His Asn Glu Asp Tyr Thr Ile Val
1160 1165 1170
Glu Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr Gly Gly Met
1175 1180 1185
Asp Glu Leu Tyr Lys
1190
<210> 64
<211> 1184
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 64
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Pro Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu
500 505 510
Asp His Ala Gly Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly
515 520 525
Tyr Thr Met His Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys
530 535 540
Glu Ser Pro Leu Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly
545 550 555 560
Ser Glu Thr Ser Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr
565 570 575
Ala Pro Leu Val Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln
580 585 590
Pro His Thr Glu Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile
595 600 605
Gly Asp Thr Pro Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln
610 615 620
Ala Arg Met Val Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys
625 630 635 640
Lys Ala Lys Gly Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly
645 650 655
Ala Ala Pro Pro Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro
660 665 670
Ala Lys Thr Pro Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro
675 680 685
Pro Lys Ser Gly Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly
690 695 700
Thr Pro Gly Ser Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr
705 710 715 720
Arg Glu Pro Lys Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro
725 730 735
Ser Ser Ala Lys Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp
740 745 750
Leu Lys Asn Val Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His
755 760 765
Gln Pro Gly Gly Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu
770 775 780
Ser Asn Val Gln Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val
785 790 795 800
Pro Gly Gly Gly Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser
805 810 815
Lys Val Thr Ser Lys Cys Gly Ser Leu Gly Asn Ile His His Lys Pro
820 825 830
Gly Gly Gly Gln Val Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp
835 840 845
Arg Val Gln Ser Lys Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro
850 855 860
Gly Gly Gly Asn Lys Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu
865 870 875 880
Asn Ala Lys Ala Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser
885 890 895
Pro Val Val Ser Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser
900 905 910
Ser Thr Gly Ser Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu
915 920 925
Ala Asp Glu Val Ser Ala Ser Leu Ala Lys Gln Gly Leu Gly Asp Pro
930 935 940
Pro Val Ala Thr Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile
945 950 955 960
Ile Lys Glu Phe Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn
965 970 975
Gly His Glu Phe Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu
980 985 990
Gly Thr Gln Thr Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro
995 1000 1005
Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys
1010 1015 1020
Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu
1025 1030 1035
Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met Asn Phe Glu
1040 1045 1050
Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser Ser Leu Gln Asp
1055 1060 1065
Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr Asn Phe Pro
1070 1075 1080
Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp Glu Ala
1085 1090 1095
Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys Gly Glu
1100 1105 1110
Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His Tyr Asp Ala
1115 1120 1125
Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln Leu Pro
1130 1135 1140
Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser His Asn
1145 1150 1155
Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly Arg
1160 1165 1170
His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys
1175 1180
<210> 65
<211> 1190
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 65
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Arg Asp Pro Pro Val Ala Thr Met Val Ser Lys Gly Glu
500 505 510
Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val His
515 520 525
Met Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly
530 535 540
Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr
545 550 555 560
Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe
565 570 575
Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp
580 585 590
Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met
595 600 605
Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser Ser Leu
610 615 620
Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr Asn Phe
625 630 635 640
Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp Glu Ala
645 650 655
Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys Gly Glu Ile
660 665 670
Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His Tyr Asp Ala Glu Val
675 680 685
Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln Leu Pro Gly Ala Tyr
690 695 700
Asn Val Asn Ile Lys Leu Asp Ile Thr Ser His Asn Glu Asp Tyr Thr
705 710 715 720
Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr Gly Gly
725 730 735
Met Asp Glu Leu Tyr Lys Ser Arg Met Ala Glu Pro Arg Gln Glu Phe
740 745 750
Glu Val Met Glu Asp His Ala Gly Thr Tyr Gly Leu Gly Asp Arg Lys
755 760 765
Asp Gln Gly Gly Tyr Thr Met His Gln Asp Gln Glu Gly Asp Thr Asp
770 775 780
Ala Gly Leu Lys Glu Ser Pro Leu Gln Thr Pro Thr Glu Asp Gly Ser
785 790 795 800
Glu Glu Pro Gly Ser Glu Thr Ser Asp Ala Lys Ser Thr Pro Thr Ala
805 810 815
Glu Asp Val Thr Ala Pro Leu Val Asp Glu Gly Ala Pro Gly Lys Gln
820 825 830
Ala Ala Ala Gln Pro His Thr Glu Ile Pro Glu Gly Thr Thr Ala Glu
835 840 845
Glu Ala Gly Ile Gly Asp Thr Pro Ser Leu Glu Asp Glu Ala Ala Gly
850 855 860
His Val Thr Gln Ala Arg Met Val Ser Lys Ser Lys Asp Gly Thr Gly
865 870 875 880
Ser Asp Asp Lys Lys Ala Lys Gly Ala Asp Gly Lys Thr Lys Ile Ala
885 890 895
Thr Pro Arg Gly Ala Ala Pro Pro Gly Gln Lys Gly Gln Ala Asn Ala
900 905 910
Thr Arg Ile Pro Ala Lys Thr Pro Pro Ala Pro Lys Thr Pro Pro Ser
915 920 925
Ser Gly Glu Pro Pro Lys Ser Gly Asp Arg Ser Gly Tyr Ser Ser Pro
930 935 940
Gly Ser Pro Gly Thr Pro Gly Ser Arg Ser Arg Thr Pro Ser Leu Pro
945 950 955 960
Thr Pro Pro Thr Arg Glu Pro Lys Lys Val Ala Val Val Arg Thr Pro
965 970 975
Pro Lys Ser Pro Ser Ser Ala Lys Ser Arg Leu Gln Thr Ala Pro Val
980 985 990
Pro Met Pro Asp Leu Lys Asn Val Lys Ser Lys Ile Gly Ser Thr Glu
995 1000 1005
Asn Leu Lys His Gln Pro Gly Gly Gly Lys Val Gln Ile Ile Asn
1010 1015 1020
Lys Lys Leu Asp Leu Ser Asn Val Gln Ser Lys Cys Gly Ser Lys
1025 1030 1035
Asp Asn Ile Lys His Val Pro Gly Gly Gly Ser Val Gln Ile Val
1040 1045 1050
Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser Lys Cys Gly Ser
1055 1060 1065
Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln Val Glu Val
1070 1075 1080
Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser Lys Ile
1085 1090 1095
Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn Lys
1100 1105 1110
Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala
1115 1120 1125
Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val
1130 1135 1140
Ser Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr
1145 1150 1155
Gly Ser Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala
1160 1165 1170
Asp Glu Val Ser Ala Ser Leu Ala Lys Gln Gly Leu Gly Asp Ser
1175 1180 1185
Arg Ser
1190
<210> 66
<211> 853
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 66
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Ser Gly Leu Thr
225 230 235 240
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
245 250 255
Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His
260 265 270
Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu
275 280 285
Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser
290 295 300
Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val
305 310 315 320
Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu
325 330 335
Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro
340 345 350
Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln Ala Arg Met Val
355 360 365
Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly
370 375 380
Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro
385 390 395 400
Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro
405 410 415
Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly
420 425 430
Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser
435 440 445
Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys
450 455 460
Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys
465 470 475 480
Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val
485 490 495
Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly
500 505 510
Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln
515 520 525
Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly
530 535 540
Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser
545 550 555 560
Lys Cys Gly Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln
565 570 575
Val Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser
580 585 590
Lys Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn
595 600 605
Lys Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala
610 615 620
Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser
625 630 635 640
Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser
645 650 655
Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val
660 665 670
Ser Ala Ser Leu Ala Lys Gln Gly Leu Arg Arg Ala Gln Arg His Thr
675 680 685
Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Trp Leu Ile Gln Ile
690 695 700
Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val Asp Thr Ser
705 710 715 720
Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr Pro Ile Val
725 730 735
Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser Asn Ala Glu
740 745 750
Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp Gly Met Val
755 760 765
Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr Ile Asn Thr
770 775 780
Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val Glu Val Val
785 790 795 800
Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu Thr Met Ile
805 810 815
Pro Val Arg Asp Glu Thr Gly Glu Tyr Arg Tyr Ser Met Gly Phe Gln
820 825 830
Cys Glu Thr Glu Ala Leu Glu Phe Cys Ser Arg Arg Tyr Arg Gly Pro
835 840 845
Gly Ile His Arg Ile
850
<210> 67
<211> 853
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 67
Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe
1 5 10 15
Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe
20 25 30
Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr
35 40 45
Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp
50 55 60
Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His
65 70 75 80
Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
85 90 95
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val
100 105 110
Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys
115 120 125
Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys
130 135 140
Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
145 150 155 160
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly
165 170 175
His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
180 185 190
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
195 200 205
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly
210 215 220
Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys Ser Gly Leu Arg
225 230 235 240
Ser Arg Ala Gln Arg His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile
245 250 255
Met Gly Trp Leu Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu
260 265 270
Leu Gly Pro Val Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys
275 280 285
Gln Lys Asp Thr Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met
290 295 300
Thr Gly Tyr Ser Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu
305 310 315 320
Gln Ser Pro Asp Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val
325 330 335
Asp Ser Asn Thr Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala
340 345 350
Glu Val Gln Val Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe
355 360 365
Val Asn Phe Leu Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Tyr
370 375 380
Arg Tyr Ser Met Gly Phe Gln Cys Glu Thr Glu Ala Leu Ala Met Ala
385 390 395 400
Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly Thr Tyr
405 410 415
Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His Gln Asp
420 425 430
Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu Gln Thr
435 440 445
Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser Asp Ala
450 455 460
Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val Asp Glu
465 470 475 480
Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu Ile Pro
485 490 495
Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro Ser Leu
500 505 510
Glu Asp Glu Ala Ala Gly His Val Thr Gln Ala Arg Met Val Ser Lys
515 520 525
Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly Ala Asp
530 535 540
Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro Gly Gln
545 550 555 560
Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro Pro Ala
565 570 575
Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly Asp Arg
580 585 590
Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser Arg Ser
595 600 605
Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys Lys Val
610 615 620
Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys Ser Arg
625 630 635 640
Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val Lys Ser
645 650 655
Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly Gly Lys
660 665 670
Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln Ser Lys
675 680 685
Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly Ser Val
690 695 700
Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser Lys Cys
705 710 715 720
Gly Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln Val Glu
725 730 735
Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser Lys Ile
740 745 750
Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn Lys Lys
755 760 765
Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala Lys Thr
770 775 780
Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser Gly Asp
785 790 795 800
Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser Ile Asp
805 810 815
Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val Ser Ala
820 825 830
Ser Leu Ala Lys Gln Gly Leu Arg Cys Ser Arg Arg Tyr Arg Gly Pro
835 840 845
Gly Ile His Arg Ile
850
<210> 68
<211> 971
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 68
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Gln Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu
500 505 510
Asp His Ala Gly Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly
515 520 525
Tyr Thr Met His Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys
530 535 540
Glu Ser Pro Leu Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly
545 550 555 560
Ser Glu Thr Ser Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr
565 570 575
Ala Pro Leu Val Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln
580 585 590
Pro His Thr Glu Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile
595 600 605
Gly Asp Thr Pro Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln
610 615 620
Ala Arg Met Val Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys
625 630 635 640
Lys Ala Lys Gly Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly
645 650 655
Ala Ala Pro Pro Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro
660 665 670
Ala Lys Thr Pro Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro
675 680 685
Pro Lys Ser Gly Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly
690 695 700
Thr Pro Gly Ser Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr
705 710 715 720
Arg Glu Pro Lys Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro
725 730 735
Ser Ser Ala Lys Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp
740 745 750
Leu Lys Asn Val Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His
755 760 765
Gln Pro Gly Gly Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu
770 775 780
Ser Asn Val Gln Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val
785 790 795 800
Pro Gly Gly Gly Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser
805 810 815
Lys Val Thr Ser Lys Cys Gly Ser Leu Gly Asn Ile His His Lys Pro
820 825 830
Gly Gly Gly Gln Val Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp
835 840 845
Arg Val Gln Ser Lys Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro
850 855 860
Gly Gly Gly Asn Lys Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu
865 870 875 880
Asn Ala Lys Ala Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser
885 890 895
Pro Val Val Ser Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser
900 905 910
Ser Thr Gly Ser Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu
915 920 925
Ala Asp Glu Val Ser Ala Ser Leu Ala Lys Gln Gly Leu Ala Thr Leu
930 935 940
Asp His Asn Gln Pro Tyr His Ile Cys Arg Gly Phe Thr Cys Phe Lys
945 950 955 960
Lys Pro Pro Thr Pro Pro Pro Glu Pro Glu Thr
965 970
<210> 69
<211> 583
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 69
Met His Thr Leu Tyr Ala Pro Gly Gly Tyr Asp Ile Met Gly Trp Leu
1 5 10 15
Ile Gln Ile Met Asn Arg Pro Asn Pro Gln Val Glu Leu Gly Pro Val
20 25 30
Asp Thr Ser Cys Ala Leu Ile Leu Cys Asp Leu Lys Gln Lys Asp Thr
35 40 45
Pro Ile Val Tyr Ala Ser Glu Ala Phe Leu Tyr Met Thr Gly Tyr Ser
50 55 60
Asn Ala Glu Val Leu Gly Arg Asn Cys Arg Phe Leu Gln Ser Pro Asp
65 70 75 80
Gly Met Val Lys Pro Lys Ser Thr Arg Lys Tyr Val Asp Ser Asn Thr
85 90 95
Ile Asn Thr Met Arg Lys Ala Ile Asp Arg Asn Ala Glu Val Gln Val
100 105 110
Glu Val Val Asn Phe Lys Lys Asn Gly Gln Arg Phe Val Asn Phe Leu
115 120 125
Thr Met Ile Pro Val Arg Asp Glu Thr Gly Glu Met Ala Glu Pro Arg
130 135 140
Gln Glu Phe Glu Val Met Glu Asp His Ala Gly Thr Tyr Gly Leu Gly
145 150 155 160
Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His Gln Asp Gln Glu Gly
165 170 175
Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu Gln Thr Pro Thr Glu
180 185 190
Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser Asp Ala Lys Ser Thr
195 200 205
Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val Asp Glu Gly Ala Pro
210 215 220
Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu Ile Pro Glu Gly Thr
225 230 235 240
Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro Ser Leu Glu Asp Glu
245 250 255
Ala Ala Gly His Val Thr Gln Ala Arg Met Val Ser Lys Ser Lys Asp
260 265 270
Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly Ala Asp Gly Lys Thr
275 280 285
Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro Gly Gln Lys Gly Gln
290 295 300
Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro Pro Ala Pro Lys Thr
305 310 315 320
Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly Asp Arg Ser Gly Tyr
325 330 335
Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser Arg Ser Arg Thr Pro
340 345 350
Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys Lys Val Ala Val Val
355 360 365
Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys Ser Arg Leu Gln Thr
370 375 380
Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val Lys Ser Lys Ile Gly
385 390 395 400
Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly Gly Lys Val Gln Ile
405 410 415
Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln Ser Lys Cys Gly Ser
420 425 430
Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly Ser Val Gln Ile Val
435 440 445
Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser Lys Cys Gly Ser Leu
450 455 460
Gly Asn Ile His His Lys Pro Gly Gly Gly Gln Val Glu Val Lys Ser
465 470 475 480
Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser Lys Ile Gly Ser Leu
485 490 495
Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn Lys Lys Ile Glu Thr
500 505 510
His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala Lys Thr Asp His Gly
515 520 525
Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser Gly Asp Thr Ser Pro
530 535 540
Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser Ile Asp Met Val Asp
545 550 555 560
Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val Ser Ala Ser Leu Ala
565 570 575
Lys Gln Gly Leu His Arg Ile
580
<210> 70
<211> 969
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 70
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
1 5 10 15
Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His
20 25 30
Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu
35 40 45
Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser
50 55 60
Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val
65 70 75 80
Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu
85 90 95
Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro
100 105 110
Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln Ala Arg Met Val
115 120 125
Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly
130 135 140
Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro
145 150 155 160
Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro
165 170 175
Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly
180 185 190
Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser
195 200 205
Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys
210 215 220
Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys
225 230 235 240
Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val
245 250 255
Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly
260 265 270
Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln
275 280 285
Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly
290 295 300
Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser
305 310 315 320
Lys Cys Gly Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln
325 330 335
Val Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser
340 345 350
Lys Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn
355 360 365
Lys Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala
370 375 380
Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser
385 390 395 400
Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser
405 410 415
Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val
420 425 430
Ser Ala Ser Leu Ala Lys Gln Gly Leu Met Lys Met Asp Lys Lys Thr
435 440 445
Ile Val Trp Phe Arg Arg Asp Leu Arg Ile Glu Asp Asn Pro Ala Leu
450 455 460
Ala Ala Ala Ala His Glu Gly Ser Val Phe Pro Val Phe Ile Trp Cys
465 470 475 480
Pro Glu Glu Glu Gly Gln Phe Tyr Pro Gly Arg Ala Ser Arg Trp Trp
485 490 495
Met Lys Gln Ser Leu Ala His Leu Ser Gln Ser Leu Lys Ala Leu Gly
500 505 510
Ser Asp Leu Thr Leu Ile Lys Thr His Asn Thr Ile Ser Ala Ile Leu
515 520 525
Asp Cys Ile Arg Val Thr Gly Ala Thr Lys Val Val Phe Asn His Leu
530 535 540
Tyr Asp Pro Val Ser Leu Val Arg Asp His Thr Val Lys Glu Lys Leu
545 550 555 560
Val Glu Arg Gly Ile Ser Val Gln Ser Tyr Asn Gly Asp Leu Leu Tyr
565 570 575
Glu Pro Trp Glu Ile Tyr Cys Glu Lys Gly Lys Pro Phe Thr Ser Phe
580 585 590
Asn Ser Tyr Trp Lys Lys Cys Leu Asp Met Ser Ile Glu Ser Val Met
595 600 605
Leu Pro Pro Pro Trp Arg Leu Met Pro Ile Thr Ala Ala Ala Glu Ala
610 615 620
Ile Trp Ala Cys Ser Ile Glu Glu Leu Gly Leu Glu Asn Glu Ala Glu
625 630 635 640
Lys Pro Ser Asn Ala Leu Leu Thr Arg Ala Trp Ser Pro Gly Trp Ser
645 650 655
Asn Ala Asp Lys Leu Leu Asn Glu Phe Ile Glu Lys Gln Leu Ile Asp
660 665 670
Tyr Ala Lys Asn Ser Lys Lys Val Val Gly Asn Ser Thr Ser Leu Leu
675 680 685
Ser Pro Tyr Leu His Phe Gly Glu Ile Ser Val Arg His Val Phe Gln
690 695 700
Cys Ala Arg Met Lys Gln Ile Ile Trp Ala Arg Asp Lys Asn Ser Glu
705 710 715 720
Gly Glu Glu Ser Ala Asp Leu Phe Leu Arg Gly Ile Gly Leu Arg Glu
725 730 735
Tyr Ser Arg Tyr Ile Cys Phe Asn Phe Pro Phe Thr His Glu Gln Ser
740 745 750
Leu Leu Ser His Leu Arg Phe Phe Pro Trp Asp Ala Asp Val Asp Lys
755 760 765
Phe Lys Ala Trp Arg Gln Gly Arg Thr Gly Tyr Pro Leu Val Asp Ala
770 775 780
Gly Met Arg Glu Leu Trp Ala Thr Gly Trp Met His Asn Arg Ile Arg
785 790 795 800
Val Ile Val Ser Ser Phe Ala Val Lys Phe Leu Leu Leu Pro Trp Lys
805 810 815
Trp Gly Met Lys Tyr Phe Trp Asp Thr Leu Leu Asp Ala Asp Leu Glu
820 825 830
Cys Asp Ile Leu Gly Trp Gln Tyr Ile Ser Gly Ser Ile Pro Asp Gly
835 840 845
His Glu Leu Asp Arg Leu Asp Asn Pro Ala Leu Gln Gly Ala Lys Tyr
850 855 860
Asp Pro Glu Gly Glu Tyr Ile Arg Gln Trp Leu Pro Glu Leu Ala Arg
865 870 875 880
Leu Pro Thr Glu Trp Ile His His Pro Trp Asp Ala Pro Leu Thr Val
885 890 895
Leu Lys Ala Ser Gly Val Glu Leu Gly Thr Asn Tyr Ala Lys Pro Ile
900 905 910
Val Asp Ile Asp Thr Ala Arg Glu Leu Leu Ala Lys Ala Ile Ser Arg
915 920 925
Thr Arg Gly Ala Gln Ile Met Ile Gly Ala Ala Ala Thr Leu Asp His
930 935 940
Asn Gln Pro Tyr His Ile Cys Arg Gly Phe Thr Cys Phe Lys Lys Pro
945 950 955 960
Pro Thr Pro Pro Pro Glu Pro Glu Thr
965
<210> 71
<211> 604
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 71
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
1 5 10 15
Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His
20 25 30
Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu
35 40 45
Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser
50 55 60
Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val
65 70 75 80
Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu
85 90 95
Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro
100 105 110
Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln Ala Arg Met Val
115 120 125
Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly
130 135 140
Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro
145 150 155 160
Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro
165 170 175
Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly
180 185 190
Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser
195 200 205
Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys
210 215 220
Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys
225 230 235 240
Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val
245 250 255
Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly
260 265 270
Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln
275 280 285
Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly
290 295 300
Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser
305 310 315 320
Lys Cys Gly Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln
325 330 335
Val Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser
340 345 350
Lys Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn
355 360 365
Lys Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala
370 375 380
Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser
385 390 395 400
Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser
405 410 415
Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val
420 425 430
Ser Ala Ser Leu Ala Lys Gln Gly Leu Pro Asp Tyr Ser Leu Val Lys
435 440 445
Ala Leu Gln Met Ala Gln Gln Asn Phe Val Ile Thr Asp Ala Ser Leu
450 455 460
Pro Asp Asn Pro Ile Val Tyr Ala Ser Arg Gly Phe Leu Thr Leu Thr
465 470 475 480
Gly Tyr Ser Leu Asp Gln Ile Leu Gly Arg Asn Cys Arg Phe Leu Gln
485 490 495
Gly Pro Glu Thr Asp Pro Arg Ala Val Asp Lys Ile Arg Asn Ala Ile
500 505 510
Thr Lys Gly Val Asp Thr Ser Val Cys Leu Leu Asn Tyr Arg Gln Asp
515 520 525
Gly Thr Thr Phe Trp Asn Leu Phe Phe Val Ala Gly Leu Arg Asp Ser
530 535 540
Lys Gly Asn Ile Val Asn Tyr Val Gly Val Gln Ser Lys Val Ser Glu
545 550 555 560
Asp Tyr Ala Lys Leu Leu Val Asn Glu Gln Asn Ile Glu Tyr Lys Gly
565 570 575
Val Arg Thr Ser Asn Met Leu Arg Arg Lys Pro Gly Leu Gln Ser Thr
580 585 590
Val Pro Arg Ala Arg Asp Pro Pro Asp Leu Asp Asn
595 600
<210> 72
<211> 607
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 72
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
1 5 10 15
Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His
20 25 30
Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu
35 40 45
Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser
50 55 60
Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val
65 70 75 80
Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu
85 90 95
Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro
100 105 110
Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln Ala Arg Met Val
115 120 125
Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly
130 135 140
Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro
145 150 155 160
Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro
165 170 175
Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly
180 185 190
Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser
195 200 205
Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys
210 215 220
Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys
225 230 235 240
Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val
245 250 255
Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly
260 265 270
Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln
275 280 285
Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly
290 295 300
Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser
305 310 315 320
Lys Cys Gly Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln
325 330 335
Val Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser
340 345 350
Lys Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn
355 360 365
Lys Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala
370 375 380
Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser
385 390 395 400
Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser
405 410 415
Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val
420 425 430
Ser Ala Ser Leu Ala Lys Gln Gly Leu His Thr Leu Tyr Ala Pro Gly
435 440 445
Gly Tyr Asp Ile Met Gly Trp Leu Ile Gln Ile Met Asn Arg Pro Asn
450 455 460
Pro Gln Val Glu Leu Gly Pro Val Asp Thr Ser Cys Ala Leu Ile Leu
465 470 475 480
Cys Asp Leu Lys Gln Lys Asp Thr Pro Ile Val Tyr Ala Ser Glu Ala
485 490 495
Phe Leu Tyr Met Thr Gly Tyr Ser Asn Ala Glu Val Leu Gly Arg Asn
500 505 510
Cys Arg Phe Leu Gln Ser Pro Asp Gly Met Val Lys Pro Lys Ser Thr
515 520 525
Arg Lys Tyr Val Asp Ser Asn Thr Ile Asn Thr Met Arg Lys Ala Ile
530 535 540
Asp Arg Asn Ala Glu Val Gln Val Glu Val Val Asn Phe Lys Lys Asn
545 550 555 560
Gly Gln Arg Phe Val Asn Phe Leu Thr Met Ile Pro Val Arg Asp Glu
565 570 575
Thr Gly Glu Tyr Arg Tyr Ser Met Gly Phe Gln Cys Glu Thr Glu Leu
580 585 590
Gln Ser Thr Val Pro Arg Ala Arg Asp Pro Pro Asp Leu Asp Asn
595 600 605
<210> 73
<211> 607
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 73
Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly
1 5 10 15
Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His
20 25 30
Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu
35 40 45
Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser
50 55 60
Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val
65 70 75 80
Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu
85 90 95
Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro
100 105 110
Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln Ala Arg Met Val
115 120 125
Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly
130 135 140
Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro
145 150 155 160
Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro
165 170 175
Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly
180 185 190
Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser
195 200 205
Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys
210 215 220
Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys
225 230 235 240
Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val
245 250 255
Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly
260 265 270
Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln
275 280 285
Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly
290 295 300
Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser
305 310 315 320
Lys Cys Gly Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln
325 330 335
Val Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser
340 345 350
Lys Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn
355 360 365
Lys Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala
370 375 380
Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser
385 390 395 400
Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser
405 410 415
Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val
420 425 430
Ser Ala Ser Leu Ala Lys Gln Gly Leu His Thr Leu Tyr Ala Pro Gly
435 440 445
Gly Tyr Asp Ile Met Gly Trp Leu Ile Gln Ile Met Asn Arg Pro Asn
450 455 460
Pro Gln Val Glu Leu Gly Pro Val Asp Thr Ser Cys Ala Leu Ile Leu
465 470 475 480
Cys Asp Leu Lys Gln Lys Asp Thr Pro Ile Val Tyr Ala Ser Glu Ala
485 490 495
Phe Leu Tyr Met Thr Gly Tyr Ser Asn Ala Glu Val Leu Gly Arg Asn
500 505 510
Cys Arg Phe Leu Gln Ser Pro Asp Gly Met Val Lys Pro Lys Ser Thr
515 520 525
Arg Lys Tyr Val Asp Ser Asn Thr Ile Asn Thr Met Arg Lys Ala Ile
530 535 540
Asp Arg Asn Ala Glu Val Gln Val Glu Val Val Asn Phe Lys Lys Asn
545 550 555 560
Gly Gln Arg Phe Val Asn Phe Leu Thr Met Ile Pro Val Arg Asp Glu
565 570 575
Thr Gly Glu Tyr Arg Tyr Ser Met Gly Phe Gln Cys Glu Thr Glu Leu
580 585 590
Gln Ser Thr Val Pro Arg Ala Arg Asp Pro Pro Asp Leu Asp Asn
595 600 605
<210> 74
<211> 608
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 74
Met Pro Asp Tyr Ser Leu Val Lys Ala Leu Gln Met Ala Gln Gln Asn
1 5 10 15
Phe Val Ile Thr Asp Ala Ser Leu Pro Asp Asn Pro Ile Val Tyr Ala
20 25 30
Ser Arg Gly Phe Leu Thr Leu Thr Gly Tyr Ser Leu Asp Gln Ile Leu
35 40 45
Gly Arg Asn Cys Arg Phe Leu Gln Gly Pro Glu Thr Asp Pro Arg Ala
50 55 60
Val Asp Lys Ile Arg Asn Ala Ile Thr Lys Gly Val Asp Thr Ser Val
65 70 75 80
Cys Leu Leu Asn Tyr Arg Gln Asp Gly Thr Thr Phe Trp Asn Leu Phe
85 90 95
Phe Val Ala Gly Leu Arg Asp Ser Lys Gly Asn Ile Val Asn Tyr Val
100 105 110
Gly Val Gln Ser Lys Val Ser Glu Asp Tyr Ala Lys Leu Leu Val Asn
115 120 125
Glu Gln Asn Ile Glu Tyr Lys Gly Val Arg Thr Ser Asn Met Leu Arg
130 135 140
Arg Lys Pro Gly Ser Leu Met Ala Glu Pro Arg Gln Glu Phe Glu Val
145 150 155 160
Met Glu Asp His Ala Gly Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln
165 170 175
Gly Gly Tyr Thr Met His Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly
180 185 190
Leu Lys Glu Ser Pro Leu Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu
195 200 205
Pro Gly Ser Glu Thr Ser Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp
210 215 220
Val Thr Ala Pro Leu Val Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala
225 230 235 240
Ala Gln Pro His Thr Glu Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala
245 250 255
Gly Ile Gly Asp Thr Pro Ser Leu Glu Asp Glu Ala Ala Gly His Val
260 265 270
Thr Gln Ala Arg Met Val Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp
275 280 285
Asp Lys Lys Ala Lys Gly Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro
290 295 300
Arg Gly Ala Ala Pro Pro Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg
305 310 315 320
Ile Pro Ala Lys Thr Pro Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly
325 330 335
Glu Pro Pro Lys Ser Gly Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser
340 345 350
Pro Gly Thr Pro Gly Ser Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro
355 360 365
Pro Thr Arg Glu Pro Lys Lys Val Ala Val Val Arg Thr Pro Pro Lys
370 375 380
Ser Pro Ser Ser Ala Lys Ser Arg Leu Gln Thr Ala Pro Val Pro Met
385 390 395 400
Pro Asp Leu Lys Asn Val Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu
405 410 415
Lys His Gln Pro Gly Gly Gly Lys Val Gln Ile Ile Asn Lys Lys Leu
420 425 430
Asp Leu Ser Asn Val Gln Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys
435 440 445
His Val Pro Gly Gly Gly Ser Val Gln Ile Val Tyr Lys Pro Val Asp
450 455 460
Leu Ser Lys Val Thr Ser Lys Cys Gly Ser Leu Gly Asn Ile His His
465 470 475 480
Lys Pro Gly Gly Gly Gln Val Glu Val Lys Ser Glu Lys Leu Asp Phe
485 490 495
Lys Asp Arg Val Gln Ser Lys Ile Gly Ser Leu Asp Asn Ile Thr His
500 505 510
Val Pro Gly Gly Gly Asn Lys Lys Ile Glu Thr His Lys Leu Thr Phe
515 520 525
Arg Glu Asn Ala Lys Ala Lys Thr Asp His Gly Ala Glu Ile Val Tyr
530 535 540
Lys Ser Pro Val Val Ser Gly Asp Thr Ser Pro Arg His Leu Ser Asn
545 550 555 560
Val Ser Ser Thr Gly Ser Ile Asp Met Val Asp Ser Pro Gln Leu Ala
565 570 575
Thr Leu Ala Asp Glu Val Ser Ala Ser Leu Ala Lys Gln Gly Leu Ser
580 585 590
Asn Ser Ala Val Asp Gly Thr Ala Gly Pro Gly Ser Thr Gly Ser Arg
595 600 605
<210> 75
<211> 1159
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 75
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Arg Gly Met Ser Glu Tyr Ile Arg Val Thr Glu Asp Glu
500 505 510
Asn Asp Glu Pro Ile Glu Ile Pro Ser Glu Asp Asp Gly Thr Val Leu
515 520 525
Leu Ser Thr Val Thr Ala Gln Phe Pro Gly Ala Cys Gly Leu Arg Tyr
530 535 540
Arg Asn Pro Val Ser Gln Cys Met Arg Gly Val Arg Leu Val Glu Gly
545 550 555 560
Ile Leu His Ala Pro Asp Ala Gly Trp Gly Asn Leu Val Tyr Val Val
565 570 575
Asn Tyr Pro Lys Asp Asn Lys Arg Lys Met Asp Glu Thr Asp Ala Ser
580 585 590
Ser Ala Val Lys Val Lys Arg Ala Val Gln Lys Thr Ser Asp Leu Ile
595 600 605
Val Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp Leu Lys Glu Tyr
610 615 620
Phe Ser Thr Phe Gly Glu Val Leu Met Val Gln Val Lys Lys Asp Leu
625 630 635 640
Lys Thr Gly His Ser Lys Gly Leu Gly Phe Val Arg Phe Thr Glu Tyr
645 650 655
Glu Thr Gln Val Lys Val Met Ser Gln Arg His Met Ile Asp Gly Arg
660 665 670
Trp Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser Gln Asp Glu Pro
675 680 685
Leu Arg Ser Arg Lys Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr
690 695 700
Glu Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp
705 710 715 720
