CN116964213A - 融合蛋白的制造方法 - Google Patents

融合蛋白的制造方法 Download PDF

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CN116964213A
CN116964213A CN202280019883.3A CN202280019883A CN116964213A CN 116964213 A CN116964213 A CN 116964213A CN 202280019883 A CN202280019883 A CN 202280019883A CN 116964213 A CN116964213 A CN 116964213A
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永田英孝
林纹连
浅田玲子
泷川健司
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Abstract

一种融合蛋白的制造方法,其中,所述融合蛋白包含BDNF以及抗转铁蛋白受体抗体或其片段,所述融合蛋白的制造方法包括以下工序:在蛋白质生产用培养基中培养含有编码上述融合蛋白的基因和编码外源性伴侣蛋白的基因的经转化的哺乳动物细胞,来生产上述融合蛋白;以及对所生产的上述融合蛋白进行回收,其中,编码上述融合蛋白的基因包含编码上述BDNF的基因的碱基序列和编码上述抗转铁蛋白受体抗体或其片段的基因的碱基序列,上述伴侣蛋白包含选自由HSP90α、HSP90β、CDC37、HSP70、HSP40、HSP60、HSP10、HSP110以及HSP27构成的组中的一种以上。

Description

融合蛋白的制造方法
技术领域
本发明涉及一种融合蛋白的制造方法。
背景技术
目前,重组蛋白在广泛的领域中使用。由于近年的生物医药品的发展,其重要性进一步提高。重组蛋白主要以大肠杆菌、酵母、昆虫细胞、哺乳动物细胞等作为宿主细胞而制造(例如,日本特表2007-524381号公报(专利文献1))。当使用这些宿主细胞时,可以在短时间内得到大量的重组蛋白。另一方面,由于所表达的重组蛋白未进行正确的折叠、或未进行翻译后修饰等(例如,糖基化等)等理由,有时无法发挥该重组蛋白所具有的原本的功能。
特别是,作为难表达性蛋白质(Difficult to Express Protein:DEP)的脑源性神经营养因子(BDNF:Brain-derived neurotrophic factor)是神经营养素家族(Neurotrophin Family)之一。已知BDNF的二聚体与位于靶细胞表面上的高亲和性BDNF受体(也被称为TrkB;酪氨酸受体激酶Tyrosine receptor kinase B,原肌球蛋白受体激酶Tropomyosin receptor kinase B,或原肌球蛋白相关激酶Tropomyosin-related KinaseB)特异性结合,对中枢神经系统和末梢神经系统的细胞的分化、功能维持、突触形成、以及损伤时的再生和修复等发挥重要的作用(非专利文献2和非专利文献3)。由此,期待BDNF作为阿尔兹海默病、帕金森病、亨廷顿病等神经退行性疾病,肌萎缩侧索硬化症等脊柱退行性疾病,以及糖尿病神经病变、脑缺血性疾病、发育障碍、精神分裂症、抑郁症以及Rett综合征等多种疾病的治疗剂的开发。然而,已知BDNF难以作为重组蛋白大量地制造。
此外,已知包含BDNF和抗转铁蛋白受体抗体的融合蛋白作为由于BDNF穿过血脑屏障而能够入脑的融合蛋白(专利文献2和专利文献3),但要求将其作为重组蛋白大量地制造的方法。
现有技术文献
专利文献
专利文献1:日本特表2007-524381号公报
专利文献2:国际公开第2016/208696号
专利文献3:国际公开第2018/124107号
非专利文献
非专利文献1:Lee et al.,Journal of Biotechnology 143(2009)34-43
非专利文献2:Moses V.Chao.Nature Reviews Neuroscience.4.299-309(2003)
非专利文献3:Bollen E.Behavioural Brain Research.257C.8-12(2013)
发明内容
发明所要解决的问题
还期望开发能够大量地制造包含上述BDNF以及抗转铁蛋白受体抗体或其片段的融合蛋白的方法。
本发明是鉴于上述情况而完成的,本发明所要解决的技术问题在于提供生产效率提高的融合蛋白的制造方法。
用于解决问题的方案
本发明人等为了解决上述技术问题而进行了深入研究,结果发现如下事实,通过在作为宿主细胞的哺乳动物细胞中使编码包含BDNF以及抗转铁蛋白受体抗体或其片段的融合蛋白的基因与编码规定的伴侣蛋白的基因共同表达,上述融合蛋白的生产效率提高,从而完成了本发明。即,本发明如下所述。
[1]本发明的融合蛋白的制造方法是包含BDNF以及抗转铁蛋白受体抗体或其片段的融合蛋白的制造方法,包括以下工序:在蛋白质生产用培养基中培养含有编码上述融合蛋白的基因和编码外源性伴侣蛋白的基因的经转化的哺乳动物细胞,来生产上述融合蛋白;以及对所生产的上述融合蛋白进行回收,其中,编码上述融合蛋白的基因包含编码上述BDNF的基因的碱基序列和编码上述抗转铁蛋白受体抗体或其片段的基因的碱基序列,上述伴侣蛋白包含选自由HSP90α、HSP90β、CDC37、HSP70、HSP40、HSP60、HSP10、HSP110以及HSP27构成的组中的一种以上。
[2]本发明的融合蛋白的制造方法是包含上述BDNF以及上述抗转铁蛋白受体抗体或其片段的融合蛋白的制造方法,包括以下工序:准备哺乳动物细胞;使用编码上述融合蛋白的基因和编码上述伴侣蛋白的基因,对上述哺乳动物细胞进行转化;在蛋白质生产用培养基中培养经转化的上述哺乳动物细胞,来生产上述融合蛋白;以及对所生产的上述融合蛋白进行回收,其中,编码上述融合蛋白的基因包含编码上述BDNF的基因的碱基序列和编码上述抗转铁蛋白受体抗体或其片段的基因的碱基序列,上述伴侣蛋白包含选自由HSP90α、HSP90β、CDC37、HSP70、HSP40、HSP60、HSP10、HSP110以及HSP27构成的组中的一种以上。
[3]优选的是,在上述[2]所述的融合蛋白的制造方法中,对上述哺乳动物细胞进行转化的工序使用含有编码上述融合蛋白的基因和编码上述伴侣蛋白的基因的一种以上重组蛋白表达载体来实施。
[4]优选的是,在上述[2]所述的融合蛋白的制造方法中,对上述哺乳动物细胞进行转化的工序通过使含有编码上述融合蛋白的基因的一种以上重组蛋白表达载体、以及含有编码上述伴侣蛋白的基因的一种以上表达增强载体同时或分别与上述哺乳动物细胞接触来实施。
[5]本发明的融合蛋白的制造方法是包含上述BDNF以及上述抗转铁蛋白受体抗体或其片段的融合蛋白的制造方法,包括以下工序:准备哺乳动物细胞,该哺乳动物细胞包含含有编码上述融合蛋白的基因的一种以上重组蛋白表达载体;使用含有编码上述伴侣蛋白的基因的至少一种表达增强载体,对上述哺乳动物细胞进行转化;在蛋白质生产用培养基中培养经转化的上述哺乳动物细胞,来生产上述融合蛋白;以及对所生产的上述融合蛋白进行回收,其中,编码上述融合蛋白的基因包含编码上述BDNF的基因的碱基序列和编码上述抗转铁蛋白受体抗体或其片段的基因的碱基序列,上述伴侣蛋白包含选自由HSP90α、HSP90β、CDC37、HSP70、HSP40、HSP60、HSP10、HSP110以及HSP27构成的组中的一种以上。
[6]优选的是,在上述[5]所述的融合蛋白的制造方法中,上述表达增强载体包含:第一表达增强载体,含有编码第一伴侣蛋白的基因;以及第二表达增强载体,含有编码第二伴侣蛋白的基因,上述第一伴侣蛋白与上述第二伴侣蛋白不同。
[7]优选的是,上述伴侣蛋白包含HSP90α和CDC37中的任一者或两者。
[8]优选的是,上述BDNF直接或借助连接肽与上述抗转铁蛋白受体抗体或其片段结合。
[9]优选的是,上述连接肽包含选自由Gly、Ser、Gly-Ser、Gly-Gly-Ser、Gly-Gly-Gly-Gly-Ser、Gly-Gly-Gly-Gly-Gly-Ser、Ser-Gly-Gly-Gly-Gly、以及这些氨基酸序列1~10个连续而成的氨基酸序列构成的组中的氨基酸序列。
[10]优选的是,上述BDNF包含相对于序列号32的氨基酸序列具有至少90%的序列一致性的氨基酸序列。
[11]优选的是,上述抗转铁蛋白受体抗体的片段为Fab片段、F(ab’)2片段、或F(ab’)片段。
[12]优选的是,上述哺乳动物细胞包含选自由CHO细胞、COS细胞、BHK细胞、HeLa细胞、HEK293细胞、NS0细胞以及Sp2/0细胞构成的组中的一种以上。
[13]本发明的重组蛋白生产用哺乳动物细胞是包含含有编码融合蛋白的基因的一种以上重组蛋白表达载体的重组蛋白生产用哺乳动物细胞,上述融合蛋白包含BDNF以及抗转铁蛋白受体抗体或其片段,编码上述融合蛋白的基因包含编码上述BDNF的基因的碱基序列和编码上述抗转铁蛋白受体抗体或其片段的基因的碱基序列,上述重组蛋白生产用哺乳动物细胞还包含:含有编码伴侣蛋白的基因的一种以上表达增强载体,上述伴侣蛋白包含选自由HSP90α、HSP90β、CDC37、HSP70、HSP40、HSP60、HSP10、HSP110以及HSP27构成的组中的一种以上。
[14]本发明的试剂盒是用于增强哺乳动物细胞中的、包含BDNF以及抗转铁蛋白受体抗体或其片段的融合蛋白的生产量的试剂盒,上述试剂盒包含:含有编码伴侣蛋白的基因的一种以上表达增强载体,上述伴侣蛋白包含选自由HSP90α、HSP90β、CDC37、HSP70、HSP40、HSP60、HSP10、HSP110以及HSP27构成的组中的至少一种。
发明效果
根据本发明,能够提供生产效率提高的融合蛋白的制造方法。
附图说明
图1是表示经转化的哺乳动物细胞中的人BDNF-人抗转铁蛋白受体抗体Fab片段的产生量的图。
图2是表示经转化的哺乳动物细胞中的人BDNF-人抗转铁蛋白受体抗体Fab片段的产生量的图。
图3是表示通过培养产生人BDNF-人抗转铁蛋白受体抗体Fab片段后的、经转化的哺乳动物细胞的活细胞数的图。
具体实施方式
以下,对本发明的一个实施方式(以下有时记为“本实施方式”)进行说明。其中,本实施方式并不限定于此。在本说明书中,“A~Z”形式的表述是指范围的上限下限(即A以上且Z以下)。在A中没有记载单位、而仅在Z中记载了单位的情况下,A的单位与Z的单位相同。
本实施方式的融合蛋白的制造方法是包含BDNF以及抗转铁蛋白受体抗体或其片段的融合蛋白的制造方法,包括以下工序:在蛋白质生产用培养基中培养含有编码上述融合蛋白的基因和编码外源性伴侣蛋白的基因的经转化的哺乳动物细胞,来生产上述融合蛋白;以及对所生产的上述融合蛋白进行回收,其中,编码上述融合蛋白的基因包含编码上述BDNF的基因的碱基序列和编码上述抗转铁蛋白受体抗体或其片段的基因的碱基序列,上述伴侣蛋白包含选自由HSP90α、HSP90β、CDC37、HSP70、HSP40、HSP60、HSP10、HSP110以及HSP27构成的组中的一种以上。
在本实施方式的一个方面,上述经转化的哺乳动物细胞通过包括以下工序的方法来得到:准备哺乳动物细胞,该哺乳动物细胞包含含有编码上述融合蛋白的基因的一种以上重组蛋白表达载体;以及使用含有编码伴侣蛋白的基因的至少一种表达增强载体,对上述哺乳动物细胞进行转化。详情在后述的“融合蛋白的制造方法(1)”中进行说明。
在本实施方式的另一方面,上述经转化的哺乳动物细胞通过包括以下工序的方法来得到:准备哺乳动物细胞;以及使用编码上述融合蛋白的基因和编码伴侣蛋白的基因,对上述哺乳动物细胞进行转化。详情在后述的“融合蛋白的制造方法(2)”中进行说明。
《融合蛋白的制造方法(1)》
本实施方式的第一融合蛋白的制造方法是包含BDNF以及抗转铁蛋白受体抗体或其片段的融合蛋白的制造方法,包括以下工序:准备哺乳动物细胞,该哺乳动物细胞包含含有编码上述融合蛋白的基因的一种以上重组蛋白表达载体;使用含有编码伴侣蛋白的基因的至少一种表达增强载体,对上述哺乳动物细胞进行转化;在蛋白质生产用培养基中培养经转化的上述哺乳动物细胞,来生产上述融合蛋白;以及对所生产的上述融合蛋白进行回收,其中,编码上述融合蛋白的基因包含编码上述BDNF的基因的碱基序列和编码上述抗转铁蛋白受体抗体或其片段(以下,有时称为“附加蛋白”)的基因的碱基序列,上述伴侣蛋白包含选自由HSP90α、HSP90β、CDC37、HSP70、HSP40、HSP60、HSP10、HSP110以及HSP27构成的组中的一种以上。以下详细地进行说明。
<准备包含重组蛋白表达载体的哺乳动物细胞的工序>
在本工序中,准备哺乳动物细胞,该哺乳动物细胞包含含有编码融合蛋白的基因的一种以上重组蛋白表达载体。编码上述融合蛋白的基因包含编码上述BDNF的基因的碱基序列和编码上述附加蛋白的基因的碱基序列。
(融合蛋白)
本实施方式中的“融合蛋白”包含BDNF以及抗转铁蛋白受体抗体或其片段(以下,有时称为“附加蛋白”)。在本实施方式的一个方面,上述融合蛋白可以仅由BDNF和附加蛋白构成。在本实施方式的另一方面,上述融合蛋白可以由BDNF、上述附加蛋白以及连接BDNF与上述附加蛋白的连接肽构成。即,上述BDNF优选直接或借助连接肽与上述抗转铁蛋白受体抗体或其片段结合。
连接肽只要具有公知的氨基酸序列就没有特别限制。作为上述连接肽的氨基酸序列,例如可列举出:用氨基酸的1个字母标记由“GGGGS”表示的氨基酸序列(序列号76)重复5次的氨基酸序列(序列号75)。此外,也可列举出“EAAAAK”所表示的H4连接子(序列号77)连续2~4次而得到的肽连接子等。在本实施方式的一个方面,上述连接肽优选包含选自由Gly、Ser、Gly-Ser、Gly-Gly-Ser、Gly-Gly-Gly-Gly-Ser、Gly-Gly-Gly-Gly-Gly-Ser、Ser-Gly-Gly-Gly-Gly、以及这些氨基酸序列的相同或不同的氨基酸序列1~10个连续而成的氨基酸序列构成的组中的氨基酸序列。
在上述融合蛋白中,也可以在N末端侧配置有BDNF,在C末端侧配置有上述附加蛋白。在上述融合蛋白中,也可以在N末端侧配置有上述附加蛋白,在C末端侧配置有BDNF。即,也可以是,上述BDNF直接或借助连接肽与上述抗转铁蛋白受体抗体或其片段的重链和/或轻链的C末端侧或N末端侧结合。
作为上述融合蛋白,具体而言,可列举出国际公开公报:WO2016/208696(专利文献2)、或WO2018/124107(专利文献3)中记载的融合蛋白(BDNF与抗转铁蛋白受体抗体的融合蛋白)。
(BDNF)
在此,上述的BDNF是1982年由Barde等发现、1990年由Jones等克隆的公知的蛋白质(EMBO J,(1982)1:549-553,Proc.Natl.Acad.Sci.USA(1990)87:8060-8064)。BDNF包含:在生物体内发挥其功能的成熟BDNF、成熟前的BDNF前体(也称为“pro BDNF”)、以及在上述BDNF前体的N末端附加了信号肽的BDNF前体的前驱体(也称为“pre-pro BDNF”)。即,就BDNF而言,从其基因转录产物起,首先生成为pre-pro BDNF,从其中切断信号肽而成为proBDNF。之后,从上述pro BDNF切断N末端的110个氨基酸残基而成为成熟BDNF。
(附加蛋白)
在本实施方式中“附加蛋白”是指与上述BDNF一起构成上述融合蛋白的抗转铁蛋白受体抗体或抗转铁蛋白受体抗体片段。上述附加蛋白可以是单体,也可以是由两个亚基构成的二聚体,也可以是由多个亚基构成的多聚体。作为抗体片段,例如,可列举出由抗体的重链(H链)片段和抗体的轻链(L链)片段构成的Fab片段、F(ab’)2片段、F(ab’)片段、在抗体恒定区附加有该Fab片段的Fc片段、单链抗体(scFv)以及双特异抗体(diabody)。
(重组蛋白表达载体)
在本实施方式中,“重组蛋白表达载体”是指引入了编码目标重组蛋白的基因以便能够在宿主细胞内表达的DNA构建体。“重组蛋白”是指相对于上述宿主细胞为外源性的蛋白质。在本实施方式中,上述目标重组蛋白为上述融合蛋白。即,上述重组蛋白表达载体含有编码上述融合蛋白的基因。编码上述融合蛋白的基因包含编码上述BDNF的基因的碱基序列和编码上述附加蛋白的基因的碱基序列。
在上述附加蛋白为二聚体的情况下,编码上述融合蛋白的基因可以由第一基因和第二基因构成,所述第一基因包含编码上述BDNF的基因的碱基序列和编码构成上述附加蛋白的第一亚基的基因的碱基序列,所述第二基因包含编码构成上述附加蛋白的第二亚基的基因的碱基序列。在该情况下,上述重组蛋白表达载体可以由含有上述第一基因的第一重组蛋白表达载体和含有上述第二基因的第二重组蛋白表达载体构成。此外,上述重组蛋白表达载体可以同时含有上述第一基因和上述第二基因。需要说明的是,在上述附加蛋白为多聚体的情况下,也可以按照上述二聚体的情况进行编码融合蛋白的基因的设计、重组蛋白表达载体的设计。
在本实施方式中,编码上述BDNF的基因的碱基序列可以为野生型碱基序列,也可以为对野生型碱基序列引入了一种以上变异的碱基序列。即,编码上述BDNF的基因的碱基序列可以为以下碱基序列:(A)相对于编码上述BDNF的野生型碱基序列具有90%以上且100%以下的序列一致性(sequence identity)的碱基序列、(B)在编码BDNF的野生型碱基序列中缺失、置换、插入或者附加了一个或者多个碱基的碱基序列、(C)在严谨条件下与具有与编码BDNF的野生型碱基序列互补的碱基序列的寡核苷酸进行杂交的碱基序列、(D)编码相对于上述BDNF的野生型氨基酸序列具有90%以上且100%以下的序列一致性的氨基酸序列的碱基序列、或、(E)编码在上述BDNF的野生型氨基酸序列中缺失、置换、插入或者附加一个或者多个氨基酸残基的氨基酸序列的碱基序列,并且编码保持上述BDNF中的原有功能的蛋白质的碱基序列。
在此,“保持原有功能”是指具有与野生型BDNF同质的功能。“同质的功能”是指例如从生理学或药理学来看,其性质定性地相同,功能的程度(例,约0.1~约10倍、优选为0.5~2倍)或蛋白质的分子量等量的要素可以不同。此外,将具有野生型BDNF所具有的功能例如(1)对BDNF受体(TrkB)的结合亲和力(binding affinity)、(2)BDNF受体的磷酸化活性、(3)对神经细胞的增殖促进作用、(4)对神经细胞的生存维持作用、(5)对神经细胞的神经突延伸作用(neurite extension effect),或(6)可被特异性识别由序列号74的氨基酸序列构成的蛋白质的抗体识别的蛋白质视为与BDNF“具有同质的功能的蛋白质”。
此外,在BDNF为pre-pro BDNF的情况下,“原有功能”是指例如能够生成pro BDNF。在BDNF为pro BDNF的情况下,“原有功能”是指例如能够生成成熟BDNF、或具有对p75受体的结合亲和力。
在本实施方式中“序列一致性”是指使用本技术领域中公知的数学算法来比对两个碱基序列的情况下的最佳比对(优选的是,该算法可考虑为了最佳比对而向序列的一方或双方引入空位)中的、同一碱基相对于重叠的全部碱基序列的比例(%)。本领域技术人员能够容易地确认碱基序列的“序列一致性”。例如可以使用NCBI BLAST(National Centerfor Biotechnology Information Basic Local Alignment Search Tool;美国国立生物技术信息中心基本局部比对搜索工具)。氨基酸序列的序列一致性也可以通过与上述同样的方法进行确认。
编码上述BDNF的基因的碱基序列相对于编码上述BDNF的野生型碱基序列可以具有95%以上且100%以下的序列一致性,也可以具有98%以上且100%以下的序列一致性,也可以具有100%的序列一致性。
在本实施方式中,作为“缺失、置换、插入或附加了一个或多个碱基的碱基序列”,例如可列举出通过缺失、置换、插入或附加,相对于缺失、置换、插入或附加前的碱基序列具有80%以上、85%以上、90%以上、95%以上、97%以上、98%以上、或99%以上的序列一致性的碱基序列。作为“一个或多个碱基”的具体数量,上述缺失、置换、插入或附加可以分别独立地存在于一处、两处、三处、四处、或五处,也可以多种组合发生。
在本实施方式中“严谨条件”是指在包含6×SSC(1×SSC的组成:0.15M的NaCl、0.015M的柠檬酸钠、pH7.0)、0.5%SDS、5×Denhardt溶液、100μg/mL的变性鲑鱼精子DNA以及50%(v/v)甲酰胺的溶液中,在室温下培养(incubate)12小时,进一步用0.5×SSC在50℃以上的温度下进行清洗的条件。进而,也包括更严谨条件,例如在45℃或60℃下培养12小时;用0.2×SSC或0.1×SSC进行清洗;在清洗时在60℃或65℃以上的温度条件下进行清洗等更严格的条件。
在本实施方式的一个方面,编码上述BDNF的基因的碱基序列也可以为考虑到引入该基因的哺乳动物细胞中的密码子使用频率,进行了密码子优化的碱基序列。上述密码子优化例如通过以下的方式进行。即,可以使用如Codon W所代表的那样,能进行转录、翻译效果、折叠形成的优化的算法来进行密码子优化(例如,参照http://codonw.sourceforge.net/index.html)。
在本实施方式中,作为编码BDNF的基因的碱基序列,可列举出编码上述pre-proBDNF的碱基序列、编码pro BDNF的碱基序列以及编码成熟BDNF的碱基序列。作为编码上述pre-pro BDNF的碱基序列,例如可列举出序列号71(GenBank No.NM_170735.6、人源化野生碱基序列)的碱基序列。作为编码上述pro BDNF的碱基序列,例如可列举出编码上述pre-pro BDNF的相当于N末端18个氨基酸残基的信号肽缺失的pro BDNF的氨基酸序列的碱基序列(例如,序列号31)。作为编码上述成熟BDNF的碱基序列,例如可列举出编码上述pro BDNF的N末端110个氨基酸残基缺失的成熟BDNF的碱基序列(例如,序列号73)。在此,上述pre-pro BDNF中的信号肽可以是野生pre-pro BDNF所具有的信号肽,也可以是源自其他蛋白质的信号肽(例如,由序列号36的氨基酸序列构成的信号肽)。
上述BDNF的氨基酸序列相对于上述BDNF的野生型氨基酸序列可以具有95%以上且100%以下的序列一致性,也可以具有98%以上且100%以下的序列一致性,也可以具有100%的序列一致性。
在本实施方式中,作为“缺失、置换、插入或附加了一个或多个氨基酸残基的氨基酸序列”,例如可列举出通过缺失、置换、插入或附加,相对于缺失、置换、插入或附加前的氨基酸序列具有80%以上、85%以上、90%以上、95%以上、97%以上、98%以上、或99%以上的序列一致性的氨基酸序列。作为“一个或多个氨基酸残基”的具体数量,上述缺失、置换、插入或附加可以分别独立地存在于一处、两处、三处、四处、或五处,也可以多种组合发生。
在本实施方式中,作为BDNF的氨基酸序列,可列举出:上述的pre-pro BDNF的氨基酸序列、pro BDNF的氨基酸序列以及成熟BDNF的氨基酸序列。作为上述pre-pro BDNF的氨基酸序列,例如可列举出序列号72(GenBank No.NP_733931)的氨基酸序列。作为上述proBDNF的氨基酸序列,例如可列举出上述pre-pro BDNF的N末端信号肽缺失的氨基酸序列(例如,序列号32)。作为上述成熟BDNF的氨基酸序列,例如可列举出上述pro BDNF的N末端110个氨基酸残基缺失的氨基酸序列(例如,序列号74)。
在本实施方式中,编码上述附加蛋白的基因的碱基序列可以为野生型碱基序列,也可以为对上述野生型碱基序列引入了一种以上变异的碱基序列。即,编码上述附加蛋白的基因的碱基序列可以为以下碱基序列:(A)相对于编码上述附加蛋白的野生型碱基序列具有90%以上且100%以下的序列一致性的碱基序列、(B)在编码上述附加蛋白的野生型碱基序列中缺失、置换、插入或者附加了一个或者多个碱基的碱基序列、(C)在严谨条件下与具有与编码上述附加蛋白的野生型碱基序列互补的碱基序列的寡核苷酸进行杂交的碱基序列、(D)编码相对于上述附加蛋白的野生型氨基酸序列具有90%以上且100%以下的序列一致性的氨基酸序列的碱基序列、或、(E)编码在上述附加蛋白的野生型氨基酸序列中缺失、置换、插入或者附加了一个或者多个氨基酸残基的氨基酸序列的碱基序列,并且编码保持上述附加蛋白中的原有功能的蛋白质的碱基序列。
需要说明的是,在上述附加蛋白为二聚体或多聚体的情况下,对于编码构成上述附加蛋白的亚基的基因分别应用上述事项。
编码上述附加蛋白的基因的碱基序列相对于编码上述附加蛋白的野生型碱基序列可以具有95%以上且100%以下的序列一致性,也可以具有98%以上且100%以下的序列一致性,也可以具有100%的序列一致性。
在本实施方式的一个方面,编码上述附加蛋白的基因的碱基序列也可以为考虑到引入该基因的哺乳动物细胞中的密码子使用频率,进行了密码子优化的碱基序列。上述密码子优化例如通过上述方法进行。
在本实施方式中,在附加蛋白为Fab片段的情况下,作为编码抗体的重链片段(第一亚基)的基因的碱基序列,例如可列举出序列号37的碱基序列。作为编码抗体的轻链片段(第二亚基)的基因的碱基序列,例如可列举出序列号41的碱基序列。
上述附加蛋白的氨基酸序列相对于上述附加蛋白的野生型(在该情况下,包含由上述序列号37的碱基序列编码的蛋白质和由序列号41的碱基序列编码的蛋白质的Fab片段)的氨基酸序列,可以具有95%以上且100%以下的序列一致性,也可以具有98%以上且100%以下的序列一致性,也可以具有100%的序列一致性。
就上述附加蛋白而言,在专利文献3中记载了包含序列号38的重链片段和序列号42的轻链片段的附加蛋白的Fab片段、以及具有上述序列一致性的附加蛋白。
在本实施方式中,在附加蛋白为Fab片段的情况下,作为抗体的重链片段(第一亚基)的氨基酸序列,例如可列举出序列号38的氨基酸序列。作为抗体的轻链片段(第二亚基)的氨基酸序列,例如可列举出序列号42的氨基酸序列。
需要说明的是,在专利文献3中记载了包含序列号38的重链片段和序列号42的轻链片段的附加蛋白的Fab片段。
上述重组蛋白表达载体除了编码上述融合蛋白的基因以外,还包含启动子序列(例如,巨细胞病毒(CMV)启动子、单纯疱疹病毒(HSV)的胸苷激酶(TK)启动子、SV40启动子、EF-1启动子、肌动蛋白启动子、β球蛋白启动子以及增强子等)、Kozak序列、终止子序列、mRNA稳定化序列。在本实施方式的一个方面,上述重组蛋白表达载体可以进一步包含选自由复制起始点、增强子序列、信号序列、耐药基因(例如,对氨苄西林(Ampicillin)、四环素(Tetracycline)、卡那霉素(Kanamycin)、氯霉素(Chloramphenicol)、新霉素(Neomycin)、潮霉素(Hygromycin)、嘌呤霉素(Puromycin)、吉欧霉素(Zeocin)等的耐药基因)等选择标记基因、以及编码GFP等荧光蛋白的基因构成的组中的一种以上。
上述重组蛋白表达载体只要发挥本发明的效果就没有特别限制,例如可以为质粒载体、病毒载体。在本实施方式的一个方面,上述重组蛋白表达载体优选为质粒载体。
作为上述质粒载体,例如可列举出:pcDNA3.1(+)载体、pEGF-BOS载体、pEF载体、pCDM8载体、pCXN载体、pCI载体、附加型载体(Episomal Vector)、转座子载体(TransposonVector)等。在本实施方式的一个方面,上述质粒载体优选为pcDNA3.1(+)载体。
作为上述病毒载体,可列举出:慢病毒载体、腺病毒载体、腺相关病毒载体、仙台病毒载体、哺乳类表达型杆状病毒载体等。例如可列举出:pLenti4/V5-GW/lacZ、pLVSIN-CMV、pLVSIN-EF1α、pAxcwit2、pAxEFwit2、pAAV-RCS、pSeV载体、pFastBacMam、pFastBacMam2.0(VSV-G)等。
(哺乳动物细胞)
在本实施方式中,“哺乳动物细胞”是指源自哺乳动物的细胞。作为哺乳动物,例如可列举出人、仓鼠(例如,中国仓鼠)、小鼠、大鼠、绿猴等。上述哺乳动物细胞也可以是永生化细胞。
上述哺乳动物细胞只要是用作用于表达上述重组蛋白的宿主细胞的细胞就没有特别限制。作为这些哺乳动物细胞,例如可列举出:CHO细胞(源自中国仓鼠的卵巢的细胞株)、COS细胞(源自非洲绿猴的肾脏的细胞株)、BHK细胞(源自幼仓鼠的肾脏的细胞株)、HeLa细胞(源自人的子宫颈癌的细胞株)、HEK293细胞(源自人胚胎的肾的细胞株)、NS0细胞(源自小鼠的骨髓瘤的细胞株)以及Sp2/0细胞(源自小鼠的骨髓瘤的细胞株)。即,上述哺乳动物细胞优选包含选自由CHO细胞、COS细胞、BHK细胞、HeLa细胞、HEK293细胞、NS0细胞以及Sp2/0细胞构成的组中的一种以上。
<使用表达增强载体对哺乳动物细胞进行转化的工序>
在本工序中,使用含有编码伴侣蛋白的基因的至少一种表达增强载体对上述哺乳动物细胞进行转化。
(伴侣蛋白)
在本实施方式中,“伴侣蛋白”是指协助上述融合蛋白进行正确的折叠而获得原有功能的蛋白质。“融合蛋白的原有功能”是指构成上述融合蛋白的BDNF和附加蛋白各自所具有的原有功能。上述伴侣蛋白包含选自由HSP90α、HSP90β、CDC37(细胞分裂周期CellDivision Cycle 37,HSP90协同伴侣分子cochaperone)、HSP70、HSP40、HSP60、HSP10、HSP110以及HSP27构成的组中的一种以上。在此,“HSP”为热休克蛋白的简称。在本实施方式的一个方面,上述伴侣蛋白优选包含HSP90α、HSP90β、HSP40以及CDC37中的任一者、或包含HSP90α、HSP90β或者HSP40与CDC37这两者。
在本实施方式的另一方面,上述伴侣蛋白优选包含HSP90α以及CDC37中的任一者或两者。
在本实施方式的一个方面,上述伴侣蛋白的来源动物种可以与半胱氨酸结蛋白的来源动物种相同,也可以不同。
在本实施方式的一个方面,上述伴侣蛋白的来源动物种可以与宿主细胞的来源动物种相同,也可以不同。
在本实施方式的一个方面,上述伴侣蛋白的来源动物种优选与半胱氨酸结蛋白的来源动物种或宿主细胞的来源动物种中的任一者相同。
在本实施方式的一个方面,上述伴侣蛋白可以为人源化伴侣蛋白,也可以为源自中国仓鼠的伴侣蛋白。优选可以为人源化伴侣蛋白。
在本实施方式的一个方面,在上述融合蛋白包含BDNF和Fab片段的情况下,上述伴侣蛋白优选包含选自由HSP90α、HSP90β、HSP60、HSP10、HSP70以及HSP27构成的组中的一种以上。
(表达增强载体)
在本实施方式中,“表达增强载体”是指引入了编码上述伴侣蛋白的基因以便能够在宿主细胞内表达的DNA构建体。
在本实施方式中,编码上述伴侣蛋白的基因的碱基序列可以为野生型碱基序列,也可以为对上述野生型碱基序列引入了一种以上变异的碱基序列。即,编码上述伴侣蛋白的基因的碱基序列可以为以下碱基序列:(A)相对于编码上述伴侣蛋白的野生型碱基序列具有90%以上且100%以下的序列一致性的碱基序列、(B)在编码上述伴侣蛋白的野生型碱基序列中缺失、置换、插入或者附加了一个或者多个碱基的碱基序列、(C)在严谨条件下与具有与编码上述伴侣蛋白的野生型碱基序列互补的碱基序列的寡核苷酸进行杂交的碱基序列、(D)编码相对于上述伴侣蛋白的野生型氨基酸序列具有90%以上且100%以下的序列一致性的氨基酸序列的碱基序列、或、(E)编码在上述伴侣蛋白的野生型氨基酸序列中缺失、置换、插入或者附加了一个或者多个氨基酸残基的氨基酸序列的碱基序列,并且编码协助上述BDNF进行正确的折叠而获得原有功能的蛋白质的碱基序列。
编码上述伴侣蛋白的基因的碱基序列相对于编码上述伴侣蛋白的野生型碱基序列可以具有95%以上且100%以下的序列一致性,也可以具有98%以上且100%以下的序列一致性,也可以具有100%的序列一致性。
在本实施方式的一个方面,编码上述伴侣蛋白的基因的碱基序列也可以为考虑到引入该基因的哺乳动物细胞中的密码子使用频率,进行了密码子优化的碱基序列。上述密码子优化例如通过上述方法进行。
在本实施方式中,作为编码HSP90α的基因的碱基序列,例如可列举出:序列号45(GenBank No.NM_001017963、人源化野生碱基序列)、序列号47(GenBank No.NM_005348、人源化野生碱基序列)、序列号1、序列号3、序列号49(GenBank No.NM_001246821、源自中国仓鼠的野生碱基序列)以及序列号5的碱基序列。
作为编码HSP90β的基因的碱基序列,例如可列举出:序列号53(GenBank No.NM_001271970、人源化野生碱基序列)、序列号55(GenBank No.NM_001271971、人源化野生碱基序列)、序列号51(GenBank No.NM_001271972、人源化野生碱基序列)、序列号7、序列号9、序列号11、序列号57(GenBank No.XM_003501668.2、源自中国仓鼠的野生碱基序列)、以及序列号13的碱基序列。
作为编码CDC37的基因的碱基序列,例如可列举出:序列号59(GenBank No.NM_007065、人源化野生碱基序列)、序列号15、序列号61(GenBank No.XM_003499737、源自中国仓鼠的野生碱基序列)以及序列号17的碱基序列。
作为编码HSP60的基因的碱基序列,例如可列举出:序列号63(GenBank No.NM_199440、人源化野生碱基序列)、以及序列号19的碱基序列。
作为编码HSP40的基因的碱基序列,例如可列举出:序列号65(GenBank No.NM_001539、人源化野生碱基序列)、以及序列号21的碱基序列。
作为编码HSP10的基因的碱基序列,例如可列举出:序列号67(GenBank No.NM_002157、人源化野生碱基序列)、以及序列号23的碱基序列。
作为编码HSP110的基因的碱基序列,例如可列举出:序列号69(GenBank No.NM_006644、人源化野生碱基序列)、以及序列号25的碱基序列。
作为编码HSP70的基因的碱基序列,例如可列举出:Journal ofBiotechnology143(2009)34-43中记载的源自CHO的野生碱基序列、以及序列号27的碱基序列。
作为编码HSP27的基因的碱基序列,例如可列举出:Journal ofBiotechnology143(2009)34-43中记载的源自CHO的野生碱基序列、以及序列号29的碱基序列。
上述伴侣蛋白的氨基酸序列相对于上述伴侣蛋白的野生型氨基酸序列可以具有95%以上且100%以下的序列一致性,可以具有98%以上且100%以下的序列一致性,可以具有100%的序列一致性。
在本实施方式中,作为HSP90α的氨基酸序列,例如可列举出:序列号2(GenBankNo.NP_001017963)、序列号4(GenBank No.NP_005339)以及序列号6(GenBank No.NP_001233750)的氨基酸序列。
作为HSP90β的氨基酸序列,例如可列举出:序列号8(GenBank No.NP_001258899)、序列号10(GenBank No.NP_001258900)、序列号12(GenBank No.NP_001258901)以及序列号14(GenBank No.XP_003501716)的氨基酸序列。
作为CDC37的氨基酸序列,例如可列举出序列号16(Genbank No.NP_008996)和序列号18(GenBank No.XP_003499785)的氨基酸序列。
作为HSP60的氨基酸序列,例如可列举出序列号20的氨基酸序列(GenBankNo.NP_955472)的氨基酸序列。
作为HSP40的氨基酸序列,例如可列举出序列号22的氨基酸序列(GenBankNo.NP_001530)的氨基酸序列。
作为HSP10的氨基酸序列,例如可列举出序列号24(GenBank No.NP_002148)的氨基酸序列。
作为HSP110的氨基酸序列,例如可列举出序列号26(GenBank No.NP_006635)的氨基酸序列。
作为HSP70的氨基酸序列,例如可列举出序列号28(Journal ofBiotechnology143(2009)34-43记载)的氨基酸序列。
作为HSP27的氨基酸序列,例如可列举出序列号30(Journal ofBiotechnology143(2009)34-43记载)的氨基酸序列。
上述表达增强载体除了编码上述伴侣蛋白的基因以外,还包含启动子序列(例如,巨细胞病毒(CMV)启动子、单纯疱疹病毒(HSV)的胸苷激酶(TK)启动子、SV40启动子、EF-1启动子、肌动蛋白启动子、β球蛋白启动子以及增强子等)、Kozak序列、终止子序列、mRNA稳定化序列。在本实施方式的一个方面,上述表达增强载体可以进一步包含选自由复制起始点、增强子序列、信号序列、耐药基因(例如,对氨苄西林、四环素、卡那霉素、氯霉素、新霉素、潮霉素、嘌呤霉素、吉欧霉素等的耐药基因)等选择标记基因、以及编码GFP等荧光蛋白的基因构成的组中的一种以上。
上述表达增强载体只要发挥本发明的效果就没有特别限制,例如可以是质粒载体、病毒载体。在本实施方式的一个方面,上述表达增强载体优选为质粒载体。
作为上述质粒载体,例如可列举出:pcDNA3.1(+)载体、pEGF-BOS载体、pEF载体、pCDM8载体、pCXN载体、pCI载体、附加型载体、转座子载体等。在本实施方式的一个方面,上述质粒载体优选为pcDNA3.1(+)载体。
作为上述病毒载体,可列举出:慢病毒载体、腺病毒载体、腺相关病毒载体、仙台病毒载体、哺乳类表达型杆状病毒载体等。例如可列举出:pLenti4/V5-GW/lacZ、pLVSIN-CMV、pLVSIN-EF1α、pAxcwit2、pAxEFwit2、pAAV-RCS、pSeV载体、pFastBacMam、pFastBacMam2.0(VSV-G)等。
在本实施方式中,编码上述融合蛋白的基因的设计、编码上述BDNF的基因片段的获取、编码上述附加蛋白的基因片段的获取、编码上述伴侣蛋白的基因片段的获取、以及上述质粒载体的构建可以依据分子生物学、生物工程、基因工程领域中惯用的技术来进行(例如,Sambrook et al.”Molecular Cloning-A Laboratory Manual,second edition1989”)。质粒载体的制备中使用的宿主细胞例如可列举出本技术领域中通常使用的大肠杆菌。
在本工序中,使用至少一种表达增强载体对上述哺乳动物细胞进行转化即可,但也可以使用多种表达增强载体对上述哺乳动物细胞进行转化。在此,上述哺乳动物细胞是包含一种以上重组蛋白表达载体的哺乳动物细胞,上述重组蛋白表达载体含有编码前一工序中准备的上述融合蛋白的基因。即,在本实施方式的一个方面,优选的是,上述表达增强载体包含:第一表达增强载体,含有编码第一伴侣蛋白的基因;以及第二表达增强载体,含有编码第二伴侣蛋白的基因,上述第一伴侣蛋白与上述第二伴侣蛋白不同。此时,更优选的是,上述第一伴侣蛋白为HSP90α,上述第二伴侣蛋白为CDC37。
或者,也可以用包含两个以上编码伴侣蛋白的基因的表达增强载体对哺乳动物细胞进行转化。
(使用表达增强载体的转化)
在本实施方式中,使用表达增强载体的转化的方法只要发挥本发明的效果就没有特别限制,可以使用公知的方法(例如,Sambrook et al.”Molecular Cloning-ALaboratory Manual,second edition 1989”)。作为公知的转化方法,例如可列举出:脂质体转染法、磷酸钙法、DEAE葡聚糖法、电穿孔法、聚乙烯亚胺法以及聚乙二醇法等。此外,也可以使用市售的试剂盒来进行上述的转化。作为这样的试剂盒,例如可列举出ThermoFisher Scientific K.K.公司制的Gibco(商标)Expi(商标)表达系统(ExpressionSystem)(Cat.No.A29133)等。
在脂质体转染法的情况下,例如,相对于细胞密度1×106cells/mL~9×106cells/mL,使用3μg~30μg的表达载体。例如,对于放入至25mL容器的细胞(6×106cells/mL),使用总计20μg的表达增强载体。
<生产融合蛋白的工序>
在本工序中,在蛋白质生产用培养基中培养经转化的上述哺乳动物细胞,来生产上述融合蛋白。
以往,已知将大肠杆菌作为宿主细胞来大量生产重组蛋白的方法,但将哺乳动物细胞用作宿主细胞且将作为难表达性蛋白质的半胱氨酸结蛋白(例如,BDNF)或包含上述半胱氨酸结蛋白的融合蛋白作为保持有呈现功能的构象(conformation)的可溶性组分来大量生产的方法是未知的。在本实施方式的融合蛋白的制造方法中,通过在上述哺乳动物细胞中使编码融合蛋白的基因与编码规定的伴侣蛋白的基因共同表达,上述融合蛋白的生产效率提高。
就经转化的上述哺乳动物细胞的培养而言,对培养基的组成、培养基的pH、葡萄糖浓度、培养温度、培养时间、表达激发子的使用量以及使用时间等条件进行适当调整,使得上述融合蛋白和上述伴侣蛋白高效表达。
经转化的上述哺乳动物细胞的培养中所使用的蛋白质生产用培养基只要是适于蛋白质的生产的公知的培养基就没有特别限制,可以是固体培养基,也可以是液体培养基。上述蛋白质生产用培养基优选为液体培养基。作为上述蛋白质生产用培养基,例如可列举出Dulbecco改良Eagle培养基(DMEM)、Eagle最低基础培养基(MEM)、Roswell Park纪念研究所培养基1640(RPMI1640)、Iscove改良Dulbecco培养基(IMDM)、F10培养基、F12培养基、DMEM/F12、FreeStyle293表达培养基、Freestyle CHO培养基等。上述蛋白质生产用培养基也可以包含胎牛血清(FCS)。上述蛋白质生产用培养基也可以是无血清培养基。
<对融合蛋白进行回收的工序>
在本工序中,对所生产的上述融合蛋白进行回收。本工序包括:从培养结束后的培养上清液中对所生产的上述融合蛋白进行回收。例如,可以在培养结束后,通过各种提纯法处理所得到的培养上清液,得到经提纯的高纯度的融合蛋白。
提纯法例如可以从培养上清液的热处理、盐析以及阴离子交换色谱、凝胶过滤色谱、疏水色谱、羟基磷灰石色谱以及亲和色谱等各种色谱中选择至少一种。
《融合蛋白的制造方法(2)》
本实施方式的第二融合蛋白的制造方法是包含BDNF以及抗转铁蛋白受体抗体或其片段的融合蛋白的制造方法,包括以下工序:准备哺乳动物细胞;使用编码上述融合蛋白的基因和编码伴侣蛋白的基因,对上述哺乳动物细胞进行转化;在蛋白质生产用培养基中培养经转化的上述哺乳动物细胞,来生产上述融合蛋白;以及对所生产的上述融合蛋白进行回收,其中,编码上述融合蛋白的基因包含编码上述BDNF的基因的碱基序列和编码上述抗转铁蛋白受体抗体或其片段的基因的碱基序列,上述伴侣蛋白包含选自由HSP90α、HSP90β、CDC37、HSP70、HSP40、HSP60、HSP10、HSP110以及HSP27构成的组中的一种以上。
<准备哺乳动物细胞的工序>
在本工序中,准备哺乳动物细胞。上述哺乳动物细胞可以使用上述的“融合蛋白的制造方法(1)”中举例示出的哺乳动物细胞。即,上述哺乳动物细胞优选包含选自由CHO细胞、COS细胞、BHK细胞、HeLa细胞、HEK293细胞、NS0细胞以及Sp2/0细胞构成的组中的一种以上。
<对哺乳动物细胞进行转化的工序>
在本工序中,使用编码融合蛋白的基因和编码伴侣蛋白的基因,对哺乳动物细胞进行转化。编码上述融合蛋白的基因包含编码上述BDNF的基因的碱基序列和编码上述抗转铁蛋白受体抗体或其片段的基因的碱基序列。
上述融合蛋白可以使用上述的“融合蛋白的制造方法(1)”中举例示出的融合蛋白。
即,上述融合蛋白包含BDNF以及抗转铁蛋白受体抗体或其片段。作为抗转铁蛋白受体抗体的片段,例如,可列举出由抗体的重链(H链)片段和抗体的轻链(L链)片段构成的Fab片段、在抗体恒定区附加有该Fab片段的Fc片段、单链抗体(scFv)以及双特异抗体(diabody)。
上述伴侣蛋白可以使用上述的“融合蛋白的制造方法(1)”中举例示出的伴侣蛋白。即,上述伴侣蛋白包含选自由HSP90α、HSP90β、CDC37、HSP70、HSP40、HSP60、HSP10、HSP110以及HSP27构成的组中的一种以上。在本实施方式的一个方面,上述伴侣蛋白优选包含HSP90α、HSP90β、HSP40以及CDC37中的任一者、或包含HSP90α、HSP90β或者HSP40与CDC37这两者。在本实施方式的另一方面,上述伴侣蛋白优选包含HSP90α以及CDC37中的任一者或两者。
在本实施方式中,将编码融合蛋白的基因和编码伴侣蛋白的基因引入至作为宿主细胞的哺乳动物细胞的顺序没有特别限制。可以是将编码融合蛋白的基因引入至上述哺乳动物细胞,然后将编码伴侣蛋白的基因引入至上述哺乳动物细胞。也可以是将编码伴侣蛋白的基因引入至上述哺乳动物细胞,然后将编码融合蛋白的基因引入至上述哺乳动物细胞。此外,也可以将编码融合蛋白的基因和编码伴侣蛋白的基因同时引入至上述哺乳动物细胞。
例如,在将两种基因引入至宿主细胞的情况下的、编码融合蛋白的基因与编码伴侣蛋白的基因的比率为1∶1~10∶1,更具体地可以为4∶1。
在本实施方式的一个方面,对上述哺乳动物细胞进行转化的工序优选使用含有编码上述融合蛋白的基因和编码上述伴侣蛋白的基因的一种以上重组蛋白表达载体来实施。上述重组蛋白表达载体含有编码上述融合蛋白的基因和编码上述伴侣蛋白的基因,因此也可以理解为表达增强载体。
在该情况下,上述重组蛋白表达载体可以在编码上述融合蛋白的基因和编码上述伴侣蛋白的基因各自的上游配置相同或相互不同的启动子序列。通过像这样构建重组蛋白表达载体,能够单独地表达控制上述融合蛋白和上述伴侣蛋白。
在本实施方式的另一方面,上述重组蛋白表达载体可以从5’末端侧依次配置启动子序列、编码上述融合蛋白的基因以及编码上述伴侣蛋白的基因,也可以从5’末端侧依次配置启动子序列、编码上述伴侣蛋白的基因以及编码上述融合蛋白的基因。通过像这样构建重组蛋白表达载体,能够通过单一启动子序列同时控制上述融合蛋白和上述伴侣蛋白各自的表达。可认为表达的多肽在适当的部位被切断而成为上述融合蛋白和上述伴侣蛋白。
在本实施方式的另一方面,在上述附加蛋白为二聚体的情况下,编码上述融合蛋白的基因可以由第一基因和第二基因构成,所述第一基因包含编码上述BDNF的基因的碱基序列和编码构成上述附加蛋白的第一亚基的基因的碱基序列,所述第二基因包含编码构成上述附加蛋白的第二亚基的基因的碱基序列。在该情况下,对上述哺乳动物细胞进行转化的工序优选使用含有上述第一基因、上述第二基因以及编码上述伴侣蛋白的基因的一种以上重组蛋白表达载体来实施。
在本实施方式的另一方面,对上述哺乳动物细胞进行转化的工序优选通过使含有编码上述融合蛋白的基因的一种以上重组蛋白表达载体、以及含有编码上述伴侣蛋白的基因的一种以上表达增强载体同时或分别与上述哺乳动物细胞接触来实施。
在本实施方式的另一方面,在上述附加蛋白为二聚体的情况下,对上述哺乳动物细胞进行转化的工序优选通过使含有上述第一基因的第一重组蛋白表达载体、含有上述第二基因的第二重组蛋白表达载体、以及含有编码上述伴侣蛋白的基因的一种以上表达增强载体同时或分别与上述哺乳动物细胞接触来实施。
<生产融合蛋白的工序>
在本工序中,在蛋白质生产用培养基中培养经转化的上述哺乳动物细胞,来生成上述融合蛋白。具体的方法可以使用上述的“融合蛋白的制造方法(1)”中叙述的方法。
<对融合蛋白进行回收的工序>
在本工序中,对所生产的上述融合蛋白进行回收。具体的方法可以使用在上述的“融合蛋白的制造方法(1)”中叙述的方法。
《重组蛋白生产用哺乳动物细胞》
本实施方式中的重组蛋白生产用哺乳动物细胞是包含含有编码融合蛋白的基因的一种以上重组蛋白表达载体的重组蛋白生产用哺乳动物细胞,上述融合蛋白包含BDNF以及抗转铁蛋白受体抗体或其片段,编码上述融合蛋白的基因包含编码上述BDNF的基因的碱基序列和编码上述抗转铁蛋白受体抗体或其片段的基因的碱基序列,上述重组蛋白生产用哺乳动物细胞还包含:含有编码伴侣蛋白的基因的一种以上表达增强载体,上述伴侣蛋白包含选自由HSP90α、HSP90β、CDC37、HSP70、HSP40、HSP60、HSP10、HSP110以及HSP27构成的组中的一种以上。
《用于增强融合蛋白的生产量的试剂盒》
本实施方式中的试剂盒是用于增强哺乳动物细胞中的、包含BDNF以及抗转铁蛋白受体抗体或其片段的融合蛋白的生产量的试剂盒,上述试剂盒包含:含有编码伴侣蛋白的基因的一种以上表达增强载体,上述伴侣蛋白包含选自由HSP90α、HSP90β、CDC37、HSP70、HSP40、HSP60、HSP10、HSP110以及HSP27构成的组中的至少一种。
在本实施方式中,上述试剂盒可以进一步含有选自由缓冲溶液、作为宿主细胞的哺乳动物细胞、重组蛋白表达载体、蛋白质生产用培养基、样品管、微孔板、针对试剂盒使用者的操作说明书、以及转染试剂构成的组中的一种以上。
《医药组合物》
通过本发明的制造方法制造的融合蛋白可以用作含有该融合蛋白作为有效成分的医药组合物的原料。本申请发明包括该医药组合物的制造方法,上述制造方法包括使添加物与该融合蛋白接触的工序。上述添加物只要是作为医药组合物中所含的添加物通常已知的成分就没有特别限制,可以适当选择。
实施例
以下,对本发明的实施例进行说明,但本发明并不限定于这些。
《表达增强因子的哺乳类表达质粒(表达增强载体)的制备》
将以下的九种基因作为表达增强因子(伴侣蛋白)用于研究。
(1)人热休克蛋白90α(HSP90α)基因(HSP90AA1)(GenBank No.NP_001017963、氨基酸序列:序列号2)(密码子优化后的碱基序列:序列号1)、(2)人细胞分裂周期37,HSP90协同伴侣分子(CDC37)基因(Genbank No.NP_008996、氨基酸序列:序列号16)(密码子优化后的碱基序列:序列号15)、(3)人HSP60基因(GenBank No.NP_955472、氨基酸序列:序列号20)(密码子优化后的碱基序列:序列号19)、(4)人HSP10基因(GenBank No.NP_002148、氨基酸序列:序列号24)(密码子优化后的碱基序列:序列号23)、(5)人HSP110基因(GenBankNo.NP_006635、氨基酸序列:序列号26)(密码子优化后的碱基序列:序列号25)、(6)人HSP40基因(GenBank No.NP_NP_001530、氨基酸序列:序列号22)(密码子优化后的碱基序列:序列号21)、(7)人HSJ1基因(GenBank No.AAA09034、氨基酸序列:序列号34)(密码子优化后的碱基序列:序列号33)、(8)源自中国仓鼠卵巢的细胞CHO的HSP70基因(J.Biotechnology 143(2009)34-43)(密码子优化后的碱基序列:序列号27、氨基酸序列:序列号28)、以及(9)源自中国仓鼠卵巢的细胞CHO的HSP27基因(J.Biotechnology 143(2009)34-43)(密码子优化后的碱基序列:序列号29、氨基酸序列:序列号30)。
针对上述九种基因,分别使用Genscript公司的OptimumGene(密码子优化),确定出在使用CHO细胞的表达系统中最佳的碱基序列。对于上述九种基因,分别通过化学合成法制作在所确定的最佳碱基序列中的N末端附加了Kozak序列(ccacc)、在C末端附加了终止密码子(TGA)的基因片段。在哺乳类用表达载体pcDNA3.1(+)载体(Cat.No.V79020,Invitrogen)的HindIII-EcoRI位点插入各自的基因片段,制备表达增强因子的质粒载体(1mg/mL)。通过以上的工序,得到九种表达增强载体。
作为针对上述表达增强因子的对照,使用了增强绿色荧光蛋白(EGFP:EnhancedGreen Fluorescent Protein)基因(GenBank No.AAF62891.1)。针对上述EGFP基因,使用Genscript公司的OptimumGene(密码子优化),确定出在使用CHO细胞的表达系统中最佳的碱基序列。通过化学合成法制作在所确定的最佳碱基序列中的N末端附加了Kozak序列(ccacc)、在C末端附加了终止密码子(TGA)的基因片段。在哺乳类用表达载体pcDNA3.1(+)载体(Cat.No.V79020,Invitrogen)的HindIII-EcoRI位点插入上述基因片段,制备对照质粒载体(1mg/mL)。
《由BDNF和附加蛋白构成的融合蛋白的哺乳类表达质粒(重组蛋白表达载体)的制备》
准备以下基因作为编码由BDNF和附加蛋白构成的融合蛋白的基因。
(1)第一基因:hBDNF-hFab(H)基因(密码子优化后的碱基序列:序列号39、氨基酸序列:序列号40、其中hFab(H)为抗转铁蛋白受体抗体的Fab重链)、以及(2)第二基因:hFab(L)基因(密码子优化后的碱基序列:序列号43、氨基酸序列:序列号44、其中hFab(L)为抗转铁蛋白受体抗体的Fab轻链)。
上述hBDNF-hFab(H)基因是编码多肽的基因,该多肽按从N末端侧起的顺序由IgG信号序列(GenBank No.6SVL_B、密码子优化后的碱基序列:序列号35、氨基酸序列:序列号36)、人BDNF(密码子优化后的碱基序列:序列号31、氨基酸序列:序列号32)、甘氨酸连接子(氨基酸序列:序列号75)以及作为第一亚基的人抗转铁蛋白受体抗体Fab H链片段(密码子优化后的碱基序列:序列号37、氨基酸序列:序列号38)构成。
上述hFab(L)基因是编码多肽的基因,该多肽按从N末端侧起的顺序由IgG信号序列(GenBank No.6SVL_B、密码子优化后的碱基序列:序列号35、氨基酸序列:序列号36)以及作为第二亚基的人抗转铁蛋白受体抗体Fab L链片段(密码子优化后的碱基序列:序列号41、氨基酸序列:序列号42)构成。
针对上述两种基因,分别使用Genscript公司的OptimumGene(密码子优化),确定出在使用CHO细胞的表达系统中最佳的碱基序列。针对上述两种基因,分别通过化学合成法制作在所确定的最佳碱基序列中的N末端附加了Kozak序列(ccacc)、在C末端附加了终止密码子(TAA)的基因片段。在哺乳类用表达载体pcDNA3.1(+)载体(Cat.No.V79020,Invitrogen)的HindIII-EcoRI位点插入各自的基因片段,制备各重组蛋白的质粒载体(1mg/mL)。通过以上的工序,得到两种重组蛋白表达载体。
《使用Expi-CHO表达系统的、人BDNF-人抗转铁蛋白受体抗体Fab片段的产生中的、基于表达增强因子的增强效果的研究》
利用Gibco(商标)Expi(商标)表达系统(Cat.No.A29133,ThermoFisherScientific K.K.),按照Max Titer Protocol实施以下的操作。首先,将培养的Expi-CHO细胞(6×106cells/mL)加入至装有ExpiCHO(商标)表达培养基(Expression Medium)(Cat.No.A29100-01,ThermoFisher Scientific K.K.)(25mL)的125mL容量的锥形瓶(Corning Inc.Cat.No.431143)中。接着,分别制备以下的表1所示的包含质粒载体的试剂(1ml)。此外,在与上述包含质粒载体的试剂不同的管中加入Expifectamine(Cat.No.A12129)(80μL)和OptiPRO(商标)SFM(Cat.No.12309050)(920μL)。分别搅拌上述包含质粒载体的试剂和上述包含Expifectamine的试剂,在室温下放置5分钟。然后,慢慢混合两种试剂,制成ExpiFectamine(商标)CHO/质粒DNA复合物(plasmid DNA complexes),在室温下放置1~5分钟。将该复合物加入至装有Expi-CHO细胞的125mL容量的锥形瓶中,在37℃、8%CO2、125rpm下实施一晚搅拌培养。
[表1]
转染各质粒载体后,在18~22小时内,将ExpiFectamine(商标)CHO增强子(Enhancer)(150μL)和ExpiCHO(商标)Feed(4mL)加入至培养液中,在32℃、5%CO2、125rpm下进行培养。培养后第5天,将ExpiCHO(商标)Feed(4mL)进一步加入至上述培养液中,在32℃、5%CO2、125rpm下进行培养。在培养后第7天至第13天的期间,回收培养上清液,通过ELISA计算人BDNF-人抗转铁蛋白受体抗体Fab片段(以下,有时称为“融合蛋白”、“BDNF-hFab”)的生产率。此外,关于细胞活性(cell viability),通过使用Countess II FL自动细胞计数仪(Cat.No.AMQAF1000,ThermoFisher Scientific K.K.)测定总细胞数和活细胞数来计算出。
培养上清液中的融合蛋白的浓度使用ELISA(Biosensis,Cat.No.BEK-2211-1P/2P)计算出。培养后第13天回收细胞,使用Countess II FL自动细胞计数仪对活细胞数进行计数,以10000xg离心5分钟后回收培养上清液。将回收到的培养上清液稀释至能用标准品(standards)定量的范围(7.8~500pg/mL)(稀释倍率:30000倍~1000000倍)。在微孔板,在各孔中加入100μL标准品、试剂盒内所含的QC样品、以及稀释后的培养上清液,在室温下搅拌45分钟。然后,将样品从各孔中除去,使用清洗溶液,将各孔清洗五次(200μL/孔×5次)。以100μL/well加入检测抗体,在室温下搅拌30分钟。从各孔中除去抗体,同样地进行清洗。向各孔中加入四甲基联苯胺试剂(TMB试剂)使其反应,确认到适度的蓝色反应后,向各孔中加入终止液。使用酶标仪(SpectraMax M5e,Molecular Devices LLC.)测定450nm波长下的吸光度,由标准品计算出培养上清液中的融合蛋白的产生量(浓度),确认了基于有无表达增强因子带来的产生增强效果(图1)。其结果是,HSP90α(试样1-2)和源自CHO的HSP70(试样No.1-3)最能增强融合蛋白的产生。此外,在源自CHO的HSP27(试样No.1-4)、人CDC37(试样No.1-5)、HSP40(试样No.1-6)、HSP10(试样No.1-7)、HSP110(试样No.1-8)中也确认到融合蛋白的产生增强作用。另一方面,HSJ1(试样No.1-14)完全没有体现出效果。
接着,确认了HSP90α和已知在细胞内形成分子伴侣(chaperone)的CDC37的效果(图2)。判明了:与HSP90α单独表达相比,共表达CDC37对融合蛋白的产生增强作用更高(图2的试样No.1-2和试样No.1-10)。可知即使在Expi-CHO中表达融合蛋白,细胞增殖也没有变化,此外,即使共表达HSP90α等伴侣蛋白,细胞增殖也没有变化(图3)。
如以上那样对本发明的实施方式和实施例进行了说明,但最初也预定将上述的各实施方式和各实施例的构成适当组合。
应该认为本次公开的实施方式和实施例在所有方面都是示例性的而不是限制性的。本发明的范围并不是由上述的实施方式和实施例示出,而是由权利要求书示出,意图在于包括与权利要求书等同的含义和范围内的所有变更。
序列表
<110> 住友制药株式会社
<120> 融合蛋白的制造方法
<130> 9220118WO01
<150> JP 2021-038368
<151> 2021-03-10
<160> 77
<170> PatentIn 3.5版
<210> 1
<211> 2583
<212> DNA
<213> 人工序列
<220>
<223> NP_001017963 (hHSP90 α)的密码子优化基因
<220>
<221> CDS
<222> (13)..(2577)
<400> 1
aagcttgcca cc atg ccc cct tgc agc ggc ggc gac ggc tct acc cca ccc 51
Met Pro Pro Cys Ser Gly Gly Asp Gly Ser Thr Pro Pro
1 5 10
gga cca agc ctg aga gat cgc gac tgt cca gcc cag tct gct gag tat 99
Gly Pro Ser Leu Arg Asp Arg Asp Cys Pro Ala Gln Ser Ala Glu Tyr
15 20 25
ccc agg gat cgg ctg gac cca agg ccc ggc tct ccc tct gag gcc tcc 147
Pro Arg Asp Arg Leu Asp Pro Arg Pro Gly Ser Pro Ser Glu Ala Ser
30 35 40 45
agc cct cca ttc ctg aga tcc cgc gct cct gtg aac tgg tat cag gag 195
Ser Pro Pro Phe Leu Arg Ser Arg Ala Pro Val Asn Trp Tyr Gln Glu
50 55 60
aag gcc cag gtg ttt ctg tgg cac ctg atg gtg agc ggc tct acc aca 243
Lys Ala Gln Val Phe Leu Trp His Leu Met Val Ser Gly Ser Thr Thr
65 70 75
ctg ctg tgc ctg tgg aag cag cct ttc cat gtg agc gct ttt cca gtg 291
Leu Leu Cys Leu Trp Lys Gln Pro Phe His Val Ser Ala Phe Pro Val
80 85 90
acc gcc tcc ctg gct ttc agg cag tct cag gga gct gga cag cac ctg 339
Thr Ala Ser Leu Ala Phe Arg Gln Ser Gln Gly Ala Gly Gln His Leu
95 100 105
tac aag gat ctg cag ccc ttt atc ctg ctg cgg ctg ctg atg cct gag 387
Tyr Lys Asp Leu Gln Pro Phe Ile Leu Leu Arg Leu Leu Met Pro Glu
110 115 120 125
gag aca cag aca cag gac cag cca atg gag gag gag gag gtg gag aca 435
Glu Thr Gln Thr Gln Asp Gln Pro Met Glu Glu Glu Glu Val Glu Thr
130 135 140
ttc gcc ttt cag gct gag atc gcc cag ctg atg tct ctg atc atc aac 483
Phe Ala Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile Asn
145 150 155
aca ttc tac tcc aat aag gag atc ttt ctg agg gag ctg atc agc aat 531
Thr Phe Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser Asn
160 165 170
tct tcc gat gcc ctg gac aag atc cgg tat gag tct ctg acc gat cca 579
Ser Ser Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp Pro
175 180 185
tct aag ctg gac tcc ggc aag gag ctg cac atc aac ctg atc ccc aat 627
Ser Lys Leu Asp Ser Gly Lys Glu Leu His Ile Asn Leu Ile Pro Asn
190 195 200 205
aag cag gat cgg acc ctg aca atc gtg gac acc ggc atc ggc atg aca 675
Lys Gln Asp Arg Thr Leu Thr Ile Val Asp Thr Gly Ile Gly Met Thr
210 215 220
aag gct gac ctg atc aac aat ctg ggc acc atc gcc aag agc ggc aca 723
Lys Ala Asp Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys Ser Gly Thr
225 230 235
aag gct ttc atg gag gcc ctg cag gct gga gct gat atc tcc atg atc 771
Lys Ala Phe Met Glu Ala Leu Gln Ala Gly Ala Asp Ile Ser Met Ile
240 245 250
ggc cag ttc ggc gtg ggc ttt tac agc gct tat ctg gtg gcc gag aag 819
Gly Gln Phe Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val Ala Glu Lys
255 260 265
gtg acc gtg atc aca aag cat aac gac gat gag cag tac gct tgg gag 867
Val Thr Val Ile Thr Lys His Asn Asp Asp Glu Gln Tyr Ala Trp Glu
270 275 280 285
agc tct gcc ggc ggc tct ttt acc gtg agg acc gat aca ggc gag cct 915
Ser Ser Ala Gly Gly Ser Phe Thr Val Arg Thr Asp Thr Gly Glu Pro
290 295 300
atg ggc cgg ggc acc aaa gtg atc ctg cac ctg aag gag gac cag aca 963
Met Gly Arg Gly Thr Lys Val Ile Leu His Leu Lys Glu Asp Gln Thr
305 310 315
gag tac ctg gag gag agg cgg atc aag gag atc gtg aag aag cat tcc 1011
Glu Tyr Leu Glu Glu Arg Arg Ile Lys Glu Ile Val Lys Lys His Ser
320 325 330
cag ttc atc ggc tat cca atc aca ctg ttt gtg gag aag gag agg gat 1059
Gln Phe Ile Gly Tyr Pro Ile Thr Leu Phe Val Glu Lys Glu Arg Asp
335 340 345
aag gag gtg agc gac gat gag gct gag gag aag gag gac aag gag gag 1107
Lys Glu Val Ser Asp Asp Glu Ala Glu Glu Lys Glu Asp Lys Glu Glu
350 355 360 365
gag aag gag aag gag gag aag gag tct gag gac aag ccc gag atc gag 1155
Glu Lys Glu Lys Glu Glu Lys Glu Ser Glu Asp Lys Pro Glu Ile Glu
370 375 380
gat gtg ggc tcc gac gag gag gag gag aag aag gat ggc gac aag aag 1203
Asp Val Gly Ser Asp Glu Glu Glu Glu Lys Lys Asp Gly Asp Lys Lys
385 390 395
aag aag aag aag atc aag gag aag tat atc gat cag gag gag ctg aat 1251
Lys Lys Lys Lys Ile Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu Asn
400 405 410
aag acc aag ccc atc tgg aca cgg aac cct gac gat atc acc aat gag 1299
Lys Thr Lys Pro Ile Trp Thr Arg Asn Pro Asp Asp Ile Thr Asn Glu
415 420 425
gag tac ggc gag ttc tat aag tcc ctg aca aac gat tgg gag gac cac 1347
Glu Tyr Gly Glu Phe Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp His
430 435 440 445
ctg gcc gtg aag cat ttt agc gtg gag ggc cag ctg gag ttc aga gct 1395
Leu Ala Val Lys His Phe Ser Val Glu Gly Gln Leu Glu Phe Arg Ala
450 455 460
ctg ctg ttt gtg cct aga cgc gcc cca ttc gac ctg ttt gag aat agg 1443
Leu Leu Phe Val Pro Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn Arg
465 470 475
aag aag aag aac aat atc aag ctg tac gtg agg cgg gtg ttc atc atg 1491
Lys Lys Lys Asn Asn Ile Lys Leu Tyr Val Arg Arg Val Phe Ile Met
480 485 490
gat aac tgc gag gag ctg atc cct gag tat ctg aat ttt atc aga ggc 1539
Asp Asn Cys Glu Glu Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg Gly
495 500 505
gtg gtg gat tct gag gac ctg cca ctg aat atc agc aga gag atg ctg 1587
Val Val Asp Ser Glu Asp Leu Pro Leu Asn Ile Ser Arg Glu Met Leu
510 515 520 525
cag cag tct aag atc ctg aaa gtg atc cgc aag aac ctg gtg aag aag 1635
Gln Gln Ser Lys Ile Leu Lys Val Ile Arg Lys Asn Leu Val Lys Lys
530 535 540
tgt ctg gag ctg ttc acc gag ctg gct gag gac aag gag aac tac aag 1683
Cys Leu Glu Leu Phe Thr Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys
545 550 555
aag ttc tat gag cag ttt tcc aag aat atc aag ctg ggc atc cac gag 1731
Lys Phe Tyr Glu Gln Phe Ser Lys Asn Ile Lys Leu Gly Ile His Glu
560 565 570
gat tcc cag aac agg aag aag ctg agc gag ctg ctg cgg tac tat acc 1779
Asp Ser Gln Asn Arg Lys Lys Leu Ser Glu Leu Leu Arg Tyr Tyr Thr
575 580 585
tcc gcc agc ggc gat gag atg gtg agc ctg aag gac tac tgt aca cgc 1827
Ser Ala Ser Gly Asp Glu Met Val Ser Leu Lys Asp Tyr Cys Thr Arg
590 595 600 605
atg aag gag aat cag aag cac atc tac tat atc acc ggc gag aca aag 1875
Met Lys Glu Asn Gln Lys His Ile Tyr Tyr Ile Thr Gly Glu Thr Lys
610 615 620
gac cag gtg gct aac tct gcc ttc gtg gag agg ctg cgg aag cat ggc 1923
Asp Gln Val Ala Asn Ser Ala Phe Val Glu Arg Leu Arg Lys His Gly
625 630 635
ctg gaa gtg atc tac atg atc gag cca atc gat gag tat tgc gtg cag 1971
Leu Glu Val Ile Tyr Met Ile Glu Pro Ile Asp Glu Tyr Cys Val Gln
640 645 650
cag ctg aag gag ttt gag ggc aag acc ctg gtg tcc gtg aca aag gag 2019
Gln Leu Lys Glu Phe Glu Gly Lys Thr Leu Val Ser Val Thr Lys Glu
655 660 665
ggc ctg gag ctg cct gag gat gag gag gag aag aag aag cag gag gag 2067
Gly Leu Glu Leu Pro Glu Asp Glu Glu Glu Lys Lys Lys Gln Glu Glu
670 675 680 685
aag aag acc aag ttc gag aat ctg tgt aag atc atg aag gat atc ctg 2115
Lys Lys Thr Lys Phe Glu Asn Leu Cys Lys Ile Met Lys Asp Ile Leu
690 695 700
gag aag aag gtg gag aag gtg gtg gtg tct aac aga ctg gtg acc tcc 2163
Glu Lys Lys Val Glu Lys Val Val Val Ser Asn Arg Leu Val Thr Ser
705 710 715
ccc tgc tgt atc gtg acc tct aca tac ggc tgg aca gct aat atg gag 2211
Pro Cys Cys Ile Val Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met Glu
720 725 730
aga atc atg aag gcc cag gct ctg cgc gat aac tcc acc atg ggc tat 2259
Arg Ile Met Lys Ala Gln Ala Leu Arg Asp Asn Ser Thr Met Gly Tyr
735 740 745
atg gcc gct aag aag cac ctg gag atc aat cct gac cat tct atc atc 2307
Met Ala Ala Lys Lys His Leu Glu Ile Asn Pro Asp His Ser Ile Ile
750 755 760 765
gag aca ctg cgc cag aag gcc gag gct gat aag aac gac aag tcc gtg 2355
Glu Thr Leu Arg Gln Lys Ala Glu Ala Asp Lys Asn Asp Lys Ser Val
770 775 780
aag gac ctg gtc atc ctg ctg tac gag aca gct ctg ctg tcc agc ggc 2403
Lys Asp Leu Val Ile Leu Leu Tyr Glu Thr Ala Leu Leu Ser Ser Gly
785 790 795
ttt agc ctg gag gac ccc cag aca cat gcc aac aga atc tat cgc atg 2451
Phe Ser Leu Glu Asp Pro Gln Thr His Ala Asn Arg Ile Tyr Arg Met
800 805 810
atc aag ctg ggc ctg ggc atc gat gag gac gat cct acc gcc gac gat 2499
Ile Lys Leu Gly Leu Gly Ile Asp Glu Asp Asp Pro Thr Ala Asp Asp
815 820 825
aca tct gct gct gtg aca gag gag atg ccc cct ctg gag ggc gac gat 2547
Thr Ser Ala Ala Val Thr Glu Glu Met Pro Pro Leu Glu Gly Asp Asp
830 835 840 845
gac acc tcc agg atg gag gag gtg gac tga gaattc 2583
Asp Thr Ser Arg Met Glu Glu Val Asp
850
<210> 2
<211> 854
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 2
Met Pro Pro Cys Ser Gly Gly Asp Gly Ser Thr Pro Pro Gly Pro Ser
1 5 10 15
Leu Arg Asp Arg Asp Cys Pro Ala Gln Ser Ala Glu Tyr Pro Arg Asp
20 25 30
Arg Leu Asp Pro Arg Pro Gly Ser Pro Ser Glu Ala Ser Ser Pro Pro
35 40 45
Phe Leu Arg Ser Arg Ala Pro Val Asn Trp Tyr Gln Glu Lys Ala Gln
50 55 60
Val Phe Leu Trp His Leu Met Val Ser Gly Ser Thr Thr Leu Leu Cys
65 70 75 80
Leu Trp Lys Gln Pro Phe His Val Ser Ala Phe Pro Val Thr Ala Ser
85 90 95
Leu Ala Phe Arg Gln Ser Gln Gly Ala Gly Gln His Leu Tyr Lys Asp
100 105 110
Leu Gln Pro Phe Ile Leu Leu Arg Leu Leu Met Pro Glu Glu Thr Gln
115 120 125
Thr Gln Asp Gln Pro Met Glu Glu Glu Glu Val Glu Thr Phe Ala Phe
130 135 140
Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile Asn Thr Phe Tyr
145 150 155 160
Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser Asn Ser Ser Asp
165 170 175
Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp Pro Ser Lys Leu
180 185 190
Asp Ser Gly Lys Glu Leu His Ile Asn Leu Ile Pro Asn Lys Gln Asp
195 200 205
Arg Thr Leu Thr Ile Val Asp Thr Gly Ile Gly Met Thr Lys Ala Asp
210 215 220
Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys Ser Gly Thr Lys Ala Phe
225 230 235 240
Met Glu Ala Leu Gln Ala Gly Ala Asp Ile Ser Met Ile Gly Gln Phe
245 250 255
Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val Ala Glu Lys Val Thr Val
260 265 270
