神经退行性疾病病理的光遗传学诱导

文档序号:1471337 发布日期:2020-02-21 浏览:27次 >En<

阅读说明:本技术 神经退行性疾病病理的光遗传学诱导 (Optogenetic induction of neurodegenerative disease pathology ) 是由 C·J·唐纳利 J·R·曼恩 于 2018-03-07 设计创作,主要内容包括: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。(The present disclosure relates to compounds, compositions and methods for inducing a neurodegenerative disease pathology. In one aspect, disclosed herein is a nucleotide sequence encoding a chimeric polypeptide, the nucleotide sequence comprising: a first nucleotide sequence encoding a light-induced oligomerization domain and a second nucleotide sequence encoding a neurodegenerative disease target protein. Disclosed herein is a method of inducing a neurodegenerative disease pathology in a cell, the method comprising the steps of: introducing into a cell an expression vector encoding a chimeric polypeptide, said expression vector comprising: a first nucleotide sequence encoding a light-induced oligomerization domain and a second nucleotide sequence encoding a low complexity domain from a neurodegenerative disease target protein, wherein the first nucleotide sequence is operably linked to a promoter; expressing the chimeric polypeptide; and inducing oligomerization of the chimeric polypeptide by stimulation with blue light.)

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、***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***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***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

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<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

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<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

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<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

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<220>

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<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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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<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

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<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

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<213> 人工序列

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<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

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<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

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<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

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<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

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<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

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<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

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<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

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<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

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<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

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<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

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