Val Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala
725 730 735
Asp Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys
740 745 750
Gly Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn
755 760 765
Arg Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe
770 775 780
Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu
785 790 795 800
Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala
805 810 815
Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln
820 825 830
Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser
835 840 845
Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro
850 855 860
Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser
865 870 875 880
Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser
885 890 895
Gly Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly
900 905 910
Trp Gly Met Ser Arg Asp Pro Pro Val Ala Thr Met Val Ser Lys Gly
915 920 925
Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val
930 935 940
His Met Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu
945 950 955 960
Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val
965 970 975
Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln
980 985 990
Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro
995 1000 1005
Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg
1010 1015 1020
Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp
1025 1030 1035
Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg
1040 1045 1050
Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr
1055 1060 1065
Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
1070 1075 1080
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly
1085 1090 1095
Gly His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys
1100 1105 1110
Pro Val Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp
1115 1120 1125
Ile Thr Ser His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu
1130 1135 1140
Arg Ala Glu Gly Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr
1145 1150 1155
Lys
<210> 76
<211> 1159
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 76
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Arg Gly Met Ser Glu Tyr Ile Arg Val Thr Glu Asp Glu
500 505 510
Asn Asp Glu Pro Ile Glu Ile Pro Ser Glu Asp Asp Gly Thr Val Leu
515 520 525
Leu Ser Thr Val Thr Ala Gln Phe Pro Gly Ala Cys Gly Leu Arg Tyr
530 535 540
Arg Asn Pro Val Ser Gln Cys Met Arg Gly Val Arg Leu Val Glu Gly
545 550 555 560
Ile Leu His Ala Pro Asp Ala Gly Trp Gly Asn Leu Val Tyr Val Val
565 570 575
Asn Tyr Pro Lys Asp Asn Lys Arg Lys Met Asp Glu Thr Asp Ala Ser
580 585 590
Ser Ala Val Lys Val Lys Arg Ala Val Gln Lys Thr Ser Asp Leu Ile
595 600 605
Val Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp Leu Lys Glu Tyr
610 615 620
Phe Ser Thr Phe Gly Glu Val Leu Met Val Gln Val Lys Lys Asp Leu
625 630 635 640
Lys Thr Gly His Ser Lys Gly Phe Gly Phe Val Arg Phe Thr Glu Tyr
645 650 655
Glu Thr Gln Val Lys Val Met Ser Gln Arg His Met Ile Asp Gly Arg
660 665 670
Trp Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser Gln Asp Glu Pro
675 680 685
Leu Arg Ser Arg Lys Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr
690 695 700
Glu Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp
705 710 715 720
Val Phe Ile Pro Lys Pro Phe Arg Ala Leu Ala Phe Val Thr Phe Ala
725 730 735
Asp Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys
740 745 750
Gly Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn
755 760 765
Arg Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe
770 775 780
Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu
785 790 795 800
Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala
805 810 815
Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln
820 825 830
Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser
835 840 845
Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro
850 855 860
Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser
865 870 875 880
Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser
885 890 895
Gly Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly
900 905 910
Trp Gly Met Ser Arg Asp Pro Pro Val Ala Thr Met Val Ser Lys Gly
915 920 925
Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val
930 935 940
His Met Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu
945 950 955 960
Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val
965 970 975
Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln
980 985 990
Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro
995 1000 1005
Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg
1010 1015 1020
Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp
1025 1030 1035
Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg
1040 1045 1050
Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr
1055 1060 1065
Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly
1070 1075 1080
Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly
1085 1090 1095
Gly His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys
1100 1105 1110
Pro Val Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp
1115 1120 1125
Ile Thr Ser His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu
1130 1135 1140
Arg Ala Glu Gly Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr
1145 1150 1155
Lys
<210> 77
<211> 1157
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 77
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Gln Met Ser Glu Tyr Ile Arg Val Thr Glu Asp Glu Asn
500 505 510
Asp Glu Pro Ile Glu Ile Pro Ser Glu Asp Asp Gly Thr Val Leu Leu
515 520 525
Ser Thr Val Thr Ala Gln Phe Pro Gly Ala Cys Gly Leu Arg Tyr Arg
530 535 540
Asn Pro Val Ser Gln Cys Met Arg Gly Val Arg Leu Val Glu Gly Ile
545 550 555 560
Leu His Ala Pro Asp Ala Gly Trp Gly Asn Leu Val Tyr Val Val Asn
565 570 575
Tyr Pro Lys Asp Asn Lys Arg Lys Met Asp Glu Thr Asp Ala Ser Ser
580 585 590
Ala Val Lys Val Lys Arg Ala Val Gln Lys Thr Ser Asp Leu Ile Val
595 600 605
Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp Leu Lys Glu Tyr Phe
610 615 620
Ser Thr Phe Gly Glu Val Leu Met Val Gln Val Lys Lys Asp Leu Lys
625 630 635 640
Thr Gly His Ser Lys Gly Phe Gly Phe Val Arg Phe Thr Glu Tyr Glu
645 650 655
Thr Gln Val Lys Val Met Ser Gln Arg His Met Ile Asp Gly Arg Trp
660 665 670
Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser Gln Asp Glu Pro Leu
675 680 685
Arg Ser Arg Lys Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr Glu
690 695 700
Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val
705 710 715 720
Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala Asp
725 730 735
Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly
740 745 750
Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg
755 760 765
Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly
770 775 780
Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly
785 790 795 800
Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe
805 810 815
Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser
820 825 830
Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly
835 840 845
Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn
850 855 860
Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly
865 870 875 880
Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly
885 890 895
Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ala Ala Gly Trp
900 905 910
Gly Met Trp Asp Pro Pro Val Ala Thr Met Val Ser Lys Gly Glu Glu
915 920 925
Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val His Met
930 935 940
Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly Glu
945 950 955 960
Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr Lys
965 970 975
Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe Met
980 985 990
Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp Tyr
995 1000 1005
Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met
1010 1015 1020
Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser Ser
1025 1030 1035
Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr
1040 1045 1050
Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly
1055 1060 1065
Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu
1070 1075 1080
Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His
1085 1090 1095
Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
1100 1105 1110
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr
1115 1120 1125
Ser His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala
1130 1135 1140
Glu Gly Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys
1145 1150 1155
<210> 78
<211> 1157
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 78
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Gln Met Ser Glu Tyr Ile Arg Val Thr Glu Asp Glu Asn
500 505 510
Asp Glu Pro Ile Glu Ile Pro Ser Glu Asp Asp Gly Thr Val Leu Leu
515 520 525
Ser Thr Val Thr Ala Gln Phe Pro Gly Ala Cys Gly Leu Arg Tyr Arg
530 535 540
Asn Pro Val Ser Gln Cys Met Arg Gly Val Arg Leu Val Glu Gly Ile
545 550 555 560
Leu His Ala Pro Asp Ala Gly Trp Gly Asn Leu Val Tyr Val Val Asn
565 570 575
Tyr Pro Lys Asp Asn Lys Arg Lys Met Asp Glu Thr Asp Ala Ser Ser
580 585 590
Ala Val Lys Val Lys Arg Ala Val Gln Lys Thr Ser Asp Leu Ile Val
595 600 605
Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp Leu Lys Glu Tyr Phe
610 615 620
Ser Thr Phe Gly Glu Val Leu Met Val Gln Val Lys Lys Asp Leu Lys
625 630 635 640
Thr Gly His Ser Lys Gly Phe Gly Phe Val Arg Phe Thr Glu Tyr Glu
645 650 655
Thr Gln Val Lys Val Met Ser Gln Arg His Met Ile Asp Gly Arg Trp
660 665 670
Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser Gln Asp Glu Pro Leu
675 680 685
Arg Ser Arg Lys Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr Glu
690 695 700
Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val
705 710 715 720
Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala Asp
725 730 735
Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly
740 745 750
Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg
755 760 765
Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly
770 775 780
Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly
785 790 795 800
Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe
805 810 815
Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser
820 825 830
Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly
835 840 845
Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn
850 855 860
Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly
865 870 875 880
Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly
885 890 895
Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Asp Asp Gly Trp
900 905 910
Gly Met Trp Asp Pro Pro Val Ala Thr Met Val Ser Lys Gly Glu Glu
915 920 925
Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val His Met
930 935 940
Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly Glu
945 950 955 960
Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr Lys
965 970 975
Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe Met
980 985 990
Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp Tyr
995 1000 1005
Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met
1010 1015 1020
Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser Ser
1025 1030 1035
Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr
1040 1045 1050
Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly
1055 1060 1065
Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu
1070 1075 1080
Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His
1085 1090 1095
Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
1100 1105 1110
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr
1115 1120 1125
Ser His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala
1130 1135 1140
Glu Gly Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys
1145 1150 1155
<210> 79
<211> 1156
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 79
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Gln Met Ser Glu Tyr Ile Arg Val Thr Glu Asp Glu Asn
500 505 510
Asp Glu Pro Ile Glu Ile Pro Ser Glu Asp Asp Gly Thr Val Leu Leu
515 520 525
Ser Thr Val Thr Ala Gln Phe Pro Gly Ala Cys Gly Leu Arg Tyr Arg
530 535 540
Asn Pro Val Ser Gln Cys Met Arg Gly Val Arg Leu Val Glu Gly Ile
545 550 555 560
Leu His Ala Pro Asp Ala Gly Trp Gly Asn Leu Val Tyr Val Val Asn
565 570 575
Tyr Pro Lys Asp Asn Lys Arg Lys Met Asp Glu Thr Asp Ala Ser Ser
580 585 590
Ala Val Lys Val Lys Arg Ala Val Gln Lys Thr Ser Asp Leu Ile Val
595 600 605
Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp Leu Lys Glu Tyr Phe
610 615 620
Ser Thr Phe Gly Glu Val Leu Met Val Gln Val Lys Lys Asp Leu Lys