Ile Thr Lys His Asn Asp Asp Glu Gln Tyr Ala Trp Glu Ser Ser Ala
275 280 285
Gly Gly Ser Phe Thr Val Arg Thr Asp Thr Gly Glu Pro Met Gly Arg
290 295 300
Gly Thr Lys Val Ile Leu His Leu Lys Glu Asp Gln Thr Glu Tyr Leu
305 310 315 320
Glu Glu Arg Arg Ile Lys Glu Ile Val Lys Lys His Ser Gln Phe Ile
325 330 335
Gly Tyr Pro Ile Thr Leu Phe Val Glu Lys Glu Arg Asp Lys Glu Val
340 345 350
Ser Asp Asp Glu Ala Glu Glu Lys Glu Asp Lys Glu Glu Glu Lys Glu
355 360 365
Lys Glu Glu Lys Glu Ser Glu Asp Lys Pro Glu Ile Glu Asp Val Gly
370 375 380
Ser Asp Glu Glu Glu Glu Lys Lys Asp Gly Asp Lys Lys Lys Lys Lys
385 390 395 400
Lys Ile Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu Asn Lys Thr Lys
405 410 415
Pro Ile Trp Thr Arg Asn Pro Asp Asp Ile Thr Asn Glu Glu Tyr Gly
420 425 430
Glu Phe Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala Val
435 440 445
Lys His Phe Ser Val Glu Gly Gln Leu Glu Phe Arg Ala Leu Leu Phe
450 455 460
Val Pro Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn Arg Lys Lys Lys
465 470 475 480
Asn Asn Ile Lys Leu Tyr Val Arg Arg Val Phe Ile Met Asp Asn Cys
485 490 495
Glu Glu Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg Gly Val Val Asp
500 505 510
Ser Glu Asp Leu Pro Leu Asn Ile Ser Arg Glu Met Leu Gln Gln Ser
515 520 525
Lys Ile Leu Lys Val Ile Arg Lys Asn Leu Val Lys Lys Cys Leu Glu
530 535 540
Leu Phe Thr Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys Lys Phe Tyr
545 550 555 560
Glu Gln Phe Ser Lys Asn Ile Lys Leu Gly Ile His Glu Asp Ser Gln
565 570 575
Asn Arg Lys Lys Leu Ser Glu Leu Leu Arg Tyr Tyr Thr Ser Ala Ser
580 585 590
Gly Asp Glu Met Val Ser Leu Lys Asp Tyr Cys Thr Arg Met Lys Glu
595 600 605
Asn Gln Lys His Ile Tyr Tyr Ile Thr Gly Glu Thr Lys Asp Gln Val
610 615 620
Ala Asn Ser Ala Phe Val Glu Arg Leu Arg Lys His Gly Leu Glu Val
625 630 635 640
Ile Tyr Met Ile Glu Pro Ile Asp Glu Tyr Cys Val Gln Gln Leu Lys
645 650 655
Glu Phe Glu Gly Lys Thr Leu Val Ser Val Thr Lys Glu Gly Leu Glu
660 665 670
Leu Pro Glu Asp Glu Glu Glu Lys Lys Lys Gln Glu Glu Lys Lys Thr
675 680 685
Lys Phe Glu Asn Leu Cys Lys Ile Met Lys Asp Ile Leu Glu Lys Lys
690 695 700
Val Glu Lys Val Val Val Ser Asn Arg Leu Val Thr Ser Pro Cys Cys
705 710 715 720
Ile Val Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met Glu Arg Ile Met
725 730 735
Lys Ala Gln Ala Leu Arg Asp Asn Ser Thr Met Gly Tyr Met Ala Ala
740 745 750
Lys Lys His Leu Glu Ile Asn Pro Asp His Ser Ile Ile Glu Thr Leu
755 760 765
Arg Gln Lys Ala Glu Ala Asp Lys Asn Asp Lys Ser Val Lys Asp Leu
770 775 780
Val Ile Leu Leu Tyr Glu Thr Ala Leu Leu Ser Ser Gly Phe Ser Leu
785 790 795 800
Glu Asp Pro Gln Thr His Ala Asn Arg Ile Tyr Arg Met Ile Lys Leu
805 810 815
Gly Leu Gly Ile Asp Glu Asp Asp Pro Thr Ala Asp Asp Thr Ser Ala
820 825 830
Ala Val Thr Glu Glu Met Pro Pro Leu Glu Gly Asp Asp Asp Thr Ser
835 840 845
Arg Met Glu Glu Val Asp
850
<210> 3
<211> 2217
<212> DNA
<213> 人工序列
<220>
<223> NP_005339 (hHSP90 α)的密码子优化基因
<220>
<221> CDS
<222> (13)..(2211)
<400> 3
aagcttgcca cc atg ccc gag gag acc cag aca cag gac cag cct atg gag 51
Met Pro Glu Glu Thr Gln Thr Gln Asp Gln Pro Met Glu
1 5 10
gag gag gag gtg gag acc ttc gcc ttt cag gct gag atc gcc cag ctg 99
Glu Glu Glu Val Glu Thr Phe Ala Phe Gln Ala Glu Ile Ala Gln Leu
15 20 25
atg agc ctg atc atc aac aca ttc tac tct aat aag gag atc ttt ctg 147
Met Ser Leu Ile Ile Asn Thr Phe Tyr Ser Asn Lys Glu Ile Phe Leu
30 35 40 45
aga gag ctg atc agc aat tcc agc gat gcc ctg gac aag atc cgc tat 195
Arg Glu Leu Ile Ser Asn Ser Ser Asp Ala Leu Asp Lys Ile Arg Tyr
50 55 60
gag tct ctg acc gat cca tct aag ctg gac tcc ggc aag gag ctg cac 243
Glu Ser Leu Thr Asp Pro Ser Lys Leu Asp Ser Gly Lys Glu Leu His
65 70 75
atc aac ctg atc ccc aat aag cag gat agg acc ctg aca atc gtg gac 291
Ile Asn Leu Ile Pro Asn Lys Gln Asp Arg Thr Leu Thr Ile Val Asp
80 85 90
acc ggc atc ggc atg aca aag gct gac ctg atc aac aat ctg ggc acc 339
Thr Gly Ile Gly Met Thr Lys Ala Asp Leu Ile Asn Asn Leu Gly Thr
95 100 105
atc gcc aag tct ggc aca aag gct ttc atg gag gcc ctg cag gct gga 387
Ile Ala Lys Ser Gly Thr Lys Ala Phe Met Glu Ala Leu Gln Ala Gly
110 115 120 125
gct gat atc tcc atg atc ggc cag ttc ggc gtg ggc ttt tac tcc gcc 435
Ala Asp Ile Ser Met Ile Gly Gln Phe Gly Val Gly Phe Tyr Ser Ala
130 135 140
tat ctg gtg gcc gag aag gtg acc gtg atc aca aag cat aac gac gat 483
Tyr Leu Val Ala Glu Lys Val Thr Val Ile Thr Lys His Asn Asp Asp
145 150 155
gag cag tac gct tgg gag tct tcc gcc ggc ggc tcc ttt acc gtg aga 531
Glu Gln Tyr Ala Trp Glu Ser Ser Ala Gly Gly Ser Phe Thr Val Arg
160 165 170
acc gat aca ggc gag cct atg ggc cgc ggc acc aaa gtg atc ctg cac 579
Thr Asp Thr Gly Glu Pro Met Gly Arg Gly Thr Lys Val Ile Leu His
175 180 185
ctg aag gag gac cag aca gag tac ctg gag gag agg cgg atc aag gag 627
Leu Lys Glu Asp Gln Thr Glu Tyr Leu Glu Glu Arg Arg Ile Lys Glu
190 195 200 205
atc gtg aag aag cat tcc cag ttc atc ggc tat cca atc acc ctg ttt 675
Ile Val Lys Lys His Ser Gln Phe Ile Gly Tyr Pro Ile Thr Leu Phe
210 215 220
gtg gag aag gag agg gat aag gag gtg agc gac gat gag gct gag gag 723
Val Glu Lys Glu Arg Asp Lys Glu Val Ser Asp Asp Glu Ala Glu Glu
225 230 235
aag gag gac aag gag gag gag aag gag aag gag gag aag gag tct gag 771
Lys Glu Asp Lys Glu Glu Glu Lys Glu Lys Glu Glu Lys Glu Ser Glu
240 245 250
gac aag cca gag atc gag gat gtg ggc tcc gac gag gag gag gag aag 819
Asp Lys Pro Glu Ile Glu Asp Val Gly Ser Asp Glu Glu Glu Glu Lys
255 260 265
aag gat ggc gac aag aag aag aag aag aag atc aag gag aag tat atc 867
Lys Asp Gly Asp Lys Lys Lys Lys Lys Lys Ile Lys Glu Lys Tyr Ile
270 275 280 285
gat cag gag gag ctg aat aag acc aag cct atc tgg aca cgg aac cca 915
Asp Gln Glu Glu Leu Asn Lys Thr Lys Pro Ile Trp Thr Arg Asn Pro
290 295 300
gac gat atc acc aat gag gag tac ggc gag ttc tat aag tcc ctg aca 963
Asp Asp Ile Thr Asn Glu Glu Tyr Gly Glu Phe Tyr Lys Ser Leu Thr
305 310 315
aac gat tgg gag gac cac ctg gcc gtg aag cac ttc tcc gtg gag ggc 1011
Asn Asp Trp Glu Asp His Leu Ala Val Lys His Phe Ser Val Glu Gly
320 325 330
cag ctg gag ttc agg gct ctg ctg ttt gtg cca aga cgc gcc ccc ttc 1059
Gln Leu Glu Phe Arg Ala Leu Leu Phe Val Pro Arg Arg Ala Pro Phe
335 340 345
gac ctg ttt gag aac agg aag aag aag aac aac atc aag ctg tac gtg 1107
Asp Leu Phe Glu Asn Arg Lys Lys Lys Asn Asn Ile Lys Leu Tyr Val
350 355 360 365
agg cgg gtg ttc atc atg gat aac tgc gag gag ctg atc cct gag tat 1155
Arg Arg Val Phe Ile Met Asp Asn Cys Glu Glu Leu Ile Pro Glu Tyr
370 375 380
ctg aac ttc atc aga ggc gtg gtg gat tcc gag gac ctg cca ctg aat 1203
Leu Asn Phe Ile Arg Gly Val Val Asp Ser Glu Asp Leu Pro Leu Asn
385 390 395
atc tcc agg gag atg ctg cag cag agc aag atc ctg aaa gtg atc cgg 1251
Ile Ser Arg Glu Met Leu Gln Gln Ser Lys Ile Leu Lys Val Ile Arg
400 405 410
aag aac ctg gtg aag aag tgt ctg gag ctg ttc acc gag ctg gct gag 1299
Lys Asn Leu Val Lys Lys Cys Leu Glu Leu Phe Thr Glu Leu Ala Glu
415 420 425
gac aag gag aac tac aag aag ttc tat gag cag ttt agc aag aat atc 1347
Asp Lys Glu Asn Tyr Lys Lys Phe Tyr Glu Gln Phe Ser Lys Asn Ile
430 435 440 445
aag ctg ggc atc cac gag gat tct cag aac aga aag aag ctg tcc gag 1395
Lys Leu Gly Ile His Glu Asp Ser Gln Asn Arg Lys Lys Leu Ser Glu
450 455 460
ctg ctg cgc tac tat acc tcc gcc agc ggc gat gag atg gtg agc ctg 1443
Leu Leu Arg Tyr Tyr Thr Ser Ala Ser Gly Asp Glu Met Val Ser Leu
465 470 475
aag gac tac tgc aca cgc atg aag gag aat cag aag cac atc tac tat 1491
Lys Asp Tyr Cys Thr Arg Met Lys Glu Asn Gln Lys His Ile Tyr Tyr
480 485 490
atc acc ggc gag aca aag gac cag gtg gct aac tct gcc ttc gtg gag 1539
Ile Thr Gly Glu Thr Lys Asp Gln Val Ala Asn Ser Ala Phe Val Glu
495 500 505
aga ctg cgc aag cat ggc ctg gaa gtg atc tac atg atc gag cca atc 1587
Arg Leu Arg Lys His Gly Leu Glu Val Ile Tyr Met Ile Glu Pro Ile
510 515 520 525
gat gag tat tgc gtg cag cag ctg aag gag ttt gag ggc aag acc ctg 1635
Asp Glu Tyr Cys Val Gln Gln Leu Lys Glu Phe Glu Gly Lys Thr Leu
530 535 540
gtg agc gtg aca aag gag gga ctg gag ctg cca gag gac gag gag gag 1683
Val Ser Val Thr Lys Glu Gly Leu Glu Leu Pro Glu Asp Glu Glu Glu
545 550 555
aag aag aag cag gag gag aag aag acc aag ttc gag aac ctg tgc aag 1731
Lys Lys Lys Gln Glu Glu Lys Lys Thr Lys Phe Glu Asn Leu Cys Lys
560 565 570
atc atg aag gat atc ctg gag aag aag gtg gag aag gtg gtg gtg agc 1779
Ile Met Lys Asp Ile Leu Glu Lys Lys Val Glu Lys Val Val Val Ser
575 580 585
aac aga ctg gtg acc tct ccc tgc tgt atc gtg acc tct aca tac ggc 1827
Asn Arg Leu Val Thr Ser Pro Cys Cys Ile Val Thr Ser Thr Tyr Gly
590 595 600 605
tgg aca gct aat atg gag agg atc atg aag gcc cag gct ctg cgg gat 1875
Trp Thr Ala Asn Met Glu Arg Ile Met Lys Ala Gln Ala Leu Arg Asp
610 615 620
aac tcc acc atg ggc tat atg gcc gct aag aag cac ctg gag atc aat 1923
Asn Ser Thr Met Gly Tyr Met Ala Ala Lys Lys His Leu Glu Ile Asn
625 630 635
cct gac cat tct atc atc gag aca ctg cgc cag aag gcc gag gct gat 1971
Pro Asp His Ser Ile Ile Glu Thr Leu Arg Gln Lys Ala Glu Ala Asp
640 645 650
aag aac gac aag tcc gtg aag gac ctg gtc atc ctg ctg tac gag acc 2019
Lys Asn Asp Lys Ser Val Lys Asp Leu Val Ile Leu Leu Tyr Glu Thr
655 660 665
gct ctg ctg agc tct ggc ttt tct ctg gag gac ccc cag aca cat gcc 2067
Ala Leu Leu Ser Ser Gly Phe Ser Leu Glu Asp Pro Gln Thr His Ala
670 675 680 685
aac agg atc tat cgg atg atc aag ctg ggc ctg ggc atc gat gag gac 2115
Asn Arg Ile Tyr Arg Met Ile Lys Leu Gly Leu Gly Ile Asp Glu Asp
690 695 700
gat cct acc gcc gac gat aca agc gcc gct gtg acc gag gag atg cca 2163
Asp Pro Thr Ala Asp Asp Thr Ser Ala Ala Val Thr Glu Glu Met Pro
705 710 715
cct ctg gag ggc gac gat gac aca tct aga atg gag gag gtg gac tga 2211
Pro Leu Glu Gly Asp Asp Asp Thr Ser Arg Met Glu Glu Val Asp
720 725 730
gaattc 2217
<210> 4
<211> 732
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 4
Met Pro Glu Glu Thr Gln Thr Gln Asp Gln Pro Met Glu Glu Glu Glu
1 5 10 15
Val Glu Thr Phe Ala Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu
20 25 30
Ile Ile Asn Thr Phe Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu
35 40 45
Ile Ser Asn Ser Ser Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu
50 55 60
Thr Asp Pro Ser Lys Leu Asp Ser Gly Lys Glu Leu His Ile Asn Leu
65 70 75 80
Ile Pro Asn Lys Gln Asp Arg Thr Leu Thr Ile Val Asp Thr Gly Ile
85 90 95
Gly Met Thr Lys Ala Asp Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys
100 105 110
Ser Gly Thr Lys Ala Phe Met Glu Ala Leu Gln Ala Gly Ala Asp Ile
115 120 125
Ser Met Ile Gly Gln Phe Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val
130 135 140
Ala Glu Lys Val Thr Val Ile Thr Lys His Asn Asp Asp Glu Gln Tyr
145 150 155 160
Ala Trp Glu Ser Ser Ala Gly Gly Ser Phe Thr Val Arg Thr Asp Thr
165 170 175
Gly Glu Pro Met Gly Arg Gly Thr Lys Val Ile Leu His Leu Lys Glu
180 185 190
Asp Gln Thr Glu Tyr Leu Glu Glu Arg Arg Ile Lys Glu Ile Val Lys
195 200 205
Lys His Ser Gln Phe Ile Gly Tyr Pro Ile Thr Leu Phe Val Glu Lys
210 215 220
Glu Arg Asp Lys Glu Val Ser Asp Asp Glu Ala Glu Glu Lys Glu Asp
225 230 235 240
Lys Glu Glu Glu Lys Glu Lys Glu Glu Lys Glu Ser Glu Asp Lys Pro
245 250 255
Glu Ile Glu Asp Val Gly Ser Asp Glu Glu Glu Glu Lys Lys Asp Gly
260 265 270
Asp Lys Lys Lys Lys Lys Lys Ile Lys Glu Lys Tyr Ile Asp Gln Glu
275 280 285
Glu Leu Asn Lys Thr Lys Pro Ile Trp Thr Arg Asn Pro Asp Asp Ile
290 295 300
Thr Asn Glu Glu Tyr Gly Glu Phe Tyr Lys Ser Leu Thr Asn Asp Trp
305 310 315 320
Glu Asp His Leu Ala Val Lys His Phe Ser Val Glu Gly Gln Leu Glu
325 330 335
Phe Arg Ala Leu Leu Phe Val Pro Arg Arg Ala Pro Phe Asp Leu Phe
340 345 350
Glu Asn Arg Lys Lys Lys Asn Asn Ile Lys Leu Tyr Val Arg Arg Val
355 360 365
Phe Ile Met Asp Asn Cys Glu Glu Leu Ile Pro Glu Tyr Leu Asn Phe
370 375 380
Ile Arg Gly Val Val Asp Ser Glu Asp Leu Pro Leu Asn Ile Ser Arg
385 390 395 400
Glu Met Leu Gln Gln Ser Lys Ile Leu Lys Val Ile Arg Lys Asn Leu
405 410 415
Val Lys Lys Cys Leu Glu Leu Phe Thr Glu Leu Ala Glu Asp Lys Glu
420 425 430
Asn Tyr Lys Lys Phe Tyr Glu Gln Phe Ser Lys Asn Ile Lys Leu Gly
435 440 445
Ile His Glu Asp Ser Gln Asn Arg Lys Lys Leu Ser Glu Leu Leu Arg
450 455 460
Tyr Tyr Thr Ser Ala Ser Gly Asp Glu Met Val Ser Leu Lys Asp Tyr
465 470 475 480
Cys Thr Arg Met Lys Glu Asn Gln Lys His Ile Tyr Tyr Ile Thr Gly
485 490 495
Glu Thr Lys Asp Gln Val Ala Asn Ser Ala Phe Val Glu Arg Leu Arg
500 505 510
Lys His Gly Leu Glu Val Ile Tyr Met Ile Glu Pro Ile Asp Glu Tyr
515 520 525
Cys Val Gln Gln Leu Lys Glu Phe Glu Gly Lys Thr Leu Val Ser Val
530 535 540
Thr Lys Glu Gly Leu Glu Leu Pro Glu Asp Glu Glu Glu Lys Lys Lys
545 550 555 560
Gln Glu Glu Lys Lys Thr Lys Phe Glu Asn Leu Cys Lys Ile Met Lys
565 570 575
Asp Ile Leu Glu Lys Lys Val Glu Lys Val Val Val Ser Asn Arg Leu
580 585 590
Val Thr Ser Pro Cys Cys Ile Val Thr Ser Thr Tyr Gly Trp Thr Ala
595 600 605
Asn Met Glu Arg Ile Met Lys Ala Gln Ala Leu Arg Asp Asn Ser Thr
610 615 620
Met Gly Tyr Met Ala Ala Lys Lys His Leu Glu Ile Asn Pro Asp His
625 630 635 640
Ser Ile Ile Glu Thr Leu Arg Gln Lys Ala Glu Ala Asp Lys Asn Asp
645 650 655
Lys Ser Val Lys Asp Leu Val Ile Leu Leu Tyr Glu Thr Ala Leu Leu
660 665 670
Ser Ser Gly Phe Ser Leu Glu Asp Pro Gln Thr His Ala Asn Arg Ile
675 680 685
Tyr Arg Met Ile Lys Leu Gly Leu Gly Ile Asp Glu Asp Asp Pro Thr
690 695 700
Ala Asp Asp Thr Ser Ala Ala Val Thr Glu Glu Met Pro Pro Leu Glu
705 710 715 720
Gly Asp Asp Asp Thr Ser Arg Met Glu Glu Val Asp
725 730
<210> 5
<211> 2220
<212> DNA
<213> 人工序列
<220>
<223> NP_001233750 (chHSP90 α)的密码子优化基因
<220>
<221> CDS
<222> (13)..(2214)
<400> 5
aagcttgcca cc atg ccc gag gag acc cag aca cag gac cag cct atg gag 51
Met Pro Glu Glu Thr Gln Thr Gln Asp Gln Pro Met Glu
1 5 10
gag gag gag gtg gag acc ttc gcc ttt cag gct gag atc gcc cag ctg 99
Glu Glu Glu Val Glu Thr Phe Ala Phe Gln Ala Glu Ile Ala Gln Leu
15 20 25
atg agc ctg atc atc aac aca ttc tac tct aat aag gag atc ttt ctg 147
Met Ser Leu Ile Ile Asn Thr Phe Tyr Ser Asn Lys Glu Ile Phe Leu
30 35 40 45
aga gag ctg atc tcc aat tcc agc gat gct ctg gac aag atc cgc tat 195
Arg Glu Leu Ile Ser Asn Ser Ser Asp Ala Leu Asp Lys Ile Arg Tyr
50 55 60
gag agc ctg acc gat cca tct aag ctg gac tcc ggc aag gag ctg cac 243
Glu Ser Leu Thr Asp Pro Ser Lys Leu Asp Ser Gly Lys Glu Leu His
65 70 75
atc aac atc atc ccc aat aag cag gat agg acc ctg aca atc gtg gac 291
Ile Asn Ile Ile Pro Asn Lys Gln Asp Arg Thr Leu Thr Ile Val Asp
80 85 90
acc ggc atc ggc atg aca aag gct gac ctg atc aac aat ctg ggc acc 339
Thr Gly Ile Gly Met Thr Lys Ala Asp Leu Ile Asn Asn Leu Gly Thr
95 100 105
atc gcc aag agc ggc aca aag gct ttc atg gag gcc ctg cag gct gga 387
Ile Ala Lys Ser Gly Thr Lys Ala Phe Met Glu Ala Leu Gln Ala Gly
110 115 120 125
gct gat atc tct atg atc ggc cag ttc ggc gtg ggc ttt tac acc gct 435
Ala Asp Ile Ser Met Ile Gly Gln Phe Gly Val Gly Phe Tyr Thr Ala
130 135 140
tat ctg gtg gcc gag aag gtg acc gtg atc aca aag cat aac gac gat 483
Tyr Leu Val Ala Glu Lys Val Thr Val Ile Thr Lys His Asn Asp Asp
145 150 155
gag cag tac gct tgg gag tct tcc gcc gga ggc tcc ttt acc gtg agg 531
Glu Gln Tyr Ala Trp Glu Ser Ser Ala Gly Gly Ser Phe Thr Val Arg
160 165 170
acc gat aca ggc gag cct atg ggc cgg ggc acc aaa gtg atc ctg cac 579
Thr Asp Thr Gly Glu Pro Met Gly Arg Gly Thr Lys Val Ile Leu His
175 180 185
ctg aag gag gac cag aca gag tac atg gag gag agg cgg atc aag gag 627
Leu Lys Glu Asp Gln Thr Glu Tyr Met Glu Glu Arg Arg Ile Lys Glu
190 195 200 205
atc gtg aag aag cat agc cag ttc atc ggc tat cca atc acc ctg ttt 675
Ile Val Lys Lys His Ser Gln Phe Ile Gly Tyr Pro Ile Thr Leu Phe
210 215 220
gtg gag aag gag aga gat aag gag gtg tct gac gat gag gct gag gag 723
Val Glu Lys Glu Arg Asp Lys Glu Val Ser Asp Asp Glu Ala Glu Glu
225 230 235
aag gag gac aag gag gag gag aag gag aag gag gag aag ggc atc gac 771
Lys Glu Asp Lys Glu Glu Glu Lys Glu Lys Glu Glu Lys Gly Ile Asp
240 245 250
gat aag cca gag atc gag gat gtg ggc agc gac gag gag gag gag gag 819
Asp Lys Pro Glu Ile Glu Asp Val Gly Ser Asp Glu Glu Glu Glu Glu
255 260 265
aag aag gat ggc gac aag aag aag aag aag aag atc aag gag aag tac 867
Lys Lys Asp Gly Asp Lys Lys Lys Lys Lys Lys Ile Lys Glu Lys Tyr
270 275 280 285
atc gac cag gag gag ctg aat aag acc aag cct atc tgg aca cgc aac 915
Ile Asp Gln Glu Glu Leu Asn Lys Thr Lys Pro Ile Trp Thr Arg Asn
290 295 300
cca gac gat atc acc aat gag gag tac ggc gag ttc tat aag tct ctg 963
Pro Asp Asp Ile Thr Asn Glu Glu Tyr Gly Glu Phe Tyr Lys Ser Leu
305 310 315
aca aac gat tgg gag gag cac ctg gcc gtg aag cat ttt tcc gtg gag 1011
Thr Asn Asp Trp Glu Glu His Leu Ala Val Lys His Phe Ser Val Glu
320 325 330
ggc cag ctg gag ttc aga gct ctg ctg ttt gtg cca aga cgc gcc ccc 1059
Gly Gln Leu Glu Phe Arg Ala Leu Leu Phe Val Pro Arg Arg Ala Pro
335 340 345
ttc gac ctg ttt gag aac agg aag aag aag aac aac atc aag ctg tac 1107
Phe Asp Leu Phe Glu Asn Arg Lys Lys Lys Asn Asn Ile Lys Leu Tyr
350 355 360 365
gtg agg cgg gtg ttc atc atg gat aac tgc gag gag ctg ttc cct gag 1155
Val Arg Arg Val Phe Ile Met Asp Asn Cys Glu Glu Leu Phe Pro Glu
370 375 380
tat ctg aac ttc atc agg ggc gtg gtg gat agc gag gac ctg cca ctg 1203
Tyr Leu Asn Phe Ile Arg Gly Val Val Asp Ser Glu Asp Leu Pro Leu
385 390 395
aat atc tcc cgg gag atc ctg cag cag agc aag atc ctg aaa gtg atc 1251
Asn Ile Ser Arg Glu Ile Leu Gln Gln Ser Lys Ile Leu Lys Val Ile
400 405 410
aga aag aac ctg gtg cgc aag tgt ctg gag ctg ttt cac gag ctg gct 1299
Arg Lys Asn Leu Val Arg Lys Cys Leu Glu Leu Phe His Glu Leu Ala
415 420 425
gag gac aag gag aac tac aag aag ttc tat gag cag ttt tct aag aat 1347
Glu Asp Lys Glu Asn Tyr Lys Lys Phe Tyr Glu Gln Phe Ser Lys Asn
430 435 440 445
atc aag ctg ggc atc cat gag gat tct cag aac agg aag aag ctg tcc 1395
Ile Lys Leu Gly Ile His Glu Asp Ser Gln Asn Arg Lys Lys Leu Ser
450 455 460
gag ctg ctg cgg tac tat acc tcc gcc agc ggc gat gag atg gtg tct 1443
Glu Leu Leu Arg Tyr Tyr Thr Ser Ala Ser Gly Asp Glu Met Val Ser
465 470 475
ctg aag gac tac tgc aca agg atg aag gag aat cag aag cac atc tat 1491
Leu Lys Asp Tyr Cys Thr Arg Met Lys Glu Asn Gln Lys His Ile Tyr
480 485 490
ttc atc acc ggc gag aca aag gac cag gtg gct aac tcc gcc ttt gtg 1539
Phe Ile Thr Gly Glu Thr Lys Asp Gln Val Ala Asn Ser Ala Phe Val
495 500 505
gag aga ctg cgc aag cat ggc ctg gaa gtg atc tac atg atc gag cca 1587
Glu Arg Leu Arg Lys His Gly Leu Glu Val Ile Tyr Met Ile Glu Pro
510 515 520 525
atc gat gag tat tgc gtg cag cag ctg aag gag ttc gag ggc aag acc 1635
Ile Asp Glu Tyr Cys Val Gln Gln Leu Lys Glu Phe Glu Gly Lys Thr
530 535 540
ctg gtg tct gtg aca aag gag gga ctg gag ctg cca gag gac gag gag 1683
Leu Val Ser Val Thr Lys Glu Gly Leu Glu Leu Pro Glu Asp Glu Glu
545 550 555
gag aag aag aag cag gag gag aag aag acc aag ttt gag aac ctg tgc 1731
Glu Lys Lys Lys Gln Glu Glu Lys Lys Thr Lys Phe Glu Asn Leu Cys
560 565 570
aag atc atg aag gat atc ctg gag aag aag gtg gag aag gtg gtg gtg 1779
Lys Ile Met Lys Asp Ile Leu Glu Lys Lys Val Glu Lys Val Val Val
575 580 585
agc aac agg ctg gtg acc tct ccc tgc tgt atc gtg acc tcc aca tac 1827
Ser Asn Arg Leu Val Thr Ser Pro Cys Cys Ile Val Thr Ser Thr Tyr
590 595 600 605
ggc tgg aca gcc aat atg gag aga atc atc aag gcc cag gct ctg cgc 1875
Gly Trp Thr Ala Asn Met Glu Arg Ile Ile Lys Ala Gln Ala Leu Arg
610 615 620
gat aac agc acc atg ggc tat atg gcc gct aag aag cac ctg gag atc 1923
Asp Asn Ser Thr Met Gly Tyr Met Ala Ala Lys Lys His Leu Glu Ile
625 630 635
aat cct gac cat tcc atc atc gag aca ctg cgg cag aag gcc gag gct 1971
Asn Pro Asp His Ser Ile Ile Glu Thr Leu Arg Gln Lys Ala Glu Ala
640 645 650
gat aag aac gac aag agc gtg aag gac ctg gtc atc ctg ctg tac gag 2019
Asp Lys Asn Asp Lys Ser Val Lys Asp Leu Val Ile Leu Leu Tyr Glu
655 660 665
acc gct ctg ctg agc tct ggc ttc tcc ctg gag gac ccc cag aca cac 2067
Thr Ala Leu Leu Ser Ser Gly Phe Ser Leu Glu Asp Pro Gln Thr His
670 675 680 685
gcc aac agg atc tat cgg atg atc aag ctg ggc ctg ggc atc gat gag 2115
Ala Asn Arg Ile Tyr Arg Met Ile Lys Leu Gly Leu Gly Ile Asp Glu
690 695 700
gac gat cct acc gtg gac gat aca tct gcc gct gtg acc gag gag atg 2163
Asp Asp Pro Thr Val Asp Asp Thr Ser Ala Ala Val Thr Glu Glu Met
705 710 715
cca cct ctg gag ggc gac gat gac aca tcc aga atg gag gag gtg gac 2211
Pro Pro Leu Glu Gly Asp Asp Asp Thr Ser Arg Met Glu Glu Val Asp
720 725 730
tga gaattc 2220
<210> 6
<211> 733
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 6
Met Pro Glu Glu Thr Gln Thr Gln Asp Gln Pro Met Glu Glu Glu Glu
1 5 10 15
Val Glu Thr Phe Ala Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu
20 25 30
Ile Ile Asn Thr Phe Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu
35 40 45
Ile Ser Asn Ser Ser Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu
50 55 60
Thr Asp Pro Ser Lys Leu Asp Ser Gly Lys Glu Leu His Ile Asn Ile
65 70 75 80
Ile Pro Asn Lys Gln Asp Arg Thr Leu Thr Ile Val Asp Thr Gly Ile
85 90 95
Gly Met Thr Lys Ala Asp Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys
100 105 110
Ser Gly Thr Lys Ala Phe Met Glu Ala Leu Gln Ala Gly Ala Asp Ile
115 120 125
Ser Met Ile Gly Gln Phe Gly Val Gly Phe Tyr Thr Ala Tyr Leu Val
130 135 140
Ala Glu Lys Val Thr Val Ile Thr Lys His Asn Asp Asp Glu Gln Tyr
145 150 155 160
Ala Trp Glu Ser Ser Ala Gly Gly Ser Phe Thr Val Arg Thr Asp Thr
165 170 175
Gly Glu Pro Met Gly Arg Gly Thr Lys Val Ile Leu His Leu Lys Glu
180 185 190
Asp Gln Thr Glu Tyr Met Glu Glu Arg Arg Ile Lys Glu Ile Val Lys
195 200 205
Lys His Ser Gln Phe Ile Gly Tyr Pro Ile Thr Leu Phe Val Glu Lys
210 215 220
Glu Arg Asp Lys Glu Val Ser Asp Asp Glu Ala Glu Glu Lys Glu Asp
225 230 235 240
Lys Glu Glu Glu Lys Glu Lys Glu Glu Lys Gly Ile Asp Asp Lys Pro
245 250 255
Glu Ile Glu Asp Val Gly Ser Asp Glu Glu Glu Glu Glu Lys Lys Asp
260 265 270
Gly Asp Lys Lys Lys Lys Lys Lys Ile Lys Glu Lys Tyr Ile Asp Gln
275 280 285
Glu Glu Leu Asn Lys Thr Lys Pro Ile Trp Thr Arg Asn Pro Asp Asp
290 295 300
Ile Thr Asn Glu Glu Tyr Gly Glu Phe Tyr Lys Ser Leu Thr Asn Asp
305 310 315 320
Trp Glu Glu His Leu Ala Val Lys His Phe Ser Val Glu Gly Gln Leu
325 330 335
Glu Phe Arg Ala Leu Leu Phe Val Pro Arg Arg Ala Pro Phe Asp Leu
340 345 350
Phe Glu Asn Arg Lys Lys Lys Asn Asn Ile Lys Leu Tyr Val Arg Arg
355 360 365
Val Phe Ile Met Asp Asn Cys Glu Glu Leu Phe Pro Glu Tyr Leu Asn
370 375 380
Phe Ile Arg Gly Val Val Asp Ser Glu Asp Leu Pro Leu Asn Ile Ser
385 390 395 400
Arg Glu Ile Leu Gln Gln Ser Lys Ile Leu Lys Val Ile Arg Lys Asn
405 410 415
Leu Val Arg Lys Cys Leu Glu Leu Phe His Glu Leu Ala Glu Asp Lys
420 425 430
Glu Asn Tyr Lys Lys Phe Tyr Glu Gln Phe Ser Lys Asn Ile Lys Leu
435 440 445
Gly Ile His Glu Asp Ser Gln Asn Arg Lys Lys Leu Ser Glu Leu Leu
450 455 460
Arg Tyr Tyr Thr Ser Ala Ser Gly Asp Glu Met Val Ser Leu Lys Asp
465 470 475 480
Tyr Cys Thr Arg Met Lys Glu Asn Gln Lys His Ile Tyr Phe Ile Thr
485 490 495
Gly Glu Thr Lys Asp Gln Val Ala Asn Ser Ala Phe Val Glu Arg Leu
500 505 510
Arg Lys His Gly Leu Glu Val Ile Tyr Met Ile Glu Pro Ile Asp Glu
515 520 525
Tyr Cys Val Gln Gln Leu Lys Glu Phe Glu Gly Lys Thr Leu Val Ser
530 535 540
Val Thr Lys Glu Gly Leu Glu Leu Pro Glu Asp Glu Glu Glu Lys Lys
545 550 555 560
Lys Gln Glu Glu Lys Lys Thr Lys Phe Glu Asn Leu Cys Lys Ile Met
565 570 575
Lys Asp Ile Leu Glu Lys Lys Val Glu Lys Val Val Val Ser Asn Arg
580 585 590
Leu Val Thr Ser Pro Cys Cys Ile Val Thr Ser Thr Tyr Gly Trp Thr
595 600 605
Ala Asn Met Glu Arg Ile Ile Lys Ala Gln Ala Leu Arg Asp Asn Ser
610 615 620
Thr Met Gly Tyr Met Ala Ala Lys Lys His Leu Glu Ile Asn Pro Asp
625 630 635 640
His Ser Ile Ile Glu Thr Leu Arg Gln Lys Ala Glu Ala Asp Lys Asn
645 650 655
Asp Lys Ser Val Lys Asp Leu Val Ile Leu Leu Tyr Glu Thr Ala Leu
660 665 670
Leu Ser Ser Gly Phe Ser Leu Glu Asp Pro Gln Thr His Ala Asn Arg
675 680 685
Ile Tyr Arg Met Ile Lys Leu Gly Leu Gly Ile Asp Glu Asp Asp Pro
690 695 700
Thr Val Asp Asp Thr Ser Ala Ala Val Thr Glu Glu Met Pro Pro Leu
705 710 715 720
Glu Gly Asp Asp Asp Thr Ser Arg Met Glu Glu Val Asp
725 730
<210> 7
<211> 2193
<212> DNA
<213> 人工序列
<220>
<223> NP_001258899 (hHSP90 β)的密码子优化基因
<220>
<221> CDS
<222> (13)..(2187)
<400> 7
aagcttgcca cc atg ccc gag gag gtg cac cat ggc gag gag gag gtg gag 51
Met Pro Glu Glu Val His His Gly Glu Glu Glu Val Glu
1 5 10
acc ttc gcc ttt cag gct gag atc gcc cag ctg atg tcc ctg atc atc 99
Thr Phe Ala Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile
15 20 25
aac aca ttc tac agc aat aag gag atc ttt ctg agg gag ctg atc agc 147
Asn Thr Phe Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser
30 35 40 45
aat gct tct gac gcc ctg gat aag atc cgg tat gag tcc ctg acc gac 195
Asn Ala Ser Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp
50 55 60
cct tct aag ctg gat tcc ggc aag gag ctg aag atc gac atc atc cca 243
Pro Ser Lys Leu Asp Ser Gly Lys Glu Leu Lys Ile Asp Ile Ile Pro
65 70 75
aac ccc cag gag agg acc ctg aca ctg gtg gac acc ggc atc ggc atg 291
Asn Pro Gln Glu Arg Thr Leu Thr Leu Val Asp Thr Gly Ile Gly Met
80 85 90
aca aag gct gat ctg atc aac aat ctg ggc acc atc gcc aag agc ggc 339
Thr Lys Ala Asp Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys Ser Gly
95 100 105
aca aag gct ttc atg gag gcc ctg cag gct gga gct gat atc tcc atg 387
Thr Lys Ala Phe Met Glu Ala Leu Gln Ala Gly Ala Asp Ile Ser Met
110 115 120 125
atc ggc cag ttc ggc gtg ggc ttt tac tcc gcc tat ctg gtg gcc gag 435
Ile Gly Gln Phe Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val Ala Glu
130 135 140
aag gtg gtg gtc atc acc aag cac aac gac gat gag cag tac gct tgg 483
Lys Val Val Val Ile Thr Lys His Asn Asp Asp Glu Gln Tyr Ala Trp
145 150 155
gag tcc agc gcc gga ggc agc ttc aca gtg agg gct gac cac gga gag 531
Glu Ser Ser Ala Gly Gly Ser Phe Thr Val Arg Ala Asp His Gly Glu
160 165 170
cca atc gga agg ggc acc aaa gtg atc ctg cat ctg aag gag gat cag 579
Pro Ile Gly Arg Gly Thr Lys Val Ile Leu His Leu Lys Glu Asp Gln
175 180 185
aca gag tat ctg gag gag agg cgg gtg aag gag gtg gtg aag aag cat 627
Thr Glu Tyr Leu Glu Glu Arg Arg Val Lys Glu Val Val Lys Lys His
190 195 200 205
agc cag ttt atc ggc tac cct atc acc ctg tat ctg gag aag gag cgg 675
Ser Gln Phe Ile Gly Tyr Pro Ile Thr Leu Tyr Leu Glu Lys Glu Arg
210 215 220
gag aag gag atc tct gac gat gag gcc gag gag gag aag ggc gag aag 723
Glu Lys Glu Ile Ser Asp Asp Glu Ala Glu Glu Glu Lys Gly Glu Lys
225 230 235
gag gag gag gac aag gac gat gag gag aag cca aag atc gag gac gtg 771
Glu Glu Glu Asp Lys Asp Asp Glu Glu Lys Pro Lys Ile Glu Asp Val
240 245 250
ggc agc gat gag gag gac gat tct ggc aag gac aag aag aag aag acc 819
Gly Ser Asp Glu Glu Asp Asp Ser Gly Lys Asp Lys Lys Lys Lys Thr
255 260 265
aag aag atc aag gag aag tac atc gat cag gag gag ctg aac aag acc 867
Lys Lys Ile Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu Asn Lys Thr
270 275 280 285
aag cct atc tgg aca agg aat cca gac gat atc acc cag gag gag tac 915
Lys Pro Ile Trp Thr Arg Asn Pro Asp Asp Ile Thr Gln Glu Glu Tyr
290 295 300
ggc gag ttc tat aag agc ctg aca aat gac tgg gag gat cac ctg gcc 963
Gly Glu Phe Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala
305 310 315
gtg aag cat ttt tct gtg gag ggc cag ctg gag ttc cgg gct ctg ctg 1011
Val Lys His Phe Ser Val Glu Gly Gln Leu Glu Phe Arg Ala Leu Leu
320 325 330
ttt atc ccc aga cgc gcc cct ttc gac ctg ttt gag aac aag aag aag 1059
Phe Ile Pro Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn Lys Lys Lys
335 340 345
aag aac aac atc aag ctg tac gtg agg cgg gtg ttc atc atg gac tct 1107
Lys Asn Asn Ile Lys Leu Tyr Val Arg Arg Val Phe Ile Met Asp Ser
350 355 360 365
tgc gat gag ctg atc ccc gag tat ctg aac ttc atc aga ggc gtg gtg 1155
Cys Asp Glu Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg Gly Val Val
370 375 380
gac tcc gag gat ctg cct ctg aac atc tcc aga gag atg ctg cag cag 1203
Asp Ser Glu Asp Leu Pro Leu Asn Ile Ser Arg Glu Met Leu Gln Gln
385 390 395
agc aag atc ctg aaa gtg atc cgc aag aat atc gtg aag aag tgt ctg 1251
Ser Lys Ile Leu Lys Val Ile Arg Lys Asn Ile Val Lys Lys Cys Leu
400 405 410
gag ctg ttt tcc gag ctg gct gag gac aag gag aac tac aag aag ttc 1299
Glu Leu Phe Ser Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys Lys Phe
415 420 425
tat gag gcc ttt agc aag aat ctg aag ctg ggc atc cac gag gac tct 1347
Tyr Glu Ala Phe Ser Lys Asn Leu Lys Leu Gly Ile His Glu Asp Ser
430 435 440 445
acc aac aga cgc agg ctg tcc gag ctg ctg aga tac cat acc tcc cag 1395
Thr Asn Arg Arg Arg Leu Ser Glu Leu Leu Arg Tyr His Thr Ser Gln
450 455 460
agc ggc gat gag atg aca tct ctg tcc gag tac gtg tcc cgc atg aag 1443
Ser Gly Asp Glu Met Thr Ser Leu Ser Glu Tyr Val Ser Arg Met Lys
465 470 475
gag acc cag aag tcc atc tac tat atc aca ggc gag agc aag gag cag 1491
Glu Thr Gln Lys Ser Ile Tyr Tyr Ile Thr Gly Glu Ser Lys Glu Gln
480 485 490
gtg gct aac tct gcc ttc gtg gag cgg gtg aga aag cgc ggc ttt gag 1539
Val Ala Asn Ser Ala Phe Val Glu Arg Val Arg Lys Arg Gly Phe Glu
495 500 505
gtg gtg tac atg acc gag cca atc gac gag tat tgc gtg cag cag ctg 1587
Val Val Tyr Met Thr Glu Pro Ile Asp Glu Tyr Cys Val Gln Gln Leu
510 515 520 525
aag gag ttc gat ggc aag tcc ctg gtg agc gtg aca aag gag gga ctg 1635
Lys Glu Phe Asp Gly Lys Ser Leu Val Ser Val Thr Lys Glu Gly Leu
530 535 540
gag ctg cca gag gac gag gag gag aag aag aag atg gag gag tct aag 1683
Glu Leu Pro Glu Asp Glu Glu Glu Lys Lys Lys Met Glu Glu Ser Lys
545 550 555
gct aag ttt gag aac ctg tgc aag ctg atg aag gag atc ctg gat aag 1731
Ala Lys Phe Glu Asn Leu Cys Lys Leu Met Lys Glu Ile Leu Asp Lys
560 565 570
aag gtg gag aag gtg acc atc tct aac aga ctg gtg tct tcc cca tgc 1779
Lys Val Glu Lys Val Thr Ile Ser Asn Arg Leu Val Ser Ser Pro Cys
575 580 585
tgt atc gtg acc tcc aca tac ggc tgg acc gct aat atg gag aga atc 1827
Cys Ile Val Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met Glu Arg Ile
590 595 600 605
atg aag gcc cag gct ctg cgc gac aac tcc aca atg ggc tat atg atg 1875
Met Lys Ala Gln Ala Leu Arg Asp Asn Ser Thr Met Gly Tyr Met Met
610 615 620
gcc aag aag cac ctg gag atc aat cct gat cat cca atc gtg gag acc 1923
Ala Lys Lys His Leu Glu Ile Asn Pro Asp His Pro Ile Val Glu Thr
625 630 635
ctg agg cag aag gct gag gct gac aag aac gat aag gct gtg aag gac 1971
Leu Arg Gln Lys Ala Glu Ala Asp Lys Asn Asp Lys Ala Val Lys Asp
640 645 650
ctg gtg gtg ctg ctg ttc gag acc gcc ctg ctg agc tct ggc ttt agc 2019
Leu Val Val Leu Leu Phe Glu Thr Ala Leu Leu Ser Ser Gly Phe Ser
655 660 665
ctg gag gat ccc cag aca cac tct aat agg atc tac cgg atg atc aag 2067
Leu Glu Asp Pro Gln Thr His Ser Asn Arg Ile Tyr Arg Met Ile Lys
670 675 680 685
ctg ggc ctg ggc atc gac gag gat gag gtg gct gct gag gag cca aac 2115
Leu Gly Leu Gly Ile Asp Glu Asp Glu Val Ala Ala Glu Glu Pro Asn
690 695 700
gct gct gtg cca gac gag atc cca cct ctg gag ggc gac gag gat gct 2163
Ala Ala Val Pro Asp Glu Ile Pro Pro Leu Glu Gly Asp Glu Asp Ala
705 710 715
tct cgc atg gag gag gtg gat tga gaattc 2193
Ser Arg Met Glu Glu Val Asp
720
<210> 8
<211> 724
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 8
Met Pro Glu Glu Val His His Gly Glu Glu Glu Val Glu Thr Phe Ala
1 5 10 15
Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile Asn Thr Phe
20 25 30
Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser Asn Ala Ser
35 40 45
Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp Pro Ser Lys
50 55 60
Leu Asp Ser Gly Lys Glu Leu Lys Ile Asp Ile Ile Pro Asn Pro Gln
65 70 75 80
Glu Arg Thr Leu Thr Leu Val Asp Thr Gly Ile Gly Met Thr Lys Ala
85 90 95
Asp Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys Ser Gly Thr Lys Ala
100 105 110
Phe Met Glu Ala Leu Gln Ala Gly Ala Asp Ile Ser Met Ile Gly Gln
115 120 125
Phe Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val Ala Glu Lys Val Val
130 135 140
Val Ile Thr Lys His Asn Asp Asp Glu Gln Tyr Ala Trp Glu Ser Ser
145 150 155 160
Ala Gly Gly Ser Phe Thr Val Arg Ala Asp His Gly Glu Pro Ile Gly
165 170 175
Arg Gly Thr Lys Val Ile Leu His Leu Lys Glu Asp Gln Thr Glu Tyr
180 185 190
Leu Glu Glu Arg Arg Val Lys Glu Val Val Lys Lys His Ser Gln Phe
195 200 205
Ile Gly Tyr Pro Ile Thr Leu Tyr Leu Glu Lys Glu Arg Glu Lys Glu
210 215 220
Ile Ser Asp Asp Glu Ala Glu Glu Glu Lys Gly Glu Lys Glu Glu Glu
225 230 235 240
Asp Lys Asp Asp Glu Glu Lys Pro Lys Ile Glu Asp Val Gly Ser Asp
245 250 255
Glu Glu Asp Asp Ser Gly Lys Asp Lys Lys Lys Lys Thr Lys Lys Ile
260 265 270
Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu Asn Lys Thr Lys Pro Ile
275 280 285
Trp Thr Arg Asn Pro Asp Asp Ile Thr Gln Glu Glu Tyr Gly Glu Phe
290 295 300
Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala Val Lys His
305 310 315 320
Phe Ser Val Glu Gly Gln Leu Glu Phe Arg Ala Leu Leu Phe Ile Pro
325 330 335
Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn Lys Lys Lys Lys Asn Asn
340 345 350
Ile Lys Leu Tyr Val Arg Arg Val Phe Ile Met Asp Ser Cys Asp Glu
355 360 365
Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg Gly Val Val Asp Ser Glu
370 375 380
Asp Leu Pro Leu Asn Ile Ser Arg Glu Met Leu Gln Gln Ser Lys Ile
385 390 395 400
Leu Lys Val Ile Arg Lys Asn Ile Val Lys Lys Cys Leu Glu Leu Phe
405 410 415
Ser Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys Lys Phe Tyr Glu Ala
420 425 430
Phe Ser Lys Asn Leu Lys Leu Gly Ile His Glu Asp Ser Thr Asn Arg
435 440 445
Arg Arg Leu Ser Glu Leu Leu Arg Tyr His Thr Ser Gln Ser Gly Asp
450 455 460
Glu Met Thr Ser Leu Ser Glu Tyr Val Ser Arg Met Lys Glu Thr Gln
465 470 475 480
Lys Ser Ile Tyr Tyr Ile Thr Gly Glu Ser Lys Glu Gln Val Ala Asn
485 490 495
Ser Ala Phe Val Glu Arg Val Arg Lys Arg Gly Phe Glu Val Val Tyr
500 505 510
Met Thr Glu Pro Ile Asp Glu Tyr Cys Val Gln Gln Leu Lys Glu Phe
515 520 525
Asp Gly Lys Ser Leu Val Ser Val Thr Lys Glu Gly Leu Glu Leu Pro
530 535 540
Glu Asp Glu Glu Glu Lys Lys Lys Met Glu Glu Ser Lys Ala Lys Phe
545 550 555 560
Glu Asn Leu Cys Lys Leu Met Lys Glu Ile Leu Asp Lys Lys Val Glu
565 570 575
Lys Val Thr Ile Ser Asn Arg Leu Val Ser Ser Pro Cys Cys Ile Val
580 585 590
Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met Glu Arg Ile Met Lys Ala
595 600 605
Gln Ala Leu Arg Asp Asn Ser Thr Met Gly Tyr Met Met Ala Lys Lys
610 615 620
His Leu Glu Ile Asn Pro Asp His Pro Ile Val Glu Thr Leu Arg Gln
625 630 635 640
Lys Ala Glu Ala Asp Lys Asn Asp Lys Ala Val Lys Asp Leu Val Val
645 650 655
Leu Leu Phe Glu Thr Ala Leu Leu Ser Ser Gly Phe Ser Leu Glu Asp
660 665 670
Pro Gln Thr His Ser Asn Arg Ile Tyr Arg Met Ile Lys Leu Gly Leu
675 680 685
Gly Ile Asp Glu Asp Glu Val Ala Ala Glu Glu Pro Asn Ala Ala Val
690 695 700
Pro Asp Glu Ile Pro Pro Leu Glu Gly Asp Glu Asp Ala Ser Arg Met
705 710 715 720
Glu Glu Val Asp
<210> 9
<211> 2049
<212> DNA
<213> 人工序列
<220>
<223> NP_001258900 (hHSP90 β)的密码子优化基因
<220>
<221> CDS
<222> (13)..(2043)
<400> 9
aagcttgcca cc atg cct gag gag gtg cac cat ggc gag gag gag gtg gag 51
Met Pro Glu Glu Val His His Gly Glu Glu Glu Val Glu
1 5 10
acc ttc gcc ttt cag gct gag atc gcc cag ctg atg tcc ctg atc atc 99
Thr Phe Ala Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile
15 20 25
aac aca ttc tac agc aat aag gag atc ttt ctg agg gag ctg atc agc 147
Asn Thr Phe Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser
30 35 40 45
aat gct tct gac gcc ctg gat aag atc cgg tat gag tcc ctg acc gac 195
Asn Ala Ser Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp
50 55 60
cca tct aag ctg gat tcc ggc aag gag ctg aag atc gac atc tcc atg 243
Pro Ser Lys Leu Asp Ser Gly Lys Glu Leu Lys Ile Asp Ile Ser Met
65 70 75
atc ggc cag ttc ggc gtg ggc ttt tac tcc gcc tat ctg gtg gcc gag 291
Ile Gly Gln Phe Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val Ala Glu
80 85 90
aag gtg gtg gtc atc acc aag cac aac gac gat gag cag tac gct tgg 339
Lys Val Val Val Ile Thr Lys His Asn Asp Asp Glu Gln Tyr Ala Trp
95 100 105
gag tcc agc gcc gga ggc agc ttc aca gtg agg gct gac cac gga gag 387
Glu Ser Ser Ala Gly Gly Ser Phe Thr Val Arg Ala Asp His Gly Glu
110 115 120 125
cca atc gga agg ggc acc aaa gtg atc ctg cat ctg aag gag gat cag 435
Pro Ile Gly Arg Gly Thr Lys Val Ile Leu His Leu Lys Glu Asp Gln
130 135 140
aca gag tat ctg gag gag agg cgg gtg aag gag gtg gtg aag aag cat 483
Thr Glu Tyr Leu Glu Glu Arg Arg Val Lys Glu Val Val Lys Lys His
145 150 155
agc cag ttt atc ggc tac cca atc acc ctg tat ctg gag aag gag agg 531
Ser Gln Phe Ile Gly Tyr Pro Ile Thr Leu Tyr Leu Glu Lys Glu Arg
160 165 170
gag aag gag atc tct gac gat gag gcc gag gag gag aag ggc gag aag 579
Glu Lys Glu Ile Ser Asp Asp Glu Ala Glu Glu Glu Lys Gly Glu Lys
175 180 185
gag gag gag gac aag gac gat gag gag aag ccc aag atc gag gac gtg 627
Glu Glu Glu Asp Lys Asp Asp Glu Glu Lys Pro Lys Ile Glu Asp Val
190 195 200 205
ggc agc gat gag gag gac gat tct ggc aag gac aag aag aag aag acc 675
Gly Ser Asp Glu Glu Asp Asp Ser Gly Lys Asp Lys Lys Lys Lys Thr
210 215 220
aag aag atc aag gag aag tac atc gat cag gag gag ctg aac aag acc 723
Lys Lys Ile Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu Asn Lys Thr
225 230 235
aag cca atc tgg aca agg aat ccc gac gat atc acc cag gag gag tac 771
Lys Pro Ile Trp Thr Arg Asn Pro Asp Asp Ile Thr Gln Glu Glu Tyr
240 245 250
ggc gag ttc tat aag agc ctg aca aat gac tgg gag gat cac ctg gcc 819
Gly Glu Phe Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala
255 260 265
gtg aag cat ttt tct gtg gag ggc cag ctg gag ttc cgg gct ctg ctg 867
Val Lys His Phe Ser Val Glu Gly Gln Leu Glu Phe Arg Ala Leu Leu
270 275 280 285
ttt atc cct aga cgc gcc cca ttc gac ctg ttt gag aac aag aag aag 915
Phe Ile Pro Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn Lys Lys Lys
290 295 300
aag aac aac atc aag ctg tac gtg agg cgg gtg ttc atc atg gac tct 963
Lys Asn Asn Ile Lys Leu Tyr Val Arg Arg Val Phe Ile Met Asp Ser
305 310 315
tgc gat gag ctg atc cct gag tat ctg aac ttc atc aga ggc gtg gtg 1011
Cys Asp Glu Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg Gly Val Val
320 325 330
gac tcc gag gat ctg cca ctg aac atc tcc aga gag atg ctg cag cag 1059
Asp Ser Glu Asp Leu Pro Leu Asn Ile Ser Arg Glu Met Leu Gln Gln
335 340 345
agc aag atc ctg aaa gtg atc cgc aag aat atc gtg aag aag tgt ctg 1107
Ser Lys Ile Leu Lys Val Ile Arg Lys Asn Ile Val Lys Lys Cys Leu
350 355 360 365
gag ctg ttc tcc gag ctg gct gag gat aag gag aac tac aag aag ttc 1155
Glu Leu Phe Ser Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys Lys Phe
370 375 380
tat gag gcc ttt agc aag aat ctg aag ctg ggc atc cac gag gac tct 1203
Tyr Glu Ala Phe Ser Lys Asn Leu Lys Leu Gly Ile His Glu Asp Ser
385 390 395
acc aac aga cgc agg ctg tcc gag ctg ctg aga tac cat acc tcc cag 1251
Thr Asn Arg Arg Arg Leu Ser Glu Leu Leu Arg Tyr His Thr Ser Gln
400 405 410
agc ggc gat gag atg aca tct ctg tcc gag tac gtg tcc cgc atg aag 1299
Ser Gly Asp Glu Met Thr Ser Leu Ser Glu Tyr Val Ser Arg Met Lys
415 420 425
gag acc cag aag tcc atc tac tat atc aca ggc gag agc aag gag cag 1347
Glu Thr Gln Lys Ser Ile Tyr Tyr Ile Thr Gly Glu Ser Lys Glu Gln
430 435 440 445
gtg gct aac tct gcc ttc gtg gag cgg gtg aga aag cgc ggc ttt gag 1395
Val Ala Asn Ser Ala Phe Val Glu Arg Val Arg Lys Arg Gly Phe Glu
450 455 460
gtg gtg tac atg acc gag ccc atc gac gag tat tgc gtg cag cag ctg 1443
Val Val Tyr Met Thr Glu Pro Ile Asp Glu Tyr Cys Val Gln Gln Leu
465 470 475
aag gag ttc gat ggc aag tcc ctg gtg agc gtg aca aag gag ggc ctg 1491
Lys Glu Phe Asp Gly Lys Ser Leu Val Ser Val Thr Lys Glu Gly Leu
480 485 490
gag ctg cct gag gac gag gag gag aag aag aag atg gag gag tct aag 1539
Glu Leu Pro Glu Asp Glu Glu Glu Lys Lys Lys Met Glu Glu Ser Lys
495 500 505
gct aag ttt gag aac ctg tgc aag ctg atg aag gag atc ctg gat aag 1587
Ala Lys Phe Glu Asn Leu Cys Lys Leu Met Lys Glu Ile Leu Asp Lys
510 515 520 525
aag gtg gag aag gtg acc atc tct aac aga ctg gtg tct tcc ccc tgc 1635
Lys Val Glu Lys Val Thr Ile Ser Asn Arg Leu Val Ser Ser Pro Cys
530 535 540
tgt atc gtg acc tcc aca tac ggc tgg acc gct aat atg gag aga atc 1683
Cys Ile Val Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met Glu Arg Ile
545 550 555
atg aag gcc cag gct ctg cgc gac aac tcc aca atg ggc tat atg atg 1731
Met Lys Ala Gln Ala Leu Arg Asp Asn Ser Thr Met Gly Tyr Met Met
560 565 570
gcc aag aag cac ctg gag atc aat cca gat cat ccc atc gtg gag aca 1779
Ala Lys Lys His Leu Glu Ile Asn Pro Asp His Pro Ile Val Glu Thr
575 580 585
ctg cgc cag aag gcc gag gct gac aag aac gat aag gct gtg aag gac 1827
Leu Arg Gln Lys Ala Glu Ala Asp Lys Asn Asp Lys Ala Val Lys Asp
590 595 600 605
ctg gtg gtg ctg ctg ttc gag acc gcc ctg ctg agc tct ggc ttt agc 1875
Leu Val Val Leu Leu Phe Glu Thr Ala Leu Leu Ser Ser Gly Phe Ser
610 615 620
ctg gag gat cct cag aca cac tct aat agg atc tac cgg atg atc aag 1923
Leu Glu Asp Pro Gln Thr His Ser Asn Arg Ile Tyr Arg Met Ile Lys
625 630 635
ctg ggc ctg ggc atc gac gag gat gag gtg gct gct gag gag cca aac 1971
Leu Gly Leu Gly Ile Asp Glu Asp Glu Val Ala Ala Glu Glu Pro Asn
640 645 650
gct gct gtg cct gac gag atc cca cct ctg gag ggc gac gag gat gct 2019
Ala Ala Val Pro Asp Glu Ile Pro Pro Leu Glu Gly Asp Glu Asp Ala
655 660 665
tcc agg atg gag gag gtg gat tga gaattc 2049
Ser Arg Met Glu Glu Val Asp
670 675
<210> 10
<211> 676
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 10
Met Pro Glu Glu Val His His Gly Glu Glu Glu Val Glu Thr Phe Ala
1 5 10 15
Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile Asn Thr Phe
20 25 30
Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser Asn Ala Ser
35 40 45
Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp Pro Ser Lys
50 55 60
Leu Asp Ser Gly Lys Glu Leu Lys Ile Asp Ile Ser Met Ile Gly Gln
65 70 75 80
Phe Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val Ala Glu Lys Val Val
85 90 95
Val Ile Thr Lys His Asn Asp Asp Glu Gln Tyr Ala Trp Glu Ser Ser
100 105 110
Ala Gly Gly Ser Phe Thr Val Arg Ala Asp His Gly Glu Pro Ile Gly
115 120 125
Arg Gly Thr Lys Val Ile Leu His Leu Lys Glu Asp Gln Thr Glu Tyr
130 135 140
Leu Glu Glu Arg Arg Val Lys Glu Val Val Lys Lys His Ser Gln Phe
145 150 155 160
Ile Gly Tyr Pro Ile Thr Leu Tyr Leu Glu Lys Glu Arg Glu Lys Glu
165 170 175
Ile Ser Asp Asp Glu Ala Glu Glu Glu Lys Gly Glu Lys Glu Glu Glu
180 185 190
Asp Lys Asp Asp Glu Glu Lys Pro Lys Ile Glu Asp Val Gly Ser Asp
195 200 205
Glu Glu Asp Asp Ser Gly Lys Asp Lys Lys Lys Lys Thr Lys Lys Ile
210 215 220
Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu Asn Lys Thr Lys Pro Ile
225 230 235 240
Trp Thr Arg Asn Pro Asp Asp Ile Thr Gln Glu Glu Tyr Gly Glu Phe
245 250 255
Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala Val Lys His
260 265 270
Phe Ser Val Glu Gly Gln Leu Glu Phe Arg Ala Leu Leu Phe Ile Pro
275 280 285
Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn Lys Lys Lys Lys Asn Asn
290 295 300
Ile Lys Leu Tyr Val Arg Arg Val Phe Ile Met Asp Ser Cys Asp Glu
305 310 315 320
Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg Gly Val Val Asp Ser Glu
325 330 335
Asp Leu Pro Leu Asn Ile Ser Arg Glu Met Leu Gln Gln Ser Lys Ile
340 345 350
Leu Lys Val Ile Arg Lys Asn Ile Val Lys Lys Cys Leu Glu Leu Phe
355 360 365
Ser Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys Lys Phe Tyr Glu Ala
370 375 380
Phe Ser Lys Asn Leu Lys Leu Gly Ile His Glu Asp Ser Thr Asn Arg
385 390 395 400
Arg Arg Leu Ser Glu Leu Leu Arg Tyr His Thr Ser Gln Ser Gly Asp
405 410 415
Glu Met Thr Ser Leu Ser Glu Tyr Val Ser Arg Met Lys Glu Thr Gln
420 425 430
Lys Ser Ile Tyr Tyr Ile Thr Gly Glu Ser Lys Glu Gln Val Ala Asn
435 440 445
Ser Ala Phe Val Glu Arg Val Arg Lys Arg Gly Phe Glu Val Val Tyr
450 455 460
Met Thr Glu Pro Ile Asp Glu Tyr Cys Val Gln Gln Leu Lys Glu Phe
465 470 475 480
Asp Gly Lys Ser Leu Val Ser Val Thr Lys Glu Gly Leu Glu Leu Pro
485 490 495
Glu Asp Glu Glu Glu Lys Lys Lys Met Glu Glu Ser Lys Ala Lys Phe
500 505 510
Glu Asn Leu Cys Lys Leu Met Lys Glu Ile Leu Asp Lys Lys Val Glu
515 520 525
Lys Val Thr Ile Ser Asn Arg Leu Val Ser Ser Pro Cys Cys Ile Val
530 535 540
Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met Glu Arg Ile Met Lys Ala
545 550 555 560
Gln Ala Leu Arg Asp Asn Ser Thr Met Gly Tyr Met Met Ala Lys Lys
565 570 575
His Leu Glu Ile Asn Pro Asp His Pro Ile Val Glu Thr Leu Arg Gln
580 585 590
Lys Ala Glu Ala Asp Lys Asn Asp Lys Ala Val Lys Asp Leu Val Val
595 600 605
Leu Leu Phe Glu Thr Ala Leu Leu Ser Ser Gly Phe Ser Leu Glu Asp
610 615 620
Pro Gln Thr His Ser Asn Arg Ile Tyr Arg Met Ile Lys Leu Gly Leu
625 630 635 640
Gly Ile Asp Glu Asp Glu Val Ala Ala Glu Glu Pro Asn Ala Ala Val
645 650 655
Pro Asp Glu Ile Pro Pro Leu Glu Gly Asp Glu Asp Ala Ser Arg Met
660 665 670
Glu Glu Val Asp
675
<210> 11
<211> 2163
<212> DNA
<213> 人工序列
<220>
<223> NP_001258901 (hHSP90 β)的密码子优化基因
<220>
<221> CDS
<222> (13)..(2157)
<400> 11
aagcttgcca cc atg ccc gag gag gtg cac cat ggc gag gag gag gtg gag 51
Met Pro Glu Glu Val His His Gly Glu Glu Glu Val Glu
1 5 10
acc ttc gcc ttt cag gct gag atc gcc cag ctg atg tcc ctg atc atc 99
Thr Phe Ala Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile
15 20 25
aac aca ttc tac agc aat aag gag atc ttt ctg agg gag ctg atc agc 147
Asn Thr Phe Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser
30 35 40 45
aat gct tct gac gcc ctg gat aag atc cgg tat gag tct ctg acc gac 195
Asn Ala Ser Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp
50 55 60
cct tct aag ctg gat tcc ggc aag gag ctg aag atc gac atc atc cca 243
Pro Ser Lys Leu Asp Ser Gly Lys Glu Leu Lys Ile Asp Ile Ile Pro
65 70 75
aac ccc cag gag agg acc ctg aca ctg gtg gac acc ggc atc ggc atg 291
Asn Pro Gln Glu Arg Thr Leu Thr Leu Val Asp Thr Gly Ile Gly Met
80 85 90
aca aag gct gat ctg atc aac aat ctg ggc acc atc gcc aag agc ggc 339
Thr Lys Ala Asp Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys Ser Gly
95 100 105
aca aag gct ttc atg gag gcc ctg cag ttc ggc gtg ggc ttt tac tct 387
Thr Lys Ala Phe Met Glu Ala Leu Gln Phe Gly Val Gly Phe Tyr Ser
110 115 120 125
gct tat ctg gtg gcc gag aag gtg gtg gtc atc acc aag cac aac gac 435
Ala Tyr Leu Val Ala Glu Lys Val Val Val Ile Thr Lys His Asn Asp
130 135 140
gat gag cag tac gct tgg gag tcc agc gcc gga ggc tcc ttt aca gtg 483
Asp Glu Gln Tyr Ala Trp Glu Ser Ser Ala Gly Gly Ser Phe Thr Val
145 150 155
agg gct gac cac gga gag cca atc gga agg ggc acc aaa gtg atc ctg 531
Arg Ala Asp His Gly Glu Pro Ile Gly Arg Gly Thr Lys Val Ile Leu
160 165 170
cat ctg aag gag gat cag aca gag tat ctg gag gag agg cgg gtg aag 579
His Leu Lys Glu Asp Gln Thr Glu Tyr Leu Glu Glu Arg Arg Val Lys
175 180 185
gag gtg gtg aag aag cat agc cag ttc atc ggc tac cct atc acc ctg 627
Glu Val Val Lys Lys His Ser Gln Phe Ile Gly Tyr Pro Ile Thr Leu
190 195 200 205
tat ctg gag aag gag cgg gag aag gag atc tct gac gat gag gcc gag 675
Tyr Leu Glu Lys Glu Arg Glu Lys Glu Ile Ser Asp Asp Glu Ala Glu
210 215 220
gag gag aag ggc gag aag gag gag gag gac aag gac gat gag gag aag 723
Glu Glu Lys Gly Glu Lys Glu Glu Glu Asp Lys Asp Asp Glu Glu Lys
225 230 235
cca aag atc gag gac gtg ggc agc gat gag gag gac gat tct ggc aag 771
Pro Lys Ile Glu Asp Val Gly Ser Asp Glu Glu Asp Asp Ser Gly Lys
240 245 250
gac aag aag aag aag acc aag aag atc aag gag aag tac atc gat cag 819
Asp Lys Lys Lys Lys Thr Lys Lys Ile Lys Glu Lys Tyr Ile Asp Gln
255 260 265
gag gag ctg aac aag acc aag cct atc tgg aca agg aat cca gac gat 867
Glu Glu Leu Asn Lys Thr Lys Pro Ile Trp Thr Arg Asn Pro Asp Asp
270 275 280 285
atc acc cag gag gag tac ggc gag ttc tat aag tct ctg aca aat gac 915
Ile Thr Gln Glu Glu Tyr Gly Glu Phe Tyr Lys Ser Leu Thr Asn Asp
290 295 300
tgg gag gat cac ctg gcc gtg aag cat ttt tcc gtg gag gga cag ctg 963
Trp Glu Asp His Leu Ala Val Lys His Phe Ser Val Glu Gly Gln Leu
305 310 315
gag ttc cgg gct ctg ctg ttt atc ccc aga cgc gcc cct ttc gac ctg 1011
Glu Phe Arg Ala Leu Leu Phe Ile Pro Arg Arg Ala Pro Phe Asp Leu
320 325 330
ttt gag aac aag aag aag aag aac aac atc aag ctg tac gtg agg cgg 1059
Phe Glu Asn Lys Lys Lys Lys Asn Asn Ile Lys Leu Tyr Val Arg Arg
335 340 345
gtg ttc atc atg gac tct tgc gat gag ctg atc ccc gag tat ctg aac 1107
Val Phe Ile Met Asp Ser Cys Asp Glu Leu Ile Pro Glu Tyr Leu Asn
350 355 360 365
ttc atc aga ggc gtg gtg gac tcc gag gat ctg cct ctg aac atc tcc 1155
Phe Ile Arg Gly Val Val Asp Ser Glu Asp Leu Pro Leu Asn Ile Ser
370 375 380
aga gag atg ctg cag cag agc aag atc ctg aaa gtg atc cgc aag aat 1203
Arg Glu Met Leu Gln Gln Ser Lys Ile Leu Lys Val Ile Arg Lys Asn
385 390 395
atc gtg aag aag tgt ctg gag ctg ttt tcc gag ctg gct gag gat aag 1251
Ile Val Lys Lys Cys Leu Glu Leu Phe Ser Glu Leu Ala Glu Asp Lys
400 405 410
gag aac tac aag aag ttc tat gag gcc ttt agc aag aat ctg aag ctg 1299
Glu Asn Tyr Lys Lys Phe Tyr Glu Ala Phe Ser Lys Asn Leu Lys Leu
415 420 425
ggc atc cac gag gac tct acc aac aga cgc agg ctg tcc gag ctg ctg 1347
Gly Ile His Glu Asp Ser Thr Asn Arg Arg Arg Leu Ser Glu Leu Leu
430 435 440 445
aga tac cat acc tcc cag agc ggc gat gag atg aca tct ctg tcc gag 1395
Arg Tyr His Thr Ser Gln Ser Gly Asp Glu Met Thr Ser Leu Ser Glu
450 455 460
tac gtg tcc cgc atg aag gag acc cag aag tcc atc tac tat atc aca 1443
Tyr Val Ser Arg Met Lys Glu Thr Gln Lys Ser Ile Tyr Tyr Ile Thr
465 470 475
ggc gag agc aag gag cag gtg gct aac tct gcc ttc gtg gag cgg gtg 1491
Gly Glu Ser Lys Glu Gln Val Ala Asn Ser Ala Phe Val Glu Arg Val
480 485 490
aga aag cgc ggc ttt gag gtg gtg tac atg acc gag cca atc gac gag 1539
Arg Lys Arg Gly Phe Glu Val Val Tyr Met Thr Glu Pro Ile Asp Glu
495 500 505
tat tgc gtg cag cag ctg aag gag ttc gat ggc aag tcc ctg gtg agc 1587
Tyr Cys Val Gln Gln Leu Lys Glu Phe Asp Gly Lys Ser Leu Val Ser
510 515 520 525
gtg aca aag gag gga ctg gag ctg cca gag gac gag gag gag aag aag 1635
Val Thr Lys Glu Gly Leu Glu Leu Pro Glu Asp Glu Glu Glu Lys Lys
530 535 540
aag atg gag gag tcc aag gct aag ttt gag aac ctg tgc aag ctg atg 1683
Lys Met Glu Glu Ser Lys Ala Lys Phe Glu Asn Leu Cys Lys Leu Met
545 550 555
aag gag atc ctg gat aag aag gtg gag aag gtg acc atc tcc aac aga 1731
Lys Glu Ile Leu Asp Lys Lys Val Glu Lys Val Thr Ile Ser Asn Arg
560 565 570
ctg gtg tct tcc cca tgc tgt atc gtg acc agc aca tac ggc tgg acc 1779
Leu Val Ser Ser Pro Cys Cys Ile Val Thr Ser Thr Tyr Gly Trp Thr
575 580 585
gct aat atg gag aga atc atg aag gcc cag gct ctg cgc gac aac agc 1827
Ala Asn Met Glu Arg Ile Met Lys Ala Gln Ala Leu Arg Asp Asn Ser
590 595 600 605
aca atg ggc tat atg atg gcc aag aag cac ctg gag atc aat cct gat 1875
Thr Met Gly Tyr Met Met Ala Lys Lys His Leu Glu Ile Asn Pro Asp
610 615 620
cat cca atc gtg gag acc ctg agg cag aag gct gag gct gac aag aac 1923
His Pro Ile Val Glu Thr Leu Arg Gln Lys Ala Glu Ala Asp Lys Asn
625 630 635
gat aag gct gtg aag gac ctg gtg gtg ctg ctg ttc gag acc gcc ctg 1971
Asp Lys Ala Val Lys Asp Leu Val Val Leu Leu Phe Glu Thr Ala Leu
640 645 650
ctg agc tct ggc ttt agc ctg gag gat ccc cag aca cac tct aat agg 2019
Leu Ser Ser Gly Phe Ser Leu Glu Asp Pro Gln Thr His Ser Asn Arg
655 660 665
atc tac cgg atg atc aag ctg ggc ctg ggc atc gac gag gat gag gtg 2067
Ile Tyr Arg Met Ile Lys Leu Gly Leu Gly Ile Asp Glu Asp Glu Val
670 675 680 685
gct gct gag gag cca aac gct gct gtg cca gac gag atc cca cct ctg 2115
Ala Ala Glu Glu Pro Asn Ala Ala Val Pro Asp Glu Ile Pro Pro Leu
690 695 700
gag ggc gac gag gat gct tcc cgc atg gag gag gtg gat tga gaattc 2163
Glu Gly Asp Glu Asp Ala Ser Arg Met Glu Glu Val Asp
705 710
<210> 12
<211> 714
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 12
Met Pro Glu Glu Val His His Gly Glu Glu Glu Val Glu Thr Phe Ala
1 5 10 15
Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile Asn Thr Phe
20 25 30
Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser Asn Ala Ser
35 40 45
Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp Pro Ser Lys
50 55 60
Leu Asp Ser Gly Lys Glu Leu Lys Ile Asp Ile Ile Pro Asn Pro Gln
65 70 75 80
Glu Arg Thr Leu Thr Leu Val Asp Thr Gly Ile Gly Met Thr Lys Ala
85 90 95
Asp Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys Ser Gly Thr Lys Ala
100 105 110
Phe Met Glu Ala Leu Gln Phe Gly Val Gly Phe Tyr Ser Ala Tyr Leu
115 120 125
Val Ala Glu Lys Val Val Val Ile Thr Lys His Asn Asp Asp Glu Gln
130 135 140
Tyr Ala Trp Glu Ser Ser Ala Gly Gly Ser Phe Thr Val Arg Ala Asp
145 150 155 160
His Gly Glu Pro Ile Gly Arg Gly Thr Lys Val Ile Leu His Leu Lys
165 170 175
Glu Asp Gln Thr Glu Tyr Leu Glu Glu Arg Arg Val Lys Glu Val Val
180 185 190
Lys Lys His Ser Gln Phe Ile Gly Tyr Pro Ile Thr Leu Tyr Leu Glu
195 200 205
Lys Glu Arg Glu Lys Glu Ile Ser Asp Asp Glu Ala Glu Glu Glu Lys
210 215 220
Gly Glu Lys Glu Glu Glu Asp Lys Asp Asp Glu Glu Lys Pro Lys Ile
225 230 235 240
Glu Asp Val Gly Ser Asp Glu Glu Asp Asp Ser Gly Lys Asp Lys Lys
245 250 255
Lys Lys Thr Lys Lys Ile Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu
260 265 270
Asn Lys Thr Lys Pro Ile Trp Thr Arg Asn Pro Asp Asp Ile Thr Gln
275 280 285
Glu Glu Tyr Gly Glu Phe Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp
290 295 300
His Leu Ala Val Lys His Phe Ser Val Glu Gly Gln Leu Glu Phe Arg
305 310 315 320
Ala Leu Leu Phe Ile Pro Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn
325 330 335
Lys Lys Lys Lys Asn Asn Ile Lys Leu Tyr Val Arg Arg Val Phe Ile
340 345 350
Met Asp Ser Cys Asp Glu Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg
355 360 365
Gly Val Val Asp Ser Glu Asp Leu Pro Leu Asn Ile Ser Arg Glu Met
370 375 380
Leu Gln Gln Ser Lys Ile Leu Lys Val Ile Arg Lys Asn Ile Val Lys
385 390 395 400
Lys Cys Leu Glu Leu Phe Ser Glu Leu Ala Glu Asp Lys Glu Asn Tyr
405 410 415
Lys Lys Phe Tyr Glu Ala Phe Ser Lys Asn Leu Lys Leu Gly Ile His
420 425 430
Glu Asp Ser Thr Asn Arg Arg Arg Leu Ser Glu Leu Leu Arg Tyr His
435 440 445
Thr Ser Gln Ser Gly Asp Glu Met Thr Ser Leu Ser Glu Tyr Val Ser
450 455 460
Arg Met Lys Glu Thr Gln Lys Ser Ile Tyr Tyr Ile Thr Gly Glu Ser
465 470 475 480
Lys Glu Gln Val Ala Asn Ser Ala Phe Val Glu Arg Val Arg Lys Arg
485 490 495
Gly Phe Glu Val Val Tyr Met Thr Glu Pro Ile Asp Glu Tyr Cys Val
500 505 510
Gln Gln Leu Lys Glu Phe Asp Gly Lys Ser Leu Val Ser Val Thr Lys
515 520 525
Glu Gly Leu Glu Leu Pro Glu Asp Glu Glu Glu Lys Lys Lys Met Glu
530 535 540
Glu Ser Lys Ala Lys Phe Glu Asn Leu Cys Lys Leu Met Lys Glu Ile
545 550 555 560
Leu Asp Lys Lys Val Glu Lys Val Thr Ile Ser Asn Arg Leu Val Ser
565 570 575
Ser Pro Cys Cys Ile Val Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met
580 585 590
Glu Arg Ile Met Lys Ala Gln Ala Leu Arg Asp Asn Ser Thr Met Gly
595 600 605
Tyr Met Met Ala Lys Lys His Leu Glu Ile Asn Pro Asp His Pro Ile
610 615 620
Val Glu Thr Leu Arg Gln Lys Ala Glu Ala Asp Lys Asn Asp Lys Ala
625 630 635 640
Val Lys Asp Leu Val Val Leu Leu Phe Glu Thr Ala Leu Leu Ser Ser
645 650 655
Gly Phe Ser Leu Glu Asp Pro Gln Thr His Ser Asn Arg Ile Tyr Arg
660 665 670
Met Ile Lys Leu Gly Leu Gly Ile Asp Glu Asp Glu Val Ala Ala Glu
675 680 685
Glu Pro Asn Ala Ala Val Pro Asp Glu Ile Pro Pro Leu Glu Gly Asp
690 695 700
Glu Asp Ala Ser Arg Met Glu Glu Val Asp
705 710
<210> 13
<211> 2193
<212> DNA
<213> 人工序列
<220>
<223> XP_003501716 (chHSP90 β)的密码子优化基因
<220>
<221> CDS
<222> (13)..(2187)
<400> 13
aagcttgcca cc atg cca gag gag gtg cac cat ggc gag gag gag gtg gag 51
Met Pro Glu Glu Val His His Gly Glu Glu Glu Val Glu
1 5 10
acc ttc gcc ttt cag gct gag atc gcc cag ctg atg tcc ctg atc atc 99
Thr Phe Ala Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile
15 20 25
aac aca ttc tac agc aat aag gag atc ttt ctg cgc gag ctg atc agc 147
Asn Thr Phe Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser
30 35 40 45
aat gct tct gac gcc ctg gat aag atc aga tat gag tct ctg acc gac 195
Asn Ala Ser Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp
50 55 60
ccc tct aag ctg gat tcc ggc aag gag ctg aag atc gac atc atc cca 243
Pro Ser Lys Leu Asp Ser Gly Lys Glu Leu Lys Ile Asp Ile Ile Pro
65 70 75
aac ccc cag gag cgc acc ctg aca ctg gtg gac acc ggc atc ggc atg 291
Asn Pro Gln Glu Arg Thr Leu Thr Leu Val Asp Thr Gly Ile Gly Met
80 85 90
aca aag gct gat ctg atc aac aat ctg ggc acc atc gcc aag tcc ggc 339
Thr Lys Ala Asp Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys Ser Gly
95 100 105
aca aag gct ttc atg gag gcc ctg cag gct gga gct gat atc tcc atg 387
Thr Lys Ala Phe Met Glu Ala Leu Gln Ala Gly Ala Asp Ile Ser Met
110 115 120 125
atc ggc cag ttc ggc gtg ggc ttt tac tcc gcc tat ctg gtg gcc gag 435
Ile Gly Gln Phe Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val Ala Glu
130 135 140
aag gtg gtg gtc atc acc aag cac aat gac gat gag cag tac gct tgg 483
Lys Val Val Val Ile Thr Lys His Asn Asp Asp Glu Gln Tyr Ala Trp
145 150 155
gag tcc agc gcc gga ggc tcc ttc aca gtg cgc gct gac cac gga gag 531
Glu Ser Ser Ala Gly Gly Ser Phe Thr Val Arg Ala Asp His Gly Glu
160 165 170
cct atc gga agg gga acc aaa gtg atc ctg cat ctg aag gag gat cag 579
Pro Ile Gly Arg Gly Thr Lys Val Ile Leu His Leu Lys Glu Asp Gln
175 180 185
aca gag tat ctg gag gag agg cgg gtg aag gag gtg gtg aag aag cat 627
Thr Glu Tyr Leu Glu Glu Arg Arg Val Lys Glu Val Val Lys Lys His
190 195 200 205
tcc cag ttt atc ggc tac cct atc acc ctg tat ctg gag aag gag agg 675
Ser Gln Phe Ile Gly Tyr Pro Ile Thr Leu Tyr Leu Glu Lys Glu Arg
210 215 220
gag aag gag atc agc gac gat gag gcc gag gag gag aag ggc gag aag 723
Glu Lys Glu Ile Ser Asp Asp Glu Ala Glu Glu Glu Lys Gly Glu Lys
225 230 235
gag gag gag gac aag gac gat gag gag aag cca aag atc gag gac gtg 771
Glu Glu Glu Asp Lys Asp Asp Glu Glu Lys Pro Lys Ile Glu Asp Val
240 245 250
ggc agc gat gag gag gac gat tct ggc aag gac aag aag aag aag acc 819
Gly Ser Asp Glu Glu Asp Asp Ser Gly Lys Asp Lys Lys Lys Lys Thr
255 260 265
aag aag atc aag gag aag tac atc gat cag gag gag ctg aac aag acc 867
Lys Lys Ile Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu Asn Lys Thr
270 275 280 285
aag cct atc tgg aca cgc aat cca gac gat atc acc cag gag gag tac 915
Lys Pro Ile Trp Thr Arg Asn Pro Asp Asp Ile Thr Gln Glu Glu Tyr
290 295 300
ggc gac ttc tat aag agc ctg aca aat gac tgg gag gat cac ctg gcc 963
Gly Asp Phe Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala
305 310 315
gtg aag cat ttt tct gtg gag ggc cag ctg gag ttc agg gct ctg ctg 1011
Val Lys His Phe Ser Val Glu Gly Gln Leu Glu Phe Arg Ala Leu Leu
320 325 330
ttt atc ccc aga cgc gcc cct ttc gat ctg ttt gag aac aag aag aag 1059
Phe Ile Pro Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn Lys Lys Lys
335 340 345
aag aac aac atc aag ctg tac gtg agg cgg gtg ttc atc atg gac agc 1107
Lys Asn Asn Ile Lys Leu Tyr Val Arg Arg Val Phe Ile Met Asp Ser
350 355 360 365
tgc gat gag ctg atc cca gag tat ctg aac ttc atc aga ggc gtg gtg 1155
Cys Asp Glu Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg Gly Val Val
370 375 380
gac tct gag gat ctg ccc ctg aac atc tcc cgg gag atg ctg cag cag 1203
Asp Ser Glu Asp Leu Pro Leu Asn Ile Ser Arg Glu Met Leu Gln Gln
385 390 395
agc aag atc ctg aaa gtg atc aga aag aat atc gtg aag aag tgt ctg 1251
Ser Lys Ile Leu Lys Val Ile Arg Lys Asn Ile Val Lys Lys Cys Leu
400 405 410
gag ctg ttt tcc gag ctg gct gag gac aag gag aac tac aag aag ttc 1299
Glu Leu Phe Ser Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys Lys Phe
415 420 425
tat gag gcc ttt agc aag aat ctg aag ctg ggc atc cac gag gac tct 1347
Tyr Glu Ala Phe Ser Lys Asn Leu Lys Leu Gly Ile His Glu Asp Ser
430 435 440 445
acc aac aga cgc agg ctg tcc gag ctg ctg cgg tac cat acc tcc cag 1395
Thr Asn Arg Arg Arg Leu Ser Glu Leu Leu Arg Tyr His Thr Ser Gln
450 455 460
agc ggc gat gag atg aca tct ctg tcc gag tac gtg tcc aga atg aag 1443
Ser Gly Asp Glu Met Thr Ser Leu Ser Glu Tyr Val Ser Arg Met Lys
465 470 475
gag acc cag aag tcc atc tac tat atc aca ggc gag agc aag gag cag 1491
Glu Thr Gln Lys Ser Ile Tyr Tyr Ile Thr Gly Glu Ser Lys Glu Gln
480 485 490
gtg gct aac tct gcc ttc gtg gag agg gtg cca aag agg gga ttt gag 1539
Val Ala Asn Ser Ala Phe Val Glu Arg Val Pro Lys Arg Gly Phe Glu
495 500 505
gcc gtg tac atg acc gag cct atc gac gag tat tgc gtg cag cag ctg 1587
Ala Val Tyr Met Thr Glu Pro Ile Asp Glu Tyr Cys Val Gln Gln Leu
510 515 520 525
aag gag ttc gat ggc aag tcc ctg gtg agc gtg aca aag gag gga ctg 1635
Lys Glu Phe Asp Gly Lys Ser Leu Val Ser Val Thr Lys Glu Gly Leu
530 535 540
gag ctg cca gag gac gag gag gag aag aag aag atg gag gag agc aag 1683
Glu Leu Pro Glu Asp Glu Glu Glu Lys Lys Lys Met Glu Glu Ser Lys
545 550 555
gcc aag ttt gag aac ctg tgc aag ctg atg aag gag atc ctg gat aag 1731
Ala Lys Phe Glu Asn Leu Cys Lys Leu Met Lys Glu Ile Leu Asp Lys
560 565 570
aag gtg gag aag gtg acc atc tct aac cgg ctg gtg tct tcc cct tgc 1779
Lys Val Glu Lys Val Thr Ile Ser Asn Arg Leu Val Ser Ser Pro Cys
575 580 585
tgt atc gtg acc tcc aca tac ggc tgg acc gct aat atg gag cgg atc 1827
Cys Ile Val Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met Glu Arg Ile
590 595 600 605
atg aag gcc cag gct ctg aga gac aac tct aca atg ggc tat atg atg 1875
Met Lys Ala Gln Ala Leu Arg Asp Asn Ser Thr Met Gly Tyr Met Met
610 615 620
gcc aag aag cac ctg gag atc aat cct gat cat cca atc gtg gag aca 1923
Ala Lys Lys His Leu Glu Ile Asn Pro Asp His Pro Ile Val Glu Thr
625 630 635
ctg aga cag aag gcc gag gct gac aag aac gat aag gct gtg aag gac 1971
Leu Arg Gln Lys Ala Glu Ala Asp Lys Asn Asp Lys Ala Val Lys Asp
640 645 650
ctg gtg gtg ctg ctg ttc gag acc gcc ctg ctg agc tct ggc ttt agc 2019
Leu Val Val Leu Leu Phe Glu Thr Ala Leu Leu Ser Ser Gly Phe Ser
655 660 665
ctg gag gat cca cag aca cac tct aac cgg atc tac aga atg atc aag 2067
Leu Glu Asp Pro Gln Thr His Ser Asn Arg Ile Tyr Arg Met Ile Lys
670 675 680 685
ctg ggc ctg ggc atc gac gag gat gag gtg acc gct gag gag cca tct 2115
Leu Gly Leu Gly Ile Asp Glu Asp Glu Val Thr Ala Glu Glu Pro Ser
690 695 700
gcc gct gtg cca gac gag atc cca cct ctg gag ggc gac gag gat gct 2163
Ala Ala Val Pro Asp Glu Ile Pro Pro Leu Glu Gly Asp Glu Asp Ala
705 710 715
tcc agg atg gag gag gtg gat tga gaattc 2193
Ser Arg Met Glu Glu Val Asp
720
<210> 14
<211> 724
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 14
Met Pro Glu Glu Val His His Gly Glu Glu Glu Val Glu Thr Phe Ala
1 5 10 15
Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile Asn Thr Phe
20 25 30
Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser Asn Ala Ser
35 40 45
Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp Pro Ser Lys
50 55 60
Leu Asp Ser Gly Lys Glu Leu Lys Ile Asp Ile Ile Pro Asn Pro Gln
65 70 75 80
Glu Arg Thr Leu Thr Leu Val Asp Thr Gly Ile Gly Met Thr Lys Ala
85 90 95
Asp Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys Ser Gly Thr Lys Ala
100 105 110
Phe Met Glu Ala Leu Gln Ala Gly Ala Asp Ile Ser Met Ile Gly Gln
115 120 125
Phe Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val Ala Glu Lys Val Val
130 135 140
Val Ile Thr Lys His Asn Asp Asp Glu Gln Tyr Ala Trp Glu Ser Ser
145 150 155 160
Ala Gly Gly Ser Phe Thr Val Arg Ala Asp His Gly Glu Pro Ile Gly
165 170 175
Arg Gly Thr Lys Val Ile Leu His Leu Lys Glu Asp Gln Thr Glu Tyr
180 185 190
Leu Glu Glu Arg Arg Val Lys Glu Val Val Lys Lys His Ser Gln Phe
195 200 205
Ile Gly Tyr Pro Ile Thr Leu Tyr Leu Glu Lys Glu Arg Glu Lys Glu
210 215 220
Ile Ser Asp Asp Glu Ala Glu Glu Glu Lys Gly Glu Lys Glu Glu Glu
225 230 235 240
Asp Lys Asp Asp Glu Glu Lys Pro Lys Ile Glu Asp Val Gly Ser Asp
245 250 255
Glu Glu Asp Asp Ser Gly Lys Asp Lys Lys Lys Lys Thr Lys Lys Ile
260 265 270
Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu Asn Lys Thr Lys Pro Ile
275 280 285
Trp Thr Arg Asn Pro Asp Asp Ile Thr Gln Glu Glu Tyr Gly Asp Phe
290 295 300
Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala Val Lys His
305 310 315 320
Phe Ser Val Glu Gly Gln Leu Glu Phe Arg Ala Leu Leu Phe Ile Pro
325 330 335
Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn Lys Lys Lys Lys Asn Asn
340 345 350
Ile Lys Leu Tyr Val Arg Arg Val Phe Ile Met Asp Ser Cys Asp Glu
355 360 365
Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg Gly Val Val Asp Ser Glu
370 375 380
Asp Leu Pro Leu Asn Ile Ser Arg Glu Met Leu Gln Gln Ser Lys Ile
385 390 395 400
Leu Lys Val Ile Arg Lys Asn Ile Val Lys Lys Cys Leu Glu Leu Phe
405 410 415
Ser Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys Lys Phe Tyr Glu Ala
420 425 430
Phe Ser Lys Asn Leu Lys Leu Gly Ile His Glu Asp Ser Thr Asn Arg
435 440 445
Arg Arg Leu Ser Glu Leu Leu Arg Tyr His Thr Ser Gln Ser Gly Asp
450 455 460
Glu Met Thr Ser Leu Ser Glu Tyr Val Ser Arg Met Lys Glu Thr Gln
465 470 475 480
Lys Ser Ile Tyr Tyr Ile Thr Gly Glu Ser Lys Glu Gln Val Ala Asn
485 490 495
Ser Ala Phe Val Glu Arg Val Pro Lys Arg Gly Phe Glu Ala Val Tyr
500 505 510
Met Thr Glu Pro Ile Asp Glu Tyr Cys Val Gln Gln Leu Lys Glu Phe
515 520 525
Asp Gly Lys Ser Leu Val Ser Val Thr Lys Glu Gly Leu Glu Leu Pro
530 535 540
Glu Asp Glu Glu Glu Lys Lys Lys Met Glu Glu Ser Lys Ala Lys Phe
545 550 555 560
Glu Asn Leu Cys Lys Leu Met Lys Glu Ile Leu Asp Lys Lys Val Glu
565 570 575
Lys Val Thr Ile Ser Asn Arg Leu Val Ser Ser Pro Cys Cys Ile Val
580 585 590
Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met Glu Arg Ile Met Lys Ala
595 600 605
Gln Ala Leu Arg Asp Asn Ser Thr Met Gly Tyr Met Met Ala Lys Lys
610 615 620
His Leu Glu Ile Asn Pro Asp His Pro Ile Val Glu Thr Leu Arg Gln
625 630 635 640
Lys Ala Glu Ala Asp Lys Asn Asp Lys Ala Val Lys Asp Leu Val Val
645 650 655
Leu Leu Phe Glu Thr Ala Leu Leu Ser Ser Gly Phe Ser Leu Glu Asp
660 665 670
Pro Gln Thr His Ser Asn Arg Ile Tyr Arg Met Ile Lys Leu Gly Leu
675 680 685
Gly Ile Asp Glu Asp Glu Val Thr Ala Glu Glu Pro Ser Ala Ala Val
690 695 700
Pro Asp Glu Ile Pro Pro Leu Glu Gly Asp Glu Asp Ala Ser Arg Met
705 710 715 720
Glu Glu Val Asp
<210> 15
<211> 1155
<212> DNA
<213> 人工序列
<220>
<223> NP_008996 (hCDC37)的密码子优化基因
<220>
<221> CDS
<222> (13)..(1149)
<400> 15
aagcttgcca cc atg gtg gac tac tcc gtg tgg gat cac atc gag gtg agc 51
Met Val Asp Tyr Ser Val Trp Asp His Ile Glu Val Ser
1 5 10
gac gat gag gac gag aca cat cct aac atc gat aca gcc agc ctg ttc 99
Asp Asp Glu Asp Glu Thr His Pro Asn Ile Asp Thr Ala Ser Leu Phe
15 20 25
aga tgg aga cac cag gct cgc gtg gag agg atg gag cag ttt cag aag 147
Arg Trp Arg His Gln Ala Arg Val Glu Arg Met Glu Gln Phe Gln Lys
30 35 40 45
gag aag gag gag ctg gac cgg ggc tgc aga gag tgt aag cgg aag gtg 195
Glu Lys Glu Glu Leu Asp Arg Gly Cys Arg Glu Cys Lys Arg Lys Val
50 55 60
gcc gag tgc cag aga aag ctg aag gag ctg gag gtg gct gag ggc ggc 243
Ala Glu Cys Gln Arg Lys Leu Lys Glu Leu Glu Val Ala Glu Gly Gly
65 70 75
aag gct gag ctg gag aga ctg cag gct gag gct cag cag ctg cgg aag 291
Lys Ala Glu Leu Glu Arg Leu Gln Ala Glu Ala Gln Gln Leu Arg Lys
80 85 90
gag gag aga tcc tgg gag cag aag ctg gag gag atg agg aag aag gag 339
Glu Glu Arg Ser Trp Glu Gln Lys Leu Glu Glu Met Arg Lys Lys Glu
95 100 105
aag tct atg ccc tgg aac gtg gac acc ctg tcc aag gat ggc ttc tcc 387
Lys Ser Met Pro Trp Asn Val Asp Thr Leu Ser Lys Asp Gly Phe Ser
110 115 120 125
aag agc atg gtg aat acc aag cct gag aag aca gag gag gat agc gag 435
Lys Ser Met Val Asn Thr Lys Pro Glu Lys Thr Glu Glu Asp Ser Glu
130 135 140
gag gtg cgc gag cag aag cac aag aca ttc gtg gag aag tat gag aag 483
Glu Val Arg Glu Gln Lys His Lys Thr Phe Val Glu Lys Tyr Glu Lys
145 150 155
cag atc aag cat ttt ggc atg ctg agg cgg tgg gac gat agc cag aag 531
Gln Ile Lys His Phe Gly Met Leu Arg Arg Trp Asp Asp Ser Gln Lys
160 165 170
tac ctg tct gac aac gtg cac ctg gtg tgc gag gag aca gct aat tac 579
Tyr Leu Ser Asp Asn Val His Leu Val Cys Glu Glu Thr Ala Asn Tyr
175 180 185
ctg gtc atc tgg tgc atc gat ctg gag gtg gag gag aag tgt gcc ctg 627
Leu Val Ile Trp Cys Ile Asp Leu Glu Val Glu Glu Lys Cys Ala Leu
190 195 200 205
atg gag cag gtg gct cat cag aca atc gtg atg cag ttc atc ctg gag 675
Met Glu Gln Val Ala His Gln Thr Ile Val Met Gln Phe Ile Leu Glu
210 215 220
ctg gcc aag tct ctg aag gtg gac cca cgc gct tgt ttt agg cag ttc 723
Leu Ala Lys Ser Leu Lys Val Asp Pro Arg Ala Cys Phe Arg Gln Phe
225 230 235
ttt acc aag atc aag aca gcc gac cgg cag tac atg gag ggc ttc aac 771
Phe Thr Lys Ile Lys Thr Ala Asp Arg Gln Tyr Met Glu Gly Phe Asn
240 245 250
gat gag ctg gag gct ttt aag gag agg gtg cgg ggc aga gcc aag ctg 819
Asp Glu Leu Glu Ala Phe Lys Glu Arg Val Arg Gly Arg Ala Lys Leu
255 260 265
aga atc gag aag gct atg aag gag tac gag gag gag gag cgc aag aag 867
Arg Ile Glu Lys Ala Met Lys Glu Tyr Glu Glu Glu Glu Arg Lys Lys
270 275 280 285
agg ctg gga ccc ggc ggc ctg gac ccc gtg gag gtg tat gag tcc ctg 915
Arg Leu Gly Pro Gly Gly Leu Asp Pro Val Glu Val Tyr Glu Ser Leu
290 295 300
cca gag gag ctg cag aag tgc ttt gac gtg aag gat gtg cag atg ctg 963
Pro Glu Glu Leu Gln Lys Cys Phe Asp Val Lys Asp Val Gln Met Leu
305 310 315
cag gac gcc atc agc aag atg gac cct acc gat gct aag tat cat atg 1011
Gln Asp Ala Ile Ser Lys Met Asp Pro Thr Asp Ala Lys Tyr His Met
320 325 330
cag agg tgt atc gat tct ggc ctg tgg gtg cca aat tct aag gcc tcc 1059
Gln Arg Cys Ile Asp Ser Gly Leu Trp Val Pro Asn Ser Lys Ala Ser
335 340 345
gag gct aag gag gga gag gag gct gga cct ggc gac cct ctg ctg gag 1107
Glu Ala Lys Glu Gly Glu Glu Ala Gly Pro Gly Asp Pro Leu Leu Glu
350 355 360 365
gct gtg ccc aag aca ggc gac gag aag gat gtg tct gtg tga gaattc 1155
Ala Val Pro Lys Thr Gly Asp Glu Lys Asp Val Ser Val
370 375
<210> 16
<211> 378
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 16
Met Val Asp Tyr Ser Val Trp Asp His Ile Glu Val Ser Asp Asp Glu
1 5 10 15
Asp Glu Thr His Pro Asn Ile Asp Thr Ala Ser Leu Phe Arg Trp Arg
20 25 30
His Gln Ala Arg Val Glu Arg Met Glu Gln Phe Gln Lys Glu Lys Glu
35 40 45
Glu Leu Asp Arg Gly Cys Arg Glu Cys Lys Arg Lys Val Ala Glu Cys
50 55 60
Gln Arg Lys Leu Lys Glu Leu Glu Val Ala Glu Gly Gly Lys Ala Glu
65 70 75 80
Leu Glu Arg Leu Gln Ala Glu Ala Gln Gln Leu Arg Lys Glu Glu Arg
85 90 95
Ser Trp Glu Gln Lys Leu Glu Glu Met Arg Lys Lys Glu Lys Ser Met
100 105 110
Pro Trp Asn Val Asp Thr Leu Ser Lys Asp Gly Phe Ser Lys Ser Met
115 120 125
Val Asn Thr Lys Pro Glu Lys Thr Glu Glu Asp Ser Glu Glu Val Arg
130 135 140
Glu Gln Lys His Lys Thr Phe Val Glu Lys Tyr Glu Lys Gln Ile Lys
145 150 155 160
His Phe Gly Met Leu Arg Arg Trp Asp Asp Ser Gln Lys Tyr Leu Ser
165 170 175
Asp Asn Val His Leu Val Cys Glu Glu Thr Ala Asn Tyr Leu Val Ile
180 185 190
Trp Cys Ile Asp Leu Glu Val Glu Glu Lys Cys Ala Leu Met Glu Gln
195 200 205
Val Ala His Gln Thr Ile Val Met Gln Phe Ile Leu Glu Leu Ala Lys
210 215 220
Ser Leu Lys Val Asp Pro Arg Ala Cys Phe Arg Gln Phe Phe Thr Lys
225 230 235 240
Ile Lys Thr Ala Asp Arg Gln Tyr Met Glu Gly Phe Asn Asp Glu Leu
245 250 255
Glu Ala Phe Lys Glu Arg Val Arg Gly Arg Ala Lys Leu Arg Ile Glu
260 265 270
Lys Ala Met Lys Glu Tyr Glu Glu Glu Glu Arg Lys Lys Arg Leu Gly
275 280 285
Pro Gly Gly Leu Asp Pro Val Glu Val Tyr Glu Ser Leu Pro Glu Glu
290 295 300
Leu Gln Lys Cys Phe Asp Val Lys Asp Val Gln Met Leu Gln Asp Ala
305 310 315 320
Ile Ser Lys Met Asp Pro Thr Asp Ala Lys Tyr His Met Gln Arg Cys
325 330 335
Ile Asp Ser Gly Leu Trp Val Pro Asn Ser Lys Ala Ser Glu Ala Lys