625 630 635 640
Thr Gly His Ser Lys Gly Phe Gly Phe Val Arg Phe Thr Glu Tyr Glu
645 650 655
Thr Gln Val Lys Val Met Ser Gln Arg His Met Ile Asp Gly Arg Trp
660 665 670
Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser Gln Asp Glu Pro Leu
675 680 685
Arg Ser Arg Lys Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr Glu
690 695 700
Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val
705 710 715 720
Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala Asp
725 730 735
Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly
740 745 750
Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg
755 760 765
Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly
770 775 780
Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly
785 790 795 800
Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe
805 810 815
Ser Ile Asn Pro Val Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser
820 825 830
Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly
835 840 845
Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn
850 855 860
Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly
865 870 875 880
Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly
885 890 895
Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp
900 905 910
Gly Trp Asp Pro Pro Val Ala Thr Met Val Ser Lys Gly Glu Glu Asp
915 920 925
Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val His Met Glu
930 935 940
Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly Glu Gly
945 950 955 960
Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr Lys Gly
965 970 975
Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe Met Tyr
980 985 990
Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp Tyr Leu
995 1000 1005
Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met Asn
1010 1015 1020
Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser Ser Leu
1025 1030 1035
Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr Asn
1040 1045 1050
Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp
1055 1060 1065
Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys
1070 1075 1080
Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His Tyr
1085 1090 1095
Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln
1100 1105 1110
Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
1115 1120 1125
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu
1130 1135 1140
Gly Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys
1145 1150 1155
<210> 80
<211> 1156
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 80
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Gln Met Ser Glu Tyr Ile Arg Val Thr Glu Asp Glu Asn
500 505 510
Asp Glu Pro Ile Glu Ile Pro Ser Glu Asp Asp Gly Thr Val Leu Leu
515 520 525
Ser Thr Val Thr Ala Gln Phe Pro Gly Ala Cys Gly Leu Arg Tyr Arg
530 535 540
Asn Pro Val Ser Gln Cys Met Arg Gly Val Arg Leu Val Glu Gly Ile
545 550 555 560
Leu His Ala Pro Asp Ala Gly Trp Gly Asn Leu Val Tyr Val Val Asn
565 570 575
Tyr Pro Lys Asp Asn Lys Arg Lys Met Asp Glu Thr Asp Ala Ser Ser
580 585 590
Ala Val Lys Val Lys Arg Ala Val Gln Lys Thr Ser Asp Leu Ile Val
595 600 605
Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp Leu Lys Glu Tyr Phe
610 615 620
Ser Thr Phe Gly Glu Val Leu Met Val Gln Val Lys Lys Asp Leu Lys
625 630 635 640
Thr Gly His Ser Lys Gly Phe Gly Phe Val Arg Phe Thr Glu Tyr Glu
645 650 655
Thr Gln Val Lys Val Met Ser Gln Arg His Met Ile Asp Gly Arg Trp
660 665 670
Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser Gln Asp Glu Pro Leu
675 680 685
Arg Ser Arg Lys Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr Glu
690 695 700
Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val
705 710 715 720
Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala Asp
725 730 735
Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly
740 745 750
Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg
755 760 765
Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly
770 775 780
Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly
785 790 795 800
Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe
805 810 815
Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser
820 825 830
Ser Trp Gly Met Val Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly
835 840 845
Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn
850 855 860
Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly
865 870 875 880
Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly
885 890 895
Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp
900 905 910
Gly Trp Asp Pro Pro Val Ala Thr Met Val Ser Lys Gly Glu Glu Asp
915 920 925
Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val His Met Glu
930 935 940
Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly Glu Gly
945 950 955 960
Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr Lys Gly
965 970 975
Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe Met Tyr
980 985 990
Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp Tyr Leu
995 1000 1005
Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met Asn
1010 1015 1020
Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser Ser Leu
1025 1030 1035
Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr Asn
1040 1045 1050
Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp
1055 1060 1065
Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys
1070 1075 1080
Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His Tyr
1085 1090 1095
Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln
1100 1105 1110
Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser
1115 1120 1125
His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu
1130 1135 1140
Gly Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys
1145 1150 1155
<210> 81
<211> 884
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 81
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Gln Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn
500 505 510
Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn
515 520 525
Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser
530 535 540
Ile Asn Pro Val Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser
545 550 555 560
Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro
565 570 575
Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln
580 585 590
Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala
595 600 605
Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe
610 615 620
Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly
625 630 635 640
Met Arg Asp Pro Pro Val Ala Thr Met Val Ser Lys Gly Glu Glu Asp
645 650 655
Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val His Met Glu
660 665 670
Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly Glu Gly
675 680 685
Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr Lys Gly
690 695 700
Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe Met Tyr
705 710 715 720
Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp Tyr Leu
725 730 735
Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met Asn Phe
740 745 750
Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser Ser Leu Gln Asp
755 760 765
Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr Asn Phe Pro Ser
770 775 780
Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp Glu Ala Ser Ser
785 790 795 800
Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys Gly Glu Ile Lys Gln
805 810 815
Arg Leu Lys Leu Lys Asp Gly Gly His Tyr Asp Ala Glu Val Lys Thr
820 825 830
Thr Tyr Lys Ala Lys Lys Pro Val Gln Leu Pro Gly Ala Tyr Asn Val
835 840 845
Asn Ile Lys Leu Asp Ile Thr Ser His Asn Glu Asp Tyr Thr Ile Val
850 855 860
Glu Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr Gly Gly Met Asp
865 870 875 880
Glu Leu Tyr Lys
<210> 82
<211> 884
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 82
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Gln Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn
500 505 510
Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn
515 520 525
Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser
530 535 540
Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser
545 550 555 560
Trp Gly Met Val Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro
565 570 575
Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln
580 585 590
Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala
595 600 605
Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe
610 615 620
Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly
625 630 635 640
Met Arg Asp Pro Pro Val Ala Thr Met Val Ser Lys Gly Glu Glu Asp
645 650 655
Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val His Met Glu
660 665 670
Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly Glu Gly
675 680 685
Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr Lys Gly
690 695 700
Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe Met Tyr
705 710 715 720
Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp Tyr Leu
725 730 735
Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met Asn Phe
740 745 750
Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser Ser Leu Gln Asp
755 760 765
Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr Asn Phe Pro Ser
770 775 780
Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp Glu Ala Ser Ser
785 790 795 800
Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys Gly Glu Ile Lys Gln
805 810 815
Arg Leu Lys Leu Lys Asp Gly Gly His Tyr Asp Ala Glu Val Lys Thr
820 825 830
Thr Tyr Lys Ala Lys Lys Pro Val Gln Leu Pro Gly Ala Tyr Asn Val
835 840 845
Asn Ile Lys Leu Asp Ile Thr Ser His Asn Glu Asp Tyr Thr Ile Val
850 855 860
Glu Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr Gly Gly Met Asp
865 870 875 880
Glu Leu Tyr Lys
<210> 83
<211> 884
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 83
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Gln Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn
500 505 510
Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn
515 520 525
Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser
530 535 540
Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser
545 550 555 560
Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro
565 570 575
Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln
580 585 590
Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala
595 600 605
Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe
610 615 620
Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ala Ala Gly Trp Gly
625 630 635 640
Met Arg Asp Pro Pro Val Ala Thr Met Val Ser Lys Gly Glu Glu Asp
645 650 655
Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val His Met Glu
660 665 670
Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly Glu Gly
675 680 685
Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr Lys Gly
690 695 700
Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe Met Tyr
705 710 715 720
Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp Tyr Leu
725 730 735
Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met Asn Phe
740 745 750
Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser Ser Leu Gln Asp
755 760 765
Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr Asn Phe Pro Ser
770 775 780
Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp Glu Ala Ser Ser
785 790 795 800
Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys Gly Glu Ile Lys Gln
805 810 815
Arg Leu Lys Leu Lys Asp Gly Gly His Tyr Asp Ala Glu Val Lys Thr
820 825 830
Thr Tyr Lys Ala Lys Lys Pro Val Gln Leu Pro Gly Ala Tyr Asn Val
835 840 845
Asn Ile Lys Leu Asp Ile Thr Ser His Asn Glu Asp Tyr Thr Ile Val
850 855 860
Glu Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr Gly Gly Met Asp
865 870 875 880
Glu Leu Tyr Lys
<210> 84
<211> 885
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 84
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Pro Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn
500 505 510
Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn
515 520 525
Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser
530 535 540
Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser
545 550 555 560
Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro
565 570 575
Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln
580 585 590
Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala
595 600 605
Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe
610 615 620
Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Asp Asp Gly Trp Gly
625 630 635 640
Met Thr Arg Asp Pro Pro Val Ala Thr Met Val Ser Lys Gly Glu Glu
645 650 655
Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val His Met
660 665 670
Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly Glu
675 680 685
Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr Lys
690 695 700
Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe Met
705 710 715 720
Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp Tyr
725 730 735
Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met Asn
740 745 750
Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser Ser Leu Gln
755 760 765
Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr Asn Phe Pro
770 775 780
Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp Glu Ala Ser
785 790 795 800
Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys Gly Glu Ile Lys
805 810 815
Gln Arg Leu Lys Leu Lys Asp Gly Gly His Tyr Asp Ala Glu Val Lys
820 825 830
Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln Leu Pro Gly Ala Tyr Asn
835 840 845
Val Asn Ile Lys Leu Asp Ile Thr Ser His Asn Glu Asp Tyr Thr Ile
850 855 860
Val Glu Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr Gly Gly Met
865 870 875 880
Asp Glu Leu Tyr Lys
885
<210> 85
<211> 1157
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 85
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Gln Met Ser Glu Tyr Ile Arg Val Thr Glu Asp Glu Asn
500 505 510
Asp Glu Pro Ile Glu Ile Pro Ser Glu Asp Asp Gly Thr Val Leu Leu
515 520 525
Ser Thr Val Thr Ala Gln Phe Pro Gly Ala Cys Gly Leu Arg Tyr Arg
530 535 540
Asn Pro Val Ser Gln Cys Met Arg Gly Val Arg Leu Val Glu Gly Ile
545 550 555 560
Leu His Ala Pro Asp Ala Gly Trp Gly Asn Leu Val Tyr Val Val Asn
565 570 575
Tyr Pro Lys Asp Asn Lys Arg Lys Met Asp Glu Thr Asp Ala Ser Ser
580 585 590
Ala Val Lys Val Lys Arg Ala Val Gln Lys Thr Ser Asp Leu Ile Val
595 600 605
Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp Leu Lys Glu Tyr Phe
610 615 620
Ser Thr Phe Gly Glu Val Leu Met Val Gln Val Lys Lys Asp Leu Lys
625 630 635 640
Thr Gly His Ser Lys Gly Leu Gly Leu Val Arg Phe Thr Glu Tyr Glu
645 650 655
Thr Gln Val Lys Val Met Ser Gln Arg His Met Ile Asp Gly Arg Trp
660 665 670
Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser Gln Asp Glu Pro Leu
675 680 685
Arg Ser Arg Lys Val Leu Val Gly Arg Cys Thr Glu Asp Met Thr Glu
690 695 700
Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val
705 710 715 720
Phe Ile Pro Lys Pro Phe Arg Ala Leu Ala Leu Val Thr Phe Ala Asp
725 730 735
Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly
740 745 750
Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg
755 760 765
Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly
770 775 780
Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly
785 790 795 800
Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe
805 810 815
Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser
820 825 830
Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly
835 840 845
Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn
850 855 860
Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly
865 870 875 880
Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly
885 890 895
Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp
900 905 910
Gly Met Trp Asp Pro Pro Val Ala Thr Met Val Ser Lys Gly Glu Glu
915 920 925
Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val His Met
930 935 940
Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly Glu
945 950 955 960
Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr Lys
965 970 975
Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe Met
980 985 990
Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp Tyr
995 1000 1005
Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met
1010 1015 1020
Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser Ser
1025 1030 1035
Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr
1040 1045 1050
Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly
1055 1060 1065
Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu
1070 1075 1080
Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His
1085 1090 1095
Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val
1100 1105 1110
Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr
1115 1120 1125
Ser His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala
1130 1135 1140
Glu Gly Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys
1145 1150 1155
<210> 86
<211> 829
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 86
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Gln Asp Leu Ile Val Leu Gly Leu Pro Trp Lys Thr Thr
500 505 510
Glu Gln Asp Leu Lys Glu Tyr Phe Ser Thr Phe Gly Glu Val Leu Met
515 520 525
Val Gln Val Lys Lys Asp Leu Lys Thr Gly His Ser Lys Gly Phe Gly
530 535 540
Phe Val Arg Phe Thr Glu Tyr Glu Thr Gln Val Lys Val Met Ser Gln
545 550 555 560
Arg His Met Ile Asp Gly Arg Trp Cys Asp Cys Lys Leu Pro Asn Ser
565 570 575
Lys Gln Ser Gln Asp Glu Pro Leu Arg Ser Arg Asp Pro Pro Val Ala
580 585 590
Thr Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu
595 600 605
Phe Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu
610 615 620
Phe Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln
625 630 635 640
Thr Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp
645 650 655
Asp Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys
660 665 670
His Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly
675 680 685
Phe Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr
690 695 700
Val Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val
705 710 715 720
Lys Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys
725 730 735
Lys Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp
740 745 750
Gly Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly
755 760 765
Gly His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro
770 775 780
Val Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr
785 790 795 800
Ser His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu
805 810 815
Gly Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys
820 825
<210> 87
<211> 815
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 87
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Gln Arg Lys Val Phe Val Gly Arg Cys Thr Glu Asp Met
500 505 510
Thr Glu Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val Met
515 520 525
Asp Val Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val Thr Phe
530 535 540
Ala Asp Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile
545 550 555 560
Lys Gly Ile Ser Val His Ile Ser Asn Ala Glu Pro Arg Asp Pro Pro
565 570 575
Val Ala Thr Met Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile
580 585 590
Lys Glu Phe Met Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly
595 600 605
His Glu Phe Glu Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly
610 615 620
Thr Gln Thr Ala Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe
625 630 635 640
Ala Trp Asp Ile Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr
645 650 655
Val Lys His Pro Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro
660 665 670
Glu Gly Phe Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val
675 680 685
Val Thr Val Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr
690 695 700
Lys Val Lys Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met
705 710 715 720
Gln Lys Lys Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro
725 730 735
Glu Asp Gly Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys
740 745 750
Asp Gly Gly His Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys
755 760 765
Lys Pro Val Gln Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp
770 775 780
Ile Thr Ser His Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg
785 790 795 800
Ala Glu Gly Arg His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys
805 810 815
<210> 88
<211> 901
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 88
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Gln Asp Leu Ile Val Leu Gly Leu Pro Trp Lys Thr Thr
500 505 510
Glu Gln Asp Leu Lys Glu Tyr Phe Ser Thr Phe Gly Glu Val Leu Met
515 520 525
Val Gln Val Lys Lys Asp Leu Lys Thr Gly His Ser Lys Gly Phe Gly
530 535 540
Phe Val Arg Phe Thr Glu Tyr Glu Thr Gln Val Lys Val Met Ser Gln
545 550 555 560
Arg His Met Ile Asp Gly Arg Trp Cys Asp Cys Lys Leu Pro Asn Ser
565 570 575
Lys Gln Ser Gln Asp Glu Pro Leu Arg Ser Arg Lys Val Phe Val Gly
580 585 590
Arg Cys Thr Glu Asp Met Thr Glu Asp Glu Leu Arg Glu Phe Phe Ser
595 600 605
Gln Tyr Gly Asp Val Met Asp Val Phe Ile Pro Lys Pro Phe Arg Ala
610 615 620
Phe Ala Phe Val Thr Phe Ala Asp Asp Gln Ile Ala Gln Ser Leu Cys
625 630 635 640
Gly Glu Asp Leu Ile Ile Lys Gly Ile Ser Val His Ile Ser Asn Ala
645 650 655
Glu Pro Arg Asp Pro Pro Val Ala Thr Met Val Ser Lys Gly Glu Glu
660 665 670
Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val His Met
675 680 685
Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly Glu Gly Glu
690 695 700
Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys Val Thr Lys
705 710 715 720
Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro Gln Phe Met
725 730 735
Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile Pro Asp Tyr
740 745 750
Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg Val Met Asn
755 760 765
Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser Ser Leu Gln
770 775 780
Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr Asn Phe Pro
785 790 795 800
Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp Glu Ala Ser
805 810 815
Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys Gly Glu Ile Lys
820 825 830
Gln Arg Leu Lys Leu Lys Asp Gly Gly His Tyr Asp Ala Glu Val Lys
835 840 845
Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln Leu Pro Gly Ala Tyr Asn
850 855 860
Val Asn Ile Lys Leu Asp Ile Thr Ser His Asn Glu Asp Tyr Thr Ile
865 870 875 880
Val Glu Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr Gly Gly Met
885 890 895
Asp Glu Leu Tyr Lys
900
<210> 89
<211> 1016
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 89
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Gln Met Ser Glu Tyr Ile Arg Val Thr Glu Asp Glu Asn
500 505 510
Asp Glu Pro Ile Glu Ile Pro Ser Glu Asp Asp Gly Thr Val Leu Leu
515 520 525
Ser Thr Val Thr Ala Gln Phe Pro Gly Ala Cys Gly Leu Arg Tyr Arg
530 535 540
Asn Pro Val Ser Gln Cys Met Arg Gly Val Arg Leu Val Glu Gly Ile
545 550 555 560
Leu His Ala Pro Asp Ala Gly Trp Gly Asn Leu Val Tyr Val Val Asn
565 570 575
Tyr Pro Lys Asp Asn Lys Arg Lys Met Asp Glu Thr Asp Ala Ser Ser
580 585 590
Ala Val Lys Val Lys Arg Ala Val Gln Lys Thr Ser Asp Leu Ile Val
595 600 605
Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp Leu Lys Glu Tyr Phe
610 615 620
Ser Thr Phe Gly Glu Val Leu Met Val Gln Val Lys Lys Asp Leu Lys
625 630 635 640
Thr Gly His Ser Lys Gly Phe Gly Phe Val Arg Phe Thr Glu Tyr Glu
645 650 655
Thr Gln Val Lys Val Met Ser Gln Arg His Met Ile Asp Gly Arg Trp
660 665 670
Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser Gln Asp Glu Pro Leu
675 680 685
Arg Ser Arg Lys Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr Glu
690 695 700
Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val
705 710 715 720
Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala Asp
725 730 735
Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly
740 745 750
Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg
755 760 765
Gln Leu Glu Arg Ser Arg Asp Pro Pro Val Ala Thr Met Val Ser Lys
770 775 780
Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys
785 790 795 800
Val His Met Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly
805 810 815
Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu Lys
820 825 830
Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu Ser Pro
835 840 845
Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro Ala Asp Ile
850 855 860
Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys Trp Glu Arg
865 870 875 880
Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr Gln Asp Ser
885 890 895
Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu Arg Gly Thr
900 905 910
Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr Met Gly Trp
915 920 925
Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala Leu Lys Gly
930 935 940
Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His Tyr Asp Ala
945 950 955 960
Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln Leu Pro Gly
965 970 975
Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser His Asn Glu Asp
980 985 990
Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr
995 1000 1005
Gly Gly Met Asp Glu Leu Tyr Lys
1010 1015