340 345 350
Glu Gly Glu Glu Ala Gly Pro Gly Asp Pro Leu Leu Glu Ala Val Pro
355 360 365
Lys Thr Gly Asp Glu Lys Asp Val Ser Val
370 375
<210> 17
<211> 1158
<212> DNA
<213> 人工序列
<220>
<223> XP_003499785 (chCDC37)的密码子优化基因
<220>
<221> CDS
<222> (13)..(1152)
<400> 17
aagcttgcca cc atg gtg gac tac tcc gtg tgg gat cac atc gag gtg agc 51
Met Val Asp Tyr Ser Val Trp Asp His Ile Glu Val Ser
1 5 10
gac gat gag gac gag acc cat cct aac atc gat aca gcc agc ctg ttc 99
Asp Asp Glu Asp Glu Thr His Pro Asn Ile Asp Thr Ala Ser Leu Phe
15 20 25
agg tgg agg cac cag gct agg gtg gag agg atg gag cag ttt cag aag 147
Arg Trp Arg His Gln Ala Arg Val Glu Arg Met Glu Gln Phe Gln Lys
30 35 40 45
gag aag gac gag ctg gat cgg ggc tgc aga gag tgt aag cgg aag gtg 195
Glu Lys Asp Glu Leu Asp Arg Gly Cys Arg Glu Cys Lys Arg Lys Val
50 55 60
gcc gag tgc cag cgc aag ctg agg gag ctg gag gtg gct gag gga gga 243
Ala Glu Cys Gln Arg Lys Leu Arg Glu Leu Glu Val Ala Glu Gly Gly
65 70 75
gga cag gtg gag ctg gag aga ctg agg gct gag gct cag cag ctg agg 291
Gly Gln Val Glu Leu Glu Arg Leu Arg Ala Glu Ala Gln Gln Leu Arg
80 85 90
aag gag gag agg tcc tgg gag cag aag ctg gag gac atg aga aag aag 339
Lys Glu Glu Arg Ser Trp Glu Gln Lys Leu Glu Asp Met Arg Lys Lys
95 100 105
gag aag tct atg ccc tgg aac gtg gac acc ctg tcc aag gat ggc ttc 387
Glu Lys Ser Met Pro Trp Asn Val Asp Thr Leu Ser Lys Asp Gly Phe
110 115 120 125
tcc aag agc atc gtg aat atc aag cct gag aag gcc gag gag gat agc 435
Ser Lys Ser Ile Val Asn Ile Lys Pro Glu Lys Ala Glu Glu Asp Ser
130 135 140
gag gag gct cgc gag cag aag cat aag aca ttc gtg gag aag tat gag 483
Glu Glu Ala Arg Glu Gln Lys His Lys Thr Phe Val Glu Lys Tyr Glu
145 150 155
aag cag atc aag cac ttt ggc atg ctg cat aga tgg gac gat agc cag 531
Lys Gln Ile Lys His Phe Gly Met Leu His Arg Trp Asp Asp Ser Gln
160 165 170
aag tac ctg tct gac aac gtg cac ctg gtg tgc gag gag acc gcc aat 579
Lys Tyr Leu Ser Asp Asn Val His Leu Val Cys Glu Glu Thr Ala Asn
175 180 185
tac ctg gtc atc tgg tgc atc gat ctg gag gtg gag gag aag tgt gcc 627
Tyr Leu Val Ile Trp Cys Ile Asp Leu Glu Val Glu Glu Lys Cys Ala
190 195 200 205
ctg atg gag cag gtg gct cat cag aca atg gtc atg cag ttc atc ctg 675
Leu Met Glu Gln Val Ala His Gln Thr Met Val Met Gln Phe Ile Leu
210 215 220
gag ctg gcc aag tct ctg aag gtg gac cca cgg gct tgt ttt aga cag 723
Glu Leu Ala Lys Ser Leu Lys Val Asp Pro Arg Ala Cys Phe Arg Gln
225 230 235
ttc ttt acc aag atc aag aca gcc gat cag cag tac atg gag ggc ttc 771
Phe Phe Thr Lys Ile Lys Thr Ala Asp Gln Gln Tyr Met Glu Gly Phe
240 245 250
aag tat gag ctg gag gct ttt aag gag agg gtg cgg gga aga gct aag 819
Lys Tyr Glu Leu Glu Ala Phe Lys Glu Arg Val Arg Gly Arg Ala Lys
255 260 265
ctg agg atc gag aag gct atg aag gag tac gag gag gag gag cgg aag 867
Leu Arg Ile Glu Lys Ala Met Lys Glu Tyr Glu Glu Glu Glu Arg Lys
270 275 280 285
aag aga ctg gga cca gga gga ctg gac cca gtg gag gtg tat gag tcc 915
Lys Arg Leu Gly Pro Gly Gly Leu Asp Pro Val Glu Val Tyr Glu Ser
290 295 300
ctg cca gag gag ctg cag aag tgc ttc gac gtg aag gat gtg cag atg 963
Leu Pro Glu Glu Leu Gln Lys Cys Phe Asp Val Lys Asp Val Gln Met
305 310 315
ctg cag gac gcc atc agc aag atg gac cct acc gat gct aag ttt cac 1011
Leu Gln Asp Ala Ile Ser Lys Met Asp Pro Thr Asp Ala Lys Phe His
320 325 330
atg cag agg tgt atc gat tct ggc ctg tgg gtg cca aac tct aag tcc 1059
Met Gln Arg Cys Ile Asp Ser Gly Leu Trp Val Pro Asn Ser Lys Ser
335 340 345
ggc gag gcc aag gag gga gag gag gct gga cca ggc gac cct ctg ctg 1107
Gly Glu Ala Lys Glu Gly Glu Glu Ala Gly Pro Gly Asp Pro Leu Leu
350 355 360 365
gag gct gtg cca aag gct ggc aat gag aag gac gtg tcc gcc tga 1152
Glu Ala Val Pro Lys Ala Gly Asn Glu Lys Asp Val Ser Ala
370 375
gaattc 1158
<210> 18
<211> 379
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 18
Met Val Asp Tyr Ser Val Trp Asp His Ile Glu Val Ser Asp Asp Glu
1 5 10 15
Asp Glu Thr His Pro Asn Ile Asp Thr Ala Ser Leu Phe Arg Trp Arg
20 25 30
His Gln Ala Arg Val Glu Arg Met Glu Gln Phe Gln Lys Glu Lys Asp
35 40 45
Glu Leu Asp Arg Gly Cys Arg Glu Cys Lys Arg Lys Val Ala Glu Cys
50 55 60
Gln Arg Lys Leu Arg Glu Leu Glu Val Ala Glu Gly Gly Gly Gln Val
65 70 75 80
Glu Leu Glu Arg Leu Arg Ala Glu Ala Gln Gln Leu Arg Lys Glu Glu
85 90 95
Arg Ser Trp Glu Gln Lys Leu Glu Asp Met Arg Lys Lys Glu Lys Ser
100 105 110
Met Pro Trp Asn Val Asp Thr Leu Ser Lys Asp Gly Phe Ser Lys Ser
115 120 125
Ile Val Asn Ile Lys Pro Glu Lys Ala Glu Glu Asp Ser Glu Glu Ala
130 135 140
Arg Glu Gln Lys His Lys Thr Phe Val Glu Lys Tyr Glu Lys Gln Ile
145 150 155 160
Lys His Phe Gly Met Leu His Arg Trp Asp Asp Ser Gln Lys Tyr Leu
165 170 175
Ser Asp Asn Val His Leu Val Cys Glu Glu Thr Ala Asn Tyr Leu Val
180 185 190
Ile Trp Cys Ile Asp Leu Glu Val Glu Glu Lys Cys Ala Leu Met Glu
195 200 205
Gln Val Ala His Gln Thr Met Val Met Gln Phe Ile Leu Glu Leu Ala
210 215 220
Lys Ser Leu Lys Val Asp Pro Arg Ala Cys Phe Arg Gln Phe Phe Thr
225 230 235 240
Lys Ile Lys Thr Ala Asp Gln Gln Tyr Met Glu Gly Phe Lys Tyr Glu
245 250 255
Leu Glu Ala Phe Lys Glu Arg Val Arg Gly Arg Ala Lys Leu Arg Ile
260 265 270
Glu Lys Ala Met Lys Glu Tyr Glu Glu Glu Glu Arg Lys Lys Arg Leu
275 280 285
Gly Pro Gly Gly Leu Asp Pro Val Glu Val Tyr Glu Ser Leu Pro Glu
290 295 300
Glu Leu Gln Lys Cys Phe Asp Val Lys Asp Val Gln Met Leu Gln Asp
305 310 315 320
Ala Ile Ser Lys Met Asp Pro Thr Asp Ala Lys Phe His Met Gln Arg
325 330 335
Cys Ile Asp Ser Gly Leu Trp Val Pro Asn Ser Lys Ser Gly Glu Ala
340 345 350
Lys Glu Gly Glu Glu Ala Gly Pro Gly Asp Pro Leu Leu Glu Ala Val
355 360 365
Pro Lys Ala Gly Asn Glu Lys Asp Val Ser Ala
370 375
<210> 19
<211> 1740
<212> DNA
<213> 人工序列
<220>
<223> NP_955472 (hHSP60)的密码子优化基因
<220>
<221> CDS
<222> (13)..(1734)
<400> 19
aagcttgcca cc atg ctg aga ctg ccc aca gtg ttc aga cag atg cgc cct 51
Met Leu Arg Leu Pro Thr Val Phe Arg Gln Met Arg Pro
1 5 10
gtg agc agg gtg ctg gcc cca cac ctg acc cgg gcc tac gct aag gac 99
Val Ser Arg Val Leu Ala Pro His Leu Thr Arg Ala Tyr Ala Lys Asp
15 20 25
gtg aag ttt ggc gcc gat gct aga gcc ctg atg ctg cag gga gtg gac 147
Val Lys Phe Gly Ala Asp Ala Arg Ala Leu Met Leu Gln Gly Val Asp
30 35 40 45
ctg ctg gct gat gct gtg gct gtg aca atg ggc cct aag ggc cgc acc 195
Leu Leu Ala Asp Ala Val Ala Val Thr Met Gly Pro Lys Gly Arg Thr
50 55 60
gtg atc atc gag cag tct tgg ggc tcc cca aag gtg aca aag gac ggc 243
Val Ile Ile Glu Gln Ser Trp Gly Ser Pro Lys Val Thr Lys Asp Gly
65 70 75
gtg acc gtg gcc aag tct atc gac ctg aag gat aag tat aag aac atc 291
Val Thr Val Ala Lys Ser Ile Asp Leu Lys Asp Lys Tyr Lys Asn Ile
80 85 90
ggc gcc aag ctg gtg cag gac gtg gct aac aat aca aat gag gag gcc 339
Gly Ala Lys Leu Val Gln Asp Val Ala Asn Asn Thr Asn Glu Glu Ala
95 100 105
ggc gat ggc acc aca aca gct acc gtg ctg gct aga tct atc gct aag 387
Gly Asp Gly Thr Thr Thr Ala Thr Val Leu Ala Arg Ser Ile Ala Lys
110 115 120 125
gag ggc ttc gag aag atc tcc aag ggc gct aac cct gtg gag att aga 435
Glu Gly Phe Glu Lys Ile Ser Lys Gly Ala Asn Pro Val Glu Ile Arg
130 135 140
cgg ggc gtg atg ctg gct gtg gat gct gtg atc gcc gag ctg aag aag 483
Arg Gly Val Met Leu Ala Val Asp Ala Val Ile Ala Glu Leu Lys Lys
145 150 155
cag tct aag ccc gtg aca acc cct gag gag atc gct cag gtg gcc acc 531
Gln Ser Lys Pro Val Thr Thr Pro Glu Glu Ile Ala Gln Val Ala Thr
160 165 170
atc agc gcc aac ggc gac aag gag atc ggc aat atc atc tct gat gct 579
Ile Ser Ala Asn Gly Asp Lys Glu Ile Gly Asn Ile Ile Ser Asp Ala
175 180 185
atg aag aag gtg ggc aga aag ggc gtg atc aca gtg aag gac ggc aag 627
Met Lys Lys Val Gly Arg Lys Gly Val Ile Thr Val Lys Asp Gly Lys
190 195 200 205
acc ctg aac gat gag ctg gag atc atc gag ggc atg aag ttc gac cgg 675
Thr Leu Asn Asp Glu Leu Glu Ile Ile Glu Gly Met Lys Phe Asp Arg
210 215 220
ggc tac atc agc cca tat ttt atc aat aca tct aag ggc cag aag tgc 723
Gly Tyr Ile Ser Pro Tyr Phe Ile Asn Thr Ser Lys Gly Gln Lys Cys
225 230 235
gag ttt cag gat gcc tac gtg ctg ctg tcc gag aag aag atc tcc agc 771
Glu Phe Gln Asp Ala Tyr Val Leu Leu Ser Glu Lys Lys Ile Ser Ser
240 245 250
atc cag agc atc gtg cca gct ctg gag atc gcc aac gct cac agg aag 819
Ile Gln Ser Ile Val Pro Ala Leu Glu Ile Ala Asn Ala His Arg Lys
255 260 265
ccc ctg gtc atc atc gct gag gac gtg gat ggc gag gcc ctg tcc acc 867
Pro Leu Val Ile Ile Ala Glu Asp Val Asp Gly Glu Ala Leu Ser Thr
270 275 280 285
ctg gtg ctg aat agg ctg aag gtc ggc ctg cag gtg gtg gct gtg aag 915
Leu Val Leu Asn Arg Leu Lys Val Gly Leu Gln Val Val Ala Val Lys
290 295 300
gct cct gga ttt ggc gac aac aga aag aat cag ctg aag gat atg gcc 963
Ala Pro Gly Phe Gly Asp Asn Arg Lys Asn Gln Leu Lys Asp Met Ala
305 310 315
atc gct aca ggc ggc gcc gtg ttt gga gag gag ggc ctg acc ctg aac 1011
Ile Ala Thr Gly Gly Ala Val Phe Gly Glu Glu Gly Leu Thr Leu Asn
320 325 330
ctg gag gac gtg cag cct cat gat ctg ggc aag gtc ggc gaa gtg atc 1059
Leu Glu Asp Val Gln Pro His Asp Leu Gly Lys Val Gly Glu Val Ile
335 340 345
gtg acc aag gac gat gcc atg ctg ctg aag ggc aag ggc gac aag gct 1107
Val Thr Lys Asp Asp Ala Met Leu Leu Lys Gly Lys Gly Asp Lys Ala
350 355 360 365
cag atc gag aag aga atc cag gag atc atc gag cag ctg gat gtg aca 1155
Gln Ile Glu Lys Arg Ile Gln Glu Ile Ile Glu Gln Leu Asp Val Thr
370 375 380
acc agc gag tac gag aag gag aag ctg aat gag aga ctg gct aag ctg 1203
Thr Ser Glu Tyr Glu Lys Glu Lys Leu Asn Glu Arg Leu Ala Lys Leu
385 390 395
tct gat gga gtg gcc gtg ctg aag gtg ggc ggc aca agc gat gtg gag 1251
Ser Asp Gly Val Ala Val Leu Lys Val Gly Gly Thr Ser Asp Val Glu
400 405 410
gtg aac gag aag aag gac aga gtg aca gat gct ctg aat gcc acc cgc 1299
Val Asn Glu Lys Lys Asp Arg Val Thr Asp Ala Leu Asn Ala Thr Arg
415 420 425
gcc gct gtg gag gag gga atc gtg ctg ggc ggc ggc tgt gct ctg ctg 1347
Ala Ala Val Glu Glu Gly Ile Val Leu Gly Gly Gly Cys Ala Leu Leu
430 435 440 445
aga tgt atc ccc gcc ctg gac tct ctg acc cct gct aac gag gat cag 1395
Arg Cys Ile Pro Ala Leu Asp Ser Leu Thr Pro Ala Asn Glu Asp Gln
450 455 460
aag atc ggc atc gag atc atc aag cgc aca ctg aag atc cca gcc atg 1443
Lys Ile Gly Ile Glu Ile Ile Lys Arg Thr Leu Lys Ile Pro Ala Met
465 470 475
acc atc gct aag aat gct gga gtg gag ggc tcc ctg att gtg gag aag 1491
Thr Ile Ala Lys Asn Ala Gly Val Glu Gly Ser Leu Ile Val Glu Lys
480 485 490
atc atg cag tct tcc agc gaa gtg ggc tat gac gcc atg gct ggc gat 1539
Ile Met Gln Ser Ser Ser Glu Val Gly Tyr Asp Ala Met Ala Gly Asp
495 500 505
ttc gtg aat atg gtg gag aag ggc atc atc gac ccc aca aag gtg gtg 1587
Phe Val Asn Met Val Glu Lys Gly Ile Ile Asp Pro Thr Lys Val Val
510 515 520 525
agg aca gct ctg ctg gat gct gct gga gtg gcc tcc ctg ctg aca acc 1635
Arg Thr Ala Leu Leu Asp Ala Ala Gly Val Ala Ser Leu Leu Thr Thr
530 535 540
gct gag gtg gtg gtg acc gag atc cca aag gag gag aag gac ccc ggc 1683
Ala Glu Val Val Val Thr Glu Ile Pro Lys Glu Glu Lys Asp Pro Gly
545 550 555
atg ggc gct atg ggc ggc atg ggc ggc ggc atg ggc ggc ggc atg ttt 1731
Met Gly Ala Met Gly Gly Met Gly Gly Gly Met Gly Gly Gly Met Phe
560 565 570
tga gaattc 1740
<210> 20
<211> 573
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 20
Met Leu Arg Leu Pro Thr Val Phe Arg Gln Met Arg Pro Val Ser Arg
1 5 10 15
Val Leu Ala Pro His Leu Thr Arg Ala Tyr Ala Lys Asp Val Lys Phe
20 25 30
Gly Ala Asp Ala Arg Ala Leu Met Leu Gln Gly Val Asp Leu Leu Ala
35 40 45
Asp Ala Val Ala Val Thr Met Gly Pro Lys Gly Arg Thr Val Ile Ile
50 55 60
Glu Gln Ser Trp Gly Ser Pro Lys Val Thr Lys Asp Gly Val Thr Val
65 70 75 80
Ala Lys Ser Ile Asp Leu Lys Asp Lys Tyr Lys Asn Ile Gly Ala Lys
85 90 95
Leu Val Gln Asp Val Ala Asn Asn Thr Asn Glu Glu Ala Gly Asp Gly
100 105 110
Thr Thr Thr Ala Thr Val Leu Ala Arg Ser Ile Ala Lys Glu Gly Phe
115 120 125
Glu Lys Ile Ser Lys Gly Ala Asn Pro Val Glu Ile Arg Arg Gly Val
130 135 140
Met Leu Ala Val Asp Ala Val Ile Ala Glu Leu Lys Lys Gln Ser Lys
145 150 155 160
Pro Val Thr Thr Pro Glu Glu Ile Ala Gln Val Ala Thr Ile Ser Ala
165 170 175
Asn Gly Asp Lys Glu Ile Gly Asn Ile Ile Ser Asp Ala Met Lys Lys
180 185 190
Val Gly Arg Lys Gly Val Ile Thr Val Lys Asp Gly Lys Thr Leu Asn
195 200 205
Asp Glu Leu Glu Ile Ile Glu Gly Met Lys Phe Asp Arg Gly Tyr Ile
210 215 220
Ser Pro Tyr Phe Ile Asn Thr Ser Lys Gly Gln Lys Cys Glu Phe Gln
225 230 235 240
Asp Ala Tyr Val Leu Leu Ser Glu Lys Lys Ile Ser Ser Ile Gln Ser
245 250 255
Ile Val Pro Ala Leu Glu Ile Ala Asn Ala His Arg Lys Pro Leu Val
260 265 270
Ile Ile Ala Glu Asp Val Asp Gly Glu Ala Leu Ser Thr Leu Val Leu
275 280 285
Asn Arg Leu Lys Val Gly Leu Gln Val Val Ala Val Lys Ala Pro Gly
290 295 300
Phe Gly Asp Asn Arg Lys Asn Gln Leu Lys Asp Met Ala Ile Ala Thr
305 310 315 320
Gly Gly Ala Val Phe Gly Glu Glu Gly Leu Thr Leu Asn Leu Glu Asp
325 330 335
Val Gln Pro His Asp Leu Gly Lys Val Gly Glu Val Ile Val Thr Lys
340 345 350
Asp Asp Ala Met Leu Leu Lys Gly Lys Gly Asp Lys Ala Gln Ile Glu
355 360 365
Lys Arg Ile Gln Glu Ile Ile Glu Gln Leu Asp Val Thr Thr Ser Glu
370 375 380
Tyr Glu Lys Glu Lys Leu Asn Glu Arg Leu Ala Lys Leu Ser Asp Gly
385 390 395 400
Val Ala Val Leu Lys Val Gly Gly Thr Ser Asp Val Glu Val Asn Glu
405 410 415
Lys Lys Asp Arg Val Thr Asp Ala Leu Asn Ala Thr Arg Ala Ala Val
420 425 430
Glu Glu Gly Ile Val Leu Gly Gly Gly Cys Ala Leu Leu Arg Cys Ile
435 440 445
Pro Ala Leu Asp Ser Leu Thr Pro Ala Asn Glu Asp Gln Lys Ile Gly
450 455 460
Ile Glu Ile Ile Lys Arg Thr Leu Lys Ile Pro Ala Met Thr Ile Ala
465 470 475 480
Lys Asn Ala Gly Val Glu Gly Ser Leu Ile Val Glu Lys Ile Met Gln
485 490 495
Ser Ser Ser Glu Val Gly Tyr Asp Ala Met Ala Gly Asp Phe Val Asn
500 505 510
Met Val Glu Lys Gly Ile Ile Asp Pro Thr Lys Val Val Arg Thr Ala
515 520 525
Leu Leu Asp Ala Ala Gly Val Ala Ser Leu Leu Thr Thr Ala Glu Val
530 535 540
Val Val Thr Glu Ile Pro Lys Glu Glu Lys Asp Pro Gly Met Gly Ala
545 550 555 560
Met Gly Gly Met Gly Gly Gly Met Gly Gly Gly Met Phe
565 570
<210> 21
<211> 1212
<212> DNA
<213> 人工序列
<220>
<223> NP_001530 (hHSP40)的密码子优化基因
<220>
<221> CDS
<222> (13)..(1206)
<400> 21
aagcttgcca cc atg gtg aag gag aca aca tac tat gac gtg ctg ggc gtg 51
Met Val Lys Glu Thr Thr Tyr Tyr Asp Val Leu Gly Val
1 5 10
aag cca aac gcc acc cag gag gag ctg aag aag gcc tac cgg aag ctg 99
Lys Pro Asn Ala Thr Gln Glu Glu Leu Lys Lys Ala Tyr Arg Lys Leu
15 20 25
gct ctg aag tat cac ccc gat aag aac cct aat gag ggc gag aag ttc 147
Ala Leu Lys Tyr His Pro Asp Lys Asn Pro Asn Glu Gly Glu Lys Phe
30 35 40 45
aag cag atc tct cag gcc tac gag gtg ctg tcc gac gct aag aag aga 195
Lys Gln Ile Ser Gln Ala Tyr Glu Val Leu Ser Asp Ala Lys Lys Arg
50 55 60
gag ctg tat gat aag ggc ggc gag cag gcc atc aag gag ggc ggc gcc 243
Glu Leu Tyr Asp Lys Gly Gly Glu Gln Ala Ile Lys Glu Gly Gly Ala
65 70 75
ggc ggc ggc ttt ggc tct ccc atg gac atc ttt gat atg ttc ttt ggg 291
Gly Gly Gly Phe Gly Ser Pro Met Asp Ile Phe Asp Met Phe Phe Gly
80 85 90
ggc ggg gga aga atg cag aga gag agg cgg ggc aag aat gtg gtg cat 339
Gly Gly Gly Arg Met Gln Arg Glu Arg Arg Gly Lys Asn Val Val His
95 100 105
cag ctg tcc gtg acc ctg gag gac ctg tac aac ggc gcc aca cgg aag 387
Gln Leu Ser Val Thr Leu Glu Asp Leu Tyr Asn Gly Ala Thr Arg Lys
110 115 120 125
ctg gct ctg cag aag aat gtg atc tgc gat aag tgt gag ggc aga ggc 435
Leu Ala Leu Gln Lys Asn Val Ile Cys Asp Lys Cys Glu Gly Arg Gly
130 135 140
ggc aag aag ggc gct gtg gag tgc tgt cct aac tgc cgc ggc acc ggc 483
Gly Lys Lys Gly Ala Val Glu Cys Cys Pro Asn Cys Arg Gly Thr Gly
145 150 155
atg cag atc aga atc cac cag atc ggc cca ggc atg gtg cag cag atc 531
Met Gln Ile Arg Ile His Gln Ile Gly Pro Gly Met Val Gln Gln Ile
160 165 170
cag agc gtg tgc atg gag tgt cag ggc cat ggc gag cgg atc agc cct 579
Gln Ser Val Cys Met Glu Cys Gln Gly His Gly Glu Arg Ile Ser Pro
175 180 185
aag gac aga tgc aag tct tgt aat ggc cgc aag atc gtg agg gag aag 627
Lys Asp Arg Cys Lys Ser Cys Asn Gly Arg Lys Ile Val Arg Glu Lys
190 195 200 205
aag atc ctg gag gtg cac atc gac aag ggc atg aag gat ggc cag aag 675
Lys Ile Leu Glu Val His Ile Asp Lys Gly Met Lys Asp Gly Gln Lys
210 215 220
atc aca ttc cat ggc gag ggc gac cag gag cca ggc ctg gag cca ggc 723
Ile Thr Phe His Gly Glu Gly Asp Gln Glu Pro Gly Leu Glu Pro Gly
225 230 235
gat atc atc atc gtg ctg gac cag aag gat cac gcc gtg ttc acc aga 771
Asp Ile Ile Ile Val Leu Asp Gln Lys Asp His Ala Val Phe Thr Arg
240 245 250
cgc ggc gag gac ctg ttt atg tgc atg gat atc cag ctg gtg gag gct 819
Arg Gly Glu Asp Leu Phe Met Cys Met Asp Ile Gln Leu Val Glu Ala
255 260 265
ctg tgt ggc ttt cag aag cca atc tcc aca ctg gac aac cgc acc atc 867
Leu Cys Gly Phe Gln Lys Pro Ile Ser Thr Leu Asp Asn Arg Thr Ile
270 275 280 285
gtg atc aca agc cac ccc ggc cag atc gtg aag cat ggc gat atc aag 915
Val Ile Thr Ser His Pro Gly Gln Ile Val Lys His Gly Asp Ile Lys
290 295 300
tgc gtg ctg aat gag ggc atg cct atc tac agg cgg cca tat gag aag 963
Cys Val Leu Asn Glu Gly Met Pro Ile Tyr Arg Arg Pro Tyr Glu Lys
305 310 315
ggc cgc ctg atc atc gag ttc aag gtg aac ttt ccc gag aat ggc ttc 1011
Gly Arg Leu Ile Ile Glu Phe Lys Val Asn Phe Pro Glu Asn Gly Phe
320 325 330
ctg tcc cct gat aag ctg agc ctg ctg gag aag ctg ctg cca gag agg 1059
Leu Ser Pro Asp Lys Leu Ser Leu Leu Glu Lys Leu Leu Pro Glu Arg
335 340 345
aag gag gtg gag gag aca gac gag atg gat cag gtg gag ctg gtg gac 1107
Lys Glu Val Glu Glu Thr Asp Glu Met Asp Gln Val Glu Leu Val Asp
350 355 360 365
ttt gat ccc aac cag gag aga cgc agg cat tac aat ggc gag gcc tat 1155
Phe Asp Pro Asn Gln Glu Arg Arg Arg His Tyr Asn Gly Glu Ala Tyr
370 375 380
gag gac gat gag cac cat cct agg ggc ggc gtg cag tgt cag aca tct 1203
Glu Asp Asp Glu His His Pro Arg Gly Gly Val Gln Cys Gln Thr Ser
385 390 395
tga gaattc 1212
<210> 22
<211> 397
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 22
Met Val Lys Glu Thr Thr Tyr Tyr Asp Val Leu Gly Val Lys Pro Asn
1 5 10 15
Ala Thr Gln Glu Glu Leu Lys Lys Ala Tyr Arg Lys Leu Ala Leu Lys
20 25 30
Tyr His Pro Asp Lys Asn Pro Asn Glu Gly Glu Lys Phe Lys Gln Ile
35 40 45
Ser Gln Ala Tyr Glu Val Leu Ser Asp Ala Lys Lys Arg Glu Leu Tyr
50 55 60
Asp Lys Gly Gly Glu Gln Ala Ile Lys Glu Gly Gly Ala Gly Gly Gly
65 70 75 80
Phe Gly Ser Pro Met Asp Ile Phe Asp Met Phe Phe Gly Gly Gly Gly
85 90 95
Arg Met Gln Arg Glu Arg Arg Gly Lys Asn Val Val His Gln Leu Ser
100 105 110
Val Thr Leu Glu Asp Leu Tyr Asn Gly Ala Thr Arg Lys Leu Ala Leu
115 120 125
Gln Lys Asn Val Ile Cys Asp Lys Cys Glu Gly Arg Gly Gly Lys Lys
130 135 140
Gly Ala Val Glu Cys Cys Pro Asn Cys Arg Gly Thr Gly Met Gln Ile
145 150 155 160
Arg Ile His Gln Ile Gly Pro Gly Met Val Gln Gln Ile Gln Ser Val
165 170 175
Cys Met Glu Cys Gln Gly His Gly Glu Arg Ile Ser Pro Lys Asp Arg
180 185 190
Cys Lys Ser Cys Asn Gly Arg Lys Ile Val Arg Glu Lys Lys Ile Leu
195 200 205
Glu Val His Ile Asp Lys Gly Met Lys Asp Gly Gln Lys Ile Thr Phe
210 215 220
His Gly Glu Gly Asp Gln Glu Pro Gly Leu Glu Pro Gly Asp Ile Ile
225 230 235 240
Ile Val Leu Asp Gln Lys Asp His Ala Val Phe Thr Arg Arg Gly Glu
245 250 255
Asp Leu Phe Met Cys Met Asp Ile Gln Leu Val Glu Ala Leu Cys Gly
260 265 270
Phe Gln Lys Pro Ile Ser Thr Leu Asp Asn Arg Thr Ile Val Ile Thr
275 280 285
Ser His Pro Gly Gln Ile Val Lys His Gly Asp Ile Lys Cys Val Leu
290 295 300
Asn Glu Gly Met Pro Ile Tyr Arg Arg Pro Tyr Glu Lys Gly Arg Leu
305 310 315 320
Ile Ile Glu Phe Lys Val Asn Phe Pro Glu Asn Gly Phe Leu Ser Pro
325 330 335
Asp Lys Leu Ser Leu Leu Glu Lys Leu Leu Pro Glu Arg Lys Glu Val
340 345 350
Glu Glu Thr Asp Glu Met Asp Gln Val Glu Leu Val Asp Phe Asp Pro
355 360 365
Asn Gln Glu Arg Arg Arg His Tyr Asn Gly Glu Ala Tyr Glu Asp Asp
370 375 380
Glu His His Pro Arg Gly Gly Val Gln Cys Gln Thr Ser
385 390 395
<210> 23
<211> 327
<212> DNA
<213> 人工序列
<220>
<223> NP_002148 (hHSP10)的密码子优化基因
<220>
<221> CDS
<222> (13)..(321)
<400> 23
aagcttgcca cc atg gcc ggc cag gct ttc aga aag ttt ctg cca ctg ttt 51
Met Ala Gly Gln Ala Phe Arg Lys Phe Leu Pro Leu Phe
1 5 10
gac agg gtg ctg gtg gag aga tct gct gct gag aca gtg aca aag ggc 99
Asp Arg Val Leu Val Glu Arg Ser Ala Ala Glu Thr Val Thr Lys Gly
15 20 25
ggc atc atg ctg ccc gag aag tcc cag ggc aag gtg ctg cag gct aca 147
Gly Ile Met Leu Pro Glu Lys Ser Gln Gly Lys Val Leu Gln Ala Thr
30 35 40 45
gtg gtg gct gtg ggc tcc ggc agc aag ggc aag ggc ggc gag atc cag 195
Val Val Ala Val Gly Ser Gly Ser Lys Gly Lys Gly Gly Glu Ile Gln
50 55 60
ccc gtg tcc gtg aaa gtg ggc gat aag gtg ctg ctg cct gag tac ggc 243
Pro Val Ser Val Lys Val Gly Asp Lys Val Leu Leu Pro Glu Tyr Gly
65 70 75
ggc aca aag gtg gtg ctg gac gat aag gac tat ttc ctg ttt cgc gac 291
Gly Thr Lys Val Val Leu Asp Asp Lys Asp Tyr Phe Leu Phe Arg Asp
80 85 90
ggc gat atc ctg ggc aag tac gtg gat tga gaattc 327
Gly Asp Ile Leu Gly Lys Tyr Val Asp
95 100
<210> 24
<211> 102
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 24
Met Ala Gly Gln Ala Phe Arg Lys Phe Leu Pro Leu Phe Asp Arg Val
1 5 10 15
Leu Val Glu Arg Ser Ala Ala Glu Thr Val Thr Lys Gly Gly Ile Met
20 25 30
Leu Pro Glu Lys Ser Gln Gly Lys Val Leu Gln Ala Thr Val Val Ala
35 40 45
Val Gly Ser Gly Ser Lys Gly Lys Gly Gly Glu Ile Gln Pro Val Ser
50 55 60
Val Lys Val Gly Asp Lys Val Leu Leu Pro Glu Tyr Gly Gly Thr Lys
65 70 75 80
Val Val Leu Asp Asp Lys Asp Tyr Phe Leu Phe Arg Asp Gly Asp Ile
85 90 95
Leu Gly Lys Tyr Val Asp
100
<210> 25
<211> 2595
<212> DNA
<213> 人工序列
<220>
<223> NP_006635 (hHSP110)的密码子优化基因
<220>
<221> CDS
<222> (13)..(2589)
<400> 25
aagcttgcca cc atg tcc gtg gtg ggc ctg gat gtg ggc agc cag tct tgt 51
Met Ser Val Val Gly Leu Asp Val Gly Ser Gln Ser Cys
1 5 10
tac att gct gtg gct aga gcc ggc ggc att gag aca atc gcc aac gag 99
Tyr Ile Ala Val Ala Arg Ala Gly Gly Ile Glu Thr Ile Ala Asn Glu
15 20 25
ttc agc gac agg tgc acc cca tct gtg atc tcc ttt ggc agc aag aat 147
Phe Ser Asp Arg Cys Thr Pro Ser Val Ile Ser Phe Gly Ser Lys Asn
30 35 40 45
cgg acc atc ggc gtg gcc gct aag aac cag cag atc acc cac gct aac 195
Arg Thr Ile Gly Val Ala Ala Lys Asn Gln Gln Ile Thr His Ala Asn
50 55 60
aat aca gtg tct aat ttc aag agg ttt cat ggc cgg gcc ttc aac gat 243
Asn Thr Val Ser Asn Phe Lys Arg Phe His Gly Arg Ala Phe Asn Asp
65 70 75
ccc ttt atc cag aag gag aag gag aat ctg tcc tac gac ctg gtg cct 291
Pro Phe Ile Gln Lys Glu Lys Glu Asn Leu Ser Tyr Asp Leu Val Pro
80 85 90
ctg aag aac ggc ggc gtg ggc atc aaa gtg atg tat atg ggc gag gag 339
Leu Lys Asn Gly Gly Val Gly Ile Lys Val Met Tyr Met Gly Glu Glu
95 100 105
cat ctg ttc tcc gtc gag cag atc acc gct atg ctg ctg aca aag ctg 387
His Leu Phe Ser Val Glu Gln Ile Thr Ala Met Leu Leu Thr Lys Leu
110 115 120 125
aag gag aca gcc gag aat agc ctg aag aag ccc gtg aca gac tgt gtg 435
Lys Glu Thr Ala Glu Asn Ser Leu Lys Lys Pro Val Thr Asp Cys Val
130 135 140
atc tct gtg cct tcc ttc ttt acc gac gct gag agg cgg tct gtg ctg 483
Ile Ser Val Pro Ser Phe Phe Thr Asp Ala Glu Arg Arg Ser Val Leu
145 150 155
gat gcc gct cag atc gtg ggc ctg aat tgc ctg aga ctg atg aac gat 531
Asp Ala Ala Gln Ile Val Gly Leu Asn Cys Leu Arg Leu Met Asn Asp
160 165 170
atg aca gct gtg gcc ctg aac tac ggc atc tat aag cag gac ctg cct 579
Met Thr Ala Val Ala Leu Asn Tyr Gly Ile Tyr Lys Gln Asp Leu Pro
175 180 185
tcc ctg gat gag aag cca cgc atc gtg gtg ttc gtg gac atg ggc cac 627
Ser Leu Asp Glu Lys Pro Arg Ile Val Val Phe Val Asp Met Gly His
190 195 200 205
tcc gct ttc cag gtg agc gct tgt gcc ttt aat aag ggc aag ctg aag 675
Ser Ala Phe Gln Val Ser Ala Cys Ala Phe Asn Lys Gly Lys Leu Lys
210 215 220
gtg ctg ggc aca gcc ttc gat cca ttt ctg ggc ggc aag aac ttt gac 723
Val Leu Gly Thr Ala Phe Asp Pro Phe Leu Gly Gly Lys Asn Phe Asp
225 230 235
gag aag ctg gtg gag cat ttc tgc gcc gag ttt aag acc aag tac aag 771
Glu Lys Leu Val Glu His Phe Cys Ala Glu Phe Lys Thr Lys Tyr Lys
240 245 250
ctg gat gct aag agc aag atc aga gcc ctg ctg cgc ctg tat cag gag 819
Leu Asp Ala Lys Ser Lys Ile Arg Ala Leu Leu Arg Leu Tyr Gln Glu
255 260 265
tgc gag aag ctg aag aag ctg atg tcc agc aat tct acc gac ctg ccc 867
Cys Glu Lys Leu Lys Lys Leu Met Ser Ser Asn Ser Thr Asp Leu Pro
270 275 280 285
ctg aat atc gag tgt ttc atg aac gac aag gat gtg agc ggc aag atg 915
Leu Asn Ile Glu Cys Phe Met Asn Asp Lys Asp Val Ser Gly Lys Met
290 295 300
aac cgc tct cag ttt gag gag ctg tgc gct gag ctg ctg cag aag atc 963
Asn Arg Ser Gln Phe Glu Glu Leu Cys Ala Glu Leu Leu Gln Lys Ile
305 310 315
gag gtg cct ctg tat agc ctg ctg gag cag aca cac ctg aag gtg gag 1011
Glu Val Pro Leu Tyr Ser Leu Leu Glu Gln Thr His Leu Lys Val Glu
320 325 330
gat gtg tct gcc gtg gag atc gtg ggc ggc gct acc aga atc cca gcc 1059
Asp Val Ser Ala Val Glu Ile Val Gly Gly Ala Thr Arg Ile Pro Ala
335 340 345
gtg aag gag cgc atc gct aag ttc ttt ggc aag gac atc tcc acc aca 1107
Val Lys Glu Arg Ile Ala Lys Phe Phe Gly Lys Asp Ile Ser Thr Thr
350 355 360 365
ctg aac gct gat gag gct gtg gcc agg ggc tgt gct ctg cag tgt gct 1155
Leu Asn Ala Asp Glu Ala Val Ala Arg Gly Cys Ala Leu Gln Cys Ala
370 375 380
atc ctg tct ccc gct ttc aag gtg cgg gag ttt tcc gtg aca gac gcc 1203
Ile Leu Ser Pro Ala Phe Lys Val Arg Glu Phe Ser Val Thr Asp Ala
385 390 395
gtg cca ttc ccc atc tcc ctg atc tgg aat cat gac agc gag gat acc 1251
Val Pro Phe Pro Ile Ser Leu Ile Trp Asn His Asp Ser Glu Asp Thr
400 405 410
gag ggc gtg cac gag gtg ttc tcc agg aac cat gcc gct cct ttc tcc 1299
Glu Gly Val His Glu Val Phe Ser Arg Asn His Ala Ala Pro Phe Ser
415 420 425
aag gtg ctg acc ttt ctg aga cgc ggc cca ttc gag ctg gag gcc ttt 1347
Lys Val Leu Thr Phe Leu Arg Arg Gly Pro Phe Glu Leu Glu Ala Phe
430 435 440 445
tac agc gat ccc cag ggc gtg cct tat cca gag gct aag atc ggc cgc 1395
Tyr Ser Asp Pro Gln Gly Val Pro Tyr Pro Glu Ala Lys Ile Gly Arg
450 455 460
ttc gtg gtg cag aat gtg agc gcc cag aag gac ggc gag aag tct agg 1443
Phe Val Val Gln Asn Val Ser Ala Gln Lys Asp Gly Glu Lys Ser Arg
465 470 475
gtg aag gtg aag gtg cgg gtg aac aca cac ggc atc ttt acc atc agc 1491
Val Lys Val Lys Val Arg Val Asn Thr His Gly Ile Phe Thr Ile Ser
480 485 490
aca gct tct atg gtg gag aag gtg ccc acc gag gag aac gag atg tct 1539
Thr Ala Ser Met Val Glu Lys Val Pro Thr Glu Glu Asn Glu Met Ser
495 500 505
tcc gag gcc gac atg gag tgt ctg aat cag agg ccc cct gag aac cca 1587
Ser Glu Ala Asp Met Glu Cys Leu Asn Gln Arg Pro Pro Glu Asn Pro
510 515 520 525
gac aca gat aag aat gtg cag cag gat aac tct gag gct ggc acc cag 1635
Asp Thr Asp Lys Asn Val Gln Gln Asp Asn Ser Glu Ala Gly Thr Gln
530 535 540
cca cag gtg cag aca gat gct cag cag acc tcc cag agc cca ccc tct 1683
Pro Gln Val Gln Thr Asp Ala Gln Gln Thr Ser Gln Ser Pro Pro Ser
545 550 555
cct gag ctg aca tcc gag gag aat aag atc cca gac gct gat aag gcc 1731
Pro Glu Leu Thr Ser Glu Glu Asn Lys Ile Pro Asp Ala Asp Lys Ala
560 565 570
aac gag aag aag gtg gat cag cct cca gag gct aag aag ccc aag atc 1779
Asn Glu Lys Lys Val Asp Gln Pro Pro Glu Ala Lys Lys Pro Lys Ile
575 580 585
aag gtg gtg aat gtg gag ctg cct atc gag gcc aac ctg gtg tgg cag 1827
Lys Val Val Asn Val Glu Leu Pro Ile Glu Ala Asn Leu Val Trp Gln
590 595 600 605
ctg ggc aag gac ctg ctg aat atg tac atc gag aca gag ggc aag atg 1875
Leu Gly Lys Asp Leu Leu Asn Met Tyr Ile Glu Thr Glu Gly Lys Met
610 615 620
atc atg cag gac aag ctg gag aag gag aga aat gat gct aag aac gcc 1923
Ile Met Gln Asp Lys Leu Glu Lys Glu Arg Asn Asp Ala Lys Asn Ala
625 630 635
gtg gag gag tac gtg tat gag ttc cgc gat aag ctg tgc ggc cct tat 1971
Val Glu Glu Tyr Val Tyr Glu Phe Arg Asp Lys Leu Cys Gly Pro Tyr
640 645 650
gag aag ttc atc tgt gag cag gac cat cag aac ttt ctg cgg ctg ctg 2019
Glu Lys Phe Ile Cys Glu Gln Asp His Gln Asn Phe Leu Arg Leu Leu
655 660 665
acc gag aca gag gac tgg ctg tac gag gag ggc gag gat cag gct aag 2067
Thr Glu Thr Glu Asp Trp Leu Tyr Glu Glu Gly Glu Asp Gln Ala Lys
670 675 680 685
cag gcc tat gtg gac aag ctg gag gag ctg atg aag atc ggc acc cca 2115
Gln Ala Tyr Val Asp Lys Leu Glu Glu Leu Met Lys Ile Gly Thr Pro
690 695 700
gtg aag gtg agg ttc cag gag gct gag gag cgg ccc aag atg ttt gag 2163
Val Lys Val Arg Phe Gln Glu Ala Glu Glu Arg Pro Lys Met Phe Glu
705 710 715
gag ctg ggc cag aga ctg cag cac tac gcc aag atc gcc gct gac ttt 2211
Glu Leu Gly Gln Arg Leu Gln His Tyr Ala Lys Ile Ala Ala Asp Phe
720 725 730
cgc aat aag gat gag aag tat aac cat atc gat gag tcc gag atg aag 2259
Arg Asn Lys Asp Glu Lys Tyr Asn His Ile Asp Glu Ser Glu Met Lys
735 740 745
aag gtg gag aag agc gtg aat gaa gtg atg gag tgg atg aac aat gtg 2307
Lys Val Glu Lys Ser Val Asn Glu Val Met Glu Trp Met Asn Asn Val
750 755 760 765
atg aac gct cag gcc aag aag agc ctg gac cag gac ccc gtg gtg agg 2355
Met Asn Ala Gln Ala Lys Lys Ser Leu Asp Gln Asp Pro Val Val Arg
770 775 780
gct cag gag atc aag aca aag atc aag gag ctg aac aat aca tgt gag 2403
Ala Gln Glu Ile Lys Thr Lys Ile Lys Glu Leu Asn Asn Thr Cys Glu
785 790 795
cct gtg gtg acc cag ccc aag cct aag atc gag tct cca aag ctg gag 2451
Pro Val Val Thr Gln Pro Lys Pro Lys Ile Glu Ser Pro Lys Leu Glu
800 805 810
cgg acc cca aac ggc ccc aat atc gac aag aag gag gag gac ctg gag 2499
Arg Thr Pro Asn Gly Pro Asn Ile Asp Lys Lys Glu Glu Asp Leu Glu
815 820 825
gat aag aac aat ttt gga gct gag ccc cct cac cag aat gga gag tgc 2547
Asp Lys Asn Asn Phe Gly Ala Glu Pro Pro His Gln Asn Gly Glu Cys
830 835 840 845
tac cca aac gag aag aac tcc gtg aac atg gac ctg gat tga gaattc 2595
Tyr Pro Asn Glu Lys Asn Ser Val Asn Met Asp Leu Asp
850 855
<210> 26
<211> 858
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 26
Met Ser Val Val Gly Leu Asp Val Gly Ser Gln Ser Cys Tyr Ile Ala
1 5 10 15
Val Ala Arg Ala Gly Gly Ile Glu Thr Ile Ala Asn Glu Phe Ser Asp
20 25 30
Arg Cys Thr Pro Ser Val Ile Ser Phe Gly Ser Lys Asn Arg Thr Ile
35 40 45
Gly Val Ala Ala Lys Asn Gln Gln Ile Thr His Ala Asn Asn Thr Val
50 55 60
Ser Asn Phe Lys Arg Phe His Gly Arg Ala Phe Asn Asp Pro Phe Ile
65 70 75 80
Gln Lys Glu Lys Glu Asn Leu Ser Tyr Asp Leu Val Pro Leu Lys Asn
85 90 95
Gly Gly Val Gly Ile Lys Val Met Tyr Met Gly Glu Glu His Leu Phe
100 105 110
Ser Val Glu Gln Ile Thr Ala Met Leu Leu Thr Lys Leu Lys Glu Thr
115 120 125
Ala Glu Asn Ser Leu Lys Lys Pro Val Thr Asp Cys Val Ile Ser Val
130 135 140
Pro Ser Phe Phe Thr Asp Ala Glu Arg Arg Ser Val Leu Asp Ala Ala
145 150 155 160
Gln Ile Val Gly Leu Asn Cys Leu Arg Leu Met Asn Asp Met Thr Ala
165 170 175
Val Ala Leu Asn Tyr Gly Ile Tyr Lys Gln Asp Leu Pro Ser Leu Asp
180 185 190
Glu Lys Pro Arg Ile Val Val Phe Val Asp Met Gly His Ser Ala Phe
195 200 205
Gln Val Ser Ala Cys Ala Phe Asn Lys Gly Lys Leu Lys Val Leu Gly
210 215 220
Thr Ala Phe Asp Pro Phe Leu Gly Gly Lys Asn Phe Asp Glu Lys Leu
225 230 235 240
Val Glu His Phe Cys Ala Glu Phe Lys Thr Lys Tyr Lys Leu Asp Ala
245 250 255
Lys Ser Lys Ile Arg Ala Leu Leu Arg Leu Tyr Gln Glu Cys Glu Lys
260 265 270
Leu Lys Lys Leu Met Ser Ser Asn Ser Thr Asp Leu Pro Leu Asn Ile
275 280 285
Glu Cys Phe Met Asn Asp Lys Asp Val Ser Gly Lys Met Asn Arg Ser
290 295 300
Gln Phe Glu Glu Leu Cys Ala Glu Leu Leu Gln Lys Ile Glu Val Pro
305 310 315 320
Leu Tyr Ser Leu Leu Glu Gln Thr His Leu Lys Val Glu Asp Val Ser
325 330 335
Ala Val Glu Ile Val Gly Gly Ala Thr Arg Ile Pro Ala Val Lys Glu
340 345 350
Arg Ile Ala Lys Phe Phe Gly Lys Asp Ile Ser Thr Thr Leu Asn Ala
355 360 365
Asp Glu Ala Val Ala Arg Gly Cys Ala Leu Gln Cys Ala Ile Leu Ser
370 375 380
Pro Ala Phe Lys Val Arg Glu Phe Ser Val Thr Asp Ala Val Pro Phe
385 390 395 400
Pro Ile Ser Leu Ile Trp Asn His Asp Ser Glu Asp Thr Glu Gly Val
405 410 415
His Glu Val Phe Ser Arg Asn His Ala Ala Pro Phe Ser Lys Val Leu
420 425 430
Thr Phe Leu Arg Arg Gly Pro Phe Glu Leu Glu Ala Phe Tyr Ser Asp
435 440 445
Pro Gln Gly Val Pro Tyr Pro Glu Ala Lys Ile Gly Arg Phe Val Val
450 455 460
Gln Asn Val Ser Ala Gln Lys Asp Gly Glu Lys Ser Arg Val Lys Val
465 470 475 480
Lys Val Arg Val Asn Thr His Gly Ile Phe Thr Ile Ser Thr Ala Ser
485 490 495
Met Val Glu Lys Val Pro Thr Glu Glu Asn Glu Met Ser Ser Glu Ala
500 505 510
Asp Met Glu Cys Leu Asn Gln Arg Pro Pro Glu Asn Pro Asp Thr Asp
515 520 525
Lys Asn Val Gln Gln Asp Asn Ser Glu Ala Gly Thr Gln Pro Gln Val
530 535 540
Gln Thr Asp Ala Gln Gln Thr Ser Gln Ser Pro Pro Ser Pro Glu Leu
545 550 555 560
Thr Ser Glu Glu Asn Lys Ile Pro Asp Ala Asp Lys Ala Asn Glu Lys
565 570 575
Lys Val Asp Gln Pro Pro Glu Ala Lys Lys Pro Lys Ile Lys Val Val
580 585 590
Asn Val Glu Leu Pro Ile Glu Ala Asn Leu Val Trp Gln Leu Gly Lys
595 600 605
Asp Leu Leu Asn Met Tyr Ile Glu Thr Glu Gly Lys Met Ile Met Gln
610 615 620
Asp Lys Leu Glu Lys Glu Arg Asn Asp Ala Lys Asn Ala Val Glu Glu
625 630 635 640
Tyr Val Tyr Glu Phe Arg Asp Lys Leu Cys Gly Pro Tyr Glu Lys Phe
645 650 655
Ile Cys Glu Gln Asp His Gln Asn Phe Leu Arg Leu Leu Thr Glu Thr
660 665 670
Glu Asp Trp Leu Tyr Glu Glu Gly Glu Asp Gln Ala Lys Gln Ala Tyr
675 680 685
Val Asp Lys Leu Glu Glu Leu Met Lys Ile Gly Thr Pro Val Lys Val
690 695 700
Arg Phe Gln Glu Ala Glu Glu Arg Pro Lys Met Phe Glu Glu Leu Gly
705 710 715 720
Gln Arg Leu Gln His Tyr Ala Lys Ile Ala Ala Asp Phe Arg Asn Lys
725 730 735
Asp Glu Lys Tyr Asn His Ile Asp Glu Ser Glu Met Lys Lys Val Glu
740 745 750
Lys Ser Val Asn Glu Val Met Glu Trp Met Asn Asn Val Met Asn Ala
755 760 765
Gln Ala Lys Lys Ser Leu Asp Gln Asp Pro Val Val Arg Ala Gln Glu
770 775 780
Ile Lys Thr Lys Ile Lys Glu Leu Asn Asn Thr Cys Glu Pro Val Val
785 790 795 800
Thr Gln Pro Lys Pro Lys Ile Glu Ser Pro Lys Leu Glu Arg Thr Pro
805 810 815
Asn Gly Pro Asn Ile Asp Lys Lys Glu Glu Asp Leu Glu Asp Lys Asn
820 825 830
Asn Phe Gly Ala Glu Pro Pro His Gln Asn Gly Glu Cys Tyr Pro Asn
835 840 845
Glu Lys Asn Ser Val Asn Met Asp Leu Asp
850 855
<210> 27
<211> 1767
<212> DNA
<213> 人工序列
<220>
<223> chHSP70的密码子优化基因
<220>
<221> CDS
<222> (13)..(1761)
<400> 27
aagcttgcca cc atg gct aag aac acc gcc atc ggc atc gac ctg ggc acc 51
Met Ala Lys Asn Thr Ala Ile Gly Ile Asp Leu Gly Thr
1 5 10
aca tac tcc tgc gtg ggc gtg ttc cag cac ggc aag gtg gag atc atc 99
Thr Tyr Ser Cys Val Gly Val Phe Gln His Gly Lys Val Glu Ile Ile
15 20 25
gcc aac gat cag ggc aat cgg acc aca cct agc tat gtg gct ttt acc 147
Ala Asn Asp Gln Gly Asn Arg Thr Thr Pro Ser Tyr Val Ala Phe Thr
30 35 40 45
gac aca gag aga ctg atc ggc gat gcc gct aag aat cag gtg gcc ctg 195
Asp Thr Glu Arg Leu Ile Gly Asp Ala Ala Lys Asn Gln Val Ala Leu
50 55 60
aac cca cag aat acc gtg ttc gac gct aag aga ctg atc ggc cgc aag 243
Asn Pro Gln Asn Thr Val Phe Asp Ala Lys Arg Leu Ile Gly Arg Lys
65 70 75
ttt ggc gac gcc gtg gtg cag agc gat atg aag cac tgg cca ttc cag 291
Phe Gly Asp Ala Val Val Gln Ser Asp Met Lys His Trp Pro Phe Gln
80 85 90
gtg gtg aac gac ggc gat aag ccc aag gtg caa gtg aat tac aag ggc 339
Val Val Asn Asp Gly Asp Lys Pro Lys Val Gln Val Asn Tyr Lys Gly
95 100 105
gag tcc agg tcc ttc ttc ccc gag gag atc tcc agc atg gtg ctg aca 387
Glu Ser Arg Ser Phe Phe Pro Glu Glu Ile Ser Ser Met Val Leu Thr
110 115 120 125
aag atg aag gag atc gct gag gcc tac ctg ggc cat ccc gtg acc aac 435
Lys Met Lys Glu Ile Ala Glu Ala Tyr Leu Gly His Pro Val Thr Asn
130 135 140
gcc gtg atc aca gtg cct gct tac ttc aac gac tct cag cgg cag gct 483
Ala Val Ile Thr Val Pro Ala Tyr Phe Asn Asp Ser Gln Arg Gln Ala
145 150 155
acc aag gat gcc ggc gtg atc gct ggc ctg aac gtg ctg aga atc atc 531
Thr Lys Asp Ala Gly Val Ile Ala Gly Leu Asn Val Leu Arg Ile Ile
160 165 170
aat gag cct aca gcc gct gcc atc gcc tac ggc ctg gac aga aac cgc 579
Asn Glu Pro Thr Ala Ala Ala Ile Ala Tyr Gly Leu Asp Arg Asn Arg
175 180 185
cag ggc aag aag gat atc tct cag aat aag ctg gct gtg agg cgg ctg 627
Gln Gly Lys Lys Asp Ile Ser Gln Asn Lys Leu Ala Val Arg Arg Leu
190 195 200 205
agg acc gct tgc gag agg gct aag cgg acc ctg tct tcc agc aca cag 675
Arg Thr Ala Cys Glu Arg Ala Lys Arg Thr Leu Ser Ser Ser Thr Gln
210 215 220
gcc agc ctg gag atc gac tct ctg ttc gag ggc atc gac ttc tac acc 723
Ala Ser Leu Glu Ile Asp Ser Leu Phe Glu Gly Ile Asp Phe Tyr Thr
225 230 235
tcc atc aca agg gct cgg ttc gag gag ctg tgc tcc gac ctg ttt agg 771
Ser Ile Thr Arg Ala Arg Phe Glu Glu Leu Cys Ser Asp Leu Phe Arg
240 245 250
agc acc ctg gag cca gtg gag aag gcc ctg agg gac gct aag atg gat 819
Ser Thr Leu Glu Pro Val Glu Lys Ala Leu Arg Asp Ala Lys Met Asp
255 260 265
aag gcc cag atc cat gat ctg gtg ctg gtg gga ggc agc aca cgc atc 867
Lys Ala Gln Ile His Asp Leu Val Leu Val Gly Gly Ser Thr Arg Ile
270 275 280 285
cca aag gtg cag aag ctg ctg cag gac ttc ttt aac ggc agg gat ctg 915
Pro Lys Val Gln Lys Leu Leu Gln Asp Phe Phe Asn Gly Arg Asp Leu
290 295 300
aac aag tct atc aat cca gac gag gct gtg gct tat gga gct gct gtg 963
Asn Lys Ser Ile Asn Pro Asp Glu Ala Val Ala Tyr Gly Ala Ala Val
305 310 315
cag gct gct atc ctg atg ggc gat aag tcc gag aat gtg cag gac ctg 1011
Gln Ala Ala Ile Leu Met Gly Asp Lys Ser Glu Asn Val Gln Asp Leu
320 325 330
ctg ctg ctg gat gtg gct cct ctg agc ctg ggc ctg gag acc gct gga 1059
Leu Leu Leu Asp Val Ala Pro Leu Ser Leu Gly Leu Glu Thr Ala Gly
335 340 345
ggc gtg atg aca gct ctg atc aag cgc aac agc acc atc ccc aca aag 1107
Gly Val Met Thr Ala Leu Ile Lys Arg Asn Ser Thr Ile Pro Thr Lys
350 355 360 365
cag acc cag aca ttc acc aca tac tct gac aat cag cct ggc gtg ctg 1155
Gln Thr Gln Thr Phe Thr Thr Tyr Ser Asp Asn Gln Pro Gly Val Leu
370 375 380
atc cag gtg tat gag ggc gag aga gcc atg acc ggc gat aac aat ctg 1203
Ile Gln Val Tyr Glu Gly Glu Arg Ala Met Thr Gly Asp Asn Asn Leu
385 390 395
ctg ggc cgc ttc gag ctg tcc ggc atc ccc cct gct cca agg ggc gtg 1251
Leu Gly Arg Phe Glu Leu Ser Gly Ile Pro Pro Ala Pro Arg Gly Val
400 405 410
ccc cag atc gag gtg acc ttt gac atc gat gcc aac ggc ctg aat gtg 1299
Pro Gln Ile Glu Val Thr Phe Asp Ile Asp Ala Asn Gly Leu Asn Val
415 420 425
acc gct aca gac aag tct aca ggc aag gcc aac aag atc acc atc aca 1347
Thr Ala Thr Asp Lys Ser Thr Gly Lys Ala Asn Lys Ile Thr Ile Thr
430 435 440 445
aat gat aag ggc agg ctg tcc aag gag gag atc gag aga atg gtg cag 1395
Asn Asp Lys Gly Arg Leu Ser Lys Glu Glu Ile Glu Arg Met Val Gln
450 455 460
gag gcc gag agg tac aag gct gag gac gag gtg cag aga gat cgc gtg 1443
Glu Ala Glu Arg Tyr Lys Ala Glu Asp Glu Val Gln Arg Asp Arg Val
465 470 475
gct gcc aag aac gcc ctg gag tct tat gct ttt aat atg aag tcc gcc 1491
Ala Ala Lys Asn Ala Leu Glu Ser Tyr Ala Phe Asn Met Lys Ser Ala
480 485 490
gtg gag gga gag ggc ctg aag ggc aag ctg tcc gag gct gac aag aag 1539
Val Glu Gly Glu Gly Leu Lys Gly Lys Leu Ser Glu Ala Asp Lys Lys
495 500 505
aag gtg ctg gac aag tgc cag gaa gtg atc tcc tgg ctg gac agc aac 1587
Lys Val Leu Asp Lys Cys Gln Glu Val Ile Ser Trp Leu Asp Ser Asn
510 515 520 525
acc ctg gcc gat aag gag gag ttc gtg cac aag agg gag gag ctg gag 1635
Thr Leu Ala Asp Lys Glu Glu Phe Val His Lys Arg Glu Glu Leu Glu
530 535 540
agg gtg tgc tct cct atc atc tcc ggc ctg tac cag gga gct gga gct 1683
Arg Val Cys Ser Pro Ile Ile Ser Gly Leu Tyr Gln Gly Ala Gly Ala
545 550 555
cca gga gct gga ggc ttt gga gct cag gct cct aag gga gct agc ggc 1731
Pro Gly Ala Gly Gly Phe Gly Ala Gln Ala Pro Lys Gly Ala Ser Gly
560 565 570
tct gga cca aca atc gag gag gtg gac tga gaattc 1767
Ser Gly Pro Thr Ile Glu Glu Val Asp
575 580
<210> 28
<211> 582
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 28
Met Ala Lys Asn Thr Ala Ile Gly Ile Asp Leu Gly Thr Thr Tyr Ser
1 5 10 15
Cys Val Gly Val Phe Gln His Gly Lys Val Glu Ile Ile Ala Asn Asp
20 25 30
Gln Gly Asn Arg Thr Thr Pro Ser Tyr Val Ala Phe Thr Asp Thr Glu
35 40 45
Arg Leu Ile Gly Asp Ala Ala Lys Asn Gln Val Ala Leu Asn Pro Gln
50 55 60
Asn Thr Val Phe Asp Ala Lys Arg Leu Ile Gly Arg Lys Phe Gly Asp
65 70 75 80
Ala Val Val Gln Ser Asp Met Lys His Trp Pro Phe Gln Val Val Asn
85 90 95
Asp Gly Asp Lys Pro Lys Val Gln Val Asn Tyr Lys Gly Glu Ser Arg
100 105 110
Ser Phe Phe Pro Glu Glu Ile Ser Ser Met Val Leu Thr Lys Met Lys
115 120 125
Glu Ile Ala Glu Ala Tyr Leu Gly His Pro Val Thr Asn Ala Val Ile
130 135 140
Thr Val Pro Ala Tyr Phe Asn Asp Ser Gln Arg Gln Ala Thr Lys Asp
145 150 155 160
Ala Gly Val Ile Ala Gly Leu Asn Val Leu Arg Ile Ile Asn Glu Pro
165 170 175
Thr Ala Ala Ala Ile Ala Tyr Gly Leu Asp Arg Asn Arg Gln Gly Lys
180 185 190
Lys Asp Ile Ser Gln Asn Lys Leu Ala Val Arg Arg Leu Arg Thr Ala
195 200 205
Cys Glu Arg Ala Lys Arg Thr Leu Ser Ser Ser Thr Gln Ala Ser Leu
210 215 220
Glu Ile Asp Ser Leu Phe Glu Gly Ile Asp Phe Tyr Thr Ser Ile Thr
225 230 235 240
Arg Ala Arg Phe Glu Glu Leu Cys Ser Asp Leu Phe Arg Ser Thr Leu
245 250 255
Glu Pro Val Glu Lys Ala Leu Arg Asp Ala Lys Met Asp Lys Ala Gln
260 265 270
Ile His Asp Leu Val Leu Val Gly Gly Ser Thr Arg Ile Pro Lys Val
275 280 285
Gln Lys Leu Leu Gln Asp Phe Phe Asn Gly Arg Asp Leu Asn Lys Ser
290 295 300
Ile Asn Pro Asp Glu Ala Val Ala Tyr Gly Ala Ala Val Gln Ala Ala
305 310 315 320
Ile Leu Met Gly Asp Lys Ser Glu Asn Val Gln Asp Leu Leu Leu Leu
325 330 335
Asp Val Ala Pro Leu Ser Leu Gly Leu Glu Thr Ala Gly Gly Val Met
340 345 350
Thr Ala Leu Ile Lys Arg Asn Ser Thr Ile Pro Thr Lys Gln Thr Gln
355 360 365
Thr Phe Thr Thr Tyr Ser Asp Asn Gln Pro Gly Val Leu Ile Gln Val
370 375 380
Tyr Glu Gly Glu Arg Ala Met Thr Gly Asp Asn Asn Leu Leu Gly Arg
385 390 395 400
Phe Glu Leu Ser Gly Ile Pro Pro Ala Pro Arg Gly Val Pro Gln Ile
405 410 415
Glu Val Thr Phe Asp Ile Asp Ala Asn Gly Leu Asn Val Thr Ala Thr
420 425 430
Asp Lys Ser Thr Gly Lys Ala Asn Lys Ile Thr Ile Thr Asn Asp Lys
435 440 445
Gly Arg Leu Ser Lys Glu Glu Ile Glu Arg Met Val Gln Glu Ala Glu
450 455 460
Arg Tyr Lys Ala Glu Asp Glu Val Gln Arg Asp Arg Val Ala Ala Lys
465 470 475 480
Asn Ala Leu Glu Ser Tyr Ala Phe Asn Met Lys Ser Ala Val Glu Gly
485 490 495
Glu Gly Leu Lys Gly Lys Leu Ser Glu Ala Asp Lys Lys Lys Val Leu
500 505 510
Asp Lys Cys Gln Glu Val Ile Ser Trp Leu Asp Ser Asn Thr Leu Ala
515 520 525
Asp Lys Glu Glu Phe Val His Lys Arg Glu Glu Leu Glu Arg Val Cys
530 535 540
Ser Pro Ile Ile Ser Gly Leu Tyr Gln Gly Ala Gly Ala Pro Gly Ala
545 550 555 560
Gly Gly Phe Gly Ala Gln Ala Pro Lys Gly Ala Ser Gly Ser Gly Pro
565 570 575
Thr Ile Glu Glu Val Asp
580
<210> 29
<211> 630
<212> DNA
<213> 人工序列
<220>
<223> chHSP27的密码子优化基因
<220>
<221> CDS
<222> (13)..(624)
<400> 29
aagcttgcca cc atg acc gag agg cgg gtg cct ttc tcc ctg ctg agg tct 51
Met Thr Glu Arg Arg Val Pro Phe Ser Leu Leu Arg Ser
1 5 10
cca tcc tgg gag ccc ttt cgg gac tgg tac cca gct cac agc aga ctg 99
Pro Ser Trp Glu Pro Phe Arg Asp Trp Tyr Pro Ala His Ser Arg Leu
15 20 25
ttc gat cag gcc ttt ggc gtg cca agg ctg cct gac gag tgg agc cag 147
Phe Asp Gln Ala Phe Gly Val Pro Arg Leu Pro Asp Glu Trp Ser Gln
30 35 40 45
tgg ttc tct gcc gct gga tgg cca gga tat gtg agg cca ctg cca gct 195
Trp Phe Ser Ala Ala Gly Trp Pro Gly Tyr Val Arg Pro Leu Pro Ala
50 55 60
gct acc gct gag gga cct gct gct gtg aca ctg gct gct cca gcc ttt 243
Ala Thr Ala Glu Gly Pro Ala Ala Val Thr Leu Ala Ala Pro Ala Phe
65 70 75
tcc agg gct ctg aac agg cag ctg tcc agc ggc gtg agc gag atc agg 291
Ser Arg Ala Leu Asn Arg Gln Leu Ser Ser Gly Val Ser Glu Ile Arg
80 85 90
cag acc gct gac aga tgg cgc gtg tct ctg gat gtg aat cat ttc gcc 339
Gln Thr Ala Asp Arg Trp Arg Val Ser Leu Asp Val Asn His Phe Ala
95 100 105
cct gag gag ctg acc gtg aag aca aag gag ggc gtg gtg gag atc aca 387
Pro Glu Glu Leu Thr Val Lys Thr Lys Glu Gly Val Val Glu Ile Thr
110 115 120 125
ggc aag cac gag gag aga cag gat gag cat ggc tac atc tcc aga tgc 435
Gly Lys His Glu Glu Arg Gln Asp Glu His Gly Tyr Ile Ser Arg Cys
130 135 140
ttt acc cgc aag tat aca ctg cca cct gga gtg gac ccc acc ctg gtg 483
Phe Thr Arg Lys Tyr Thr Leu Pro Pro Gly Val Asp Pro Thr Leu Val
145 150 155
tct tcc agc ctg tct cct gag ggc acc ctg aca gtg gag gct cct ctg 531
Ser Ser Ser Leu Ser Pro Glu Gly Thr Leu Thr Val Glu Ala Pro Leu
160 165 170
cca aag gct gtg aca cag tcc gcc gag atc acc atc cca gtg aca ttc 579
Pro Lys Ala Val Thr Gln Ser Ala Glu Ile Thr Ile Pro Val Thr Phe
175 180 185
gag gcc cgc gct cag atc ggc ggc ccc gag gcc ggc aag gtg tga 624
Glu Ala Arg Ala Gln Ile Gly Gly Pro Glu Ala Gly Lys Val
190 195 200
gaattc 630
<210> 30
<211> 203
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 30
Met Thr Glu Arg Arg Val Pro Phe Ser Leu Leu Arg Ser Pro Ser Trp
1 5 10 15
Glu Pro Phe Arg Asp Trp Tyr Pro Ala His Ser Arg Leu Phe Asp Gln
20 25 30
Ala Phe Gly Val Pro Arg Leu Pro Asp Glu Trp Ser Gln Trp Phe Ser
35 40 45
Ala Ala Gly Trp Pro Gly Tyr Val Arg Pro Leu Pro Ala Ala Thr Ala
50 55 60
Glu Gly Pro Ala Ala Val Thr Leu Ala Ala Pro Ala Phe Ser Arg Ala
65 70 75 80
Leu Asn Arg Gln Leu Ser Ser Gly Val Ser Glu Ile Arg Gln Thr Ala
85 90 95
Asp Arg Trp Arg Val Ser Leu Asp Val Asn His Phe Ala Pro Glu Glu
100 105 110
Leu Thr Val Lys Thr Lys Glu Gly Val Val Glu Ile Thr Gly Lys His
115 120 125
Glu Glu Arg Gln Asp Glu His Gly Tyr Ile Ser Arg Cys Phe Thr Arg
130 135 140
Lys Tyr Thr Leu Pro Pro Gly Val Asp Pro Thr Leu Val Ser Ser Ser
145 150 155 160
Leu Ser Pro Glu Gly Thr Leu Thr Val Glu Ala Pro Leu Pro Lys Ala
165 170 175
Val Thr Gln Ser Ala Glu Ile Thr Ile Pro Val Thr Phe Glu Ala Arg
180 185 190
Ala Gln Ile Gly Gly Pro Glu Ala Gly Lys Val
195 200
<210> 31
<211> 687
<212> DNA
<213> 人工序列
<220>
<223> pro BDNF的密码子优化基因
<220>
<221> CDS
<222> (1)..(687)
<400> 31
gcc cca atg aag gag gct aac atc agg gga cag gga gga ctg gct tac 48
Ala Pro Met Lys Glu Ala Asn Ile Arg Gly Gln Gly Gly Leu Ala Tyr
1 5 10 15
cct ggc gtg cgg acc cac ggc aca ctg gag tcc gtg aat ggc cca aag 96
Pro Gly Val Arg Thr His Gly Thr Leu Glu Ser Val Asn Gly Pro Lys
20 25 30
gct ggc tcc cgg ggc ctg acc agc ctg gct gac aca ttc gag cat gtg 144
Ala Gly Ser Arg Gly Leu Thr Ser Leu Ala Asp Thr Phe Glu His Val
35 40 45
atc gag gag ctg ctg gac gag gat cag aag gtg aga cct aac gag gag 192
Ile Glu Glu Leu Leu Asp Glu Asp Gln Lys Val Arg Pro Asn Glu Glu
50 55 60
aac aat aag gac gct gat ctg tat acc agc cgc gtg atg ctg tcc agc 240
Asn Asn Lys Asp Ala Asp Leu Tyr Thr Ser Arg Val Met Leu Ser Ser
65 70 75 80
cag gtg cca ctg gag cca cct ctg ctg ttt ctg ctg gag gag tac aag 288
Gln Val Pro Leu Glu Pro Pro Leu Leu Phe Leu Leu Glu Glu Tyr Lys
85 90 95
aac tat ctg gat gcc gct aat atg tcc atg agg gtg agg cgg cac agc 336
Asn Tyr Leu Asp Ala Ala Asn Met Ser Met Arg Val Arg Arg His Ser
100 105 110
gac cca gct aga agg gga gag ctg tcc gtg tgc gat tcc atc agc gag 384
Asp Pro Ala Arg Arg Gly Glu Leu Ser Val Cys Asp Ser Ile Ser Glu
115 120 125
tgg gtg acc gcc gct gac aag aag aca gct gtg gat atg agc ggc ggc 432
Trp Val Thr Ala Ala Asp Lys Lys Thr Ala Val Asp Met Ser Gly Gly
130 135 140
acc gtg aca gtg ctg gag aag gtg ccc gtg tct aag ggc cag ctg aag 480
Thr Val Thr Val Leu Glu Lys Val Pro Val Ser Lys Gly Gln Leu Lys
145 150 155 160
cag tat ttc tac gag acc aag tgc aac cct atg ggc tac aca aag gag 528
Gln Tyr Phe Tyr Glu Thr Lys Cys Asn Pro Met Gly Tyr Thr Lys Glu
165 170 175
ggc tgt agg ggc atc gac aag cgg cat tgg aac tcc cag tgt aga acc 576
Gly Cys Arg Gly Ile Asp Lys Arg His Trp Asn Ser Gln Cys Arg Thr
180 185 190
aca cag tcc tat gtg cgc gcc ctg acc atg gac tcc aag aag agg atc 624
Thr Gln Ser Tyr Val Arg Ala Leu Thr Met Asp Ser Lys Lys Arg Ile
195 200 205
ggc tgg agg ttc atc cgc atc gat aca agc tgc gtg tgc acc ctg aca 672
Gly Trp Arg Phe Ile Arg Ile Asp Thr Ser Cys Val Cys Thr Leu Thr
210 215 220
atc aag agg ggc cgg 687
Ile Lys Arg Gly Arg
225
<210> 32
<211> 229
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 32
Ala Pro Met Lys Glu Ala Asn Ile Arg Gly Gln Gly Gly Leu Ala Tyr
1 5 10 15
Pro Gly Val Arg Thr His Gly Thr Leu Glu Ser Val Asn Gly Pro Lys
20 25 30
Ala Gly Ser Arg Gly Leu Thr Ser Leu Ala Asp Thr Phe Glu His Val
35 40 45
Ile Glu Glu Leu Leu Asp Glu Asp Gln Lys Val Arg Pro Asn Glu Glu
50 55 60
Asn Asn Lys Asp Ala Asp Leu Tyr Thr Ser Arg Val Met Leu Ser Ser
65 70 75 80
Gln Val Pro Leu Glu Pro Pro Leu Leu Phe Leu Leu Glu Glu Tyr Lys
85 90 95
Asn Tyr Leu Asp Ala Ala Asn Met Ser Met Arg Val Arg Arg His Ser
100 105 110
Asp Pro Ala Arg Arg Gly Glu Leu Ser Val Cys Asp Ser Ile Ser Glu
115 120 125
Trp Val Thr Ala Ala Asp Lys Lys Thr Ala Val Asp Met Ser Gly Gly
130 135 140
Thr Val Thr Val Leu Glu Lys Val Pro Val Ser Lys Gly Gln Leu Lys
145 150 155 160
Gln Tyr Phe Tyr Glu Thr Lys Cys Asn Pro Met Gly Tyr Thr Lys Glu
165 170 175
Gly Cys Arg Gly Ile Asp Lys Arg His Trp Asn Ser Gln Cys Arg Thr
180 185 190
Thr Gln Ser Tyr Val Arg Ala Leu Thr Met Asp Ser Lys Lys Arg Ile
195 200 205
Gly Trp Arg Phe Ile Arg Ile Asp Thr Ser Cys Val Cys Thr Leu Thr
210 215 220
Ile Lys Arg Gly Arg
225
<210> 33
<211> 852
<212> DNA
<213> 人工序列
<220>
<223> DNAJB2 HSJ1, HSPF3 AAA09034
<220>
<221> CDS
<222> (13)..(846)
<400> 33
aagcttgcca cc atg gcc tct tac tat gag atc ctg gac gtg ccc aga agc 51
Met Ala Ser Tyr Tyr Glu Ile Leu Asp Val Pro Arg Ser
1 5 10
gcc tct gct gac gat atc aag aag gcc tac agg cgg aag gct ctg cag 99
Ala Ser Ala Asp Asp Ile Lys Lys Ala Tyr Arg Arg Lys Ala Leu Gln
15 20 25
tgg cac ccc gac aag aac cct gat aat aag gag ttt gct gag aag aag 147
Trp His Pro Asp Lys Asn Pro Asp Asn Lys Glu Phe Ala Glu Lys Lys
30 35 40 45
ttc aag gag gtg gcc gag gct tat gag gtg ctg tcc gac aag cat aag 195
Phe Lys Glu Val Ala Glu Ala Tyr Glu Val Leu Ser Asp Lys His Lys
50 55 60
agg gag atc tac gat aga tat ggc cgg gag ggc ctg aca ggc aca ggc 243
Arg Glu Ile Tyr Asp Arg Tyr Gly Arg Glu Gly Leu Thr Gly Thr Gly
65 70 75
acc gga cct agc cgg gcc gag gct ggc tct ggc ggc cct ggc ttc acc 291
Thr Gly Pro Ser Arg Ala Glu Ala Gly Ser Gly Gly Pro Gly Phe Thr
80 85 90
ttc acc ttc agg tcc ccc gaa gag gtg ttt cgg gag ttc ttt ggc tcc 339
Phe Thr Phe Arg Ser Pro Glu Glu Val Phe Arg Glu Phe Phe Gly Ser
95 100 105
ggc gac cca ttt gcc gag ctg ttc gac gat ctg ggc ccc ttc agc gag 387
Gly Asp Pro Phe Ala Glu Leu Phe Asp Asp Leu Gly Pro Phe Ser Glu
110 115 120 125
ctg cag aac aga ggc tcc cgc cac tct gga ccc ttc ttt aca ttt tcc 435
Leu Gln Asn Arg Gly Ser Arg His Ser Gly Pro Phe Phe Thr Phe Ser
130 135 140
agc tct ttc cct ggc cat tct gat ttt tcc agc tct tcc ttt tcc ttc 483
Ser Ser Phe Pro Gly His Ser Asp Phe Ser Ser Ser Ser Phe Ser Phe
145 150 155
agc cca ggc gcc ggc gct ttt aga tct gtg tcc acc agc acc aca ttc 531
Ser Pro Gly Ala Gly Ala Phe Arg Ser Val Ser Thr Ser Thr Thr Phe
160 165 170
gtg cag ggc aga cgc atc acc aca agg cgg atc atg gag aat gga cag 579
Val Gln Gly Arg Arg Ile Thr Thr Arg Arg Ile Met Glu Asn Gly Gln
175 180 185
gag aga gtg gag gtg gag gag gac ggc cag ctg aag tcc gtg aca atc 627
Glu Arg Val Glu Val Glu Glu Asp Gly Gln Leu Lys Ser Val Thr Ile
190 195 200 205
aat ggc gtg cct gac gat ctg gcc aga ggc ctg gag ctg tcc aga cgc 675
Asn Gly Val Pro Asp Asp Leu Ala Arg Gly Leu Glu Leu Ser Arg Arg
210 215 220
gag cag cag cct tct gtg acc tct cgc tcc ggc ggc aca cag gtg cag 723
Glu Gln Gln Pro Ser Val Thr Ser Arg Ser Gly Gly Thr Gln Val Gln
225 230 235
cag acc cca gct agc tgc ccc ctg gac tct gat ctg tcc gag gac gag 771
Gln Thr Pro Ala Ser Cys Pro Leu Asp Ser Asp Leu Ser Glu Asp Glu
240 245 250
gat ctg cag ctg gcc atg gct tac agc ctg tct gag atg gag gcc gct 819
Asp Leu Gln Leu Ala Met Ala Tyr Ser Leu Ser Glu Met Glu Ala Ala
255 260 265
ggc aag aag ccc gct gat gtg ttc tga gaattc 852
Gly Lys Lys Pro Ala Asp Val Phe
270 275
<210> 34
<211> 277
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 34
Met Ala Ser Tyr Tyr Glu Ile Leu Asp Val Pro Arg Ser Ala Ser Ala
1 5 10 15
Asp Asp Ile Lys Lys Ala Tyr Arg Arg Lys Ala Leu Gln Trp His Pro
20 25 30
Asp Lys Asn Pro Asp Asn Lys Glu Phe Ala Glu Lys Lys Phe Lys Glu
35 40 45
Val Ala Glu Ala Tyr Glu Val Leu Ser Asp Lys His Lys Arg Glu Ile
50 55 60
Tyr Asp Arg Tyr Gly Arg Glu Gly Leu Thr Gly Thr Gly Thr Gly Pro
65 70 75 80
Ser Arg Ala Glu Ala Gly Ser Gly Gly Pro Gly Phe Thr Phe Thr Phe
85 90 95
Arg Ser Pro Glu Glu Val Phe Arg Glu Phe Phe Gly Ser Gly Asp Pro
100 105 110
Phe Ala Glu Leu Phe Asp Asp Leu Gly Pro Phe Ser Glu Leu Gln Asn
115 120 125
Arg Gly Ser Arg His Ser Gly Pro Phe Phe Thr Phe Ser Ser Ser Phe
130 135 140
Pro Gly His Ser Asp Phe Ser Ser Ser Ser Phe Ser Phe Ser Pro Gly
145 150 155 160
Ala Gly Ala Phe Arg Ser Val Ser Thr Ser Thr Thr Phe Val Gln Gly
165 170 175
Arg Arg Ile Thr Thr Arg Arg Ile Met Glu Asn Gly Gln Glu Arg Val
180 185 190
Glu Val Glu Glu Asp Gly Gln Leu Lys Ser Val Thr Ile Asn Gly Val
195 200 205
Pro Asp Asp Leu Ala Arg Gly Leu Glu Leu Ser Arg Arg Glu Gln Gln
210 215 220
Pro Ser Val Thr Ser Arg Ser Gly Gly Thr Gln Val Gln Gln Thr Pro
225 230 235 240
Ala Ser Cys Pro Leu Asp Ser Asp Leu Ser Glu Asp Glu Asp Leu Gln
245 250 255
Leu Ala Met Ala Tyr Ser Leu Ser Glu Met Glu Ala Ala Gly Lys Lys
260 265 270
Pro Ala Asp Val Phe
275
<210> 35
<211> 57
<212> DNA
<213> 人工序列
<220>
<223> IgG 信号序列6SVL_B
<220>
<221> CDS
<222> (1)..(57)
<400> 35
atg ggc tgg tct ctg atc ctg ctg ttc ctg gtg gct gtg gct acc agg 48
Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg
1 5 10 15
gtg gga tcc 57
Val Gly Ser
<210> 36
<211> 19
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 36
Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg
1 5 10 15
Val Gly Ser
<210> 37
<211> 678
<212> DNA
<213> 人工序列
<220>
<223> hFab 重链
<220>
<221> CDS
<222> (1)..(678)
<400> 37
gag gtg cag ctg gtg cag agc gga gct gag gtg aag aag cca ggc gag 48
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu
1 5 10 15
agc ctg aag atc tct tgc aag ggc tcc ggc tac agc ttc atg aac tat 96
Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Met Asn Tyr
20 25 30
tgg ctg ggc tgg gtg aga cag atg cct ggc aag ggc ctg gag tgg atg 144
Trp Leu Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
ggc gac atc tac ccc ggc ggc gat tac cct acc tat agc gag aag ttt 192
Gly Asp Ile Tyr Pro Gly Gly Asp Tyr Pro Thr Tyr Ser Glu Lys Phe
50 55 60
aag gtg cag gtg acc atc tct gcc gac aag tct atc tcc aca gct tat 240
Lys Val Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
ctg cag ctg tct tcc ctg aag gcc tcc gac acc gct atg tac tat tgc 288
Leu Gln Leu Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys
85 90 95
gcc cgc agc ggc aat tac gat gag gtg gct tat tgg ggc cag ggc acc 336
Ala Arg Ser Gly Asn Tyr Asp Glu Val Ala Tyr Trp Gly Gln Gly Thr
100 105 110
ctg gtg aca gtg agc tct gcc agc aca aag ggc ccc tcc gtg ttc cct 384
Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
ctg gct cca tcc agc aag agc acc tct gga gga aca gcc gct ctg gga 432
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
tgt ctg gtg aag gat tac ttc cca gag ccc gtg acc gtg tct tgg aac 480
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
tcc ggc gcc ctg acc agc gga gtg cac aca ttt cca gct gtg ctg cag 528
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
tct tcc ggc ctg tac tct ctg agc tct gtg gtg acc gtg ccc tcc agc 576
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
tct ctg ggc acc cag aca tat atc tgc aac gtg aat cac aag cca tct 624
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
aat aca aag gtg gac aag aag gtg gag ccc aag tcc tgt gat aag acc 672
Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr
210 215 220
cat aca 678
His Thr
225
<210> 38
<211> 226
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 38
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu
1 5 10 15
Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Met Asn Tyr
20 25 30
Trp Leu Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Asp Ile Tyr Pro Gly Gly Asp Tyr Pro Thr Tyr Ser Glu Lys Phe
50 55 60
Lys Val Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Leu Gln Leu Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Ser Gly Asn Tyr Asp Glu Val Ala Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr
210 215 220
His Thr
225
<210> 39
<211> 1518
<212> DNA
<213> 人工序列
<220>
<223> BDNF-hFab(H)
<220>
<221> CDS
<222> (13)..(1512)
<400> 39
gaattcgcca cc atg ggc tgg tct ctg atc ctg ctg ttc ctg gtg gct gtg 51
Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val
1 5 10
gct acc agg gtg gga tcc gcc cca atg aag gag gct aac atc agg gga 99
Ala Thr Arg Val Gly Ser Ala Pro Met Lys Glu Ala Asn Ile Arg Gly
15 20 25
cag gga gga ctg gct tac cct ggc gtg cgg acc cac ggc aca ctg gag 147
Gln Gly Gly Leu Ala Tyr Pro Gly Val Arg Thr His Gly Thr Leu Glu
30 35 40 45
tcc gtg aat ggc cca aag gct ggc tcc cgg ggc ctg acc agc ctg gct 195
Ser Val Asn Gly Pro Lys Ala Gly Ser Arg Gly Leu Thr Ser Leu Ala
50 55 60
gac aca ttc gag cat gtg atc gag gag ctg ctg gac gag gat cag aag 243
Asp Thr Phe Glu His Val Ile Glu Glu Leu Leu Asp Glu Asp Gln Lys
65 70 75
gtg aga cct aac gag gag aac aat aag gac gct gat ctg tat acc agc 291
Val Arg Pro Asn Glu Glu Asn Asn Lys Asp Ala Asp Leu Tyr Thr Ser
80 85 90
cgc gtg atg ctg tcc agc cag gtg cca ctg gag cca cct ctg ctg ttt 339
Arg Val Met Leu Ser Ser Gln Val Pro Leu Glu Pro Pro Leu Leu Phe
95 100 105
ctg ctg gag gag tac aag aac tat ctg gat gcc gct aat atg tcc atg 387
Leu Leu Glu Glu Tyr Lys Asn Tyr Leu Asp Ala Ala Asn Met Ser Met
110 115 120 125
agg gtg agg cgg cac agc gac cca gct aga agg gga gag ctg tcc gtg 435
Arg Val Arg Arg His Ser Asp Pro Ala Arg Arg Gly Glu Leu Ser Val
130 135 140
tgc gat tcc atc agc gag tgg gtg acc gcc gct gac aag aag aca gct 483
Cys Asp Ser Ile Ser Glu Trp Val Thr Ala Ala Asp Lys Lys Thr Ala
145 150 155
gtg gat atg agc ggc ggc acc gtg aca gtg ctg gag aag gtg ccc gtg 531
Val Asp Met Ser Gly Gly Thr Val Thr Val Leu Glu Lys Val Pro Val
160 165 170
tct aag ggc cag ctg aag cag tat ttc tac gag acc aag tgc aac cct 579
Ser Lys Gly Gln Leu Lys Gln Tyr Phe Tyr Glu Thr Lys Cys Asn Pro
175 180 185
atg ggc tac aca aag gag ggc tgt agg ggc atc gac aag cgg cat tgg 627
Met Gly Tyr Thr Lys Glu Gly Cys Arg Gly Ile Asp Lys Arg His Trp
190 195 200 205
aac tcc cag tgt aga acc aca cag tcc tat gtg cgc gcc ctg acc atg 675
Asn Ser Gln Cys Arg Thr Thr Gln Ser Tyr Val Arg Ala Leu Thr Met
210 215 220
gac tcc aag aag agg atc ggc tgg agg ttc atc cgc atc gat aca agc 723
Asp Ser Lys Lys Arg Ile Gly Trp Arg Phe Ile Arg Ile Asp Thr Ser
225 230 235
tgc gtg tgc acc ctg aca atc aag agg ggc cgg gga gga gga gga tct 771
Cys Val Cys Thr Leu Thr Ile Lys Arg Gly Arg Gly Gly Gly Gly Ser
240 245 250
gga gga ggc ggc tca ggc ggc ggc ggc agc ggc ggc ggc ggc tct ggc 819
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
255 260 265
ggc ggc ggc tcc gag gtg cag ctg gtg cag agc gga gct gag gtg aag 867
Gly Gly Gly Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys
270 275 280 285
aag cca ggc gag agc ctg aag atc tct tgc aag ggc tcc ggc tac agc 915
Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser
290 295 300
ttc atg aac tat tgg ctg ggc tgg gtg aga cag atg cct ggc aag ggc 963
Phe Met Asn Tyr Trp Leu Gly Trp Val Arg Gln Met Pro Gly Lys Gly
305 310 315
ctg gag tgg atg ggc gac atc tac ccc ggc ggc gat tac cct acc tat 1011
Leu Glu Trp Met Gly Asp Ile Tyr Pro Gly Gly Asp Tyr Pro Thr Tyr
320 325 330
agc gag aag ttt aag gtg cag gtg acc atc tct gcc gac aag tct atc 1059
Ser Glu Lys Phe Lys Val Gln Val Thr Ile Ser Ala Asp Lys Ser Ile
335 340 345
tcc aca gct tat ctg cag ctg tct tcc ctg aag gcc tcc gac acc gct 1107
Ser Thr Ala Tyr Leu Gln Leu Ser Ser Leu Lys Ala Ser Asp Thr Ala
350 355 360 365
atg tac tat tgc gcc cgc agc ggc aat tac gat gag gtg gct tat tgg 1155
Met Tyr Tyr Cys Ala Arg Ser Gly Asn Tyr Asp Glu Val Ala Tyr Trp
370 375 380
ggc cag ggc acc ctg gtg aca gtg agc tct gcc agc aca aag ggc ccc 1203
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
385 390 395
tcc gtg ttc cct ctg gct cca tcc agc aag agc acc tct gga gga aca 1251
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
400 405 410
gcc gct ctg gga tgt ctg gtg aag gat tac ttc cca gag ccc gtg acc 1299
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
415 420 425
gtg tct tgg aac tcc ggc gcc ctg acc agc gga gtg cac aca ttt cca 1347
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
430 435 440 445
gct gtg ctg cag tct tcc ggc ctg tac tct ctg agc tct gtg gtg acc 1395
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
450 455 460
gtg ccc tcc agc tct ctg ggc acc cag aca tat atc tgc aac gtg aat 1443
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
465 470 475
cac aag cca tct aat aca aag gtg gac aag aag gtg gag ccc aag tcc 1491
His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser
480 485 490
tgt gat aag acc cat aca taa tctaga 1518
Cys Asp Lys Thr His Thr
495
<210> 40
<211> 499
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 40
Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg
1 5 10 15
Val Gly Ser Ala Pro Met Lys Glu Ala Asn Ile Arg Gly Gln Gly Gly
20 25 30
Leu Ala Tyr Pro Gly Val Arg Thr His Gly Thr Leu Glu Ser Val Asn
35 40 45
Gly Pro Lys Ala Gly Ser Arg Gly Leu Thr Ser Leu Ala Asp Thr Phe
50 55 60
Glu His Val Ile Glu Glu Leu Leu Asp Glu Asp Gln Lys Val Arg Pro
65 70 75 80
Asn Glu Glu Asn Asn Lys Asp Ala Asp Leu Tyr Thr Ser Arg Val Met
85 90 95
Leu Ser Ser Gln Val Pro Leu Glu Pro Pro Leu Leu Phe Leu Leu Glu
100 105 110
Glu Tyr Lys Asn Tyr Leu Asp Ala Ala Asn Met Ser Met Arg Val Arg
115 120 125
Arg His Ser Asp Pro Ala Arg Arg Gly Glu Leu Ser Val Cys Asp Ser
130 135 140
Ile Ser Glu Trp Val Thr Ala Ala Asp Lys Lys Thr Ala Val Asp Met
145 150 155 160
Ser Gly Gly Thr Val Thr Val Leu Glu Lys Val Pro Val Ser Lys Gly
165 170 175
Gln Leu Lys Gln Tyr Phe Tyr Glu Thr Lys Cys Asn Pro Met Gly Tyr
180 185 190
Thr Lys Glu Gly Cys Arg Gly Ile Asp Lys Arg His Trp Asn Ser Gln
195 200 205
Cys Arg Thr Thr Gln Ser Tyr Val Arg Ala Leu Thr Met Asp Ser Lys
210 215 220
Lys Arg Ile Gly Trp Arg Phe Ile Arg Ile Asp Thr Ser Cys Val Cys
225 230 235 240
Thr Leu Thr Ile Lys Arg Gly Arg Gly Gly Gly Gly Ser Gly Gly Gly
245 250 255
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
260 265 270
Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
275 280 285
Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Met Asn
290 295 300
Tyr Trp Leu Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp
305 310 315 320
Met Gly Asp Ile Tyr Pro Gly Gly Asp Tyr Pro Thr Tyr Ser Glu Lys
325 330 335
Phe Lys Val Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala
340 345 350
Tyr Leu Gln Leu Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr
355 360 365
Cys Ala Arg Ser Gly Asn Tyr Asp Glu Val Ala Tyr Trp Gly Gln Gly
370 375 380
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
385 390 395 400
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
405 410 415
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
420 425 430
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
435 440 445
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
450 455 460
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
465 470 475 480
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
485 490 495
Thr His Thr
<210> 41
<211> 657
<212> DNA
<213> 人工序列
<220>
<223> hFab 轻链
<220>
<221> CDS
<222> (1)..(657)
<400> 41
gac atc gtg atg acc cag aca cca ctg tcc ctg agc gtg acc cca gga 48
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly
1 5 10 15
cag cca gct tct atc tcc tgc cgc tcc agc cag tcc ctg gtg cac agc 96
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
aac ggc aat acc tac ctg cat tgg tat ctg cag aag cct ggc cag tcc 144
Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
cca cag ctg ctg atc tac aag gtg tct aac agg ttc tcc gga gtg cca 192
Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
gac cgg ttt agc gga tct gga tcc ggc acc gat ttc aca ctg aag atc 240
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
tcc agg gtg gag gcc gag gat gtg ggc gtg tac tat tgc agc cag tct 288
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ser Gln Ser
85 90 95
acc cac gtg ccc tgg aca ttt ggc cag ggc acc aag gtg gag atc aag 336
Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105 110
cgg aca gtg gcc gct cct tcc gtg ttc atc ttt ccc cct agc gac gag 384
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
cag ctg aag agc ggc acc gct tct gtg gtg tgc ctg ctg aac aat ttc 432
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
tac cct aga gag gcc aag gtg cag tgg aag gtg gat aac gct ctg cag 480
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
tcc ggc aat agc cag gag tct gtg aca gag cag gac tcc aag gat agc 528
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
acc tat tct ctg tct tcc acc ctg aca ctg agc aag gcc gac tac gag 576
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
aag cac aag gtg tat gct tgc gag gtg aca cat cag ggc ctg agc tct 624
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
cca gtg acc aag tct ttt aat cgc ggc gag tgt 657
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 42
<211> 219
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 42
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ser Gln Ser
85 90 95
Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 43
<211> 735
<212> DNA
<213> 人工序列
<220>
<223> hFab(L)
<220>
<221> CDS
<222> (13)..(729)
<400> 43
gaattcgcca cc atg ggc tgg tct ctg atc ctg ctg ttc ctg gtg gcc gtg 51
Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val
1 5 10
gct aca aga gtg ggc tcc gac atc gtg atg acc cag aca cca ctg tcc 99
Ala Thr Arg Val Gly Ser Asp Ile Val Met Thr Gln Thr Pro Leu Ser
15 20 25
ctg agc gtg acc cca gga cag cca gct tct atc tcc tgc cgc tcc agc 147
Leu Ser Val Thr Pro Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser
30 35 40 45
cag tcc ctg gtg cac agc aac ggc aat acc tac ctg cat tgg tat ctg 195
Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu
50 55 60
cag aag cct ggc cag tcc cca cag ctg ctg atc tac aag gtg tct aac 243
Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn
65 70 75
agg ttc tcc gga gtg cca gac cgg ttt agc gga tct gga tcc ggc acc 291
Arg Phe Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr
80 85 90
gat ttc aca ctg aag atc tcc agg gtg gag gcc gag gat gtg ggc gtg 339
Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val
95 100 105
tac tat tgc agc cag tct acc cac gtg ccc tgg aca ttt ggc cag ggc 387
Tyr Tyr Cys Ser Gln Ser Thr His Val Pro Trp Thr Phe Gly Gln Gly
110 115 120 125
acc aag gtg gag atc aag cgg aca gtg gcc gct cct tcc gtg ttc atc 435
Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile
130 135 140
ttt ccc cct agc gac gag cag ctg aag agc ggc acc gct tct gtg gtg 483
Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val
145 150 155
tgc ctg ctg aac aat ttc tac cct aga gag gcc aag gtg cag tgg aag 531
Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys
160 165 170
gtg gat aac gct ctg cag tcc ggc aat agc cag gag tct gtg aca gag 579
Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu
175 180 185
cag gac tcc aag gat agc acc tat tct ctg tct tcc acc ctg aca ctg 627
Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu
190 195 200 205
agc aag gcc gac tac gag aag cac aag gtg tat gct tgc gag gtg aca 675
Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr
210 215 220
cat cag ggc ctg agc tct cca gtg acc aag tct ttt aat cgc ggc gag 723
His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu
225 230 235
tgt taa tctaga 735
Cys
<210> 44
<211> 238
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 44
Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg
1 5 10 15
Val Gly Ser Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val
20 25 30
Thr Pro Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu
35 40 45
Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro
50 55 60
Gly Gln Ser Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser
65 70 75 80
Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
85 90 95
Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys
100 105 110
Ser Gln Ser Thr His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Val
115 120 125
Glu Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro
130 135 140
Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu
145 150 155 160
Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn
165 170 175
Ala Leu Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser
180 185 190
Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala
195 200 205
Asp Tyr Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly
210 215 220
Leu Ser Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 45
<211> 3887
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (346)..(2910)
<223> NM_001017963 WT, CDS 346-2910
<400> 45
gactgcgcag gcgtgctcac ctggcgtgct ccacccgact gggcgtccgc aggctcctcc 60
cccgggtgtg gcctccgggc ggcatggctg cttcccaggt gatgccggct tcagctagtg 120
gggtctagtt gaccgttccg cagccgccag ggccagcgga aagccggtca gggggaaccg 180
cggcggggct ggtgtcatga gcctgaggtg aacttgaggg tgcctcctca gcggtctccc 240
gccctgccct gaggggcgcc gggaccccaa agagcggagg aagagcgcca ccccgacggc 300
caccgcttcg gagccagcac gcggggtacc ctacggggag cgcgg atg ccc ccg tgt 357
Met Pro Pro Cys
1
tcg ggc ggg gac ggc tcc acc cct cct ggg ccc tcc ctt cgg gac agg 405
Ser Gly Gly Asp Gly Ser Thr Pro Pro Gly Pro Ser Leu Arg Asp Arg
5 10 15 20
gac tgt ccc gcc cag agt gct gaa tac ccg cgc gac cgt ctg gat ccc 453
Asp Cys Pro Ala Gln Ser Ala Glu Tyr Pro Arg Asp Arg Leu Asp Pro
25 30 35
cgc cca gga agc ccc tct gaa gcc tcc tcg ccg ccg ttt ctg aga agc 501
Arg Pro Gly Ser Pro Ser Glu Ala Ser Ser Pro Pro Phe Leu Arg Ser
40 45 50
agg gca cct gtt aac tgg tac caa gaa aag gcc caa gtg ttt ctc tgg 549
Arg Ala Pro Val Asn Trp Tyr Gln Glu Lys Ala Gln Val Phe Leu Trp
55 60 65
cat ctg atg gtg tct gga tcc acc act cta ctc tgt ctc tgg aaa cag 597
His Leu Met Val Ser Gly Ser Thr Thr Leu Leu Cys Leu Trp Lys Gln
70 75 80
ccc ttc cac gtc tct gca ttc cct gtc acc gcg tca ctg gcc ttc aga 645
Pro Phe His Val Ser Ala Phe Pro Val Thr Ala Ser Leu Ala Phe Arg
85 90 95 100
cag agc caa ggt gca ggg caa cac ctc tac aag gat ctg cag cca ttt 693
Gln Ser Gln Gly Ala Gly Gln His Leu Tyr Lys Asp Leu Gln Pro Phe
105 110 115
ata ttg ctt agg cta ctg atg cct gag gaa acc cag acc caa gac caa 741
Ile Leu Leu Arg Leu Leu Met Pro Glu Glu Thr Gln Thr Gln Asp Gln
120 125 130
ccg atg gag gag gag gag gtt gag acg ttc gcc ttt cag gca gaa att 789
Pro Met Glu Glu Glu Glu Val Glu Thr Phe Ala Phe Gln Ala Glu Ile
135 140 145
gcc cag ttg atg tca ttg atc atc aat act ttc tac tcg aac aaa gag 837
Ala Gln Leu Met Ser Leu Ile Ile Asn Thr Phe Tyr Ser Asn Lys Glu
150 155 160
atc ttt ctg aga gag ctc att tca aat tca tca gat gca ttg gac aaa 885
Ile Phe Leu Arg Glu Leu Ile Ser Asn Ser Ser Asp Ala Leu Asp Lys
165 170 175 180
atc cgg tat gaa agc ttg aca gat ccc agt aaa tta gac tct ggg aaa 933
Ile Arg Tyr Glu Ser Leu Thr Asp Pro Ser Lys Leu Asp Ser Gly Lys
185 190 195
gag ctg cat att aac ctt ata ccg aac aaa caa gat cga act ctc act 981
Glu Leu His Ile Asn Leu Ile Pro Asn Lys Gln Asp Arg Thr Leu Thr
200 205 210
att gtg gat act gga att gga atg acc aag gct gac ttg atc aat aac 1029
Ile Val Asp Thr Gly Ile Gly Met Thr Lys Ala Asp Leu Ile Asn Asn
215 220 225
ctt ggt act atc gcc aag tct ggg acc aaa gcg ttc atg gaa gct ttg 1077
Leu Gly Thr Ile Ala Lys Ser Gly Thr Lys Ala Phe Met Glu Ala Leu
230 235 240
cag gct ggt gca gat atc tct atg att ggc cag ttc ggt gtt ggt ttt 1125
Gln Ala Gly Ala Asp Ile Ser Met Ile Gly Gln Phe Gly Val Gly Phe
245 250 255 260
tat tct gct tat ttg gtt gct gag aaa gta act gtg atc acc aaa cat 1173