<210> 90
<211> 1040
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 90
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Gln Cys Arg Ala Thr Met Tyr Pro Tyr Asp Val Pro Asp
500 505 510
Tyr Ala Met Ala Ser Asn Asp Tyr Thr Gln Gln Ala Thr Gln Ser Tyr
515 520 525
Gly Ala Tyr Pro Thr Gln Pro Gly Gln Gly Tyr Ser Gln Gln Ser Ser
530 535 540
Gln Pro Tyr Gly Gln Gln Ser Tyr Ser Gly Tyr Ser Gln Ser Thr Asp
545 550 555 560
Thr Ser Gly Tyr Gly Gln Ser Ser Tyr Ser Ser Tyr Gly Gln Ser Gln
565 570 575
Asn Thr Gly Tyr Gly Thr Gln Ser Thr Pro Gln Gly Tyr Gly Ser Thr
580 585 590
Gly Gly Tyr Gly Ser Ser Gln Ser Ser Gln Ser Ser Tyr Gly Gln Gln
595 600 605
Ser Ser Tyr Pro Gly Tyr Gly Gln Gln Pro Ala Pro Ser Ser Thr Ser
610 615 620
Gly Ser Tyr Gly Ser Ser Ser Gln Ser Ser Ser Tyr Gly Gln Pro Gln
625 630 635 640
Ser Gly Ser Tyr Ser Gln Gln Pro Ser Tyr Gly Gly Gln Gln Gln Ser
645 650 655
Tyr Gly Gln Gln Gln Ser Tyr Asn Pro Pro Gln Gly Tyr Gly Gln Gln
660 665 670
Asn Gln Tyr Asn Ser Ser Ser Gly Gly Gly Gly Gly Gly Gly Gly Gly
675 680 685
Gly Asn Tyr Gly Gln Asp Gln Ser Ser Met Ser Ser Gly Gly Gly Ser
690 695 700
Gly Gly Gly Tyr Gly Asn Gln Asp Gln Ser Gly Gly Gly Gly Ser Gly
705 710 715 720
Gly Tyr Gly Gln Gln Asp Arg Gly Gly Arg Gly Arg Gly Gly Ser Gly
725 730 735
Gly Gly Gly Gly Gly Gly Gly Gly Gly Tyr Asn Arg Ser Ser Gly Gly
740 745 750
Tyr Glu Pro Arg Gly Arg Gly Gly Gly Arg Gly Gly Arg Gly Gly Met
755 760 765
Gly Gly Ser Asp Arg Gly Gly Phe Asn Lys Phe Gly Gly Pro Arg Asp
770 775 780
Gln Gly Ser Arg His Asp Ser Glu Gln Asp Asn Ser Asp Asn Asn Thr
785 790 795 800
Ile Phe Val Gln Gly Leu Gly Glu Asn Val Thr Ile Glu Ser Val Ala
805 810 815
Asp Tyr Phe Lys Gln Ile Gly Ile Ile Lys Thr Asn Lys Lys Thr Gly
820 825 830
Gln Pro Met Ile Asn Leu Tyr Thr Asp Arg Glu Thr Gly Lys Leu Lys
835 840 845
Gly Glu Ala Thr Val Ser Phe Asp Asp Pro Pro Ser Ala Lys Ala Ala
850 855 860
Ile Asp Trp Phe Asp Gly Lys Glu Phe Ser Gly Asn Pro Ile Lys Val
865 870 875 880
Ser Phe Ala Thr Arg Arg Ala Asp Phe Asn Arg Gly Gly Gly Asn Gly
885 890 895
Arg Gly Gly Arg Gly Arg Gly Gly Pro Met Gly Arg Gly Gly Tyr Gly
900 905 910
Gly Gly Gly Ser Gly Gly Gly Gly Arg Gly Gly Phe Pro Ser Gly Gly
915 920 925
Gly Gly Gly Gly Gly Gln Gln Arg Ala Gly Asp Trp Lys Cys Pro Asn
930 935 940
Pro Thr Cys Glu Asn Met Asn Phe Ser Trp Arg Asn Glu Cys Asn Gln
945 950 955 960
Cys Lys Ala Pro Lys Pro Asp Gly Pro Gly Gly Gly Pro Gly Gly Ser
965 970 975
His Met Gly Gly Asn Tyr Gly Asp Asp Arg Arg Gly Gly Arg Gly Gly
980 985 990
Tyr Asp Arg Gly Gly Tyr Arg Gly Arg Gly Gly Asp Arg Gly Gly Phe
995 1000 1005
Arg Gly Gly Arg Gly Gly Gly Asp Arg Gly Gly Phe Gly Pro Gly
1010 1015 1020
Lys Met Asp Ser Arg Gly Glu His Arg Gln Asp Arg Arg Glu Arg
1025 1030 1035
Pro Tyr
1040
<210> 91
<211> 1283
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 91
Met Lys Met Asp Lys Lys Thr Ile Val Trp Phe Arg Arg Asp Leu Arg
1 5 10 15
Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala Ala His Glu Gly Ser Val
20 25 30
Phe Pro Val Phe Ile Trp Cys Pro Glu Glu Glu Gly Gln Phe Tyr Pro
35 40 45
Gly Arg Ala Ser Arg Trp Trp Met Lys Gln Ser Leu Ala His Leu Ser
50 55 60
Gln Ser Leu Lys Ala Leu Gly Ser Asp Leu Thr Leu Ile Lys Thr His
65 70 75 80
Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile Arg Val Thr Gly Ala Thr
85 90 95
Lys Val Val Phe Asn His Leu Tyr Asp Pro Val Ser Leu Val Arg Asp
100 105 110
His Thr Val Lys Glu Lys Leu Val Glu Arg Gly Ile Ser Val Gln Ser
115 120 125
Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp Glu Ile Tyr Cys Glu Lys
130 135 140
Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr Trp Lys Lys Cys Leu Asp
145 150 155 160
Met Ser Ile Glu Ser Val Met Leu Pro Pro Pro Trp Arg Leu Met Pro
165 170 175
Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala Cys Ser Ile Glu Glu Leu
180 185 190
Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser Asn Ala Leu Leu Thr Arg
195 200 205
Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp Lys Leu Leu Asn Glu Phe
210 215 220
Ile Glu Lys Gln Leu Ile Asp Tyr Ala Lys Asn Ser Lys Lys Val Val
225 230 235 240
Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr Leu His Phe Gly Glu Ile
245 250 255
Ser Val Arg His Val Phe Gln Cys Ala Arg Met Lys Gln Ile Ile Trp
260 265 270
Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu Ser Ala Asp Leu Phe Leu
275 280 285
Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg Tyr Ile Cys Phe Asn Phe
290 295 300
Pro Phe Thr His Glu Gln Ser Leu Leu Ser His Leu Arg Phe Phe Pro
305 310 315 320
Trp Asp Ala Asp Val Asp Lys Phe Lys Ala Trp Arg Gln Gly Arg Thr
325 330 335
Gly Tyr Pro Leu Val Asp Ala Gly Met Arg Glu Leu Trp Ala Thr Gly
340 345 350
Trp Met His Asn Arg Ile Arg Val Ile Val Ser Ser Phe Ala Val Lys
355 360 365
Phe Leu Leu Leu Pro Trp Lys Trp Gly Met Lys Tyr Phe Trp Asp Thr
370 375 380
Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile Leu Gly Trp Gln Tyr Ile
385 390 395 400
Ser Gly Ser Ile Pro Asp Gly His Glu Leu Asp Arg Leu Asp Asn Pro
405 410 415
Ala Leu Gln Gly Ala Lys Tyr Asp Pro Glu Gly Glu Tyr Ile Arg Gln
420 425 430
Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr Glu Trp Ile His His Pro
435 440 445
Trp Asp Ala Pro Leu Thr Val Leu Lys Ala Ser Gly Val Glu Leu Gly
450 455 460
Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile Asp Thr Ala Arg Glu Leu
465 470 475 480
Leu Ala Lys Ala Ile Ser Arg Thr Arg Gly Ala Gln Ile Met Ile Gly
485 490 495
Ala Ala Ala Gln Cys Arg Ala Thr Met Tyr Pro Tyr Asp Val Pro Asp
500 505 510
Tyr Ala Met Ala Ser Asn Asp Tyr Thr Gln Gln Ala Thr Gln Ser Tyr
515 520 525
Gly Ala Tyr Pro Thr Gln Pro Gly Gln Gly Tyr Ser Gln Gln Ser Ser
530 535 540
Gln Pro Tyr Gly Gln Gln Ser Tyr Ser Gly Tyr Ser Gln Ser Thr Asp
545 550 555 560
Thr Ser Gly Tyr Gly Gln Ser Ser Tyr Ser Ser Tyr Gly Gln Ser Gln
565 570 575
Asn Thr Gly Tyr Gly Thr Gln Ser Thr Pro Gln Gly Tyr Gly Ser Thr
580 585 590
Gly Gly Tyr Gly Ser Ser Gln Ser Ser Gln Ser Ser Tyr Gly Gln Gln
595 600 605
Ser Ser Tyr Pro Gly Tyr Gly Gln Gln Pro Ala Pro Ser Ser Thr Ser
610 615 620
Gly Ser Tyr Gly Ser Ser Ser Gln Ser Ser Ser Tyr Gly Gln Pro Gln
625 630 635 640
Ser Gly Ser Tyr Ser Gln Gln Pro Ser Tyr Gly Gly Gln Gln Gln Ser
645 650 655
Tyr Gly Gln Gln Gln Ser Tyr Asn Pro Pro Gln Gly Tyr Gly Gln Gln
660 665 670
Asn Gln Tyr Asn Ser Ser Ser Gly Gly Gly Gly Gly Gly Gly Gly Gly
675 680 685
Gly Asn Tyr Gly Gln Asp Gln Ser Ser Met Ser Ser Gly Gly Gly Ser
690 695 700
Gly Gly Gly Tyr Gly Asn Gln Asp Gln Ser Gly Gly Gly Gly Ser Gly
705 710 715 720
Gly Tyr Gly Gln Gln Asp Arg Gly Gly Arg Gly Arg Gly Gly Ser Gly
725 730 735
Gly Gly Gly Gly Gly Gly Gly Gly Gly Tyr Asn Arg Ser Ser Gly Gly
740 745 750
Tyr Glu Pro Arg Gly Arg Gly Gly Gly Arg Gly Gly Arg Gly Gly Met
755 760 765
Gly Gly Ser Asp Arg Gly Gly Phe Asn Lys Phe Gly Gly Pro Arg Asp
770 775 780
Gln Gly Ser Arg His Asp Ser Glu Gln Asp Asn Ser Asp Asn Asn Thr
785 790 795 800
Ile Phe Val Gln Gly Leu Gly Glu Asn Val Thr Ile Glu Ser Val Ala
805 810 815
Asp Tyr Phe Lys Gln Ile Gly Ile Ile Lys Thr Asn Lys Lys Thr Gly
820 825 830
Gln Pro Met Ile Asn Leu Tyr Thr Asp Arg Glu Thr Gly Lys Leu Lys
835 840 845
Gly Glu Ala Thr Val Ser Phe Asp Asp Pro Pro Ser Ala Lys Ala Ala
850 855 860
Ile Asp Trp Phe Asp Gly Lys Glu Phe Ser Gly Asn Pro Ile Lys Val
865 870 875 880
Ser Phe Ala Thr Arg Arg Ala Asp Phe Asn Arg Gly Gly Gly Asn Gly
885 890 895
Arg Gly Gly Arg Gly Arg Gly Gly Pro Met Gly Arg Gly Gly Tyr Gly
900 905 910
Gly Gly Gly Ser Gly Gly Gly Gly Arg Gly Gly Phe Pro Ser Gly Gly
915 920 925
Gly Gly Gly Gly Gly Gln Gln Arg Ala Gly Asp Trp Lys Cys Pro Asn
930 935 940
Pro Thr Cys Glu Asn Met Asn Phe Ser Trp Arg Asn Glu Cys Asn Gln
945 950 955 960
Cys Lys Ala Pro Lys Pro Asp Gly Pro Gly Gly Gly Pro Gly Gly Ser
965 970 975
His Met Gly Gly Asn Tyr Gly Asp Asp Arg Arg Gly Gly Arg Gly Gly
980 985 990
Tyr Asp Arg Gly Gly Tyr Arg Gly Arg Gly Gly Asp Arg Gly Gly Phe
995 1000 1005
Arg Gly Gly Arg Gly Gly Gly Asp Arg Gly Gly Phe Gly Pro Gly
1010 1015 1020
Lys Met Asp Ser Arg Gly Glu His Arg Gln Asp Arg Arg Glu Arg
1025 1030 1035
Pro Tyr Trp Asp Pro Pro Val Ala Thr Met Val Ser Lys Gly Glu
1040 1045 1050
Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met Arg Phe Lys Val
1055 1060 1065
His Met Glu Gly Ser Val Asn Gly His Glu Phe Glu Ile Glu Gly
1070 1075 1080
Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala Lys Leu
1085 1090 1095
Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile Leu
1100 1105 1110
Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro
1115 1120 1125
Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe
1130 1135 1140
Lys Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr
1145 1150 1155
Val Thr Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys
1160 1165 1170
Val Lys Leu Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met
1175 1180 1185
Gln Lys Lys Thr Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr
1190 1195 1200
Pro Glu Asp Gly Ala Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys
1205 1210 1215
Leu Lys Asp Gly Gly His Tyr Asp Ala Glu Val Lys Thr Thr Tyr
1220 1225 1230
Lys Ala Lys Lys Pro Val Gln Leu Pro Gly Ala Tyr Asn Val Asn
1235 1240 1245
Ile Lys Leu Asp Ile Thr Ser His Asn Glu Asp Tyr Thr Ile Val
1250 1255 1260
Glu Gln Tyr Glu Arg Ala Glu Gly Arg His Ser Thr Gly Gly Met
1265 1270 1275
Asp Glu Leu Tyr Lys
1280
<210> 92
<211> 348
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 92
Met Asn Gly Leu Thr Pro Pro Leu Met Phe Cys Ser Arg Ser Asp Asp
1 5 10 15
Pro Ser Ser Thr Ser Asn Ile Asn Leu Asp Asp Val Phe Ala Asp Val
20 25 30
Phe Phe Asn Ser Asn Gly Glu Leu Leu Asp Ile Asp Glu Ile Asp Asp
35 40 45
Phe Gly Asp Asn Thr Cys Pro Lys Ser Ser Met Ser Val Asp Asp Asp
50 55 60
Ala Ser Ser Gln Val Phe Gln Gly His Leu Phe Gly Asn Ala Leu Ser
65 70 75 80
Ser Ile Ala Leu Ser Asp Ser Gly Asp Leu Ser Thr Gly Ile Tyr Glu
85 90 95
Ser Gln Gly Asn Ala Ser Arg Gly Lys Ser Leu Arg Thr Lys Ser Ser
100 105 110
Gly Ser Ile Ser Ser Glu Leu Thr Glu Ala Gln Lys Val Glu Arg Arg
115 120 125
Glu Arg Asn Arg Glu His Ala Lys Arg Ser Arg Val Arg Lys Lys Phe
130 135 140
Leu Leu Glu Ser Leu Gln Gln Ser Val Asn Glu Leu Asn His Glu Asn
145 150 155 160
Asn Cys Leu Lys Glu Ser Ile Arg Glu His Leu Gly Pro Arg Gly Asp
165 170 175
Ser Leu Ile Ala Gln Cys Ser Pro Glu Ala Asp Thr Leu Leu Thr Asp
180 185 190
Asn Pro Ser Lys Ala Asn Arg Ile Leu Glu Asp Pro Asp Tyr Ser Leu
195 200 205
Val Lys Ala Leu Gln Met Ala Gln Gln Asn Phe Val Ile Thr Asp Ala
210 215 220
Ser Leu Pro Asp Asn Pro Ile Val Tyr Ala Ser Arg Gly Phe Leu Thr
225 230 235 240
Leu Thr Gly Tyr Ser Leu Asp Gln Ile Leu Gly Arg Asn Cys Arg Phe
245 250 255
Leu Gln Gly Pro Glu Thr Asp Pro Arg Ala Val Asp Lys Ile Arg Asn
260 265 270
Ala Ile Thr Lys Gly Val Asp Thr Ser Val Cys Leu Leu Asn Tyr Arg
275 280 285
Gln Asp Gly Thr Thr Phe Trp Asn Leu Phe Phe Val Ala Gly Leu Arg
290 295 300
Asp Ser Lys Gly Asn Ile Val Asn Tyr Val Gly Val Gln Ser Lys Val
305 310 315 320
Ser Glu Asp Tyr Ala Lys Leu Leu Val Asn Glu Gln Asn Ile Glu Tyr
325 330 335
Lys Gly Val Arg Thr Ser Asn Met Leu Arg Arg Lys
340 345
<210> 93
<211> 145
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 93
Pro Asp Tyr Ser Leu Val Lys Ala Leu Gln Met Ala Gln Gln Asn Phe
1 5 10 15
Val Ile Thr Asp Ala Ser Leu Pro Asp Asn Pro Ile Val Tyr Ala Ser
20 25 30
Arg Gly Phe Leu Thr Leu Thr Gly Tyr Ser Leu Asp Gln Ile Leu Gly
35 40 45
Arg Asn Cys Arg Phe Leu Gln Gly Pro Glu Thr Asp Pro Arg Ala Val
50 55 60
Asp Lys Ile Arg Asn Ala Ile Thr Lys Gly Val Asp Thr Ser Val Cys
65 70 75 80
Leu Leu Asn Tyr Arg Gln Asp Gly Thr Thr Phe Trp Asn Leu Phe Phe
85 90 95
Val Ala Gly Leu Arg Asp Ser Lys Gly Asn Ile Val Asn Tyr Val Gly
100 105 110
Val Gln Ser Lys Val Ser Glu Asp Tyr Ala Lys Leu Leu Val Asn Glu
115 120 125
Gln Asn Ile Glu Tyr Lys Gly Val Arg Thr Ser Asn Met Leu Arg Arg
130 135 140
Lys
145
<210> 94
<211> 435
<212> DNA
<213> VfAU1-LOV domain (No Start codon)
<400> 94
cctgactaca gtctcgtgaa ggctctgcaa atggcacaac agaattttgt cattacagac 60
gcctccctcc cagacaaccc tatcgtctac gccagtagag ggtttctgac actgacaggc 120
tattctctcg accagatcct gggcaggaac tgcaggtttc tgcaagggcc agaaacagac 180
ccaagagctg tggataagat caggaatgcc atcaccaaag gcgttgatac cagtgtctgt 240
ctgctgaatt atagacagga tggcacaacc ttctggaatc tcttcttcgt ggctggactc 300
agagattcta agggcaatat tgtcaactac gtcggagtgc agtcaaaggt gagcgaagat 360
tatgccaagc tgctggtcaa cgagcagaac attgagtaca aaggtgtgcg caccagtaac 420
atgctgcgca gaaag 435
<210> 95
<211> 414
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 95
Met Ser Glu Tyr Ile Arg Val Thr Glu Asp Glu Asn Asp Glu Pro Ile
1 5 10 15
Glu Ile Pro Ser Glu Asp Asp Gly Thr Val Leu Leu Ser Thr Val Thr