Tyr Ser Ala Tyr Leu Val Ala Glu Lys Val Thr Val Ile Thr Lys His
265 270 275
aac gat gat gag cag tac gct tgg gag tcc tca gca ggg gga tca ttc 1221
Asn Asp Asp Glu Gln Tyr Ala Trp Glu Ser Ser Ala Gly Gly Ser Phe
280 285 290
aca gtg agg aca gac aca ggt gaa cct atg ggt cgt gga aca aaa gtt 1269
Thr Val Arg Thr Asp Thr Gly Glu Pro Met Gly Arg Gly Thr Lys Val
295 300 305
atc cta cac ctg aaa gaa gac caa act gag tac ttg gag gaa cga aga 1317
Ile Leu His Leu Lys Glu Asp Gln Thr Glu Tyr Leu Glu Glu Arg Arg
310 315 320
ata aag gag att gtg aag aaa cat tct cag ttt att gga tat ccc att 1365
Ile Lys Glu Ile Val Lys Lys His Ser Gln Phe Ile Gly Tyr Pro Ile
325 330 335 340
act ctt ttt gtg gag aag gaa cgt gat aaa gaa gta agc gat gat gag 1413
Thr Leu Phe Val Glu Lys Glu Arg Asp Lys Glu Val Ser Asp Asp Glu
345 350 355
gct gaa gaa aag gaa gac aaa gaa gaa gaa aaa gaa aaa gaa gag aaa 1461
Ala Glu Glu Lys Glu Asp Lys Glu Glu Glu Lys Glu Lys Glu Glu Lys
360 365 370
gag tcg gaa gac aaa cct gaa att gaa gat gtt ggt tct gat gag gaa 1509
Glu Ser Glu Asp Lys Pro Glu Ile Glu Asp Val Gly Ser Asp Glu Glu
375 380 385
gaa gaa aag aag gat ggt gac aag aag aag aag aag aag att aag gaa 1557
Glu Glu Lys Lys Asp Gly Asp Lys Lys Lys Lys Lys Lys Ile Lys Glu
390 395 400
aag tac atc gat caa gaa gag ctc aac aaa aca aag ccc atc tgg acc 1605
Lys Tyr Ile Asp Gln Glu Glu Leu Asn Lys Thr Lys Pro Ile Trp Thr
405 410 415 420
aga aat ccc gac gat att act aat gag gag tac gga gaa ttc tat aag 1653
Arg Asn Pro Asp Asp Ile Thr Asn Glu Glu Tyr Gly Glu Phe Tyr Lys
425 430 435
agc ttg acc aat gac tgg gaa gat cac ttg gca gtg aag cat ttt tca 1701
Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala Val Lys His Phe Ser
440 445 450
gtt gaa gga cag ttg gaa ttc aga gcc ctt cta ttt gtc cca cga cgt 1749
Val Glu Gly Gln Leu Glu Phe Arg Ala Leu Leu Phe Val Pro Arg Arg
455 460 465
gct cct ttt gat ctg ttt gaa aac aga aag aaa aag aac aac atc aaa 1797
Ala Pro Phe Asp Leu Phe Glu Asn Arg Lys Lys Lys Asn Asn Ile Lys
470 475 480
ttg tat gta cgc aga gtt ttc atc atg gat aac tgt gag gag cta atc 1845
Leu Tyr Val Arg Arg Val Phe Ile Met Asp Asn Cys Glu Glu Leu Ile
485 490 495 500
cct gaa tat ctg aac ttc att aga ggg gtg gta gac tcg gag gat ctc 1893
Pro Glu Tyr Leu Asn Phe Ile Arg Gly Val Val Asp Ser Glu Asp Leu
505 510 515
cct cta aac ata tcc cgt gag atg ttg caa caa agc aaa att ttg aaa 1941
Pro Leu Asn Ile Ser Arg Glu Met Leu Gln Gln Ser Lys Ile Leu Lys
520 525 530
gtt atc agg aag aat ttg gtc aaa aaa tgc tta gaa ctc ttt act gaa 1989
Val Ile Arg Lys Asn Leu Val Lys Lys Cys Leu Glu Leu Phe Thr Glu
535 540 545
ctg gcg gaa gat aaa gag aac tac aag aaa ttc tat gag cag ttc tct 2037
Leu Ala Glu Asp Lys Glu Asn Tyr Lys Lys Phe Tyr Glu Gln Phe Ser
550 555 560
aaa aac ata aag ctt gga ata cac gaa gac tct caa aat cgg aag aag 2085
Lys Asn Ile Lys Leu Gly Ile His Glu Asp Ser Gln Asn Arg Lys Lys
565 570 575 580
ctt tca gag ctg tta agg tac tac aca tct gcc tct ggt gat gag atg 2133
Leu Ser Glu Leu Leu Arg Tyr Tyr Thr Ser Ala Ser Gly Asp Glu Met
585 590 595
gtt tct ctc aag gac tac tgc acc aga atg aag gag aac cag aaa cat 2181
Val Ser Leu Lys Asp Tyr Cys Thr Arg Met Lys Glu Asn Gln Lys His
600 605 610
atc tat tat atc aca ggt gag acc aag gac cag gta gct aac tca gcc 2229
Ile Tyr Tyr Ile Thr Gly Glu Thr Lys Asp Gln Val Ala Asn Ser Ala
615 620 625
ttt gtg gaa cgt ctt cgg aaa cat ggc tta gaa gtg atc tat atg att 2277
Phe Val Glu Arg Leu Arg Lys His Gly Leu Glu Val Ile Tyr Met Ile
630 635 640
gag ccc att gat gag tac tgt gtc caa cag ctg aag gaa ttt gag ggg 2325
Glu Pro Ile Asp Glu Tyr Cys Val Gln Gln Leu Lys Glu Phe Glu Gly
645 650 655 660
aag act tta gtg tca gtc acc aaa gaa ggc ctg gaa ctt cca gag gat 2373
Lys Thr Leu Val Ser Val Thr Lys Glu Gly Leu Glu Leu Pro Glu Asp
665 670 675
gaa gaa gag aaa aag aag cag gaa gag aaa aaa aca aag ttt gag aac 2421
Glu Glu Glu Lys Lys Lys Gln Glu Glu Lys Lys Thr Lys Phe Glu Asn
680 685 690
ctc tgc aaa atc atg aaa gac ata ttg gag aaa aaa gtt gaa aag gtg 2469
Leu Cys Lys Ile Met Lys Asp Ile Leu Glu Lys Lys Val Glu Lys Val
695 700 705
gtt gtg tca aac cga ttg gtg aca tct cca tgc tgt att gtc aca agc 2517
Val Val Ser Asn Arg Leu Val Thr Ser Pro Cys Cys Ile Val Thr Ser
710 715 720
aca tat ggc tgg aca gca aac atg gag aga atc atg aaa gct caa gcc 2565
Thr Tyr Gly Trp Thr Ala Asn Met Glu Arg Ile Met Lys Ala Gln Ala
725 730 735 740
cta aga gac aac tca aca atg ggt tac atg gca gca aag aaa cac ctg 2613
Leu Arg Asp Asn Ser Thr Met Gly Tyr Met Ala Ala Lys Lys His Leu
745 750 755
gag ata aac cct gac cat tcc att att gag acc tta agg caa aag gca 2661
Glu Ile Asn Pro Asp His Ser Ile Ile Glu Thr Leu Arg Gln Lys Ala
760 765 770
gag gct gat aag aac gac aag tct gtg aag gat ctg gtc atc ttg ctt 2709
Glu Ala Asp Lys Asn Asp Lys Ser Val Lys Asp Leu Val Ile Leu Leu
775 780 785
tat gaa act gcg ctc ctg tct tct ggc ttc agt ctg gaa gat ccc cag 2757
Tyr Glu Thr Ala Leu Leu Ser Ser Gly Phe Ser Leu Glu Asp Pro Gln
790 795 800
aca cat gct aac agg atc tac agg atg atc aaa ctt ggt ctg ggt att 2805
Thr His Ala Asn Arg Ile Tyr Arg Met Ile Lys Leu Gly Leu Gly Ile
805 810 815 820
gat gaa gat gac cct act gct gat gat acc agt gct gct gta act gaa 2853
Asp Glu Asp Asp Pro Thr Ala Asp Asp Thr Ser Ala Ala Val Thr Glu
825 830 835
gaa atg cca ccc ctt gaa gga gat gac gac aca tca cgc atg gaa gaa 2901
Glu Met Pro Pro Leu Glu Gly Asp Asp Asp Thr Ser Arg Met Glu Glu
840 845 850
gta gac taa tctctggctg agggatgact tacctgttca gtactctaca 2950
Val Asp
attcctctga taatatattt tcaaggatgt ttttctttat ttttgttaat attaaaaagt 3010
ctgtatggca tgacaactac tttaagggga agataagatt tctgtctact aagtgatgct 3070
gtgatacctt aggcactaaa gcagagctag taatgctttt tgagtttcat gttggtttat 3130
tttcacagat tggggtaacg tgcactgtaa gacgtatgta acatgatgtt aactttgtgg 3190
tctaaagtgt ttagctgtca agccggatgc ctaagtagac caaatcttgt tattgaagtg 3250
ttctgagctg tatcttgatg tttagaaaag tattcgttac atcttgtagg atctactttt 3310
tgaacttttc attccctgta gttgacaatt ctgcatgtac tagtcctcta gaaataggtt 3370
aaactgaagc aacttgatgg aaggatctct ccacagggct tgttttccaa agaaaagtat 3430
tgtttggagg agcaaagtta aaagcctacc taagcatatc gtaaagctgt tcaaaaataa 3490
ctcagaccca gtcttgtgga tggaaatgta gtgctcgagt cacattctgc ttaaagttgt 3550
aacaaataca gatgagttaa aagatattgt gtgacagtgt cttatttagg gggaaagggg 3610
agtatctgga tgacagttag tgccaaaatg taaaacatga ggcgctagca ggagatggtt 3670
aaacactagc tgctccaagg gttgacatgg tcttcccagc atgtactcag caggtgtggg 3730
gtggagcaca cgtaggcaca gaaaacagga atgcagacaa catgcatccc ctgcgtccat 3790
gagttacatg tgttctctta gtgtccacgt tgttttgatg ttattcatgg aataccttct 3850
gtgttaaata cagtcactta attccttggc cttaaaa 3887
<210> 46
<211> 854
<212> PRT
<213> 智人
<400> 46
Met Pro Pro Cys Ser Gly Gly Asp Gly Ser Thr Pro Pro Gly Pro Ser
1 5 10 15
Leu Arg Asp Arg Asp Cys Pro Ala Gln Ser Ala Glu Tyr Pro Arg Asp
20 25 30
Arg Leu Asp Pro Arg Pro Gly Ser Pro Ser Glu Ala Ser Ser Pro Pro
35 40 45
Phe Leu Arg Ser Arg Ala Pro Val Asn Trp Tyr Gln Glu Lys Ala Gln
50 55 60
Val Phe Leu Trp His Leu Met Val Ser Gly Ser Thr Thr Leu Leu Cys
65 70 75 80
Leu Trp Lys Gln Pro Phe His Val Ser Ala Phe Pro Val Thr Ala Ser
85 90 95
Leu Ala Phe Arg Gln Ser Gln Gly Ala Gly Gln His Leu Tyr Lys Asp
100 105 110
Leu Gln Pro Phe Ile Leu Leu Arg Leu Leu Met Pro Glu Glu Thr Gln
115 120 125
Thr Gln Asp Gln Pro Met Glu Glu Glu Glu Val Glu Thr Phe Ala Phe
130 135 140
Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile Asn Thr Phe Tyr
145 150 155 160
Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser Asn Ser Ser Asp
165 170 175
Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp Pro Ser Lys Leu
180 185 190
Asp Ser Gly Lys Glu Leu His Ile Asn Leu Ile Pro Asn Lys Gln Asp
195 200 205
Arg Thr Leu Thr Ile Val Asp Thr Gly Ile Gly Met Thr Lys Ala Asp
210 215 220
Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys Ser Gly Thr Lys Ala Phe
225 230 235 240
Met Glu Ala Leu Gln Ala Gly Ala Asp Ile Ser Met Ile Gly Gln Phe
245 250 255
Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val Ala Glu Lys Val Thr Val
260 265 270
Ile Thr Lys His Asn Asp Asp Glu Gln Tyr Ala Trp Glu Ser Ser Ala
275 280 285
Gly Gly Ser Phe Thr Val Arg Thr Asp Thr Gly Glu Pro Met Gly Arg
290 295 300
Gly Thr Lys Val Ile Leu His Leu Lys Glu Asp Gln Thr Glu Tyr Leu
305 310 315 320
Glu Glu Arg Arg Ile Lys Glu Ile Val Lys Lys His Ser Gln Phe Ile
325 330 335
Gly Tyr Pro Ile Thr Leu Phe Val Glu Lys Glu Arg Asp Lys Glu Val
340 345 350
Ser Asp Asp Glu Ala Glu Glu Lys Glu Asp Lys Glu Glu Glu Lys Glu
355 360 365
Lys Glu Glu Lys Glu Ser Glu Asp Lys Pro Glu Ile Glu Asp Val Gly
370 375 380
Ser Asp Glu Glu Glu Glu Lys Lys Asp Gly Asp Lys Lys Lys Lys Lys
385 390 395 400
Lys Ile Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu Asn Lys Thr Lys
405 410 415
Pro Ile Trp Thr Arg Asn Pro Asp Asp Ile Thr Asn Glu Glu Tyr Gly
420 425 430
Glu Phe Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala Val
435 440 445
Lys His Phe Ser Val Glu Gly Gln Leu Glu Phe Arg Ala Leu Leu Phe
450 455 460
Val Pro Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn Arg Lys Lys Lys
465 470 475 480
Asn Asn Ile Lys Leu Tyr Val Arg Arg Val Phe Ile Met Asp Asn Cys
485 490 495
Glu Glu Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg Gly Val Val Asp
500 505 510
Ser Glu Asp Leu Pro Leu Asn Ile Ser Arg Glu Met Leu Gln Gln Ser
515 520 525
Lys Ile Leu Lys Val Ile Arg Lys Asn Leu Val Lys Lys Cys Leu Glu
530 535 540
Leu Phe Thr Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys Lys Phe Tyr
545 550 555 560
Glu Gln Phe Ser Lys Asn Ile Lys Leu Gly Ile His Glu Asp Ser Gln
565 570 575
Asn Arg Lys Lys Leu Ser Glu Leu Leu Arg Tyr Tyr Thr Ser Ala Ser
580 585 590
Gly Asp Glu Met Val Ser Leu Lys Asp Tyr Cys Thr Arg Met Lys Glu
595 600 605
Asn Gln Lys His Ile Tyr Tyr Ile Thr Gly Glu Thr Lys Asp Gln Val
610 615 620
Ala Asn Ser Ala Phe Val Glu Arg Leu Arg Lys His Gly Leu Glu Val
625 630 635 640
Ile Tyr Met Ile Glu Pro Ile Asp Glu Tyr Cys Val Gln Gln Leu Lys
645 650 655
Glu Phe Glu Gly Lys Thr Leu Val Ser Val Thr Lys Glu Gly Leu Glu
660 665 670
Leu Pro Glu Asp Glu Glu Glu Lys Lys Lys Gln Glu Glu Lys Lys Thr
675 680 685
Lys Phe Glu Asn Leu Cys Lys Ile Met Lys Asp Ile Leu Glu Lys Lys
690 695 700
Val Glu Lys Val Val Val Ser Asn Arg Leu Val Thr Ser Pro Cys Cys
705 710 715 720
Ile Val Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met Glu Arg Ile Met
725 730 735
Lys Ala Gln Ala Leu Arg Asp Asn Ser Thr Met Gly Tyr Met Ala Ala
740 745 750
Lys Lys His Leu Glu Ile Asn Pro Asp His Ser Ile Ile Glu Thr Leu
755 760 765
Arg Gln Lys Ala Glu Ala Asp Lys Asn Asp Lys Ser Val Lys Asp Leu
770 775 780
Val Ile Leu Leu Tyr Glu Thr Ala Leu Leu Ser Ser Gly Phe Ser Leu
785 790 795 800
Glu Asp Pro Gln Thr His Ala Asn Arg Ile Tyr Arg Met Ile Lys Leu
805 810 815
Gly Leu Gly Ile Asp Glu Asp Asp Pro Thr Ala Asp Asp Thr Ser Ala
820 825 830
Ala Val Thr Glu Glu Met Pro Pro Leu Glu Gly Asp Asp Asp Thr Ser
835 840 845
Arg Met Glu Glu Val Asp
850
<210> 47
<211> 3366
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (191)..(2389)
<223> NM_005348 WT, CDS 191-2389
<400> 47
gcatgcgtag gcgcgcggcc gcggcggcgg ctggggaggg ttcttccgga aggttcggga 60
ggcttctgga aaaagcgccg cgcgctgggc gggcccgtcg ctatataagg caggcgcggg 120
ggtggcgcgt cagttgcttc agcgtcccgg tgtggctgtg ccgttggtcc tgtgcggtca 180
cttagccaag atg cct gag gaa acc cag acc caa gac caa ccg atg gag 229
Met Pro Glu Glu Thr Gln Thr Gln Asp Gln Pro Met Glu
1 5 10
gag gag gag gtt gag acg ttc gcc ttt cag gca gaa att gcc cag ttg 277
Glu Glu Glu Val Glu Thr Phe Ala Phe Gln Ala Glu Ile Ala Gln Leu
15 20 25
atg tca ttg atc atc aat act ttc tac tcg aac aaa gag atc ttt ctg 325
Met Ser Leu Ile Ile Asn Thr Phe Tyr Ser Asn Lys Glu Ile Phe Leu
30 35 40 45
aga gag ctc att tca aat tca tca gat gca ttg gac aaa atc cgg tat 373
Arg Glu Leu Ile Ser Asn Ser Ser Asp Ala Leu Asp Lys Ile Arg Tyr
50 55 60
gaa agc ttg aca gat ccc agt aaa tta gac tct ggg aaa gag ctg cat 421
Glu Ser Leu Thr Asp Pro Ser Lys Leu Asp Ser Gly Lys Glu Leu His
65 70 75
att aac ctt ata ccg aac aaa caa gat cga act ctc act att gtg gat 469
Ile Asn Leu Ile Pro Asn Lys Gln Asp Arg Thr Leu Thr Ile Val Asp
80 85 90
act gga att gga atg acc aag gct gac ttg atc aat aac ctt ggt act 517
Thr Gly Ile Gly Met Thr Lys Ala Asp Leu Ile Asn Asn Leu Gly Thr
95 100 105
atc gcc aag tct ggg acc aaa gcg ttc atg gaa gct ttg cag gct ggt 565
Ile Ala Lys Ser Gly Thr Lys Ala Phe Met Glu Ala Leu Gln Ala Gly
110 115 120 125
gca gat atc tct atg att ggc cag ttc ggt gtt ggt ttt tat tct gct 613
Ala Asp Ile Ser Met Ile Gly Gln Phe Gly Val Gly Phe Tyr Ser Ala
130 135 140
tat ttg gtt gct gag aaa gta act gtg atc acc aaa cat aac gat gat 661
Tyr Leu Val Ala Glu Lys Val Thr Val Ile Thr Lys His Asn Asp Asp
145 150 155
gag cag tac gct tgg gag tcc tca gca ggg gga tca ttc aca gtg agg 709
Glu Gln Tyr Ala Trp Glu Ser Ser Ala Gly Gly Ser Phe Thr Val Arg
160 165 170
aca gac aca ggt gaa cct atg ggt cgt gga aca aaa gtt atc cta cac 757
Thr Asp Thr Gly Glu Pro Met Gly Arg Gly Thr Lys Val Ile Leu His
175 180 185
ctg aaa gaa gac caa act gag tac ttg gag gaa cga aga ata aag gag 805
Leu Lys Glu Asp Gln Thr Glu Tyr Leu Glu Glu Arg Arg Ile Lys Glu
190 195 200 205
att gtg aag aaa cat tct cag ttt att gga tat ccc att act ctt ttt 853
Ile Val Lys Lys His Ser Gln Phe Ile Gly Tyr Pro Ile Thr Leu Phe
210 215 220
gtg gag aag gaa cgt gat aaa gaa gta agc gat gat gag gct gaa gaa 901
Val Glu Lys Glu Arg Asp Lys Glu Val Ser Asp Asp Glu Ala Glu Glu
225 230 235
aag gaa gac aaa gaa gaa gaa aaa gaa aaa gaa gag aaa gag tcg gaa 949
Lys Glu Asp Lys Glu Glu Glu Lys Glu Lys Glu Glu Lys Glu Ser Glu
240 245 250
gac aaa cct gaa att gaa gat gtt ggt tct gat gag gaa gaa gaa aag 997
Asp Lys Pro Glu Ile Glu Asp Val Gly Ser Asp Glu Glu Glu Glu Lys
255 260 265
aag gat ggt gac aag aag aag aag aag aag att aag gaa aag tac atc 1045
Lys Asp Gly Asp Lys Lys Lys Lys Lys Lys Ile Lys Glu Lys Tyr Ile
270 275 280 285
gat caa gaa gag ctc aac aaa aca aag ccc atc tgg acc aga aat ccc 1093
Asp Gln Glu Glu Leu Asn Lys Thr Lys Pro Ile Trp Thr Arg Asn Pro
290 295 300
gac gat att act aat gag gag tac gga gaa ttc tat aag agc ttg acc 1141
Asp Asp Ile Thr Asn Glu Glu Tyr Gly Glu Phe Tyr Lys Ser Leu Thr
305 310 315
aat gac tgg gaa gat cac ttg gca gtg aag cat ttt tca gtt gaa gga 1189
Asn Asp Trp Glu Asp His Leu Ala Val Lys His Phe Ser Val Glu Gly
320 325 330
cag ttg gaa ttc aga gcc ctt cta ttt gtc cca cga cgt gct cct ttt 1237
Gln Leu Glu Phe Arg Ala Leu Leu Phe Val Pro Arg Arg Ala Pro Phe
335 340 345
gat ctg ttt gaa aac aga aag aaa aag aac aac atc aaa ttg tat gta 1285
Asp Leu Phe Glu Asn Arg Lys Lys Lys Asn Asn Ile Lys Leu Tyr Val
350 355 360 365
cgc aga gtt ttc atc atg gat aac tgt gag gag cta atc cct gaa tat 1333
Arg Arg Val Phe Ile Met Asp Asn Cys Glu Glu Leu Ile Pro Glu Tyr
370 375 380
ctg aac ttc att aga ggg gtg gta gac tcg gag gat ctc cct cta aac 1381
Leu Asn Phe Ile Arg Gly Val Val Asp Ser Glu Asp Leu Pro Leu Asn
385 390 395
ata tcc cgt gag atg ttg caa caa agc aaa att ttg aaa gtt atc agg 1429
Ile Ser Arg Glu Met Leu Gln Gln Ser Lys Ile Leu Lys Val Ile Arg
400 405 410
aag aat ttg gtc aaa aaa tgc tta gaa ctc ttt act gaa ctg gcg gaa 1477
Lys Asn Leu Val Lys Lys Cys Leu Glu Leu Phe Thr Glu Leu Ala Glu
415 420 425
gat aaa gag aac tac aag aaa ttc tat gag cag ttc tct aaa aac ata 1525
Asp Lys Glu Asn Tyr Lys Lys Phe Tyr Glu Gln Phe Ser Lys Asn Ile
430 435 440 445
aag ctt gga ata cac gaa gac tct caa aat cgg aag aag ctt tca gag 1573
Lys Leu Gly Ile His Glu Asp Ser Gln Asn Arg Lys Lys Leu Ser Glu
450 455 460
ctg tta agg tac tac aca tct gcc tct ggt gat gag atg gtt tct ctc 1621
Leu Leu Arg Tyr Tyr Thr Ser Ala Ser Gly Asp Glu Met Val Ser Leu
465 470 475
aag gac tac tgc acc aga atg aag gag aac cag aaa cat atc tat tat 1669
Lys Asp Tyr Cys Thr Arg Met Lys Glu Asn Gln Lys His Ile Tyr Tyr
480 485 490
atc aca ggt gag acc aag gac cag gta gct aac tca gcc ttt gtg gaa 1717
Ile Thr Gly Glu Thr Lys Asp Gln Val Ala Asn Ser Ala Phe Val Glu
495 500 505
cgt ctt cgg aaa cat ggc tta gaa gtg atc tat atg att gag ccc att 1765
Arg Leu Arg Lys His Gly Leu Glu Val Ile Tyr Met Ile Glu Pro Ile
510 515 520 525
gat gag tac tgt gtc caa cag ctg aag gaa ttt gag ggg aag act tta 1813
Asp Glu Tyr Cys Val Gln Gln Leu Lys Glu Phe Glu Gly Lys Thr Leu
530 535 540
gtg tca gtc acc aaa gaa ggc ctg gaa ctt cca gag gat gaa gaa gag 1861
Val Ser Val Thr Lys Glu Gly Leu Glu Leu Pro Glu Asp Glu Glu Glu
545 550 555
aaa aag aag cag gaa gag aaa aaa aca aag ttt gag aac ctc tgc aaa 1909
Lys Lys Lys Gln Glu Glu Lys Lys Thr Lys Phe Glu Asn Leu Cys Lys
560 565 570
atc atg aaa gac ata ttg gag aaa aaa gtt gaa aag gtg gtt gtg tca 1957
Ile Met Lys Asp Ile Leu Glu Lys Lys Val Glu Lys Val Val Val Ser
575 580 585
aac cga ttg gtg aca tct cca tgc tgt att gtc aca agc aca tat ggc 2005
Asn Arg Leu Val Thr Ser Pro Cys Cys Ile Val Thr Ser Thr Tyr Gly
590 595 600 605
tgg aca gca aac atg gag aga atc atg aaa gct caa gcc cta aga gac 2053
Trp Thr Ala Asn Met Glu Arg Ile Met Lys Ala Gln Ala Leu Arg Asp
610 615 620
aac tca aca atg ggt tac atg gca gca aag aaa cac ctg gag ata aac 2101
Asn Ser Thr Met Gly Tyr Met Ala Ala Lys Lys His Leu Glu Ile Asn
625 630 635
cct gac cat tcc att att gag acc tta agg caa aag gca gag gct gat 2149
Pro Asp His Ser Ile Ile Glu Thr Leu Arg Gln Lys Ala Glu Ala Asp
640 645 650
aag aac gac aag tct gtg aag gat ctg gtc atc ttg ctt tat gaa act 2197
Lys Asn Asp Lys Ser Val Lys Asp Leu Val Ile Leu Leu Tyr Glu Thr
655 660 665
gcg ctc ctg tct tct ggc ttc agt ctg gaa gat ccc cag aca cat gct 2245
Ala Leu Leu Ser Ser Gly Phe Ser Leu Glu Asp Pro Gln Thr His Ala
670 675 680 685
aac agg atc tac agg atg atc aaa ctt ggt ctg ggt att gat gaa gat 2293
Asn Arg Ile Tyr Arg Met Ile Lys Leu Gly Leu Gly Ile Asp Glu Asp
690 695 700
gac cct act gct gat gat acc agt gct gct gta act gaa gaa atg cca 2341
Asp Pro Thr Ala Asp Asp Thr Ser Ala Ala Val Thr Glu Glu Met Pro
705 710 715
ccc ctt gaa gga gat gac gac aca tca cgc atg gaa gaa gta gac taa 2389
Pro Leu Glu Gly Asp Asp Asp Thr Ser Arg Met Glu Glu Val Asp
720 725 730
tctctggctg agggatgact tacctgttca gtactctaca attcctctga taatatattt 2449
tcaaggatgt ttttctttat ttttgttaat attaaaaagt ctgtatggca tgacaactac 2509
tttaagggga agataagatt tctgtctact aagtgatgct gtgatacctt aggcactaaa 2569
gcagagctag taatgctttt tgagtttcat gttggtttat tttcacagat tggggtaacg 2629
tgcactgtaa gacgtatgta acatgatgtt aactttgtgg tctaaagtgt ttagctgtca 2689
agccggatgc ctaagtagac caaatcttgt tattgaagtg ttctgagctg tatcttgatg 2749
tttagaaaag tattcgttac atcttgtagg atctactttt tgaacttttc attccctgta 2809
gttgacaatt ctgcatgtac tagtcctcta gaaataggtt aaactgaagc aacttgatgg 2869
aaggatctct ccacagggct tgttttccaa agaaaagtat tgtttggagg agcaaagtta 2929
aaagcctacc taagcatatc gtaaagctgt tcaaaaataa ctcagaccca gtcttgtgga 2989
tggaaatgta gtgctcgagt cacattctgc ttaaagttgt aacaaataca gatgagttaa 3049
aagatattgt gtgacagtgt cttatttagg gggaaagggg agtatctgga tgacagttag 3109
tgccaaaatg taaaacatga ggcgctagca ggagatggtt aaacactagc tgctccaagg 3169
gttgacatgg tcttcccagc atgtactcag caggtgtggg gtggagcaca cgtaggcaca 3229
gaaaacagga atgcagacaa catgcatccc ctgcgtccat gagttacatg tgttctctta 3289
gtgtccacgt tgttttgatg ttattcatgg aataccttct gtgttaaata cagtcactta 3349
attccttggc cttaaaa 3366
<210> 48
<211> 732
<212> PRT
<213> 智人
<400> 48
Met Pro Glu Glu Thr Gln Thr Gln Asp Gln Pro Met Glu Glu Glu Glu
1 5 10 15
Val Glu Thr Phe Ala Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu
20 25 30
Ile Ile Asn Thr Phe Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu
35 40 45
Ile Ser Asn Ser Ser Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu
50 55 60
Thr Asp Pro Ser Lys Leu Asp Ser Gly Lys Glu Leu His Ile Asn Leu
65 70 75 80
Ile Pro Asn Lys Gln Asp Arg Thr Leu Thr Ile Val Asp Thr Gly Ile
85 90 95
Gly Met Thr Lys Ala Asp Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys
100 105 110
Ser Gly Thr Lys Ala Phe Met Glu Ala Leu Gln Ala Gly Ala Asp Ile
115 120 125
Ser Met Ile Gly Gln Phe Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val
130 135 140
Ala Glu Lys Val Thr Val Ile Thr Lys His Asn Asp Asp Glu Gln Tyr
145 150 155 160
Ala Trp Glu Ser Ser Ala Gly Gly Ser Phe Thr Val Arg Thr Asp Thr
165 170 175
Gly Glu Pro Met Gly Arg Gly Thr Lys Val Ile Leu His Leu Lys Glu
180 185 190
Asp Gln Thr Glu Tyr Leu Glu Glu Arg Arg Ile Lys Glu Ile Val Lys
195 200 205
Lys His Ser Gln Phe Ile Gly Tyr Pro Ile Thr Leu Phe Val Glu Lys
210 215 220
Glu Arg Asp Lys Glu Val Ser Asp Asp Glu Ala Glu Glu Lys Glu Asp
225 230 235 240
Lys Glu Glu Glu Lys Glu Lys Glu Glu Lys Glu Ser Glu Asp Lys Pro
245 250 255
Glu Ile Glu Asp Val Gly Ser Asp Glu Glu Glu Glu Lys Lys Asp Gly
260 265 270
Asp Lys Lys Lys Lys Lys Lys Ile Lys Glu Lys Tyr Ile Asp Gln Glu
275 280 285
Glu Leu Asn Lys Thr Lys Pro Ile Trp Thr Arg Asn Pro Asp Asp Ile
290 295 300
Thr Asn Glu Glu Tyr Gly Glu Phe Tyr Lys Ser Leu Thr Asn Asp Trp
305 310 315 320
Glu Asp His Leu Ala Val Lys His Phe Ser Val Glu Gly Gln Leu Glu
325 330 335
Phe Arg Ala Leu Leu Phe Val Pro Arg Arg Ala Pro Phe Asp Leu Phe
340 345 350
Glu Asn Arg Lys Lys Lys Asn Asn Ile Lys Leu Tyr Val Arg Arg Val
355 360 365
Phe Ile Met Asp Asn Cys Glu Glu Leu Ile Pro Glu Tyr Leu Asn Phe
370 375 380
Ile Arg Gly Val Val Asp Ser Glu Asp Leu Pro Leu Asn Ile Ser Arg
385 390 395 400
Glu Met Leu Gln Gln Ser Lys Ile Leu Lys Val Ile Arg Lys Asn Leu
405 410 415
Val Lys Lys Cys Leu Glu Leu Phe Thr Glu Leu Ala Glu Asp Lys Glu
420 425 430
Asn Tyr Lys Lys Phe Tyr Glu Gln Phe Ser Lys Asn Ile Lys Leu Gly
435 440 445
Ile His Glu Asp Ser Gln Asn Arg Lys Lys Leu Ser Glu Leu Leu Arg
450 455 460
Tyr Tyr Thr Ser Ala Ser Gly Asp Glu Met Val Ser Leu Lys Asp Tyr
465 470 475 480
Cys Thr Arg Met Lys Glu Asn Gln Lys His Ile Tyr Tyr Ile Thr Gly
485 490 495
Glu Thr Lys Asp Gln Val Ala Asn Ser Ala Phe Val Glu Arg Leu Arg
500 505 510
Lys His Gly Leu Glu Val Ile Tyr Met Ile Glu Pro Ile Asp Glu Tyr
515 520 525
Cys Val Gln Gln Leu Lys Glu Phe Glu Gly Lys Thr Leu Val Ser Val
530 535 540
Thr Lys Glu Gly Leu Glu Leu Pro Glu Asp Glu Glu Glu Lys Lys Lys
545 550 555 560
Gln Glu Glu Lys Lys Thr Lys Phe Glu Asn Leu Cys Lys Ile Met Lys
565 570 575
Asp Ile Leu Glu Lys Lys Val Glu Lys Val Val Val Ser Asn Arg Leu
580 585 590
Val Thr Ser Pro Cys Cys Ile Val Thr Ser Thr Tyr Gly Trp Thr Ala
595 600 605
Asn Met Glu Arg Ile Met Lys Ala Gln Ala Leu Arg Asp Asn Ser Thr
610 615 620
Met Gly Tyr Met Ala Ala Lys Lys His Leu Glu Ile Asn Pro Asp His
625 630 635 640
Ser Ile Ile Glu Thr Leu Arg Gln Lys Ala Glu Ala Asp Lys Asn Asp
645 650 655
Lys Ser Val Lys Asp Leu Val Ile Leu Leu Tyr Glu Thr Ala Leu Leu
660 665 670
Ser Ser Gly Phe Ser Leu Glu Asp Pro Gln Thr His Ala Asn Arg Ile
675 680 685
Tyr Arg Met Ile Lys Leu Gly Leu Gly Ile Asp Glu Asp Asp Pro Thr
690 695 700
Ala Asp Asp Thr Ser Ala Ala Val Thr Glu Glu Met Pro Pro Leu Glu
705 710 715 720
Gly Asp Asp Asp Thr Ser Arg Met Glu Glu Val Asp
725 730
<210> 49
<211> 2792
<212> DNA
<213> 中国仓鼠
<220>
<221> CDS
<222> (28)..(2229)
<223> NM_001246821 WT, CDS 28-2229
<400> 49
cgtcccgtgc gcggtcactc agcgaag atg cct gag gaa acg cag acc caa gac 54
Met Pro Glu Glu Thr Gln Thr Gln Asp
1 5
cag cca atg gag gag gaa gag gtg gag acc ttt gcc ttt cag gca gag 102
Gln Pro Met Glu Glu Glu Glu Val Glu Thr Phe Ala Phe Gln Ala Glu
10 15 20 25
atc gcc cag ctg atg tcc ttg atc atc aac acc ttc tac tcc aac aaa 150
Ile Ala Gln Leu Met Ser Leu Ile Ile Asn Thr Phe Tyr Ser Asn Lys
30 35 40
gag atc ttt ctg agg gag ctc att tca aac tcg tca gat gct ctg gat 198
Glu Ile Phe Leu Arg Glu Leu Ile Ser Asn Ser Ser Asp Ala Leu Asp
45 50 55
aag atc aga tac gag agt ctg aca gac cct agt aaa tta gac tct ggg 246
Lys Ile Arg Tyr Glu Ser Leu Thr Asp Pro Ser Lys Leu Asp Ser Gly
60 65 70
aag gag ctg cac att aat att att ccc aac aaa caa gac cga acc ctt 294
Lys Glu Leu His Ile Asn Ile Ile Pro Asn Lys Gln Asp Arg Thr Leu
75 80 85
act atc gtg gat act gga att gga atg acc aag gcc gac ttg atc aat 342
Thr Ile Val Asp Thr Gly Ile Gly Met Thr Lys Ala Asp Leu Ile Asn
90 95 100 105
aac ctt ggt acc att gcc aag tct ggc acc aaa gcc ttc atg gag gct 390
Asn Leu Gly Thr Ile Ala Lys Ser Gly Thr Lys Ala Phe Met Glu Ala
110 115 120
ttg cag gct ggt gca gac atc tct atg att ggc cag ttt ggt gtt ggt 438
Leu Gln Ala Gly Ala Asp Ile Ser Met Ile Gly Gln Phe Gly Val Gly
125 130 135
ttt tac act gcg tat ttg gtt gcc gag aaa gtg act gtg atc acc aaa 486
Phe Tyr Thr Ala Tyr Leu Val Ala Glu Lys Val Thr Val Ile Thr Lys
140 145 150
cat aac gat gat gag cag tac gcc tgg gag tcc tca gcc ggg ggc tcc 534
His Asn Asp Asp Glu Gln Tyr Ala Trp Glu Ser Ser Ala Gly Gly Ser
155 160 165
ttc aca gtg agg act gac aca ggt gaa cca atg ggt cgt gga aca aag 582
Phe Thr Val Arg Thr Asp Thr Gly Glu Pro Met Gly Arg Gly Thr Lys
170 175 180 185
gtt atc tta cac ctg aaa gaa gac caa acg gag tat atg gag gaa agg 630
Val Ile Leu His Leu Lys Glu Asp Gln Thr Glu Tyr Met Glu Glu Arg
190 195 200
aga ata aag gag att gtg aag aaa cat tct caa ttt atc ggc tat ccc 678
Arg Ile Lys Glu Ile Val Lys Lys His Ser Gln Phe Ile Gly Tyr Pro
205 210 215
att act ctc ttc gtg gag aag gaa cgc gat aag gaa gtc agt gat gat 726
Ile Thr Leu Phe Val Glu Lys Glu Arg Asp Lys Glu Val Ser Asp Asp
220 225 230
gaa gct gaa gaa aaa gaa gat aaa gag gaa gag aag gaa aag gaa gaa 774
Glu Ala Glu Glu Lys Glu Asp Lys Glu Glu Glu Lys Glu Lys Glu Glu
235 240 245
aaa gga atc gac gac aaa cca gaa ata gaa gat gtg ggt tct gat gaa 822
Lys Gly Ile Asp Asp Lys Pro Glu Ile Glu Asp Val Gly Ser Asp Glu
250 255 260 265
gag gag gag gaa aag aag gat ggc gac aag aag aaa aag aag aag ata 870
Glu Glu Glu Glu Lys Lys Asp Gly Asp Lys Lys Lys Lys Lys Lys Ile
270 275 280
aag gag aag tac att gac caa gaa gag ctc aac aag aca aag cct att 918
Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu Asn Lys Thr Lys Pro Ile
285 290 295
tgg acc agg aat cct gat gac att act aat gaa gag tat gga gag ttc 966
Trp Thr Arg Asn Pro Asp Asp Ile Thr Asn Glu Glu Tyr Gly Glu Phe
300 305 310
tac aag agc tta acc aac gat tgg gaa gaa cat ttg gca gtg aag cat 1014
Tyr Lys Ser Leu Thr Asn Asp Trp Glu Glu His Leu Ala Val Lys His
315 320 325
ttt tct gtt gaa gga caa ttg gaa ttc cgg gcc ctt ctc ttt gtc cca 1062
Phe Ser Val Glu Gly Gln Leu Glu Phe Arg Ala Leu Leu Phe Val Pro
330 335 340 345
aga cgt gct cca ttt gat ctg ttt gaa aac aga aag aaa aag aac aac 1110
Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn Arg Lys Lys Lys Asn Asn
350 355 360
att aag ttg tat gtg cgc aga gtt ttc atc atg gat aac tgt gag gag 1158
Ile Lys Leu Tyr Val Arg Arg Val Phe Ile Met Asp Asn Cys Glu Glu
365 370 375
tta ttc cct gag tat cta aat ttc att aga gga gtg gtg gat tct gag 1206
Leu Phe Pro Glu Tyr Leu Asn Phe Ile Arg Gly Val Val Asp Ser Glu
380 385 390
gat ctt cct cta aat att tcc cgt gaa ata ttg cag caa agc aaa att 1254
Asp Leu Pro Leu Asn Ile Ser Arg Glu Ile Leu Gln Gln Ser Lys Ile
395 400 405
ttg aaa gtt atc aga aag aat ttg gtc agg aaa tgc tta gaa cta ttt 1302
Leu Lys Val Ile Arg Lys Asn Leu Val Arg Lys Cys Leu Glu Leu Phe
410 415 420 425
cat gaa ctg gca gaa gac aaa gag aac tac aaa aag ttt tat gag cag 1350
His Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys Lys Phe Tyr Glu Gln
430 435 440
ttc tct aaa aat ata aag ctt gga att cat gaa gac tct caa aat cgg 1398
Phe Ser Lys Asn Ile Lys Leu Gly Ile His Glu Asp Ser Gln Asn Arg
445 450 455
aag aag ctt tca gag ctg ttg cga tac tat aca tct gct tct gga gat 1446
Lys Lys Leu Ser Glu Leu Leu Arg Tyr Tyr Thr Ser Ala Ser Gly Asp
460 465 470
gag atg gtt tct ctc aag gac tat tgt acc aga atg aag gaa aac cag 1494
Glu Met Val Ser Leu Lys Asp Tyr Cys Thr Arg Met Lys Glu Asn Gln
475 480 485
aag cat atc tac ttc atc aca ggt gag acc aag gac caa gtt gct aac 1542
Lys His Ile Tyr Phe Ile Thr Gly Glu Thr Lys Asp Gln Val Ala Asn
490 495 500 505
tca gcc ttc gtg gaa cgt ctt cgg aag cat ggc tta gaa gta atc tat 1590
Ser Ala Phe Val Glu Arg Leu Arg Lys His Gly Leu Glu Val Ile Tyr
510 515 520
atg att gag ccc att gat gag tac tgt gtg caa cag ctg aag gag ttt 1638
Met Ile Glu Pro Ile Asp Glu Tyr Cys Val Gln Gln Leu Lys Glu Phe
525 530 535
gag ggc aag acc ttg gtg tct gtt acc aaa gaa gga ctg gaa ctt cca 1686
Glu Gly Lys Thr Leu Val Ser Val Thr Lys Glu Gly Leu Glu Leu Pro
540 545 550
gaa gat gaa gag gag aaa aag aaa cag gaa gag aaa aag acc aaa ttt 1734
Glu Asp Glu Glu Glu Lys Lys Lys Gln Glu Glu Lys Lys Thr Lys Phe
555 560 565
gaa aac ctc tgc aag att atg aaa gat att ttg gag aaa aaa gtt gag 1782
Glu Asn Leu Cys Lys Ile Met Lys Asp Ile Leu Glu Lys Lys Val Glu
570 575 580 585
aag gtg gtc gta tca aac cga ttg gtg acg tcc cct tgc tgt att gtc 1830
Lys Val Val Val Ser Asn Arg Leu Val Thr Ser Pro Cys Cys Ile Val
590 595 600
aca agc aca tac ggg tgg aca gca aac atg gag aga atc att aaa gct 1878
Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met Glu Arg Ile Ile Lys Ala
605 610 615
caa gct ctc aga gac aac tca acg atg ggt tac atg gca gca aag aaa 1926
Gln Ala Leu Arg Asp Asn Ser Thr Met Gly Tyr Met Ala Ala Lys Lys
620 625 630
cac ctg gag ata aac cct gat cac tcc att att gaa acc cta cga caa 1974
His Leu Glu Ile Asn Pro Asp His Ser Ile Ile Glu Thr Leu Arg Gln
635 640 645
aag gca gag gct gac aag aat gac aag tct gtg aag gat ctg gtg atc 2022
Lys Ala Glu Ala Asp Lys Asn Asp Lys Ser Val Lys Asp Leu Val Ile
650 655 660 665
ttg ctg tat gaa act gca ctc ctg tct tct ggt ttc agt ctg gaa gat 2070
Leu Leu Tyr Glu Thr Ala Leu Leu Ser Ser Gly Phe Ser Leu Glu Asp
670 675 680
ccc cag aca cat gct aac agg atc tac agg atg atc aag ctt ggt cta 2118
Pro Gln Thr His Ala Asn Arg Ile Tyr Arg Met Ile Lys Leu Gly Leu
685 690 695
ggt att gat gaa gat gat cct act gtg gat gat acc agt gct gct gta 2166
Gly Ile Asp Glu Asp Asp Pro Thr Val Asp Asp Thr Ser Ala Ala Val
700 705 710
act gaa gaa atg cca ccc ctg gaa gga gat gac gac aca tca cgc atg 2214
Thr Glu Glu Met Pro Pro Leu Glu Gly Asp Asp Asp Thr Ser Arg Met
715 720 725
gaa gaa gtc gac taa gcttcaccag agctatatgt ttgatgctta ctttcattcc 2269
Glu Glu Val Asp
730
ttctgataat atattttcaa ggatttttgt ttgatttttg ttaacattta aaacatctgt 2329
gtggcatgtt ttctaagggg aagaaaaatt tctttctact tgtgatactg tgatactcta 2389
ggcttgactc aacgggttgg tagtacattt gtgtaagaca aaatgtaacc tattaacttg 2449
tggtctgcag tgtttagctg ttgagctgat tccttagtag accaaatttg tcacttttgg 2509
aagtgttcta agatagcttc atgtttaaaa ggaaaaagat taagatgggc ctaagtttca 2569
tcttaaaatt ttcatcccct gtagttaatt ctgcatgtac tagtcttaga agtaaataca 2629
caagctaaaa caactgagga attccccatg tggcttgttt tcaaagtact gagaacaaaa 2689
ctaagcttcc ctaggtcttg taagtgagca aggcttgtga atggaaatat agtgcccaat 2749
cacattctgc tttaaaaggt aaatacagat gagataaaaa cct 2792
<210> 50
<211> 733
<212> PRT
<213> 中国仓鼠
<400> 50
Met Pro Glu Glu Thr Gln Thr Gln Asp Gln Pro Met Glu Glu Glu Glu
1 5 10 15
Val Glu Thr Phe Ala Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu
20 25 30
Ile Ile Asn Thr Phe Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu
35 40 45
Ile Ser Asn Ser Ser Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu
50 55 60
Thr Asp Pro Ser Lys Leu Asp Ser Gly Lys Glu Leu His Ile Asn Ile
65 70 75 80
Ile Pro Asn Lys Gln Asp Arg Thr Leu Thr Ile Val Asp Thr Gly Ile
85 90 95
Gly Met Thr Lys Ala Asp Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys
100 105 110
Ser Gly Thr Lys Ala Phe Met Glu Ala Leu Gln Ala Gly Ala Asp Ile
115 120 125
Ser Met Ile Gly Gln Phe Gly Val Gly Phe Tyr Thr Ala Tyr Leu Val
130 135 140
Ala Glu Lys Val Thr Val Ile Thr Lys His Asn Asp Asp Glu Gln Tyr
145 150 155 160
Ala Trp Glu Ser Ser Ala Gly Gly Ser Phe Thr Val Arg Thr Asp Thr
165 170 175
Gly Glu Pro Met Gly Arg Gly Thr Lys Val Ile Leu His Leu Lys Glu
180 185 190
Asp Gln Thr Glu Tyr Met Glu Glu Arg Arg Ile Lys Glu Ile Val Lys
195 200 205
Lys His Ser Gln Phe Ile Gly Tyr Pro Ile Thr Leu Phe Val Glu Lys
210 215 220
Glu Arg Asp Lys Glu Val Ser Asp Asp Glu Ala Glu Glu Lys Glu Asp
225 230 235 240
Lys Glu Glu Glu Lys Glu Lys Glu Glu Lys Gly Ile Asp Asp Lys Pro
245 250 255
Glu Ile Glu Asp Val Gly Ser Asp Glu Glu Glu Glu Glu Lys Lys Asp
260 265 270
Gly Asp Lys Lys Lys Lys Lys Lys Ile Lys Glu Lys Tyr Ile Asp Gln
275 280 285
Glu Glu Leu Asn Lys Thr Lys Pro Ile Trp Thr Arg Asn Pro Asp Asp
290 295 300
Ile Thr Asn Glu Glu Tyr Gly Glu Phe Tyr Lys Ser Leu Thr Asn Asp
305 310 315 320
Trp Glu Glu His Leu Ala Val Lys His Phe Ser Val Glu Gly Gln Leu
325 330 335
Glu Phe Arg Ala Leu Leu Phe Val Pro Arg Arg Ala Pro Phe Asp Leu
340 345 350
Phe Glu Asn Arg Lys Lys Lys Asn Asn Ile Lys Leu Tyr Val Arg Arg
355 360 365
Val Phe Ile Met Asp Asn Cys Glu Glu Leu Phe Pro Glu Tyr Leu Asn
370 375 380
Phe Ile Arg Gly Val Val Asp Ser Glu Asp Leu Pro Leu Asn Ile Ser
385 390 395 400
Arg Glu Ile Leu Gln Gln Ser Lys Ile Leu Lys Val Ile Arg Lys Asn
405 410 415
Leu Val Arg Lys Cys Leu Glu Leu Phe His Glu Leu Ala Glu Asp Lys
420 425 430
Glu Asn Tyr Lys Lys Phe Tyr Glu Gln Phe Ser Lys Asn Ile Lys Leu
435 440 445
Gly Ile His Glu Asp Ser Gln Asn Arg Lys Lys Leu Ser Glu Leu Leu
450 455 460
Arg Tyr Tyr Thr Ser Ala Ser Gly Asp Glu Met Val Ser Leu Lys Asp
465 470 475 480
Tyr Cys Thr Arg Met Lys Glu Asn Gln Lys His Ile Tyr Phe Ile Thr
485 490 495
Gly Glu Thr Lys Asp Gln Val Ala Asn Ser Ala Phe Val Glu Arg Leu
500 505 510
Arg Lys His Gly Leu Glu Val Ile Tyr Met Ile Glu Pro Ile Asp Glu
515 520 525
Tyr Cys Val Gln Gln Leu Lys Glu Phe Glu Gly Lys Thr Leu Val Ser
530 535 540
Val Thr Lys Glu Gly Leu Glu Leu Pro Glu Asp Glu Glu Glu Lys Lys
545 550 555 560
Lys Gln Glu Glu Lys Lys Thr Lys Phe Glu Asn Leu Cys Lys Ile Met
565 570 575
Lys Asp Ile Leu Glu Lys Lys Val Glu Lys Val Val Val Ser Asn Arg
580 585 590
Leu Val Thr Ser Pro Cys Cys Ile Val Thr Ser Thr Tyr Gly Trp Thr
595 600 605
Ala Asn Met Glu Arg Ile Ile Lys Ala Gln Ala Leu Arg Asp Asn Ser
610 615 620
Thr Met Gly Tyr Met Ala Ala Lys Lys His Leu Glu Ile Asn Pro Asp
625 630 635 640
His Ser Ile Ile Glu Thr Leu Arg Gln Lys Ala Glu Ala Asp Lys Asn
645 650 655
Asp Lys Ser Val Lys Asp Leu Val Ile Leu Leu Tyr Glu Thr Ala Leu
660 665 670
Leu Ser Ser Gly Phe Ser Leu Glu Asp Pro Gln Thr His Ala Asn Arg
675 680 685
Ile Tyr Arg Met Ile Lys Leu Gly Leu Gly Ile Asp Glu Asp Asp Pro
690 695 700
Thr Val Asp Asp Thr Ser Ala Ala Val Thr Glu Glu Met Pro Pro Leu
705 710 715 720
Glu Gly Asp Asp Asp Thr Ser Arg Met Glu Glu Val Asp
725 730
<210> 51
<211> 2525
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (96)..(2240)
<223> NM_001271972 WT, CDS 96-2240
<400> 51
ctctcgagtc actccggcgc agtgttggga ctgtctgggt atcggaaagc aagcctacgt 60
tgctcactat tacgtataat ccttttcttt tcaag atg cct gag gaa gtg cac 113
Met Pro Glu Glu Val His
1 5
cat gga gag gag gag gtg gag act ttt gcc ttt cag gca gaa att gcc 161
His Gly Glu Glu Glu Val Glu Thr Phe Ala Phe Gln Ala Glu Ile Ala
10 15 20
caa ctc atg tcc ctc atc atc aat acc ttc tat tcc aac aag gag att 209
Gln Leu Met Ser Leu Ile Ile Asn Thr Phe Tyr Ser Asn Lys Glu Ile
25 30 35
ttc ctt cgg gag ttg atc tct aat gct tct gat gcc ttg gac aag att 257
Phe Leu Arg Glu Leu Ile Ser Asn Ala Ser Asp Ala Leu Asp Lys Ile
40 45 50
cgc tat gag agc ctg aca gac cct tcg aag ttg gac agt ggt aaa gag 305
Arg Tyr Glu Ser Leu Thr Asp Pro Ser Lys Leu Asp Ser Gly Lys Glu
55 60 65 70
ctg aaa att gac atc atc ccc aac cct cag gaa cgt acc ctg act ttg 353
Leu Lys Ile Asp Ile Ile Pro Asn Pro Gln Glu Arg Thr Leu Thr Leu
75 80 85
gta gac aca ggc att ggc atg acc aaa gct gat ctc ata aat aat ttg 401
Val Asp Thr Gly Ile Gly Met Thr Lys Ala Asp Leu Ile Asn Asn Leu
90 95 100
gga acc att gcc aag tct ggt act aaa gca ttc atg gag gct ctt cag 449
Gly Thr Ile Ala Lys Ser Gly Thr Lys Ala Phe Met Glu Ala Leu Gln
105 110 115
ttt ggt gtt ggc ttt tat tct gcc tac ttg gtg gca gag aaa gtg gtt 497
Phe Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val Ala Glu Lys Val Val
120 125 130
gtg atc aca aag cac aac gat gat gaa cag tat gct tgg gag tct tct 545
Val Ile Thr Lys His Asn Asp Asp Glu Gln Tyr Ala Trp Glu Ser Ser
135 140 145 150
gct gga ggt tcc ttc act gtg cgt gct gac cat ggt gag ccc att ggc 593
Ala Gly Gly Ser Phe Thr Val Arg Ala Asp His Gly Glu Pro Ile Gly
155 160 165
agg ggt acc aaa gtg atc ctc cat ctt aaa gaa gat cag aca gag tac 641
Arg Gly Thr Lys Val Ile Leu His Leu Lys Glu Asp Gln Thr Glu Tyr
170 175 180
cta gaa gag agg cgg gtc aaa gaa gta gtg aag aag cat tct cag ttc 689
Leu Glu Glu Arg Arg Val Lys Glu Val Val Lys Lys His Ser Gln Phe
185 190 195
ata ggc tat ccc atc acc ctt tat ttg gag aag gaa cga gag aag gaa 737
Ile Gly Tyr Pro Ile Thr Leu Tyr Leu Glu Lys Glu Arg Glu Lys Glu
200 205 210
att agt gat gat gag gca gag gaa gag aaa ggt gag aaa gaa gag gaa 785
Ile Ser Asp Asp Glu Ala Glu Glu Glu Lys Gly Glu Lys Glu Glu Glu
215 220 225 230
gat aaa gat gat gaa gaa aaa ccc aag atc gaa gat gtg ggt tca gat 833
Asp Lys Asp Asp Glu Glu Lys Pro Lys Ile Glu Asp Val Gly Ser Asp
235 240 245
gag gag gat gac agc ggt aag gat aag aag aag aaa act aag aag atc 881
Glu Glu Asp Asp Ser Gly Lys Asp Lys Lys Lys Lys Thr Lys Lys Ile
250 255 260
aaa gag aaa tac att gat cag gaa gaa cta aac aag acc aag cct att 929
Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu Asn Lys Thr Lys Pro Ile
265 270 275
tgg acc aga aac cct gat gac atc acc caa gag gag tat gga gaa ttc 977
Trp Thr Arg Asn Pro Asp Asp Ile Thr Gln Glu Glu Tyr Gly Glu Phe
280 285 290
tac aag agc ctc act aat gac tgg gaa gac cac ttg gca gtc aag cac 1025
Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala Val Lys His
295 300 305 310
ttt tct gta gaa ggt cag ttg gaa ttc agg gca ttg cta ttt att cct 1073
Phe Ser Val Glu Gly Gln Leu Glu Phe Arg Ala Leu Leu Phe Ile Pro
315 320 325
cgt cgg gct ccc ttt gac ctt ttt gag aac aag aag aaa aag aac aac 1121
Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn Lys Lys Lys Lys Asn Asn
330 335 340
atc aaa ctc tat gtc cgc cgt gtg ttc atc atg gac agc tgt gat gag 1169
Ile Lys Leu Tyr Val Arg Arg Val Phe Ile Met Asp Ser Cys Asp Glu
345 350 355
ttg ata cca gag tat ctc aat ttt atc cgt ggt gtg gtt gac tct gag 1217
Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg Gly Val Val Asp Ser Glu
360 365 370
gat ctg ccc ctg aac atc tcc cga gaa atg ctc cag cag agc aaa atc 1265
Asp Leu Pro Leu Asn Ile Ser Arg Glu Met Leu Gln Gln Ser Lys Ile
375 380 385 390
ttg aaa gtc att cgc aaa aac att gtt aag aag tgc ctt gag ctc ttc 1313
Leu Lys Val Ile Arg Lys Asn Ile Val Lys Lys Cys Leu Glu Leu Phe
395 400 405
tct gag ctg gca gaa gac aag gag aat tac aag aaa ttc tat gag gca 1361
Ser Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys Lys Phe Tyr Glu Ala
410 415 420
ttc tct aaa aat ctc aag ctt gga atc cac gaa gac tcc act aac cgc 1409
Phe Ser Lys Asn Leu Lys Leu Gly Ile His Glu Asp Ser Thr Asn Arg
425 430 435
cgc cgc ctg tct gag ctg ctg cgc tat cat acc tcc cag tct gga gat 1457
Arg Arg Leu Ser Glu Leu Leu Arg Tyr His Thr Ser Gln Ser Gly Asp
440 445 450
gag atg aca tct ctg tca gag tat gtt tct cgc atg aag gag aca cag 1505
Glu Met Thr Ser Leu Ser Glu Tyr Val Ser Arg Met Lys Glu Thr Gln
455 460 465 470
aag tcc atc tat tac atc act ggt gag agc aaa gag cag gtg gcc aac 1553
Lys Ser Ile Tyr Tyr Ile Thr Gly Glu Ser Lys Glu Gln Val Ala Asn
475 480 485
tca gct ttt gtg gag cga gtg cgg aaa cgg ggc ttc gag gtg gta tat 1601
Ser Ala Phe Val Glu Arg Val Arg Lys Arg Gly Phe Glu Val Val Tyr
490 495 500
atg acc gag ccc att gac gag tac tgt gtg cag cag ctc aag gaa ttt 1649
Met Thr Glu Pro Ile Asp Glu Tyr Cys Val Gln Gln Leu Lys Glu Phe
505 510 515
gat ggg aag agc ctg gtc tca gtt acc aag gag ggt ctg gag ctg cct 1697
Asp Gly Lys Ser Leu Val Ser Val Thr Lys Glu Gly Leu Glu Leu Pro
520 525 530
gag gat gag gag gag aag aag aag atg gaa gag agc aag gca aag ttt 1745
Glu Asp Glu Glu Glu Lys Lys Lys Met Glu Glu Ser Lys Ala Lys Phe
535 540 545 550
gag aac ctc tgc aag ctc atg aaa gaa atc tta gat aag aag gtt gag 1793
Glu Asn Leu Cys Lys Leu Met Lys Glu Ile Leu Asp Lys Lys Val Glu
555 560 565
aag gtg aca atc tcc aat aga ctt gtg tct tca cct tgc tgc att gtg 1841
Lys Val Thr Ile Ser Asn Arg Leu Val Ser Ser Pro Cys Cys Ile Val
570 575 580
acc agc acc tac ggc tgg aca gcc aat atg gag cgg atc atg aaa gcc 1889
Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met Glu Arg Ile Met Lys Ala
585 590 595
cag gca ctt cgg gac aac tcc acc atg ggc tat atg atg gcc aaa aag 1937
Gln Ala Leu Arg Asp Asn Ser Thr Met Gly Tyr Met Met Ala Lys Lys
600 605 610
cac ctg gag atc aac cct gac cac ccc att gtg gag acg ctg cgg cag 1985
His Leu Glu Ile Asn Pro Asp His Pro Ile Val Glu Thr Leu Arg Gln
615 620 625 630
aag gct gag gcc gac aag aat gat aag gca gtt aag gac ctg gtg gtg 2033
Lys Ala Glu Ala Asp Lys Asn Asp Lys Ala Val Lys Asp Leu Val Val
635 640 645
ctg ctg ttt gaa acc gcc ctg cta tct tct ggc ttt tcc ctt gag gat 2081
Leu Leu Phe Glu Thr Ala Leu Leu Ser Ser Gly Phe Ser Leu Glu Asp
650 655 660
ccc cag acc cac tcc aac cgc atc tat cgc atg atc aag cta ggt cta 2129
Pro Gln Thr His Ser Asn Arg Ile Tyr Arg Met Ile Lys Leu Gly Leu
665 670 675
ggt att gat gaa gat gaa gtg gca gca gag gaa ccc aat gct gca gtt 2177
Gly Ile Asp Glu Asp Glu Val Ala Ala Glu Glu Pro Asn Ala Ala Val
680 685 690
cct gat gag atc ccc cct ctc gag ggc gat gag gat gcg tct cgc atg 2225
Pro Asp Glu Ile Pro Pro Leu Glu Gly Asp Glu Asp Ala Ser Arg Met
695 700 705 710
gaa gaa gtc gat tag gttaggagtt catagttgga aaacttgtgc ccttgtatag 2280
Glu Glu Val Asp
tgtccccatg ggctcccact gcagcctcga gtgcccctgt cccacctggc tccccctgct 2340
ggtgtctagt gtttttttcc ctctcctgtc cttgtgttga aggcagtaaa ctaagggtgt 2400
caagccccat tccctctcta ctcttgacag caggattgga tgttgtgtat tgtggtttat 2460
tttattttct tcattttgtt ctgaaattaa agtatgcaaa ataaagaata tgccgttttt 2520
ataca 2525
<210> 52
<211> 714
<212> PRT
<213> 智人
<400> 52
Met Pro Glu Glu Val His His Gly Glu Glu Glu Val Glu Thr Phe Ala
1 5 10 15
Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile Asn Thr Phe
20 25 30
Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser Asn Ala Ser
35 40 45
Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp Pro Ser Lys
50 55 60
Leu Asp Ser Gly Lys Glu Leu Lys Ile Asp Ile Ile Pro Asn Pro Gln
65 70 75 80
Glu Arg Thr Leu Thr Leu Val Asp Thr Gly Ile Gly Met Thr Lys Ala
85 90 95
Asp Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys Ser Gly Thr Lys Ala
100 105 110
Phe Met Glu Ala Leu Gln Phe Gly Val Gly Phe Tyr Ser Ala Tyr Leu
115 120 125
Val Ala Glu Lys Val Val Val Ile Thr Lys His Asn Asp Asp Glu Gln
130 135 140
Tyr Ala Trp Glu Ser Ser Ala Gly Gly Ser Phe Thr Val Arg Ala Asp
145 150 155 160
His Gly Glu Pro Ile Gly Arg Gly Thr Lys Val Ile Leu His Leu Lys
165 170 175
Glu Asp Gln Thr Glu Tyr Leu Glu Glu Arg Arg Val Lys Glu Val Val
180 185 190
Lys Lys His Ser Gln Phe Ile Gly Tyr Pro Ile Thr Leu Tyr Leu Glu
195 200 205
Lys Glu Arg Glu Lys Glu Ile Ser Asp Asp Glu Ala Glu Glu Glu Lys
210 215 220
Gly Glu Lys Glu Glu Glu Asp Lys Asp Asp Glu Glu Lys Pro Lys Ile
225 230 235 240
Glu Asp Val Gly Ser Asp Glu Glu Asp Asp Ser Gly Lys Asp Lys Lys
245 250 255
Lys Lys Thr Lys Lys Ile Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu
260 265 270
Asn Lys Thr Lys Pro Ile Trp Thr Arg Asn Pro Asp Asp Ile Thr Gln
275 280 285
Glu Glu Tyr Gly Glu Phe Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp
290 295 300
His Leu Ala Val Lys His Phe Ser Val Glu Gly Gln Leu Glu Phe Arg
305 310 315 320
Ala Leu Leu Phe Ile Pro Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn
325 330 335
Lys Lys Lys Lys Asn Asn Ile Lys Leu Tyr Val Arg Arg Val Phe Ile
340 345 350
Met Asp Ser Cys Asp Glu Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg
355 360 365
Gly Val Val Asp Ser Glu Asp Leu Pro Leu Asn Ile Ser Arg Glu Met
370 375 380
Leu Gln Gln Ser Lys Ile Leu Lys Val Ile Arg Lys Asn Ile Val Lys
385 390 395 400
Lys Cys Leu Glu Leu Phe Ser Glu Leu Ala Glu Asp Lys Glu Asn Tyr
405 410 415
Lys Lys Phe Tyr Glu Ala Phe Ser Lys Asn Leu Lys Leu Gly Ile His
420 425 430
Glu Asp Ser Thr Asn Arg Arg Arg Leu Ser Glu Leu Leu Arg Tyr His
435 440 445
Thr Ser Gln Ser Gly Asp Glu Met Thr Ser Leu Ser Glu Tyr Val Ser
450 455 460
Arg Met Lys Glu Thr Gln Lys Ser Ile Tyr Tyr Ile Thr Gly Glu Ser
465 470 475 480
Lys Glu Gln Val Ala Asn Ser Ala Phe Val Glu Arg Val Arg Lys Arg
485 490 495
Gly Phe Glu Val Val Tyr Met Thr Glu Pro Ile Asp Glu Tyr Cys Val
500 505 510
Gln Gln Leu Lys Glu Phe Asp Gly Lys Ser Leu Val Ser Val Thr Lys
515 520 525
Glu Gly Leu Glu Leu Pro Glu Asp Glu Glu Glu Lys Lys Lys Met Glu
530 535 540
Glu Ser Lys Ala Lys Phe Glu Asn Leu Cys Lys Leu Met Lys Glu Ile
545 550 555 560
Leu Asp Lys Lys Val Glu Lys Val Thr Ile Ser Asn Arg Leu Val Ser
565 570 575
Ser Pro Cys Cys Ile Val Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met
580 585 590
Glu Arg Ile Met Lys Ala Gln Ala Leu Arg Asp Asn Ser Thr Met Gly
595 600 605
Tyr Met Met Ala Lys Lys His Leu Glu Ile Asn Pro Asp His Pro Ile
610 615 620
Val Glu Thr Leu Arg Gln Lys Ala Glu Ala Asp Lys Asn Asp Lys Ala
625 630 635 640
Val Lys Asp Leu Val Val Leu Leu Phe Glu Thr Ala Leu Leu Ser Ser
645 650 655
Gly Phe Ser Leu Glu Asp Pro Gln Thr His Ser Asn Arg Ile Tyr Arg
660 665 670
Met Ile Lys Leu Gly Leu Gly Ile Asp Glu Asp Glu Val Ala Ala Glu
675 680 685
Glu Pro Asn Ala Ala Val Pro Asp Glu Ile Pro Pro Leu Glu Gly Asp
690 695 700
Glu Asp Ala Ser Arg Met Glu Glu Val Asp
705 710
<210> 53
<211> 2611
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (152)..(2326)
<223> NM_001271970 WT, CDS 152-2326
<400> 53
actctcagtc tgcaaaagtg tacgcccgca gagccgcccc aggtgcctgg gtgttgtgtg 60
attgacgcgg ggaaggaggg gtcagccgat ccctccccaa ccctccatcc catccctgag 120
gattgggctg gtacccgcgt ctctcggaca g atg cct gag gaa gtg cac cat 172
Met Pro Glu Glu Val His His
1 5
gga gag gag gag gtg gag act ttt gcc ttt cag gca gaa att gcc caa 220
Gly Glu Glu Glu Val Glu Thr Phe Ala Phe Gln Ala Glu Ile Ala Gln
10 15 20
ctc atg tcc ctc atc atc aat acc ttc tat tcc aac aag gag att ttc 268
Leu Met Ser Leu Ile Ile Asn Thr Phe Tyr Ser Asn Lys Glu Ile Phe
25 30 35
ctt cgg gag ttg atc tct aat gct tct gat gcc ttg gac aag att cgc 316
Leu Arg Glu Leu Ile Ser Asn Ala Ser Asp Ala Leu Asp Lys Ile Arg
40 45 50 55
tat gag agc ctg aca gac cct tcg aag ttg gac agt ggt aaa gag ctg 364
Tyr Glu Ser Leu Thr Asp Pro Ser Lys Leu Asp Ser Gly Lys Glu Leu
60 65 70
aaa att gac atc atc ccc aac cct cag gaa cgt acc ctg act ttg gta 412
Lys Ile Asp Ile Ile Pro Asn Pro Gln Glu Arg Thr Leu Thr Leu Val
75 80 85
gac aca ggc att ggc atg acc aaa gct gat ctc ata aat aat ttg gga 460
Asp Thr Gly Ile Gly Met Thr Lys Ala Asp Leu Ile Asn Asn Leu Gly
90 95 100
acc att gcc aag tct ggt act aaa gca ttc atg gag gct ctt cag gct 508
Thr Ile Ala Lys Ser Gly Thr Lys Ala Phe Met Glu Ala Leu Gln Ala
105 110 115
ggt gca gac atc tcc atg att ggg cag ttt ggt gtt ggc ttt tat tct 556
Gly Ala Asp Ile Ser Met Ile Gly Gln Phe Gly Val Gly Phe Tyr Ser
120 125 130 135
gcc tac ttg gtg gca gag aaa gtg gtt gtg atc aca aag cac aac gat 604
Ala Tyr Leu Val Ala Glu Lys Val Val Val Ile Thr Lys His Asn Asp
140 145 150
gat gaa cag tat gct tgg gag tct tct gct gga ggt tcc ttc act gtg 652
Asp Glu Gln Tyr Ala Trp Glu Ser Ser Ala Gly Gly Ser Phe Thr Val
155 160 165
cgt gct gac cat ggt gag ccc att ggc agg ggt acc aaa gtg atc ctc 700
Arg Ala Asp His Gly Glu Pro Ile Gly Arg Gly Thr Lys Val Ile Leu
170 175 180
cat ctt aaa gaa gat cag aca gag tac cta gaa gag agg cgg gtc aaa 748
His Leu Lys Glu Asp Gln Thr Glu Tyr Leu Glu Glu Arg Arg Val Lys
185 190 195
gaa gta gtg aag aag cat tct cag ttc ata ggc tat ccc atc acc ctt 796
Glu Val Val Lys Lys His Ser Gln Phe Ile Gly Tyr Pro Ile Thr Leu
200 205 210 215
tat ttg gag aag gaa cga gag aag gaa att agt gat gat gag gca gag 844
Tyr Leu Glu Lys Glu Arg Glu Lys Glu Ile Ser Asp Asp Glu Ala Glu
220 225 230
gaa gag aaa ggt gag aaa gaa gag gaa gat aaa gat gat gaa gaa aaa 892
Glu Glu Lys Gly Glu Lys Glu Glu Glu Asp Lys Asp Asp Glu Glu Lys
235 240 245
ccc aag atc gaa gat gtg ggt tca gat gag gag gat gac agc ggt aag 940
Pro Lys Ile Glu Asp Val Gly Ser Asp Glu Glu Asp Asp Ser Gly Lys
250 255 260
gat aag aag aag aaa act aag aag atc aaa gag aaa tac att gat cag 988
Asp Lys Lys Lys Lys Thr Lys Lys Ile Lys Glu Lys Tyr Ile Asp Gln
265 270 275
gaa gaa cta aac aag acc aag cct att tgg acc aga aac cct gat gac 1036
Glu Glu Leu Asn Lys Thr Lys Pro Ile Trp Thr Arg Asn Pro Asp Asp
280 285 290 295
atc acc caa gag gag tat gga gaa ttc tac aag agc ctc act aat gac 1084
Ile Thr Gln Glu Glu Tyr Gly Glu Phe Tyr Lys Ser Leu Thr Asn Asp
300 305 310
tgg gaa gac cac ttg gca gtc aag cac ttt tct gta gaa ggt cag ttg 1132
Trp Glu Asp His Leu Ala Val Lys His Phe Ser Val Glu Gly Gln Leu
315 320 325
gaa ttc agg gca ttg cta ttt att cct cgt cgg gct ccc ttt gac ctt 1180
Glu Phe Arg Ala Leu Leu Phe Ile Pro Arg Arg Ala Pro Phe Asp Leu
330 335 340
ttt gag aac aag aag aaa aag aac aac atc aaa ctc tat gtc cgc cgt 1228
Phe Glu Asn Lys Lys Lys Lys Asn Asn Ile Lys Leu Tyr Val Arg Arg
345 350 355
gtg ttc atc atg gac agc tgt gat gag ttg ata cca gag tat ctc aat 1276
Val Phe Ile Met Asp Ser Cys Asp Glu Leu Ile Pro Glu Tyr Leu Asn
360 365 370 375
ttt atc cgt ggt gtg gtt gac tct gag gat ctg ccc ctg aac atc tcc 1324
Phe Ile Arg Gly Val Val Asp Ser Glu Asp Leu Pro Leu Asn Ile Ser
380 385 390
cga gaa atg ctc cag cag agc aaa atc ttg aaa gtc att cgc aaa aac 1372
Arg Glu Met Leu Gln Gln Ser Lys Ile Leu Lys Val Ile Arg Lys Asn
395 400 405
att gtt aag aag tgc ctt gag ctc ttc tct gag ctg gca gaa gac aag 1420
Ile Val Lys Lys Cys Leu Glu Leu Phe Ser Glu Leu Ala Glu Asp Lys
410 415 420
gag aat tac aag aaa ttc tat gag gca ttc tct aaa aat ctc aag ctt 1468
Glu Asn Tyr Lys Lys Phe Tyr Glu Ala Phe Ser Lys Asn Leu Lys Leu
425 430 435
gga atc cac gaa gac tcc act aac cgc cgc cgc ctg tct gag ctg ctg 1516
Gly Ile His Glu Asp Ser Thr Asn Arg Arg Arg Leu Ser Glu Leu Leu
440 445 450 455
cgc tat cat acc tcc cag tct gga gat gag atg aca tct ctg tca gag 1564
Arg Tyr His Thr Ser Gln Ser Gly Asp Glu Met Thr Ser Leu Ser Glu
460 465 470
tat gtt tct cgc atg aag gag aca cag aag tcc atc tat tac atc act 1612
Tyr Val Ser Arg Met Lys Glu Thr Gln Lys Ser Ile Tyr Tyr Ile Thr
475 480 485
ggt gag agc aaa gag cag gtg gcc aac tca gct ttt gtg gag cga gtg 1660
Gly Glu Ser Lys Glu Gln Val Ala Asn Ser Ala Phe Val Glu Arg Val
490 495 500
cgg aaa cgg ggc ttc gag gtg gta tat atg acc gag ccc att gac gag 1708
Arg Lys Arg Gly Phe Glu Val Val Tyr Met Thr Glu Pro Ile Asp Glu
505 510 515
tac tgt gtg cag cag ctc aag gaa ttt gat ggg aag agc ctg gtc tca 1756
Tyr Cys Val Gln Gln Leu Lys Glu Phe Asp Gly Lys Ser Leu Val Ser
520 525 530 535
gtt acc aag gag ggt ctg gag ctg cct gag gat gag gag gag aag aag 1804
Val Thr Lys Glu Gly Leu Glu Leu Pro Glu Asp Glu Glu Glu Lys Lys
540 545 550
aag atg gaa gag agc aag gca aag ttt gag aac ctc tgc aag ctc atg 1852
Lys Met Glu Glu Ser Lys Ala Lys Phe Glu Asn Leu Cys Lys Leu Met
555 560 565
aaa gaa atc tta gat aag aag gtt gag aag gtg aca atc tcc aat aga 1900
Lys Glu Ile Leu Asp Lys Lys Val Glu Lys Val Thr Ile Ser Asn Arg
570 575 580
ctt gtg tct tca cct tgc tgc att gtg acc agc acc tac ggc tgg aca 1948
Leu Val Ser Ser Pro Cys Cys Ile Val Thr Ser Thr Tyr Gly Trp Thr
585 590 595
gcc aat atg gag cgg atc atg aaa gcc cag gca ctt cgg gac aac tcc 1996
Ala Asn Met Glu Arg Ile Met Lys Ala Gln Ala Leu Arg Asp Asn Ser
600 605 610 615
acc atg ggc tat atg atg gcc aaa aag cac ctg gag atc aac cct gac 2044
Thr Met Gly Tyr Met Met Ala Lys Lys His Leu Glu Ile Asn Pro Asp
620 625 630
cac ccc att gtg gag acg ctg cgg cag aag gct gag gcc gac aag aat 2092
His Pro Ile Val Glu Thr Leu Arg Gln Lys Ala Glu Ala Asp Lys Asn
635 640 645
gat aag gca gtt aag gac ctg gtg gtg ctg ctg ttt gaa acc gcc ctg 2140
Asp Lys Ala Val Lys Asp Leu Val Val Leu Leu Phe Glu Thr Ala Leu
650 655 660
cta tct tct ggc ttt tcc ctt gag gat ccc cag acc cac tcc aac cgc 2188
Leu Ser Ser Gly Phe Ser Leu Glu Asp Pro Gln Thr His Ser Asn Arg
665 670 675
atc tat cgc atg atc aag cta ggt cta ggt att gat gaa gat gaa gtg 2236
Ile Tyr Arg Met Ile Lys Leu Gly Leu Gly Ile Asp Glu Asp Glu Val
680 685 690 695
gca gca gag gaa ccc aat gct gca gtt cct gat gag atc ccc cct ctc 2284
Ala Ala Glu Glu Pro Asn Ala Ala Val Pro Asp Glu Ile Pro Pro Leu
700 705 710
gag ggc gat gag gat gcg tct cgc atg gaa gaa gtc gat tag 2326
Glu Gly Asp Glu Asp Ala Ser Arg Met Glu Glu Val Asp
715 720
gttaggagtt catagttgga aaacttgtgc ccttgtatag tgtccccatg ggctcccact 2386
gcagcctcga gtgcccctgt cccacctggc tccccctgct ggtgtctagt gtttttttcc 2446
ctctcctgtc cttgtgttga aggcagtaaa ctaagggtgt caagccccat tccctctcta 2506
ctcttgacag caggattgga tgttgtgtat tgtggtttat tttattttct tcattttgtt 2566
ctgaaattaa agtatgcaaa ataaagaata tgccgttttt ataca 2611
<210> 54
<211> 724
<212> PRT
<213> 智人
<400> 54
Met Pro Glu Glu Val His His Gly Glu Glu Glu Val Glu Thr Phe Ala
1 5 10 15
Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile Asn Thr Phe
20 25 30
Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser Asn Ala Ser
35 40 45
Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp Pro Ser Lys
50 55 60
Leu Asp Ser Gly Lys Glu Leu Lys Ile Asp Ile Ile Pro Asn Pro Gln
65 70 75 80
Glu Arg Thr Leu Thr Leu Val Asp Thr Gly Ile Gly Met Thr Lys Ala
85 90 95
Asp Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys Ser Gly Thr Lys Ala
100 105 110
Phe Met Glu Ala Leu Gln Ala Gly Ala Asp Ile Ser Met Ile Gly Gln
115 120 125
Phe Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val Ala Glu Lys Val Val
130 135 140
Val Ile Thr Lys His Asn Asp Asp Glu Gln Tyr Ala Trp Glu Ser Ser
145 150 155 160
Ala Gly Gly Ser Phe Thr Val Arg Ala Asp His Gly Glu Pro Ile Gly
165 170 175
Arg Gly Thr Lys Val Ile Leu His Leu Lys Glu Asp Gln Thr Glu Tyr
180 185 190
Leu Glu Glu Arg Arg Val Lys Glu Val Val Lys Lys His Ser Gln Phe
195 200 205
Ile Gly Tyr Pro Ile Thr Leu Tyr Leu Glu Lys Glu Arg Glu Lys Glu
210 215 220
Ile Ser Asp Asp Glu Ala Glu Glu Glu Lys Gly Glu Lys Glu Glu Glu
225 230 235 240
Asp Lys Asp Asp Glu Glu Lys Pro Lys Ile Glu Asp Val Gly Ser Asp
245 250 255
Glu Glu Asp Asp Ser Gly Lys Asp Lys Lys Lys Lys Thr Lys Lys Ile
260 265 270
Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu Asn Lys Thr Lys Pro Ile
275 280 285
Trp Thr Arg Asn Pro Asp Asp Ile Thr Gln Glu Glu Tyr Gly Glu Phe
290 295 300
Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala Val Lys His
305 310 315 320
Phe Ser Val Glu Gly Gln Leu Glu Phe Arg Ala Leu Leu Phe Ile Pro
325 330 335
Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn Lys Lys Lys Lys Asn Asn
340 345 350
Ile Lys Leu Tyr Val Arg Arg Val Phe Ile Met Asp Ser Cys Asp Glu
355 360 365
Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg Gly Val Val Asp Ser Glu
370 375 380
Asp Leu Pro Leu Asn Ile Ser Arg Glu Met Leu Gln Gln Ser Lys Ile
385 390 395 400
Leu Lys Val Ile Arg Lys Asn Ile Val Lys Lys Cys Leu Glu Leu Phe
405 410 415
Ser Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys Lys Phe Tyr Glu Ala
420 425 430
Phe Ser Lys Asn Leu Lys Leu Gly Ile His Glu Asp Ser Thr Asn Arg
435 440 445
Arg Arg Leu Ser Glu Leu Leu Arg Tyr His Thr Ser Gln Ser Gly Asp
450 455 460
Glu Met Thr Ser Leu Ser Glu Tyr Val Ser Arg Met Lys Glu Thr Gln
465 470 475 480
Lys Ser Ile Tyr Tyr Ile Thr Gly Glu Ser Lys Glu Gln Val Ala Asn
485 490 495
Ser Ala Phe Val Glu Arg Val Arg Lys Arg Gly Phe Glu Val Val Tyr
500 505 510
Met Thr Glu Pro Ile Asp Glu Tyr Cys Val Gln Gln Leu Lys Glu Phe
515 520 525
Asp Gly Lys Ser Leu Val Ser Val Thr Lys Glu Gly Leu Glu Leu Pro
530 535 540
Glu Asp Glu Glu Glu Lys Lys Lys Met Glu Glu Ser Lys Ala Lys Phe
545 550 555 560
Glu Asn Leu Cys Lys Leu Met Lys Glu Ile Leu Asp Lys Lys Val Glu
565 570 575
Lys Val Thr Ile Ser Asn Arg Leu Val Ser Ser Pro Cys Cys Ile Val
580 585 590
Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met Glu Arg Ile Met Lys Ala
595 600 605
Gln Ala Leu Arg Asp Asn Ser Thr Met Gly Tyr Met Met Ala Lys Lys
610 615 620
His Leu Glu Ile Asn Pro Asp His Pro Ile Val Glu Thr Leu Arg Gln
625 630 635 640
Lys Ala Glu Ala Asp Lys Asn Asp Lys Ala Val Lys Asp Leu Val Val
645 650 655
Leu Leu Phe Glu Thr Ala Leu Leu Ser Ser Gly Phe Ser Leu Glu Asp
660 665 670
Pro Gln Thr His Ser Asn Arg Ile Tyr Arg Met Ile Lys Leu Gly Leu
675 680 685
Gly Ile Asp Glu Asp Glu Val Ala Ala Glu Glu Pro Asn Ala Ala Val
690 695 700
Pro Asp Glu Ile Pro Pro Leu Glu Gly Asp Glu Asp Ala Ser Arg Met
705 710 715 720
Glu Glu Val Asp
<210> 55
<211> 2411
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (96)..(2126)
<223> NM_001271971 WT, CDS 96-2126
<400> 55
ctctcgagtc actccggcgc agtgttggga ctgtctgggt atcggaaagc aagcctacgt 60
tgctcactat tacgtataat ccttttcttt tcaag atg cct gag gaa gtg cac 113
Met Pro Glu Glu Val His
1 5
cat gga gag gag gag gtg gag act ttt gcc ttt cag gca gaa att gcc 161
His Gly Glu Glu Glu Val Glu Thr Phe Ala Phe Gln Ala Glu Ile Ala
10 15 20
caa ctc atg tcc ctc atc atc aat acc ttc tat tcc aac aag gag att 209
Gln Leu Met Ser Leu Ile Ile Asn Thr Phe Tyr Ser Asn Lys Glu Ile
25 30 35
ttc ctt cgg gag ttg atc tct aat gct tct gat gcc ttg gac aag att 257
Phe Leu Arg Glu Leu Ile Ser Asn Ala Ser Asp Ala Leu Asp Lys Ile
40 45 50
cgc tat gag agc ctg aca gac cct tcg aag ttg gac agt ggt aaa gag 305
Arg Tyr Glu Ser Leu Thr Asp Pro Ser Lys Leu Asp Ser Gly Lys Glu
55 60 65 70
ctg aaa att gac atc tcc atg att ggg cag ttt ggt gtt ggc ttt tat 353
Leu Lys Ile Asp Ile Ser Met Ile Gly Gln Phe Gly Val Gly Phe Tyr
75 80 85
tct gcc tac ttg gtg gca gag aaa gtg gtt gtg atc aca aag cac aac 401
Ser Ala Tyr Leu Val Ala Glu Lys Val Val Val Ile Thr Lys His Asn
90 95 100
gat gat gaa cag tat gct tgg gag tct tct gct gga ggt tcc ttc act 449
Asp Asp Glu Gln Tyr Ala Trp Glu Ser Ser Ala Gly Gly Ser Phe Thr
105 110 115
gtg cgt gct gac cat ggt gag ccc att ggc agg ggt acc aaa gtg atc 497
Val Arg Ala Asp His Gly Glu Pro Ile Gly Arg Gly Thr Lys Val Ile
120 125 130
ctc cat ctt aaa gaa gat cag aca gag tac cta gaa gag agg cgg gtc 545
Leu His Leu Lys Glu Asp Gln Thr Glu Tyr Leu Glu Glu Arg Arg Val
135 140 145 150
aaa gaa gta gtg aag aag cat tct cag ttc ata ggc tat ccc atc acc 593
Lys Glu Val Val Lys Lys His Ser Gln Phe Ile Gly Tyr Pro Ile Thr
155 160 165
ctt tat ttg gag aag gaa cga gag aag gaa att agt gat gat gag gca 641
Leu Tyr Leu Glu Lys Glu Arg Glu Lys Glu Ile Ser Asp Asp Glu Ala
170 175 180
gag gaa gag aaa ggt gag aaa gaa gag gaa gat aaa gat gat gaa gaa 689
Glu Glu Glu Lys Gly Glu Lys Glu Glu Glu Asp Lys Asp Asp Glu Glu
185 190 195
aaa ccc aag atc gaa gat gtg ggt tca gat gag gag gat gac agc ggt 737
Lys Pro Lys Ile Glu Asp Val Gly Ser Asp Glu Glu Asp Asp Ser Gly
200 205 210
aag gat aag aag aag aaa act aag aag atc aaa gag aaa tac att gat 785
Lys Asp Lys Lys Lys Lys Thr Lys Lys Ile Lys Glu Lys Tyr Ile Asp
215 220 225 230
cag gaa gaa cta aac aag acc aag cct att tgg acc aga aac cct gat 833
Gln Glu Glu Leu Asn Lys Thr Lys Pro Ile Trp Thr Arg Asn Pro Asp
235 240 245
gac atc acc caa gag gag tat gga gaa ttc tac aag agc ctc act aat 881
Asp Ile Thr Gln Glu Glu Tyr Gly Glu Phe Tyr Lys Ser Leu Thr Asn
250 255 260
gac tgg gaa gac cac ttg gca gtc aag cac ttt tct gta gaa ggt cag 929
Asp Trp Glu Asp His Leu Ala Val Lys His Phe Ser Val Glu Gly Gln
265 270 275
ttg gaa ttc agg gca ttg cta ttt att cct cgt cgg gct ccc ttt gac 977
Leu Glu Phe Arg Ala Leu Leu Phe Ile Pro Arg Arg Ala Pro Phe Asp
280 285 290
ctt ttt gag aac aag aag aaa aag aac aac atc aaa ctc tat gtc cgc 1025
Leu Phe Glu Asn Lys Lys Lys Lys Asn Asn Ile Lys Leu Tyr Val Arg
295 300 305 310
cgt gtg ttc atc atg gac agc tgt gat gag ttg ata cca gag tat ctc 1073
Arg Val Phe Ile Met Asp Ser Cys Asp Glu Leu Ile Pro Glu Tyr Leu
315 320 325
aat ttt atc cgt ggt gtg gtt gac tct gag gat ctg ccc ctg aac atc 1121
Asn Phe Ile Arg Gly Val Val Asp Ser Glu Asp Leu Pro Leu Asn Ile
330 335 340
tcc cga gaa atg ctc cag cag agc aaa atc ttg aaa gtc att cgc aaa 1169
Ser Arg Glu Met Leu Gln Gln Ser Lys Ile Leu Lys Val Ile Arg Lys
345 350 355
aac att gtt aag aag tgc ctt gag ctc ttc tct gag ctg gca gaa gac 1217
Asn Ile Val Lys Lys Cys Leu Glu Leu Phe Ser Glu Leu Ala Glu Asp
360 365 370
aag gag aat tac aag aaa ttc tat gag gca ttc tct aaa aat ctc aag 1265
Lys Glu Asn Tyr Lys Lys Phe Tyr Glu Ala Phe Ser Lys Asn Leu Lys
375 380 385 390
ctt gga atc cac gaa gac tcc act aac cgc cgc cgc ctg tct gag ctg 1313
Leu Gly Ile His Glu Asp Ser Thr Asn Arg Arg Arg Leu Ser Glu Leu
395 400 405
ctg cgc tat cat acc tcc cag tct gga gat gag atg aca tct ctg tca 1361
Leu Arg Tyr His Thr Ser Gln Ser Gly Asp Glu Met Thr Ser Leu Ser
410 415 420
gag tat gtt tct cgc atg aag gag aca cag aag tcc atc tat tac atc 1409
Glu Tyr Val Ser Arg Met Lys Glu Thr Gln Lys Ser Ile Tyr Tyr Ile
425 430 435
act ggt gag agc aaa gag cag gtg gcc aac tca gct ttt gtg gag cga 1457
Thr Gly Glu Ser Lys Glu Gln Val Ala Asn Ser Ala Phe Val Glu Arg
440 445 450
gtg cgg aaa cgg ggc ttc gag gtg gta tat atg acc gag ccc att gac 1505
Val Arg Lys Arg Gly Phe Glu Val Val Tyr Met Thr Glu Pro Ile Asp
455 460 465 470
gag tac tgt gtg cag cag ctc aag gaa ttt gat ggg aag agc ctg gtc 1553
Glu Tyr Cys Val Gln Gln Leu Lys Glu Phe Asp Gly Lys Ser Leu Val
475 480 485
tca gtt acc aag gag ggt ctg gag ctg cct gag gat gag gag gag aag 1601
Ser Val Thr Lys Glu Gly Leu Glu Leu Pro Glu Asp Glu Glu Glu Lys
490 495 500
aag aag atg gaa gag agc aag gca aag ttt gag aac ctc tgc aag ctc 1649
Lys Lys Met Glu Glu Ser Lys Ala Lys Phe Glu Asn Leu Cys Lys Leu
505 510 515
atg aaa gaa atc tta gat aag aag gtt gag aag gtg aca atc tcc aat 1697
Met Lys Glu Ile Leu Asp Lys Lys Val Glu Lys Val Thr Ile Ser Asn
520 525 530
aga ctt gtg tct tca cct tgc tgc att gtg acc agc acc tac ggc tgg 1745
Arg Leu Val Ser Ser Pro Cys Cys Ile Val Thr Ser Thr Tyr Gly Trp
535 540 545 550
aca gcc aat atg gag cgg atc atg aaa gcc cag gca ctt cgg gac aac 1793
Thr Ala Asn Met Glu Arg Ile Met Lys Ala Gln Ala Leu Arg Asp Asn
555 560 565
tcc acc atg ggc tat atg atg gcc aaa aag cac ctg gag atc aac cct 1841
Ser Thr Met Gly Tyr Met Met Ala Lys Lys His Leu Glu Ile Asn Pro
570 575 580
gac cac ccc att gtg gag acg ctg cgg cag aag gct gag gcc gac aag 1889
Asp His Pro Ile Val Glu Thr Leu Arg Gln Lys Ala Glu Ala Asp Lys
585 590 595
aat gat aag gca gtt aag gac ctg gtg gtg ctg ctg ttt gaa acc gcc 1937
Asn Asp Lys Ala Val Lys Asp Leu Val Val Leu Leu Phe Glu Thr Ala
600 605 610
ctg cta tct tct ggc ttt tcc ctt gag gat ccc cag acc cac tcc aac 1985
Leu Leu Ser Ser Gly Phe Ser Leu Glu Asp Pro Gln Thr His Ser Asn
615 620 625 630
cgc atc tat cgc atg atc aag cta ggt cta ggt att gat gaa gat gaa 2033
Arg Ile Tyr Arg Met Ile Lys Leu Gly Leu Gly Ile Asp Glu Asp Glu
635 640 645
gtg gca gca gag gaa ccc aat gct gca gtt cct gat gag atc ccc cct 2081
Val Ala Ala Glu Glu Pro Asn Ala Ala Val Pro Asp Glu Ile Pro Pro
650 655 660
ctc gag ggc gat gag gat gcg tct cgc atg gaa gaa gtc gat tag 2126
Leu Glu Gly Asp Glu Asp Ala Ser Arg Met Glu Glu Val Asp
665 670 675
gttaggagtt catagttgga aaacttgtgc ccttgtatag tgtccccatg ggctcccact 2186
gcagcctcga gtgcccctgt cccacctggc tccccctgct ggtgtctagt gtttttttcc 2246
ctctcctgtc cttgtgttga aggcagtaaa ctaagggtgt caagccccat tccctctcta 2306
ctcttgacag caggattgga tgttgtgtat tgtggtttat tttattttct tcattttgtt 2366
ctgaaattaa agtatgcaaa ataaagaata tgccgttttt ataca 2411
<210> 56
<211> 676
<212> PRT
<213> 智人
<400> 56
Met Pro Glu Glu Val His His Gly Glu Glu Glu Val Glu Thr Phe Ala
1 5 10 15
Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile Asn Thr Phe
20 25 30
Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser Asn Ala Ser
35 40 45
Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp Pro Ser Lys
50 55 60
Leu Asp Ser Gly Lys Glu Leu Lys Ile Asp Ile Ser Met Ile Gly Gln
65 70 75 80
Phe Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val Ala Glu Lys Val Val
85 90 95
Val Ile Thr Lys His Asn Asp Asp Glu Gln Tyr Ala Trp Glu Ser Ser
100 105 110
Ala Gly Gly Ser Phe Thr Val Arg Ala Asp His Gly Glu Pro Ile Gly
115 120 125
Arg Gly Thr Lys Val Ile Leu His Leu Lys Glu Asp Gln Thr Glu Tyr
130 135 140
Leu Glu Glu Arg Arg Val Lys Glu Val Val Lys Lys His Ser Gln Phe
145 150 155 160
Ile Gly Tyr Pro Ile Thr Leu Tyr Leu Glu Lys Glu Arg Glu Lys Glu
165 170 175
Ile Ser Asp Asp Glu Ala Glu Glu Glu Lys Gly Glu Lys Glu Glu Glu
180 185 190
Asp Lys Asp Asp Glu Glu Lys Pro Lys Ile Glu Asp Val Gly Ser Asp
195 200 205
Glu Glu Asp Asp Ser Gly Lys Asp Lys Lys Lys Lys Thr Lys Lys Ile
210 215 220
Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu Asn Lys Thr Lys Pro Ile
225 230 235 240
Trp Thr Arg Asn Pro Asp Asp Ile Thr Gln Glu Glu Tyr Gly Glu Phe
245 250 255
Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala Val Lys His
260 265 270
Phe Ser Val Glu Gly Gln Leu Glu Phe Arg Ala Leu Leu Phe Ile Pro
275 280 285
Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn Lys Lys Lys Lys Asn Asn
290 295 300
Ile Lys Leu Tyr Val Arg Arg Val Phe Ile Met Asp Ser Cys Asp Glu
305 310 315 320
Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg Gly Val Val Asp Ser Glu
325 330 335
Asp Leu Pro Leu Asn Ile Ser Arg Glu Met Leu Gln Gln Ser Lys Ile
340 345 350
Leu Lys Val Ile Arg Lys Asn Ile Val Lys Lys Cys Leu Glu Leu Phe
355 360 365
Ser Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys Lys Phe Tyr Glu Ala
370 375 380
Phe Ser Lys Asn Leu Lys Leu Gly Ile His Glu Asp Ser Thr Asn Arg
385 390 395 400
Arg Arg Leu Ser Glu Leu Leu Arg Tyr His Thr Ser Gln Ser Gly Asp
405 410 415
Glu Met Thr Ser Leu Ser Glu Tyr Val Ser Arg Met Lys Glu Thr Gln
420 425 430
Lys Ser Ile Tyr Tyr Ile Thr Gly Glu Ser Lys Glu Gln Val Ala Asn
435 440 445
Ser Ala Phe Val Glu Arg Val Arg Lys Arg Gly Phe Glu Val Val Tyr
450 455 460
Met Thr Glu Pro Ile Asp Glu Tyr Cys Val Gln Gln Leu Lys Glu Phe
465 470 475 480
Asp Gly Lys Ser Leu Val Ser Val Thr Lys Glu Gly Leu Glu Leu Pro
485 490 495
Glu Asp Glu Glu Glu Lys Lys Lys Met Glu Glu Ser Lys Ala Lys Phe
500 505 510
Glu Asn Leu Cys Lys Leu Met Lys Glu Ile Leu Asp Lys Lys Val Glu
515 520 525
Lys Val Thr Ile Ser Asn Arg Leu Val Ser Ser Pro Cys Cys Ile Val
530 535 540
Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met Glu Arg Ile Met Lys Ala
545 550 555 560
Gln Ala Leu Arg Asp Asn Ser Thr Met Gly Tyr Met Met Ala Lys Lys
565 570 575
His Leu Glu Ile Asn Pro Asp His Pro Ile Val Glu Thr Leu Arg Gln
580 585 590
Lys Ala Glu Ala Asp Lys Asn Asp Lys Ala Val Lys Asp Leu Val Val
595 600 605
Leu Leu Phe Glu Thr Ala Leu Leu Ser Ser Gly Phe Ser Leu Glu Asp
610 615 620
Pro Gln Thr His Ser Asn Arg Ile Tyr Arg Met Ile Lys Leu Gly Leu
625 630 635 640
Gly Ile Asp Glu Asp Glu Val Ala Ala Glu Glu Pro Asn Ala Ala Val
645 650 655
Pro Asp Glu Ile Pro Pro Leu Glu Gly Asp Glu Asp Ala Ser Arg Met
660 665 670
Glu Glu Val Asp
675
<210> 57
<211> 2414
<212> DNA
<213> 中国仓鼠
<220>
<221> CDS
<222> (30)..(2204)
<223> XM_003501668.2 WT, CDS 30-2204
<400> 57
ttagtaatta atgtgtaatg ctttcttag atg cct gag gag gtg cac cat ggc 53
Met Pro Glu Glu Val His His Gly
1 5
gag gaa gag gtg gag acc ttt gcc ttc cag gca gaa atc gcc cag ctc 101
Glu Glu Glu Val Glu Thr Phe Ala Phe Gln Ala Glu Ile Ala Gln Leu
10 15 20
atg tcc ttg atc ata aat act ttc tac tca aac aag gag att ttc ctt 149
Met Ser Leu Ile Ile Asn Thr Phe Tyr Ser Asn Lys Glu Ile Phe Leu
25 30 35 40
cga gaa ttg atc tcc aat gct tct gat gcc ttg gac aag att cgc tat 197
Arg Glu Leu Ile Ser Asn Ala Ser Asp Ala Leu Asp Lys Ile Arg Tyr
45 50 55
gag agc ctg aca gac cct tcc aaa ttg gac agc ggc aaa gag ctg aag 245
Glu Ser Leu Thr Asp Pro Ser Lys Leu Asp Ser Gly Lys Glu Leu Lys
60 65 70
att gac atc atc ccc aac cct cag gag cgc acg ctg act ttg gtg gac 293
Ile Asp Ile Ile Pro Asn Pro Gln Glu Arg Thr Leu Thr Leu Val Asp
75 80 85
acg ggc att ggc atg acc aaa gct gat ctc ata aat aac ttg gga acc 341
Thr Gly Ile Gly Met Thr Lys Ala Asp Leu Ile Asn Asn Leu Gly Thr
90 95 100
att gct aag tct ggc aca aag gct ttc atg gag gct ctc cag gct ggt 389
Ile Ala Lys Ser Gly Thr Lys Ala Phe Met Glu Ala Leu Gln Ala Gly
105 110 115 120
gca gac ata tcc atg att ggg cag ttt ggt gtt gga ttc tac tct gcc 437
Ala Asp Ile Ser Met Ile Gly Gln Phe Gly Val Gly Phe Tyr Ser Ala
125 130 135
tat ctc gtg gca gag aaa gtg gtt gtg atc aca aag cac aat gat gac 485
Tyr Leu Val Ala Glu Lys Val Val Val Ile Thr Lys His Asn Asp Asp
140 145 150
gag cag tat gct tgg gag tcc tct gct ggt gga tcc ttc aca gtg cgt 533
Glu Gln Tyr Ala Trp Glu Ser Ser Ala Gly Gly Ser Phe Thr Val Arg
155 160 165
gca gac cat ggt gag ccc att ggc cgg ggt acc aaa gtc atc ctt cat 581
Ala Asp His Gly Glu Pro Ile Gly Arg Gly Thr Lys Val Ile Leu His
170 175 180
ctc aaa gaa gac cag aca gag tac tta gag gag agg agg gtc aag gaa 629
Leu Lys Glu Asp Gln Thr Glu Tyr Leu Glu Glu Arg Arg Val Lys Glu
185 190 195 200
gtg gtg aag aaa cac tcg cag ttc ata ggc tat ccc atc acc ctc tat 677
Val Val Lys Lys His Ser Gln Phe Ile Gly Tyr Pro Ile Thr Leu Tyr
205 210 215
ttg gag aag gaa cga gag aag gag atc agt gat gat gag gca gaa gaa 725
Leu Glu Lys Glu Arg Glu Lys Glu Ile Ser Asp Asp Glu Ala Glu Glu
220 225 230
gag aag ggt gag aaa gag gaa gaa gat aag gat gat gag gaa aag cca 773
Glu Lys Gly Glu Lys Glu Glu Glu Asp Lys Asp Asp Glu Glu Lys Pro
235 240 245
aag att gaa gat gta gga tca gat gag gag gat gac agt ggc aaa gat 821
Lys Ile Glu Asp Val Gly Ser Asp Glu Glu Asp Asp Ser Gly Lys Asp
250 255 260
aag aaa aag aaa acg aag aag att aag gag aaa tac att gat cag gaa 869
Lys Lys Lys Lys Thr Lys Lys Ile Lys Glu Lys Tyr Ile Asp Gln Glu
265 270 275 280
gag ttg aat aag act aag ccc att tgg acc aga aac cct gat gac atc 917
Glu Leu Asn Lys Thr Lys Pro Ile Trp Thr Arg Asn Pro Asp Asp Ile
285 290 295
act caa gaa gaa tat ggt gat ttc tat aag agc ctc acc aat gat tgg 965
Thr Gln Glu Glu Tyr Gly Asp Phe Tyr Lys Ser Leu Thr Asn Asp Trp
300 305 310
gag gac cac ttg gca gtc aag cac ttc tct gta gag ggt cag ttg gaa 1013
Glu Asp His Leu Ala Val Lys His Phe Ser Val Glu Gly Gln Leu Glu
315 320 325
ttc aga gca ttg ctc ttc att cct cgg cga gct ccc ttt gac ctt ttt 1061
Phe Arg Ala Leu Leu Phe Ile Pro Arg Arg Ala Pro Phe Asp Leu Phe
330 335 340
gag aac aag aag aag aag aac aat atc aaa ctg tac gtc cgt cgt gtg 1109
Glu Asn Lys Lys Lys Lys Asn Asn Ile Lys Leu Tyr Val Arg Arg Val
345 350 355 360
ttc atc atg gac agc tgt gat gag ctg atc ccc gag tac ctc aac ttt 1157
Phe Ile Met Asp Ser Cys Asp Glu Leu Ile Pro Glu Tyr Leu Asn Phe
365 370 375
atc cgt ggc gtg gtg gac tct gag gac ctg ccc ctg aac atc tct cga 1205
Ile Arg Gly Val Val Asp Ser Glu Asp Leu Pro Leu Asn Ile Ser Arg
380 385 390
gaa atg ctc caa cag agc aag atc ctg aaa gtt atc cgt aaa aac att 1253
Glu Met Leu Gln Gln Ser Lys Ile Leu Lys Val Ile Arg Lys Asn Ile
395 400 405
gtg aag aag tgc ctt gag ctc ttc tct gag ctg gct gaa gac aaa gag 1301
Val Lys Lys Cys Leu Glu Leu Phe Ser Glu Leu Ala Glu Asp Lys Glu
410 415 420
aac tat aag aaa ttc tac gag gcc ttc tcc aag aac tta aag ctt gga 1349
Asn Tyr Lys Lys Phe Tyr Glu Ala Phe Ser Lys Asn Leu Lys Leu Gly
425 430 435 440
atc cat gaa gat tcc act aac cgt cgg cgt ctc tct gag ctg ctg cgc 1397
Ile His Glu Asp Ser Thr Asn Arg Arg Arg Leu Ser Glu Leu Leu Arg
445 450 455
tat cat acc tct cag tct gga gat gag atg act tcc ctg tca gaa tat 1445
Tyr His Thr Ser Gln Ser Gly Asp Glu Met Thr Ser Leu Ser Glu Tyr
460 465 470
gtg tcc cgc atg aag gag aca cag aag tcc atc tat tac atc act ggt 1493
Val Ser Arg Met Lys Glu Thr Gln Lys Ser Ile Tyr Tyr Ile Thr Gly
475 480 485
gag agc aaa gag cag gta gcc aac tct gcc ttt gtg gag cgt gtg ccg 1541