20 25 30
Ala Gln Phe Pro Gly Ala Cys Gly Leu Arg Tyr Arg Asn Pro Val Ser
35 40 45
Gln Cys Met Arg Gly Val Arg Leu Val Glu Gly Ile Leu His Ala Pro
50 55 60
Asp Ala Gly Trp Gly Asn Leu Val Tyr Val Val Asn Tyr Pro Lys Asp
65 70 75 80
Asn Lys Arg Lys Met Asp Glu Thr Asp Ala Ser Ser Ala Val Lys Val
85 90 95
Lys Arg Ala Val Gln Lys Thr Ser Asp Leu Ile Val Leu Gly Leu Pro
100 105 110
Trp Lys Thr Thr Glu Gln Asp Leu Lys Glu Tyr Phe Ser Thr Phe Gly
115 120 125
Glu Val Leu Met Val Gln Val Lys Lys Asp Leu Lys Thr Gly His Ser
130 135 140
Lys Gly Phe Gly Phe Val Arg Phe Thr Glu Tyr Glu Thr Gln Val Lys
145 150 155 160
Val Met Ser Gln Arg His Met Ile Asp Gly Arg Trp Cys Asp Cys Lys
165 170 175
Leu Pro Asn Ser Lys Gln Ser Gln Asp Glu Pro Leu Arg Ser Arg Lys
180 185 190
Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr Glu Asp Glu Leu Arg
195 200 205
Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val Phe Ile Pro Lys
210 215 220
Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala Asp Asp Gln Ile Ala
225 230 235 240
Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly Ile Ser Val His
245 250 255
Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg Gln Leu Glu Arg
260 265 270
Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn Gln Gly Gly
275 280 285
Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn Asn Gln Gly
290 295 300
Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser Ile Asn Pro
305 310 315 320
Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser Trp Gly Met
325 330 335
Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro Ser Gly Asn
340 345 350
Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln Ala Phe Gly
355 360 365
Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala Ala Ile Gly
370 375 380
Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe Asn Gly Gly
385 390 395 400
Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly Met
405 410
<210> 96
<211> 311
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 96
Met Asp Leu Ile Val Leu Gly Leu Pro Trp Lys Thr Thr Glu Gln Asp
1 5 10 15
Leu Lys Glu Tyr Phe Ser Thr Phe Gly Glu Val Leu Met Val Gln Val
20 25 30
Lys Lys Asp Leu Lys Thr Gly His Ser Lys Gly Phe Gly Phe Val Arg
35 40 45
Phe Thr Glu Tyr Glu Thr Gln Val Lys Val Met Ser Gln Arg His Met
50 55 60
Ile Asp Gly Arg Trp Cys Asp Cys Lys Leu Pro Asn Ser Lys Gln Ser
65 70 75 80
Gln Asp Glu Pro Leu Arg Ser Arg Lys Val Phe Val Gly Arg Cys Thr
85 90 95
Glu Asp Met Thr Glu Asp Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly
100 105 110
Asp Val Met Asp Val Phe Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe
115 120 125
Val Thr Phe Ala Asp Asp Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp
130 135 140
Leu Ile Ile Lys Gly Ile Ser Val His Ile Ser Asn Ala Glu Pro Lys
145 150 155 160
His Asn Ser Asn Arg Gln Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn
165 170 175
Pro Gly Gly Phe Gly Asn Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly
180 185 190
Gly Ala Gly Leu Gly Asn Asn Gln Gly Ser Asn Met Gly Gly Gly Met
195 200 205
Asn Phe Gly Ala Phe Ser Ile Asn Pro Ala Met Met Ala Ala Ala Gln
210 215 220
Ala Ala Leu Gln Ser Ser Trp Gly Met Met Gly Met Leu Ala Ser Gln
225 230 235 240
Gln Asn Gln Ser Gly Pro Ser Gly Asn Asn Gln Asn Gln Gly Asn Met
245 250 255
Gln Arg Glu Pro Asn Gln Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser
260 265 270
Gly Ser Asn Ser Gly Ala Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala
275 280 285
Gly Ser Gly Ser Gly Phe Asn Gly Gly Phe Gly Ser Ser Met Asp Ser
290 295 300
Lys Ser Ser Gly Trp Gly Met
305 310
<210> 97
<211> 225
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 97
Met Arg Lys Val Phe Val Gly Arg Cys Thr Glu Asp Met Thr Glu Asp
1 5 10 15
Glu Leu Arg Glu Phe Phe Ser Gln Tyr Gly Asp Val Met Asp Val Phe
20 25 30
Ile Pro Lys Pro Phe Arg Ala Phe Ala Phe Val Thr Phe Ala Asp Asp
35 40 45
Gln Ile Ala Gln Ser Leu Cys Gly Glu Asp Leu Ile Ile Lys Gly Ile
50 55 60
Ser Val His Ile Ser Asn Ala Glu Pro Lys His Asn Ser Asn Arg Gln
65 70 75 80
Leu Glu Arg Ser Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn
85 90 95
Gln Gly Gly Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn
100 105 110
Asn Gln Gly Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser
115 120 125
Ile Asn Pro Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser
130 135 140
Trp Gly Met Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro
145 150 155 160
Ser Gly Asn Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln
165 170 175
Ala Phe Gly Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala
180 185 190
Ala Ile Gly Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe
195 200 205
Asn Gly Gly Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly
210 215 220
Met
225
<210> 98
<211> 142
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 98
Met Gly Arg Phe Gly Gly Asn Pro Gly Gly Phe Gly Asn Gln Gly Gly
1 5 10 15
Phe Gly Asn Ser Arg Gly Gly Gly Ala Gly Leu Gly Asn Asn Gln Gly
20 25 30
Ser Asn Met Gly Gly Gly Met Asn Phe Gly Ala Phe Ser Ile Asn Pro
35 40 45
Ala Met Met Ala Ala Ala Gln Ala Ala Leu Gln Ser Ser Trp Gly Met
50 55 60
Met Gly Met Leu Ala Ser Gln Gln Asn Gln Ser Gly Pro Ser Gly Asn
65 70 75 80
Asn Gln Asn Gln Gly Asn Met Gln Arg Glu Pro Asn Gln Ala Phe Gly
85 90 95
Ser Gly Asn Asn Ser Tyr Ser Gly Ser Asn Ser Gly Ala Ala Ile Gly
100 105 110
Trp Gly Ser Ala Ser Asn Ala Gly Ser Gly Ser Gly Phe Asn Gly Gly
115 120 125
Phe Gly Ser Ser Met Asp Ser Lys Ser Ser Gly Trp Gly Met
130 135 140
<210> 99
<211> 161
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 99
Gly Glu Phe Leu Ala Thr Thr Leu Glu Arg Ile Glu Lys Asn Phe Val
1 5 10 15
Ile Thr Asp Pro Arg Leu Pro Asp Asn Pro Ile Ile Phe Ala Ser Asp
20 25 30
Ser Phe Leu Gln Leu Thr Glu Tyr Ser Arg Glu Glu Ile Leu Gly Arg
35 40 45
Asn Cys Arg Phe Leu Gln Gly Pro Glu Thr Asp Arg Ala Thr Val Arg
50 55 60
Lys Ile Arg Asp Ala Ile Asp Asn Gln Thr Glu Val Thr Val Gln Leu
65 70 75 80
Ile Asn Tyr Thr Lys Ser Gly Lys Lys Phe Trp Asn Leu Phe His Leu
85 90 95
Gln Pro Met Arg Asp Gln Lys Gly Asp Val Gln Tyr Phe Ile Gly Val
100 105 110
Gln Leu Asp Gly Thr Glu His Val Arg Asp Ala Ala Glu Arg Glu Gly
115 120 125
Val Met Leu Ile Lys Lys Thr Ala Glu Asn Ile Asp Glu Ala Ala Lys
130 135 140
Glu Leu Pro Asp Ala Asn Leu Arg Pro Glu Asp Leu Trp Ala Asn His
145 150 155 160
Gly
<210> 100
<211> 225
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 100
Met Leu Asp Met Gly Gln Asp Arg Pro Ile Asp Gly Ser Gly Ala Pro
1 5 10 15
Gly Ala Asp Asp Thr Arg Val Glu Val Gln Pro Pro Ala Gln Trp Val
20 25 30
Leu Asp Leu Ile Glu Ala Ser Pro Ile Ala Ser Val Val Ser Asp Pro
35 40 45
Arg Leu Ala Asp Asn Pro Leu Ile Ala Ile Asn Gln Ala Phe Thr Asp
50 55 60
Leu Thr Gly Tyr Ser Glu Glu Glu Cys Val Gly Arg Asn Cys Arg Phe
65 70 75 80
Leu Ala Gly Ser Gly Thr Glu Pro Trp Leu Thr Asp Lys Ile Arg Gln
85 90 95
Gly Val Arg Glu His Lys Pro Val Leu Val Glu Ile Leu Asn Tyr Lys
100 105 110
Lys Asp Gly Thr Pro Phe Arg Asn Ala Val Leu Val Ala Pro Ile Tyr
115 120 125
Asp Asp Asp Asp Glu Leu Leu Tyr Phe Leu Gly Ser Gln Val Glu Val
130 135 140
Asp Asp Asp Gln Pro Asn Met Gly Met Ala Arg Arg Glu Arg Ala Ala
145 150 155 160
Glu Met Leu Lys Thr Leu Ser Pro Arg Gln Leu Glu Val Thr Thr Leu
165 170 175
Val Ala Ser Gly Leu Arg Asn Lys Glu Val Ala Ala Arg Leu Gly Leu
180 185 190
Ser Glu Lys Thr Val Lys Met His Arg Gly Leu Val Met Glu Lys Leu
195 200 205
Asn Leu Lys Thr Ser Ala Asp Leu Val Arg Ile Ala Val Glu Ala Gly
210 215 220
Ile
225
<210> 101
<211> 261
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 101
Met Ala Ser Phe Gln Ser Phe Gly Ile Pro Gly Gln Leu Glu Val Ile
1 5 10 15
Lys Lys Ala Leu Asp His Val Arg Val Gly Val Val Ile Thr Asp Pro
20 25 30
Ala Leu Glu Asp Asn Pro Ile Val Tyr Val Asn Gln Gly Phe Val Gln
35 40 45
Met Thr Gly Tyr Glu Thr Glu Glu Ile Leu Gly Lys Asn Cys Arg Phe
50 55 60
Leu Gln Gly Lys His Thr Asp Pro Ala Glu Val Asp Asn Ile Arg Thr
65 70 75 80
Ala Leu Gln Asn Lys Glu Pro Val Thr Val Gln Ile Gln Asn Tyr Lys
85 90 95
Lys Asp Gly Thr Met Phe Trp Asn Glu Leu Asn Ile Asp Pro Met Glu
100 105 110
Ile Glu Asp Lys Thr Tyr Phe Val Gly Ile Gln Asn Asp Ile Thr Lys
115 120 125
Gln Lys Glu Tyr Glu Lys Leu Leu Glu Asp Ser Leu Thr Glu Ile Thr
130 135 140
Ala Leu Ser Thr Pro Ile Val Pro Ile Arg Asn Gly Ile Ser Ala Leu
145 150 155 160
Pro Leu Val Gly Asn Leu Thr Glu Glu Arg Phe Asn Ser Ile Val Cys
165 170 175
Thr Leu Thr Asn Ile Leu Ser Thr Ser Lys Asp Asp Tyr Leu Ile Ile
180 185 190
Asp Leu Ser Gly Leu Ala Gln Val Asn Glu Gln Thr Ala Asp Gln Ile
195 200 205
Phe Lys Leu Ser His Leu Leu Lys Leu Thr Gly Thr Glu Leu Ile Ile
210 215 220
Thr Gly Ile Lys Pro Glu Leu Ala Met Lys Met Asn Lys Leu Asp Ala
225 230 235 240
Asn Phe Ser Ser Leu Lys Thr Tyr Ser Asn Val Lys Asp Ala Val Lys
245 250 255
Val Leu Pro Ile Met
260
<210> 102
<211> 176
<212> PRT
<213> 人工序列
<220>
<223> 合成构建体
<400> 102
Met Asp Gln Lys Gln Phe Glu Lys Ile Arg Ala Val Phe Asp Arg Ser
1 5 10 15
Gly Val Ala Leu Thr Leu Val Asp Met Ser Leu Pro Glu Gln Pro Val
20 25 30
Val Leu Ala Asn Pro Pro Phe Leu Arg Met Thr Gly Tyr Thr Glu Gly
35 40 45
Gln Ile Leu Gly Phe Asn Cys Arg Phe Leu Gln Arg Gly Asp Glu Asn
50 55 60
Ala Gln Ala Arg Ala Asp Ile Arg Asp Ala Leu Lys Leu Gly Arg Glu
65 70 75 80
Leu Gln Val Val Leu Arg Asn Tyr Arg Ala Asn Asp Glu Pro Phe Asp
85 90 95
Asn Leu Leu Phe Leu His Pro Val Gly Gly Arg Pro Asp Ala Pro Asp
100 105 110
Tyr Phe Leu Gly Ser Gln Phe Glu Leu Gly Arg Ser Gly Asn Ser Glu
115 120 125
Glu Ala Ala Ala Ala Gly His Ala Gly Ala Leu Thr Gly Glu Leu Ala
130 135 140
Arg Ile Gly Thr Val Ala Ala Arg Leu Glu Met Asp Ser Arg Arg His
145 150 155 160
Leu Ala Gln Ala Ala Ala Ala Leu Val Arg Ala Trp Glu Arg Arg Gly
165 170 175

Claims (42)

1.一种编码嵌合多肽的核苷酸序列,所述核苷酸序列包含:编码光诱导的寡聚化结构域的第一核苷酸序列和编码来自神经退行性疾病靶蛋白的低复杂性结构域的第二核苷酸序列。
2.如权利要求1所述的核苷酸序列,其中,所述光诱导的寡聚化结构域选自由以下组成的组:CRYPHR、CRY2OLIG、NcVVD、NcVVDY50W、NcLOV、VfAU1、YtvA、EL222、RsLOV和AsLOV2。
3.如权利要求2所述的核苷酸序列,其中,所述光诱导的寡聚化结构域是NcVVD。
4.如权利要求2所述的核苷酸序列,其中,所述光诱导的寡聚化结构域是CRY2OLIG。
5.如权利要求2所述的核苷酸序列,其中,所述光诱导的寡聚化结构域是CRYPHR。
6.如权利要求1所述的核苷酸序列,其中,所述光诱导的寡聚化结构域包含LOV结构域。
7.如权利要求1所述的核苷酸序列,其中,所述光诱导的寡聚化结构域包含PHR结构域。
8.如权利要求1至7中任一项所述的核苷酸序列,其中,所述来自神经退行性疾病靶蛋白的低复杂性结构域选自由以下组成的组:TDP-43、ɑ突触核蛋白、Tau、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA2B1、EWS RNA结合蛋白1和TATA盒结合蛋白因子15。
9.如权利要求8所述的核苷酸序列,其中,所述来自神经退行性疾病靶蛋白的低复杂性结构域是TDP-43。
10.如权利要求8所述的核苷酸序列,其中,所述来自神经退行性疾病靶蛋白的低复杂性结构域是ɑ突触核蛋白。
11.如权利要求8所述的核苷酸序列,其中,所述来自神经退行性疾病靶蛋白的低复杂性结构域是Tau。
12.一种编码嵌合多肽的表达载体,所述表达载体包含:编码光诱导的寡聚化结构域的第一核苷酸序列和编码来自神经退行性疾病靶蛋白的低复杂性结构域的第二核苷酸序列,其中,所述第一核苷酸序列与启动子可操作地连接。
13.一种包含编码嵌合多肽的核苷酸序列的细胞,所述细胞包含:编码光诱导的寡聚化结构域的第一核苷酸序列和编码神经退行性疾病靶蛋白的第二核苷酸序列。
14.一种嵌合多肽,其包含:
光诱导的寡聚化结构域;和
来自神经退行性疾病靶蛋白的低复杂性结构域。
15.一种在细胞中诱导神经退行性疾病病理的方法,所述方法包括以下步骤:
将编码嵌合多肽的表达载体导入细胞,所述表达载体包含:
编码光诱导的寡聚化结构域的第一核苷酸序列和编码来自神经退行性疾病靶蛋白的低复杂性结构域的第二核苷酸序列,其中,所述第一核苷酸序列与启动子可操作地连接;
表达所述嵌合多肽;和
通过用蓝光刺激而诱导所述嵌合多肽的寡聚化。
16.如权利要求15所述的方法,其中,所述光诱导的寡聚化结构域选自以下组成的组:CRYPHR、CRY2OLIG、NcVVD、NcVVDY50W、NcLOV、VfAU1、YtvA、EL222、RsLOV和AsLOV2。
17.如权利要求16所述的方法,其中,所述光诱导的寡聚化结构域是NcVVD。
18.如权利要求16所述的方法,其中,所述光诱导的寡聚化结构域是CRY2OLIG。
19.如权利要求16所述的方法,其中,所述光诱导的寡聚化结构域是CRYPHR。
20.如权利要求15所述的方法,其中,所述光诱导的寡聚化结构域包含LOV结构域。
21.如权利要求15所述的方法,其中,所述光诱导的寡聚化结构域包含PHR结构域。
22.如权利要求15至21中任一项所述的方法,其中,所述来自神经退行性疾病靶蛋白的低复杂性结构域选自以下组成的组:TDP-43、ɑ突触核蛋白、Tau、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA2B1、EWS RNA结合蛋白1和TATA盒结合蛋白因子15。
23.如权利要求22所述的方法,其中,所述来自神经退行性疾病靶蛋白的低复杂性结构域是TDP-43。
24.如权利要求22所述的方法,其中,所述来自神经退行性疾病靶蛋白的低复杂性结构域是ɑ突触核蛋白。
25.如权利要求22所述的方法,其中,所述来自神经退行性疾病靶蛋白的低复杂性结构域是Tau。
26.如权利要求15至25中任一项所述的方法,其中,所述细胞是哺乳动物细胞。
27.如权利要求26所述的方法,其中,所述细胞是人类细胞。
28.如权利要求15至27中任一项所述的方法,其中,所述蓝光的波长在405nm至499nm之间。
29.一种筛选调节蛋白质聚集的试剂的方法,所述方法包括以下步骤:
将编码嵌合多肽的表达载体导入细胞,所述表达载体包含:
编码光诱导的寡聚化结构域的第一核苷酸序列和编码来自神经退行性疾病靶蛋白的低复杂性结构域的第二核苷酸序列,其中,所述第一核苷酸序列与启动子可操作地连接;
表达所述嵌合多肽;
将所述试剂引入包含所述细胞的培养基中;
通过用蓝光刺激而诱导所述嵌合多肽的寡聚化;和
确定所述试剂对蛋白质聚集的调节。
30.如权利要求29所述的方法,其中,所述光诱导的寡聚化结构域选自以下组成的组:CRYPHR、CRY2OLIG、NcVVD、NcVVDY50W、NcLOV、VfAU1、YtvA、EL222、RsLOV和AsLOV2。
31.如权利要求30所述的方法,其中,所述光诱导的寡聚化结构域是NcVVD。
32.如权利要求30所述的方法,其中,所述光诱导的寡聚化结构域是CRY2OLIG。
33.如权利要求30所述的方法,其中,所述光诱导的寡聚化结构域是CRYPHR。
34.如权利要求29所述的方法,其中,所述光诱导的寡聚化结构域包含LOV结构域。
35.如权利要求29所述的方法,其中,所述光诱导的寡聚化结构域包含PHR结构域。
36.如权利要求29至35中任一项所述的方法,其中,所述来自神经退行性疾病靶蛋白的低复杂性结构域选自以下组成的组:TDP-43、ɑ突触核蛋白、Tau、TIA1、SOD1、亨廷顿蛋白、Ataxin 2、hnRNPA2B1、EWS RNA结合蛋白1和TATA盒结合蛋白因子15。
37.如权利要求36所述的方法,其中,所述来自神经退行性疾病靶蛋白的低复杂性结构域是TDP-43。
38.如权利要求36所述的方法,其中,所述来自神经退行性疾病靶蛋白的低复杂性结构域是ɑ突触核蛋白。
39.如权利要求36所述的方法,其中,所述来自神经退行性疾病靶蛋白的低复杂性结构域是Tau。
40.如权利要求29至39中任一项所述的方法,其中,所述细胞是哺乳动物细胞。
41.如权利要求40所述的方法,其中,所述细胞是人类细胞。
42.如权利要求29至41中任一项所述的方法,其中,所述蓝光的波长在405nm至499nm之间。
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