Glu Ser Lys Glu Gln Val Ala Asn Ser Ala Phe Val Glu Arg Val Pro
490 495 500
aag cga ggc ttt gaa gcg gtg tac atg act gag cct att gat gag tac 1589
Lys Arg Gly Phe Glu Ala Val Tyr Met Thr Glu Pro Ile Asp Glu Tyr
505 510 515 520
tgc gtg caa cag ctc aag gag ttt gat gga aag agt ctg gtc tca gtg 1637
Cys Val Gln Gln Leu Lys Glu Phe Asp Gly Lys Ser Leu Val Ser Val
525 530 535
act aag gaa ggc ctg gag ctg cca gaa gat gag gaa gag aag aag aaa 1685
Thr Lys Glu Gly Leu Glu Leu Pro Glu Asp Glu Glu Glu Lys Lys Lys
540 545 550
atg gag gag agc aag gca aaa ttt gag aat ctc tgc aag ctc atg aag 1733
Met Glu Glu Ser Lys Ala Lys Phe Glu Asn Leu Cys Lys Leu Met Lys
555 560 565
gag atc ttg gat aag aag gtt gag aag gtg acc atc tcc aat agg cta 1781
Glu Ile Leu Asp Lys Lys Val Glu Lys Val Thr Ile Ser Asn Arg Leu
570 575 580
gtg tct tca ccc tgc tgc att gtg aca agc acc tat ggc tgg aca gcc 1829
Val Ser Ser Pro Cys Cys Ile Val Thr Ser Thr Tyr Gly Trp Thr Ala
585 590 595 600
aac atg gag cgg atc atg aag gcc cag gca ctc aga gac aac tct acc 1877
Asn Met Glu Arg Ile Met Lys Ala Gln Ala Leu Arg Asp Asn Ser Thr
605 610 615
atg ggc tac atg atg gcc aaa aag cac cta gag atc aac cct gac cac 1925
Met Gly Tyr Met Met Ala Lys Lys His Leu Glu Ile Asn Pro Asp His
620 625 630
ccc atc gtg gag act ctg agg cag aag gct gag gca gat aaa aac gac 1973
Pro Ile Val Glu Thr Leu Arg Gln Lys Ala Glu Ala Asp Lys Asn Asp
635 640 645
aaa gct gtc aag gat ctg gtg gtg ctg ctg ttt gag act gct ctg ctc 2021
Lys Ala Val Lys Asp Leu Val Val Leu Leu Phe Glu Thr Ala Leu Leu
650 655 660
tcc tct ggt ttc tca ctt gag gat ccc caa acc cac tcc aac cgc atc 2069
Ser Ser Gly Phe Ser Leu Glu Asp Pro Gln Thr His Ser Asn Arg Ile
665 670 675 680
tac cgc atg atc aaa cta ggc ctg ggt atc gat gaa gat gag gtg aca 2117
Tyr Arg Met Ile Lys Leu Gly Leu Gly Ile Asp Glu Asp Glu Val Thr
685 690 695
gca gag gag ccc agt gct gct gtt cct gat gag atc ccc cca ctc gag 2165
Ala Glu Glu Pro Ser Ala Ala Val Pro Asp Glu Ile Pro Pro Leu Glu
700 705 710
ggt gat gag gat gcc tcc cgc atg gaa gaa gta gat tag agatcccctg 2214
Gly Asp Glu Asp Ala Ser Arg Met Glu Glu Val Asp
715 720
ggaagaccat gtcctctgta tagtttccct gagccccacc ccccatgcct tggctggccc 2274
caacctacct ggctctctgt tcaagctaga ggatctcttt atcctgtcct tgtgccttaa 2334
ggcaggaaag tcccctccca cagaatagca gggttgggta ttgtgtattg tggttttgtt 2394
tgttttattt tgttctgaaa 2414
<210> 58
<211> 724
<212> PRT
<213> 中国仓鼠
<400> 58
Met Pro Glu Glu Val His His Gly Glu Glu Glu Val Glu Thr Phe Ala
1 5 10 15
Phe Gln Ala Glu Ile Ala Gln Leu Met Ser Leu Ile Ile Asn Thr Phe
20 25 30
Tyr Ser Asn Lys Glu Ile Phe Leu Arg Glu Leu Ile Ser Asn Ala Ser
35 40 45
Asp Ala Leu Asp Lys Ile Arg Tyr Glu Ser Leu Thr Asp Pro Ser Lys
50 55 60
Leu Asp Ser Gly Lys Glu Leu Lys Ile Asp Ile Ile Pro Asn Pro Gln
65 70 75 80
Glu Arg Thr Leu Thr Leu Val Asp Thr Gly Ile Gly Met Thr Lys Ala
85 90 95
Asp Leu Ile Asn Asn Leu Gly Thr Ile Ala Lys Ser Gly Thr Lys Ala
100 105 110
Phe Met Glu Ala Leu Gln Ala Gly Ala Asp Ile Ser Met Ile Gly Gln
115 120 125
Phe Gly Val Gly Phe Tyr Ser Ala Tyr Leu Val Ala Glu Lys Val Val
130 135 140
Val Ile Thr Lys His Asn Asp Asp Glu Gln Tyr Ala Trp Glu Ser Ser
145 150 155 160
Ala Gly Gly Ser Phe Thr Val Arg Ala Asp His Gly Glu Pro Ile Gly
165 170 175
Arg Gly Thr Lys Val Ile Leu His Leu Lys Glu Asp Gln Thr Glu Tyr
180 185 190
Leu Glu Glu Arg Arg Val Lys Glu Val Val Lys Lys His Ser Gln Phe
195 200 205
Ile Gly Tyr Pro Ile Thr Leu Tyr Leu Glu Lys Glu Arg Glu Lys Glu
210 215 220
Ile Ser Asp Asp Glu Ala Glu Glu Glu Lys Gly Glu Lys Glu Glu Glu
225 230 235 240
Asp Lys Asp Asp Glu Glu Lys Pro Lys Ile Glu Asp Val Gly Ser Asp
245 250 255
Glu Glu Asp Asp Ser Gly Lys Asp Lys Lys Lys Lys Thr Lys Lys Ile
260 265 270
Lys Glu Lys Tyr Ile Asp Gln Glu Glu Leu Asn Lys Thr Lys Pro Ile
275 280 285
Trp Thr Arg Asn Pro Asp Asp Ile Thr Gln Glu Glu Tyr Gly Asp Phe
290 295 300
Tyr Lys Ser Leu Thr Asn Asp Trp Glu Asp His Leu Ala Val Lys His
305 310 315 320
Phe Ser Val Glu Gly Gln Leu Glu Phe Arg Ala Leu Leu Phe Ile Pro
325 330 335
Arg Arg Ala Pro Phe Asp Leu Phe Glu Asn Lys Lys Lys Lys Asn Asn
340 345 350
Ile Lys Leu Tyr Val Arg Arg Val Phe Ile Met Asp Ser Cys Asp Glu
355 360 365
Leu Ile Pro Glu Tyr Leu Asn Phe Ile Arg Gly Val Val Asp Ser Glu
370 375 380
Asp Leu Pro Leu Asn Ile Ser Arg Glu Met Leu Gln Gln Ser Lys Ile
385 390 395 400
Leu Lys Val Ile Arg Lys Asn Ile Val Lys Lys Cys Leu Glu Leu Phe
405 410 415
Ser Glu Leu Ala Glu Asp Lys Glu Asn Tyr Lys Lys Phe Tyr Glu Ala
420 425 430
Phe Ser Lys Asn Leu Lys Leu Gly Ile His Glu Asp Ser Thr Asn Arg
435 440 445
Arg Arg Leu Ser Glu Leu Leu Arg Tyr His Thr Ser Gln Ser Gly Asp
450 455 460
Glu Met Thr Ser Leu Ser Glu Tyr Val Ser Arg Met Lys Glu Thr Gln
465 470 475 480
Lys Ser Ile Tyr Tyr Ile Thr Gly Glu Ser Lys Glu Gln Val Ala Asn
485 490 495
Ser Ala Phe Val Glu Arg Val Pro Lys Arg Gly Phe Glu Ala Val Tyr
500 505 510
Met Thr Glu Pro Ile Asp Glu Tyr Cys Val Gln Gln Leu Lys Glu Phe
515 520 525
Asp Gly Lys Ser Leu Val Ser Val Thr Lys Glu Gly Leu Glu Leu Pro
530 535 540
Glu Asp Glu Glu Glu Lys Lys Lys Met Glu Glu Ser Lys Ala Lys Phe
545 550 555 560
Glu Asn Leu Cys Lys Leu Met Lys Glu Ile Leu Asp Lys Lys Val Glu
565 570 575
Lys Val Thr Ile Ser Asn Arg Leu Val Ser Ser Pro Cys Cys Ile Val
580 585 590
Thr Ser Thr Tyr Gly Trp Thr Ala Asn Met Glu Arg Ile Met Lys Ala
595 600 605
Gln Ala Leu Arg Asp Asn Ser Thr Met Gly Tyr Met Met Ala Lys Lys
610 615 620
His Leu Glu Ile Asn Pro Asp His Pro Ile Val Glu Thr Leu Arg Gln
625 630 635 640
Lys Ala Glu Ala Asp Lys Asn Asp Lys Ala Val Lys Asp Leu Val Val
645 650 655
Leu Leu Phe Glu Thr Ala Leu Leu Ser Ser Gly Phe Ser Leu Glu Asp
660 665 670
Pro Gln Thr His Ser Asn Arg Ile Tyr Arg Met Ile Lys Leu Gly Leu
675 680 685
Gly Ile Asp Glu Asp Glu Val Thr Ala Glu Glu Pro Ser Ala Ala Val
690 695 700
Pro Asp Glu Ile Pro Pro Leu Glu Gly Asp Glu Asp Ala Ser Arg Met
705 710 715 720
Glu Glu Val Asp
<210> 59
<211> 1618
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (64)..(1200)
<223> NM_007065 WT, CDS 64-1200
<400> 59
agtctccact gctgccgccg tcgccgccac ccgagccgga gcgggctggg ccgccaaggc 60
aag atg gtg gac tac agc gtg tgg gac cac att gag gtg tct gat gat 108
Met Val Asp Tyr Ser Val Trp Asp His Ile Glu Val Ser Asp Asp
1 5 10 15
gaa gac gag acg cac ccc aac atc gac acg gcc agt ctc ttc cgc tgg 156
Glu Asp Glu Thr His Pro Asn Ile Asp Thr Ala Ser Leu Phe Arg Trp
20 25 30
cgg cat cag gcc cgg gtg gaa cgc atg gag cag ttc cag aag gag aag 204
Arg His Gln Ala Arg Val Glu Arg Met Glu Gln Phe Gln Lys Glu Lys
35 40 45
gag gaa ctg gac agg ggc tgc cgc gag tgc aag cgc aag gtg gcc gag 252
Glu Glu Leu Asp Arg Gly Cys Arg Glu Cys Lys Arg Lys Val Ala Glu
50 55 60
tgc cag agg aaa ctg aag gag ctg gag gtg gcc gag ggc ggc aag gca 300
Cys Gln Arg Lys Leu Lys Glu Leu Glu Val Ala Glu Gly Gly Lys Ala
65 70 75
gag ctg gag cgc ctg cag gcc gag gca cag cag ctg cgc aag gag gag 348
Glu Leu Glu Arg Leu Gln Ala Glu Ala Gln Gln Leu Arg Lys Glu Glu
80 85 90 95
cgg agc tgg gag cag aag ctg gag gag atg cgc aag aag gag aag agc 396
Arg Ser Trp Glu Gln Lys Leu Glu Glu Met Arg Lys Lys Glu Lys Ser
100 105 110
atg ccc tgg aac gtg gac acg ctc agc aaa gac ggc ttc agc aag agc 444
Met Pro Trp Asn Val Asp Thr Leu Ser Lys Asp Gly Phe Ser Lys Ser
115 120 125
atg gta aat acc aag ccc gag aag acg gag gag gac tca gag gag gtg 492
Met Val Asn Thr Lys Pro Glu Lys Thr Glu Glu Asp Ser Glu Glu Val
130 135 140
agg gag cag aaa cac aag acc ttc gtg gaa aaa tac gag aaa cag atc 540
Arg Glu Gln Lys His Lys Thr Phe Val Glu Lys Tyr Glu Lys Gln Ile
145 150 155
aag cac ttt ggc atg ctt cgc cgc tgg gat gac agc caa aag tac ctg 588
Lys His Phe Gly Met Leu Arg Arg Trp Asp Asp Ser Gln Lys Tyr Leu
160 165 170 175
tca gac aac gtc cac ctg gtg tgc gag gag aca gcc aat tac ctg gtc 636
Ser Asp Asn Val His Leu Val Cys Glu Glu Thr Ala Asn Tyr Leu Val
180 185 190
att tgg tgc att gac cta gag gtg gag gag aaa tgt gca ctc atg gag 684
Ile Trp Cys Ile Asp Leu Glu Val Glu Glu Lys Cys Ala Leu Met Glu
195 200 205
cag gtg gcc cac cag aca atc gtc atg caa ttt atc ctg gag ctg gcc 732
Gln Val Ala His Gln Thr Ile Val Met Gln Phe Ile Leu Glu Leu Ala
210 215 220
aag agc cta aag gtg gac ccc cgg gcc tgc ttc cgg cag ttc ttc act 780
Lys Ser Leu Lys Val Asp Pro Arg Ala Cys Phe Arg Gln Phe Phe Thr
225 230 235
aag att aag aca gcc gat cgc cag tac atg gag ggc ttc aac gac gag 828
Lys Ile Lys Thr Ala Asp Arg Gln Tyr Met Glu Gly Phe Asn Asp Glu
240 245 250 255
ctg gaa gcc ttc aag gag cgt gtg cgg ggc cgt gcc aag ctg cgc atc 876
Leu Glu Ala Phe Lys Glu Arg Val Arg Gly Arg Ala Lys Leu Arg Ile
260 265 270
gag aag gcc atg aag gag tac gag gag gag gag cgc aag aag cgg ctc 924
Glu Lys Ala Met Lys Glu Tyr Glu Glu Glu Glu Arg Lys Lys Arg Leu
275 280 285
ggc ccc ggc ggc ctg gac ccc gtc gag gtc tac gag tcc ctc cct gag 972
Gly Pro Gly Gly Leu Asp Pro Val Glu Val Tyr Glu Ser Leu Pro Glu
290 295 300
gaa ctc cag aag tgc ttc gat gtg aag gac gtg cag atg ctg cag gac 1020
Glu Leu Gln Lys Cys Phe Asp Val Lys Asp Val Gln Met Leu Gln Asp
305 310 315
gcc atc agc aag atg gac ccc acc gac gca aag tac cac atg cag cgc 1068
Ala Ile Ser Lys Met Asp Pro Thr Asp Ala Lys Tyr His Met Gln Arg
320 325 330 335
tgc att gac tct ggc ctc tgg gtc ccc aac tct aag gcc agc gag gcc 1116
Cys Ile Asp Ser Gly Leu Trp Val Pro Asn Ser Lys Ala Ser Glu Ala
340 345 350
aag gag gga gag gag gca ggt cct ggg gac cca tta ctg gaa gct gtt 1164
Lys Glu Gly Glu Glu Ala Gly Pro Gly Asp Pro Leu Leu Glu Ala Val
355 360 365
ccc aag acg ggc gat gag aag gat gtc agt gtg tga cctgccccag 1210
Pro Lys Thr Gly Asp Glu Lys Asp Val Ser Val
370 375
ctaccaccgc cacctgcttc caggccccta tgtgcccctt ttcagaaaac agatagatgc 1270
catctcgccc gctcctgact tcctctactt gcgctgctcg gcccagcctg gggggcccgc 1330
ccagccctcc ctggcctctc cactgtctcc actctccagc gcccattcaa gtctctgctt 1390
tgagtcaagg ggcttcactg cctgcagccc cccatcagca ttatgccaaa ggcccggggg 1450
tccggggaag ggcagaggtc accaggctgg tctaccaggt agttggggag ggtccccagc 1510
caaggggccg gctctcgtca ctgggctctg ttttcactgt tcgtctgctg tctgtgtctt 1570
ctatttggca aacagcaatg atcttccaat aaaagatttc agatgctc 1618
<210> 60
<211> 378
<212> PRT
<213> 智人
<400> 60
Met Val Asp Tyr Ser Val Trp Asp His Ile Glu Val Ser Asp Asp Glu
1 5 10 15
Asp Glu Thr His Pro Asn Ile Asp Thr Ala Ser Leu Phe Arg Trp Arg
20 25 30
His Gln Ala Arg Val Glu Arg Met Glu Gln Phe Gln Lys Glu Lys Glu
35 40 45
Glu Leu Asp Arg Gly Cys Arg Glu Cys Lys Arg Lys Val Ala Glu Cys
50 55 60
Gln Arg Lys Leu Lys Glu Leu Glu Val Ala Glu Gly Gly Lys Ala Glu
65 70 75 80
Leu Glu Arg Leu Gln Ala Glu Ala Gln Gln Leu Arg Lys Glu Glu Arg
85 90 95
Ser Trp Glu Gln Lys Leu Glu Glu Met Arg Lys Lys Glu Lys Ser Met
100 105 110
Pro Trp Asn Val Asp Thr Leu Ser Lys Asp Gly Phe Ser Lys Ser Met
115 120 125
Val Asn Thr Lys Pro Glu Lys Thr Glu Glu Asp Ser Glu Glu Val Arg
130 135 140
Glu Gln Lys His Lys Thr Phe Val Glu Lys Tyr Glu Lys Gln Ile Lys
145 150 155 160
His Phe Gly Met Leu Arg Arg Trp Asp Asp Ser Gln Lys Tyr Leu Ser
165 170 175
Asp Asn Val His Leu Val Cys Glu Glu Thr Ala Asn Tyr Leu Val Ile
180 185 190
Trp Cys Ile Asp Leu Glu Val Glu Glu Lys Cys Ala Leu Met Glu Gln
195 200 205
Val Ala His Gln Thr Ile Val Met Gln Phe Ile Leu Glu Leu Ala Lys
210 215 220
Ser Leu Lys Val Asp Pro Arg Ala Cys Phe Arg Gln Phe Phe Thr Lys
225 230 235 240
Ile Lys Thr Ala Asp Arg Gln Tyr Met Glu Gly Phe Asn Asp Glu Leu
245 250 255
Glu Ala Phe Lys Glu Arg Val Arg Gly Arg Ala Lys Leu Arg Ile Glu
260 265 270
Lys Ala Met Lys Glu Tyr Glu Glu Glu Glu Arg Lys Lys Arg Leu Gly
275 280 285
Pro Gly Gly Leu Asp Pro Val Glu Val Tyr Glu Ser Leu Pro Glu Glu
290 295 300
Leu Gln Lys Cys Phe Asp Val Lys Asp Val Gln Met Leu Gln Asp Ala
305 310 315 320
Ile Ser Lys Met Asp Pro Thr Asp Ala Lys Tyr His Met Gln Arg Cys
325 330 335
Ile Asp Ser Gly Leu Trp Val Pro Asn Ser Lys Ala Ser Glu Ala Lys
340 345 350
Glu Gly Glu Glu Ala Gly Pro Gly Asp Pro Leu Leu Glu Ala Val Pro
355 360 365
Lys Thr Gly Asp Glu Lys Asp Val Ser Val
370 375
<210> 61
<211> 1250
<212> DNA
<213> 中国仓鼠
<220>
<221> CDS
<222> (111)..(1250)
<223> XM_003499737 WT, CDS 111-1250
<400> 61
gaagcggaag gggcggggct ccgcgagcgg actctctatc ccttgtgggt ccctgttcag 60
cgcccggccg tgtggagcgc cgggagccaa tccgggcctc ctaggcgaag atg gtg 116
Met Val
1
gac tac agc gtt tgg gat cac atc gag gtg tcg gac gat gag gac gag 164
Asp Tyr Ser Val Trp Asp His Ile Glu Val Ser Asp Asp Glu Asp Glu
5 10 15
acg cac ccc aac atc gac acg gcc agc ctc ttc cgc tgg cgg cac cag 212
Thr His Pro Asn Ile Asp Thr Ala Ser Leu Phe Arg Trp Arg His Gln
20 25 30
gcc cga gtg gag cgc atg gag cag ttt cag aag gag aag gac gaa ctg 260
Ala Arg Val Glu Arg Met Glu Gln Phe Gln Lys Glu Lys Asp Glu Leu
35 40 45 50
gac cgg ggc tgc cgt gaa tgc aag cga aag gta gcc gaa tgc caa cgc 308
Asp Arg Gly Cys Arg Glu Cys Lys Arg Lys Val Ala Glu Cys Gln Arg
55 60 65
aag ctg agg gag ctg gaa gtg gct gaa ggc ggt ggc cag gtg gag ctt 356
Lys Leu Arg Glu Leu Glu Val Ala Glu Gly Gly Gly Gln Val Glu Leu
70 75 80
gag cgg ctg cga gct gag gca cag cag ctg cgc aag gag gag cga agc 404
Glu Arg Leu Arg Ala Glu Ala Gln Gln Leu Arg Lys Glu Glu Arg Ser
85 90 95
tgg gag cag aag ctg gag gac atg cgc aag aag gag aag agc atg ccc 452
Trp Glu Gln Lys Leu Glu Asp Met Arg Lys Lys Glu Lys Ser Met Pro
100 105 110
tgg aac gtg gac acc ctc agc aag gac ggc ttc agc aag agc ata gtc 500
Trp Asn Val Asp Thr Leu Ser Lys Asp Gly Phe Ser Lys Ser Ile Val
115 120 125 130
aat atc aag cct gag aag gca gag gaa gac tca gag gag gca aga gag 548
Asn Ile Lys Pro Glu Lys Ala Glu Glu Asp Ser Glu Glu Ala Arg Glu
135 140 145
cag aaa cac aag acc ttc gtt gaa aag tac gag aaa cag atc aag cat 596
Gln Lys His Lys Thr Phe Val Glu Lys Tyr Glu Lys Gln Ile Lys His
150 155 160
ttc ggc atg ctc cac cgc tgg gat gac agc cag aag tac ctg tca gac 644
Phe Gly Met Leu His Arg Trp Asp Asp Ser Gln Lys Tyr Leu Ser Asp
165 170 175
aat gtc cac ctg gtg tgc gag gag acc gcc aac tac ctg gtt atc tgg 692
Asn Val His Leu Val Cys Glu Glu Thr Ala Asn Tyr Leu Val Ile Trp
180 185 190
tgc att gac ctg gaa gtg gag gag aaa tgt gca ctg atg gag cag gta 740
Cys Ile Asp Leu Glu Val Glu Glu Lys Cys Ala Leu Met Glu Gln Val
195 200 205 210
gct cac cag acc atg gtg atg cag ttc att ctg gag ctg gcc aag agt 788
Ala His Gln Thr Met Val Met Gln Phe Ile Leu Glu Leu Ala Lys Ser
215 220 225
ctg aag gtc gat ccc cgt gcc tgc ttc agg cag ttc ttc acc aag atc 836
Leu Lys Val Asp Pro Arg Ala Cys Phe Arg Gln Phe Phe Thr Lys Ile
230 235 240
aag acc gcc gac caa cag tac atg gag ggc ttc aaa tac gaa ctg gag 884
Lys Thr Ala Asp Gln Gln Tyr Met Glu Gly Phe Lys Tyr Glu Leu Glu
245 250 255
gcc ttt aag gag cgt gtg cgg ggc cgt gcc aag ctg cgc ata gag aag 932
Ala Phe Lys Glu Arg Val Arg Gly Arg Ala Lys Leu Arg Ile Glu Lys
260 265 270
gcc atg aag gag tac gag gag gag gag cgc aag aag agg ctg ggc cct 980
Ala Met Lys Glu Tyr Glu Glu Glu Glu Arg Lys Lys Arg Leu Gly Pro
275 280 285 290
ggt ggc ctg gac ccc gtg gag gtc tat gag tcc ctg cct gag gaa ctg 1028
Gly Gly Leu Asp Pro Val Glu Val Tyr Glu Ser Leu Pro Glu Glu Leu
295 300 305
cag aag tgc ttt gat gtg aag gac gtg caa atg ctg caa gat gcc atc 1076
Gln Lys Cys Phe Asp Val Lys Asp Val Gln Met Leu Gln Asp Ala Ile
310 315 320
agc aag atg gat ccc act gat gcc aag ttt cac atg cag cgt tgc atc 1124
Ser Lys Met Asp Pro Thr Asp Ala Lys Phe His Met Gln Arg Cys Ile
325 330 335
gat tct ggg ctc tgg gtc ccc aac tcc aag tct ggt gag gcc aag gag 1172
Asp Ser Gly Leu Trp Val Pro Asn Ser Lys Ser Gly Glu Ala Lys Glu
340 345 350
ggg gag gag gcg ggc ccc ggg gac cca ttg ctg gaa gcc gtc ccc aaa 1220
Gly Glu Glu Ala Gly Pro Gly Asp Pro Leu Leu Glu Ala Val Pro Lys
355 360 365 370
gcg ggc aac gag aaa gac gtc agt gcg tga 1250
Ala Gly Asn Glu Lys Asp Val Ser Ala
375
<210> 62
<211> 379
<212> PRT
<213> 中国仓鼠
<400> 62
Met Val Asp Tyr Ser Val Trp Asp His Ile Glu Val Ser Asp Asp Glu
1 5 10 15
Asp Glu Thr His Pro Asn Ile Asp Thr Ala Ser Leu Phe Arg Trp Arg
20 25 30
His Gln Ala Arg Val Glu Arg Met Glu Gln Phe Gln Lys Glu Lys Asp
35 40 45
Glu Leu Asp Arg Gly Cys Arg Glu Cys Lys Arg Lys Val Ala Glu Cys
50 55 60
Gln Arg Lys Leu Arg Glu Leu Glu Val Ala Glu Gly Gly Gly Gln Val
65 70 75 80
Glu Leu Glu Arg Leu Arg Ala Glu Ala Gln Gln Leu Arg Lys Glu Glu
85 90 95
Arg Ser Trp Glu Gln Lys Leu Glu Asp Met Arg Lys Lys Glu Lys Ser
100 105 110
Met Pro Trp Asn Val Asp Thr Leu Ser Lys Asp Gly Phe Ser Lys Ser
115 120 125
Ile Val Asn Ile Lys Pro Glu Lys Ala Glu Glu Asp Ser Glu Glu Ala
130 135 140
Arg Glu Gln Lys His Lys Thr Phe Val Glu Lys Tyr Glu Lys Gln Ile
145 150 155 160
Lys His Phe Gly Met Leu His Arg Trp Asp Asp Ser Gln Lys Tyr Leu
165 170 175
Ser Asp Asn Val His Leu Val Cys Glu Glu Thr Ala Asn Tyr Leu Val
180 185 190
Ile Trp Cys Ile Asp Leu Glu Val Glu Glu Lys Cys Ala Leu Met Glu
195 200 205
Gln Val Ala His Gln Thr Met Val Met Gln Phe Ile Leu Glu Leu Ala
210 215 220
Lys Ser Leu Lys Val Asp Pro Arg Ala Cys Phe Arg Gln Phe Phe Thr
225 230 235 240
Lys Ile Lys Thr Ala Asp Gln Gln Tyr Met Glu Gly Phe Lys Tyr Glu
245 250 255
Leu Glu Ala Phe Lys Glu Arg Val Arg Gly Arg Ala Lys Leu Arg Ile
260 265 270
Glu Lys Ala Met Lys Glu Tyr Glu Glu Glu Glu Arg Lys Lys Arg Leu
275 280 285
Gly Pro Gly Gly Leu Asp Pro Val Glu Val Tyr Glu Ser Leu Pro Glu
290 295 300
Glu Leu Gln Lys Cys Phe Asp Val Lys Asp Val Gln Met Leu Gln Asp
305 310 315 320
Ala Ile Ser Lys Met Asp Pro Thr Asp Ala Lys Phe His Met Gln Arg
325 330 335
Cys Ile Asp Ser Gly Leu Trp Val Pro Asn Ser Lys Ser Gly Glu Ala
340 345 350
Lys Glu Gly Glu Glu Ala Gly Pro Gly Asp Pro Leu Leu Glu Ala Val
355 360 365
Pro Lys Ala Gly Asn Glu Lys Asp Val Ser Ala
370 375
<210> 63
<211> 2301
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (118)..(1839)
<223> NM_199440 WT, CDS 1839
<400> 63
gccccgacgc gcaccgcgat tcgccccaag ggccctgcgc aggacgctga cgcgaagact 60
cggaggcgga agaaaaaagg agctgtttct aggcttttct aggcgcccag ccgagaa 117
atg ctt cgg tta ccc aca gtc ttt cgc cag atg aga ccg gtg tcc agg 165
Met Leu Arg Leu Pro Thr Val Phe Arg Gln Met Arg Pro Val Ser Arg
1 5 10 15
gta ctg gct cct cat ctc act cgg gct tat gcc aaa gat gta aaa ttt 213
Val Leu Ala Pro His Leu Thr Arg Ala Tyr Ala Lys Asp Val Lys Phe
20 25 30
ggt gca gat gcc cga gcc tta atg ctt caa ggt gta gac ctt tta gcc 261
Gly Ala Asp Ala Arg Ala Leu Met Leu Gln Gly Val Asp Leu Leu Ala
35 40 45
gat gct gtg gcc gtt aca atg ggg cca aag gga aga aca gtg att att 309
Asp Ala Val Ala Val Thr Met Gly Pro Lys Gly Arg Thr Val Ile Ile
50 55 60
gag cag agt tgg gga agt ccc aaa gta aca aaa gat ggt gtg act gtt 357
Glu Gln Ser Trp Gly Ser Pro Lys Val Thr Lys Asp Gly Val Thr Val
65 70 75 80
gca aag tca att gac tta aaa gat aaa tac aaa aac att gga gct aaa 405
Ala Lys Ser Ile Asp Leu Lys Asp Lys Tyr Lys Asn Ile Gly Ala Lys
85 90 95
ctt gtt caa gat gtt gcc aat aac aca aat gaa gaa gct ggg gat ggc 453
Leu Val Gln Asp Val Ala Asn Asn Thr Asn Glu Glu Ala Gly Asp Gly
100 105 110
act acc act gct act gta ctg gca cgc tct ata gcc aag gaa ggc ttc 501
Thr Thr Thr Ala Thr Val Leu Ala Arg Ser Ile Ala Lys Glu Gly Phe
115 120 125
gag aag att agc aaa ggt gct aat cca gtg gaa atc agg aga ggt gtg 549
Glu Lys Ile Ser Lys Gly Ala Asn Pro Val Glu Ile Arg Arg Gly Val
130 135 140
atg tta gct gtt gat gct gta att gct gaa ctt aaa aag cag tct aaa 597
Met Leu Ala Val Asp Ala Val Ile Ala Glu Leu Lys Lys Gln Ser Lys
145 150 155 160
cct gtg acc acc cct gaa gaa att gca cag gtt gct acg att tct gca 645
Pro Val Thr Thr Pro Glu Glu Ile Ala Gln Val Ala Thr Ile Ser Ala
165 170 175
aac gga gac aaa gaa att ggc aat atc atc tct gat gca atg aaa aaa 693
Asn Gly Asp Lys Glu Ile Gly Asn Ile Ile Ser Asp Ala Met Lys Lys
180 185 190
gtt gga aga aag ggt gtc atc aca gta aag gat gga aaa aca ctg aat 741
Val Gly Arg Lys Gly Val Ile Thr Val Lys Asp Gly Lys Thr Leu Asn
195 200 205
gat gaa tta gaa att att gaa ggc atg aag ttt gat cga ggc tat att 789
Asp Glu Leu Glu Ile Ile Glu Gly Met Lys Phe Asp Arg Gly Tyr Ile
210 215 220
tct cca tac ttt att aat aca tca aaa ggt cag aaa tgt gaa ttc cag 837
Ser Pro Tyr Phe Ile Asn Thr Ser Lys Gly Gln Lys Cys Glu Phe Gln
225 230 235 240
gat gcc tat gtt ctg ttg agt gaa aag aaa att tct agt atc cag tcc 885
Asp Ala Tyr Val Leu Leu Ser Glu Lys Lys Ile Ser Ser Ile Gln Ser
245 250 255
att gta cct gct ctt gaa att gcc aat gct cac cgt aag cct ttg gtc 933
Ile Val Pro Ala Leu Glu Ile Ala Asn Ala His Arg Lys Pro Leu Val
260 265 270
ata atc gct gaa gat gtt gat gga gaa gct cta agt aca ctc gtc ttg 981
Ile Ile Ala Glu Asp Val Asp Gly Glu Ala Leu Ser Thr Leu Val Leu
275 280 285
aat agg cta aag gtt ggt ctt cag gtt gtg gca gtc aag gct cca ggg 1029
Asn Arg Leu Lys Val Gly Leu Gln Val Val Ala Val Lys Ala Pro Gly
290 295 300
ttt ggt gac aat aga aag aac cag ctt aaa gat atg gct att gct act 1077
Phe Gly Asp Asn Arg Lys Asn Gln Leu Lys Asp Met Ala Ile Ala Thr
305 310 315 320
ggt ggt gca gtg ttt gga gaa gag gga ttg acc ctg aat ctt gaa gac 1125
Gly Gly Ala Val Phe Gly Glu Glu Gly Leu Thr Leu Asn Leu Glu Asp
325 330 335
gtt cag cct cat gac tta gga aaa gtt gga gag gtc att gtg acc aaa 1173
Val Gln Pro His Asp Leu Gly Lys Val Gly Glu Val Ile Val Thr Lys
340 345 350
gac gat gcc atg ctc tta aaa gga aaa ggt gac aag gct caa att gaa 1221
Asp Asp Ala Met Leu Leu Lys Gly Lys Gly Asp Lys Ala Gln Ile Glu
355 360 365
aaa cgt att caa gaa atc att gag cag tta gat gtc aca act agt gaa 1269
Lys Arg Ile Gln Glu Ile Ile Glu Gln Leu Asp Val Thr Thr Ser Glu
370 375 380
tat gaa aag gaa aaa ctg aat gaa cgg ctt gca aaa ctt tca gat gga 1317
Tyr Glu Lys Glu Lys Leu Asn Glu Arg Leu Ala Lys Leu Ser Asp Gly
385 390 395 400
gtg gct gtg ctg aag gtt ggt ggg aca agt gat gtt gaa gtg aat gaa 1365
Val Ala Val Leu Lys Val Gly Gly Thr Ser Asp Val Glu Val Asn Glu
405 410 415
aag aaa gac aga gtt aca gat gcc ctt aat gct aca aga gct gct gtt 1413
Lys Lys Asp Arg Val Thr Asp Ala Leu Asn Ala Thr Arg Ala Ala Val
420 425 430
gaa gaa ggc att gtt ttg gga ggg ggt tgt gcc ctc ctt cga tgc att 1461
Glu Glu Gly Ile Val Leu Gly Gly Gly Cys Ala Leu Leu Arg Cys Ile
435 440 445
cca gcc ttg gac tca ttg act cca gct aat gaa gat caa aaa att ggt 1509
Pro Ala Leu Asp Ser Leu Thr Pro Ala Asn Glu Asp Gln Lys Ile Gly
450 455 460
ata gaa att att aaa aga aca ctc aaa att cca gca atg acc att gct 1557
Ile Glu Ile Ile Lys Arg Thr Leu Lys Ile Pro Ala Met Thr Ile Ala
465 470 475 480
aag aat gca ggt gtt gaa gga tct ttg ata gtt gag aaa att atg caa 1605
Lys Asn Ala Gly Val Glu Gly Ser Leu Ile Val Glu Lys Ile Met Gln
485 490 495
agt tcc tca gaa gtt ggt tat gat gct atg gct gga gat ttt gtg aat 1653
Ser Ser Ser Glu Val Gly Tyr Asp Ala Met Ala Gly Asp Phe Val Asn
500 505 510
atg gtg gaa aaa gga atc att gac cca aca aag gtt gtg aga act gct 1701
Met Val Glu Lys Gly Ile Ile Asp Pro Thr Lys Val Val Arg Thr Ala
515 520 525
tta ttg gat gct gct ggt gtg gcc tct ctg tta act aca gca gaa gtt 1749
Leu Leu Asp Ala Ala Gly Val Ala Ser Leu Leu Thr Thr Ala Glu Val
530 535 540
gta gtc aca gaa att cct aaa gaa gag aag gac cct gga atg ggt gca 1797
Val Val Thr Glu Ile Pro Lys Glu Glu Lys Asp Pro Gly Met Gly Ala
545 550 555 560
atg ggt gga atg gga ggt ggt atg gga ggt ggc atg ttc taa 1839
Met Gly Gly Met Gly Gly Gly Met Gly Gly Gly Met Phe
565 570
ctcctagact agtgctttac ctttattaat gaactgtgac aggaagccca aggcagtgtt 1899
cctcaccaat aacttcagag aagtcagttg gagaaaatga agaaaaaggc tggctgaaaa 1959
tcactataac catcagttac tggtttcagt tgacaaaata tataatggtt tactgctgtc 2019
attgtccatg cctacagata atttattttg tatttttgaa taaaaaacat ttgtacattc 2079
ctgatactgg gtacaagagc catgtaccag tgtactgctt tcaacttaaa tcactgaggc 2139
atttttacta ctattctgtt aaaatcagga ttttagtgct tgccaccacc agatgagaag 2199
ttaagcagcc tttctgtgga gagtgagaat aattgtgtac aaagtagaga agtatccaat 2259
tatgtgacaa cctttgtgta ataaaaattt gtttaaagtt aa 2301
<210> 64
<211> 573
<212> PRT
<213> 智人
<400> 64
Met Leu Arg Leu Pro Thr Val Phe Arg Gln Met Arg Pro Val Ser Arg
1 5 10 15
Val Leu Ala Pro His Leu Thr Arg Ala Tyr Ala Lys Asp Val Lys Phe
20 25 30
Gly Ala Asp Ala Arg Ala Leu Met Leu Gln Gly Val Asp Leu Leu Ala
35 40 45
Asp Ala Val Ala Val Thr Met Gly Pro Lys Gly Arg Thr Val Ile Ile
50 55 60
Glu Gln Ser Trp Gly Ser Pro Lys Val Thr Lys Asp Gly Val Thr Val
65 70 75 80
Ala Lys Ser Ile Asp Leu Lys Asp Lys Tyr Lys Asn Ile Gly Ala Lys
85 90 95
Leu Val Gln Asp Val Ala Asn Asn Thr Asn Glu Glu Ala Gly Asp Gly
100 105 110
Thr Thr Thr Ala Thr Val Leu Ala Arg Ser Ile Ala Lys Glu Gly Phe
115 120 125
Glu Lys Ile Ser Lys Gly Ala Asn Pro Val Glu Ile Arg Arg Gly Val
130 135 140
Met Leu Ala Val Asp Ala Val Ile Ala Glu Leu Lys Lys Gln Ser Lys
145 150 155 160
Pro Val Thr Thr Pro Glu Glu Ile Ala Gln Val Ala Thr Ile Ser Ala
165 170 175
Asn Gly Asp Lys Glu Ile Gly Asn Ile Ile Ser Asp Ala Met Lys Lys
180 185 190
Val Gly Arg Lys Gly Val Ile Thr Val Lys Asp Gly Lys Thr Leu Asn
195 200 205
Asp Glu Leu Glu Ile Ile Glu Gly Met Lys Phe Asp Arg Gly Tyr Ile
210 215 220
Ser Pro Tyr Phe Ile Asn Thr Ser Lys Gly Gln Lys Cys Glu Phe Gln
225 230 235 240
Asp Ala Tyr Val Leu Leu Ser Glu Lys Lys Ile Ser Ser Ile Gln Ser
245 250 255
Ile Val Pro Ala Leu Glu Ile Ala Asn Ala His Arg Lys Pro Leu Val
260 265 270
Ile Ile Ala Glu Asp Val Asp Gly Glu Ala Leu Ser Thr Leu Val Leu
275 280 285
Asn Arg Leu Lys Val Gly Leu Gln Val Val Ala Val Lys Ala Pro Gly
290 295 300
Phe Gly Asp Asn Arg Lys Asn Gln Leu Lys Asp Met Ala Ile Ala Thr
305 310 315 320
Gly Gly Ala Val Phe Gly Glu Glu Gly Leu Thr Leu Asn Leu Glu Asp
325 330 335
Val Gln Pro His Asp Leu Gly Lys Val Gly Glu Val Ile Val Thr Lys
340 345 350
Asp Asp Ala Met Leu Leu Lys Gly Lys Gly Asp Lys Ala Gln Ile Glu
355 360 365
Lys Arg Ile Gln Glu Ile Ile Glu Gln Leu Asp Val Thr Thr Ser Glu
370 375 380
Tyr Glu Lys Glu Lys Leu Asn Glu Arg Leu Ala Lys Leu Ser Asp Gly
385 390 395 400
Val Ala Val Leu Lys Val Gly Gly Thr Ser Asp Val Glu Val Asn Glu
405 410 415
Lys Lys Asp Arg Val Thr Asp Ala Leu Asn Ala Thr Arg Ala Ala Val
420 425 430
Glu Glu Gly Ile Val Leu Gly Gly Gly Cys Ala Leu Leu Arg Cys Ile
435 440 445
Pro Ala Leu Asp Ser Leu Thr Pro Ala Asn Glu Asp Gln Lys Ile Gly
450 455 460
Ile Glu Ile Ile Lys Arg Thr Leu Lys Ile Pro Ala Met Thr Ile Ala
465 470 475 480
Lys Asn Ala Gly Val Glu Gly Ser Leu Ile Val Glu Lys Ile Met Gln
485 490 495
Ser Ser Ser Glu Val Gly Tyr Asp Ala Met Ala Gly Asp Phe Val Asn
500 505 510
Met Val Glu Lys Gly Ile Ile Asp Pro Thr Lys Val Val Arg Thr Ala
515 520 525
Leu Leu Asp Ala Ala Gly Val Ala Ser Leu Leu Thr Thr Ala Glu Val
530 535 540
Val Val Thr Glu Ile Pro Lys Glu Glu Lys Asp Pro Gly Met Gly Ala
545 550 555 560
Met Gly Gly Met Gly Gly Gly Met Gly Gly Gly Met Phe
565 570
<210> 65
<211> 2319
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (122)..(1315)
<223> NM_001539 WT, CDS 122-1315
<400> 65
gcggaacttt ccagaacgct cggtgagagg cggaggagcg gtaactaccc cggctgcgca 60
cagctcggcg ctccttcccg ctccctcaca caccggcctc agcccgcacc ggcagtagaa 120
g atg gtg aaa gaa aca act tac tac gat gtt ttg ggg gtc aaa ccc aat 169
Met Val Lys Glu Thr Thr Tyr Tyr Asp Val Leu Gly Val Lys Pro Asn
1 5 10 15
gct act cag gaa gaa ttg aaa aag gct tat agg aaa ctg gct ttg aag 217
Ala Thr Gln Glu Glu Leu Lys Lys Ala Tyr Arg Lys Leu Ala Leu Lys
20 25 30
tac cat cct gat aag aac cca aat gaa gga gag aag ttt aaa cag att 265
Tyr His Pro Asp Lys Asn Pro Asn Glu Gly Glu Lys Phe Lys Gln Ile
35 40 45
tct caa gct tac gaa gtt ctc tct gat gca aag aaa agg gaa tta tat 313
Ser Gln Ala Tyr Glu Val Leu Ser Asp Ala Lys Lys Arg Glu Leu Tyr
50 55 60
gac aaa gga gga gaa cag gca att aaa gag ggt gga gca ggt ggc ggt 361
Asp Lys Gly Gly Glu Gln Ala Ile Lys Glu Gly Gly Ala Gly Gly Gly
65 70 75 80
ttt ggc tcc ccc atg gac atc ttt gat atg ttt ttt gga gga gga gga 409
Phe Gly Ser Pro Met Asp Ile Phe Asp Met Phe Phe Gly Gly Gly Gly
85 90 95
agg atg cag aga gaa agg aga ggt aaa aat gtt gta cat cag ctc tca 457
Arg Met Gln Arg Glu Arg Arg Gly Lys Asn Val Val His Gln Leu Ser
100 105 110
gta acc cta gaa gac tta tat aat ggt gca aca aga aaa ctg gct ctg 505
Val Thr Leu Glu Asp Leu Tyr Asn Gly Ala Thr Arg Lys Leu Ala Leu
115 120 125
caa aag aat gtg att tgt gac aaa tgt gaa ggt aga gga ggt aag aaa 553
Gln Lys Asn Val Ile Cys Asp Lys Cys Glu Gly Arg Gly Gly Lys Lys
130 135 140
gga gca gta gag tgc tgt ccc aat tgc cga ggt act gga atg caa ata 601
Gly Ala Val Glu Cys Cys Pro Asn Cys Arg Gly Thr Gly Met Gln Ile
145 150 155 160
aga att cat cag ata gga cct gga atg gtt cag caa att cag tct gtg 649
Arg Ile His Gln Ile Gly Pro Gly Met Val Gln Gln Ile Gln Ser Val
165 170 175
tgc atg gag tgc cag ggc cat ggg gag cgg atc agt cct aaa gat aga 697
Cys Met Glu Cys Gln Gly His Gly Glu Arg Ile Ser Pro Lys Asp Arg
180 185 190
tgt aaa agc tgc aac gga agg aag ata gtt cga gag aag aaa att tta 745
Cys Lys Ser Cys Asn Gly Arg Lys Ile Val Arg Glu Lys Lys Ile Leu
195 200 205
gaa gtt cat att gac aaa ggc atg aaa gat ggc cag aag ata aca ttc 793
Glu Val His Ile Asp Lys Gly Met Lys Asp Gly Gln Lys Ile Thr Phe
210 215 220
cat ggt gaa gga gac caa gaa cca gga ctg gag cca ggc gat att atc 841
His Gly Glu Gly Asp Gln Glu Pro Gly Leu Glu Pro Gly Asp Ile Ile
225 230 235 240
att gtg tta gat cag aag gac cat gct gtt ttt act cga cga gga gaa 889
Ile Val Leu Asp Gln Lys Asp His Ala Val Phe Thr Arg Arg Gly Glu
245 250 255
gac ctt ttc atg tgt atg gac ata cag ctc gtt gaa gca ctg tgt ggc 937
Asp Leu Phe Met Cys Met Asp Ile Gln Leu Val Glu Ala Leu Cys Gly
260 265 270
ttc cag aag cca ata tct act ctt gac aac cga acc atc gtc atc acc 985
Phe Gln Lys Pro Ile Ser Thr Leu Asp Asn Arg Thr Ile Val Ile Thr
275 280 285
tct cat cca ggt cag att gtc aag cat gga gat atc aag tgt gta cta 1033
Ser His Pro Gly Gln Ile Val Lys His Gly Asp Ile Lys Cys Val Leu
290 295 300
aat gaa ggc atg cca att tat cgt aga cca tat gaa aag ggt cgc cta 1081
Asn Glu Gly Met Pro Ile Tyr Arg Arg Pro Tyr Glu Lys Gly Arg Leu
305 310 315 320
atc atc gaa ttt aag gta aac ttt cct gag aat ggc ttt ctc tct cct 1129
Ile Ile Glu Phe Lys Val Asn Phe Pro Glu Asn Gly Phe Leu Ser Pro
325 330 335
gat aaa ctg tct ttg ctg gaa aaa ctc cta ccc gag agg aag gaa gtg 1177
Asp Lys Leu Ser Leu Leu Glu Lys Leu Leu Pro Glu Arg Lys Glu Val
340 345 350
gaa gag act gat gag atg gac caa gta gaa ctg gtg gac ttt gat cca 1225
Glu Glu Thr Asp Glu Met Asp Gln Val Glu Leu Val Asp Phe Asp Pro
355 360 365
aat cag gaa aga cgg cgc cac tac aat gga gaa gca tat gag gat gat 1273
Asn Gln Glu Arg Arg Arg His Tyr Asn Gly Glu Ala Tyr Glu Asp Asp
370 375 380
gaa cat cat ccc aga ggt ggt gtt cag tgt cag acc tct taa 1315
Glu His His Pro Arg Gly Gly Val Gln Cys Gln Thr Ser
385 390 395
tgggccagtg aataacactc actgctggca tttaatgtgc agtagtgaat gagtgaagga 1375
ctgtaatcat aatatgctca ctacttgctc ttgtttttgt tttaataaac tatagtagtg 1435
ttttaaaaag ttaaatgaag aataaacgca aatataaaag ctctgatttt gccctgtatg 1495
tatgatgact tcagtgtgca agatgaagtt taatacctgt aaaaactaca aagaagttcc 1555
cctagcattt ctaggccaaa ccttgtaatt gacttcagct atgtacgtgg acaagcttag 1615
actgaaatgc taggtatatg tattggcttc agtgtatgac ccttcattgt taagctatga 1675
aagtaaaact ctgtatttaa ctggcaatga ggaaaaaaaa attttgtaga gaagtgttgg 1735
tctgtatagt tctttatatt aagtgggatt cattgtaatg cctctgcatt tattctgttg 1795
cctcagctgt tacttgaaga tggcgtaata tataatttat cctgtggtat cagtgataaa 1855
aatgatacct ttctgtagga ggggtttatc ataatatgct gcttcttgaa ggcttgcact 1915
tccagaattg tgtttccttc tgctgtgcca ttcatatata tatacatata tatatataat 1975
cttgaccagt cctggtcatt tgctcccctc cttgtctgtg gaccatgata agcccaagta 2035
gtgacttcag agctgggtaa cagaaattaa agtgaaaaga cctttacgtg gagaatttgc 2095
atgcgtaata taggaaggtg ttctttaggt atgttacagg attactttaa accatttgac 2155
tttcgctcca aagttatgtt ggtagtatag caaattatga tgaatagctt taattgtatg 2215
tttaaaagtc tcatatgttc acatgcttaa atctgggtat cagaatttaa gcaattcttg 2275
aaatgtattg tctccttaat atactaatta caaagcatct ccaa 2319
<210> 66
<211> 397
<212> PRT
<213> 智人
<400> 66
Met Val Lys Glu Thr Thr Tyr Tyr Asp Val Leu Gly Val Lys Pro Asn
1 5 10 15
Ala Thr Gln Glu Glu Leu Lys Lys Ala Tyr Arg Lys Leu Ala Leu Lys
20 25 30
Tyr His Pro Asp Lys Asn Pro Asn Glu Gly Glu Lys Phe Lys Gln Ile
35 40 45
Ser Gln Ala Tyr Glu Val Leu Ser Asp Ala Lys Lys Arg Glu Leu Tyr
50 55 60
Asp Lys Gly Gly Glu Gln Ala Ile Lys Glu Gly Gly Ala Gly Gly Gly
65 70 75 80
Phe Gly Ser Pro Met Asp Ile Phe Asp Met Phe Phe Gly Gly Gly Gly
85 90 95
Arg Met Gln Arg Glu Arg Arg Gly Lys Asn Val Val His Gln Leu Ser
100 105 110
Val Thr Leu Glu Asp Leu Tyr Asn Gly Ala Thr Arg Lys Leu Ala Leu
115 120 125
Gln Lys Asn Val Ile Cys Asp Lys Cys Glu Gly Arg Gly Gly Lys Lys
130 135 140
Gly Ala Val Glu Cys Cys Pro Asn Cys Arg Gly Thr Gly Met Gln Ile
145 150 155 160
Arg Ile His Gln Ile Gly Pro Gly Met Val Gln Gln Ile Gln Ser Val
165 170 175
Cys Met Glu Cys Gln Gly His Gly Glu Arg Ile Ser Pro Lys Asp Arg
180 185 190
Cys Lys Ser Cys Asn Gly Arg Lys Ile Val Arg Glu Lys Lys Ile Leu
195 200 205
Glu Val His Ile Asp Lys Gly Met Lys Asp Gly Gln Lys Ile Thr Phe
210 215 220
His Gly Glu Gly Asp Gln Glu Pro Gly Leu Glu Pro Gly Asp Ile Ile
225 230 235 240
Ile Val Leu Asp Gln Lys Asp His Ala Val Phe Thr Arg Arg Gly Glu
245 250 255
Asp Leu Phe Met Cys Met Asp Ile Gln Leu Val Glu Ala Leu Cys Gly
260 265 270
Phe Gln Lys Pro Ile Ser Thr Leu Asp Asn Arg Thr Ile Val Ile Thr
275 280 285
Ser His Pro Gly Gln Ile Val Lys His Gly Asp Ile Lys Cys Val Leu
290 295 300
Asn Glu Gly Met Pro Ile Tyr Arg Arg Pro Tyr Glu Lys Gly Arg Leu
305 310 315 320
Ile Ile Glu Phe Lys Val Asn Phe Pro Glu Asn Gly Phe Leu Ser Pro
325 330 335
Asp Lys Leu Ser Leu Leu Glu Lys Leu Leu Pro Glu Arg Lys Glu Val
340 345 350
Glu Glu Thr Asp Glu Met Asp Gln Val Glu Leu Val Asp Phe Asp Pro
355 360 365
Asn Gln Glu Arg Arg Arg His Tyr Asn Gly Glu Ala Tyr Glu Asp Asp
370 375 380
Glu His His Pro Arg Gly Gly Val Gln Cys Gln Thr Ser
385 390 395
<210> 67
<211> 557
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (59)..(367)
<223> NM_002157 WT, CDS 59-367
<400> 67
gcgagtctct ttgcggcgct acactagagc agagtacgag tctgaggcgg agggagta 58
atg gca gga caa gcg ttt aga aag ttt ctt cca ctc ttt gac cga gta 106
Met Ala Gly Gln Ala Phe Arg Lys Phe Leu Pro Leu Phe Asp Arg Val
1 5 10 15
ttg gtt gaa agg agt gct gct gaa act gta acc aaa gga ggc att atg 154
Leu Val Glu Arg Ser Ala Ala Glu Thr Val Thr Lys Gly Gly Ile Met
20 25 30
ctt cca gaa aaa tct caa gga aaa gta ttg caa gca aca gta gtc gct 202
Leu Pro Glu Lys Ser Gln Gly Lys Val Leu Gln Ala Thr Val Val Ala
35 40 45
gtt gga tcg ggt tct aaa gga aag ggt gga gag att caa cca gtt agc 250
Val Gly Ser Gly Ser Lys Gly Lys Gly Gly Glu Ile Gln Pro Val Ser
50 55 60
gtg aaa gtt gga gat aaa gtt ctt ctc cca gaa tat gga ggc acc aaa 298
Val Lys Val Gly Asp Lys Val Leu Leu Pro Glu Tyr Gly Gly Thr Lys
65 70 75 80
gta gtt cta gat gac aag gat tat ttc cta ttt aga gat ggt gac att 346
Val Val Leu Asp Asp Lys Asp Tyr Phe Leu Phe Arg Asp Gly Asp Ile
85 90 95
ctt gga aag tac gta gac tga aataagtcac tattgaaatg gcatcaacat 397
Leu Gly Lys Tyr Val Asp
100
gatgctgccc attccactga agttctgaaa tctttcgtca tgtaaataat ttccatattt 457
ctcttttata ataaactaat gataactaat gacatccagt gtctccaaaa ttgtttcctt 517
gtactgatat aaacacttcc aaataaaaat atgtaaatga 557
<210> 68
<211> 102
<212> PRT
<213> 智人
<400> 68
Met Ala Gly Gln Ala Phe Arg Lys Phe Leu Pro Leu Phe Asp Arg Val
1 5 10 15
Leu Val Glu Arg Ser Ala Ala Glu Thr Val Thr Lys Gly Gly Ile Met
20 25 30
Leu Pro Glu Lys Ser Gln Gly Lys Val Leu Gln Ala Thr Val Val Ala
35 40 45
Val Gly Ser Gly Ser Lys Gly Lys Gly Gly Glu Ile Gln Pro Val Ser
50 55 60
Val Lys Val Gly Asp Lys Val Leu Leu Pro Glu Tyr Gly Gly Thr Lys
65 70 75 80
Val Val Leu Asp Asp Lys Asp Tyr Phe Leu Phe Arg Asp Gly Asp Ile
85 90 95
Leu Gly Lys Tyr Val Asp
100
<210> 69
<211> 5244
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (323)..(2899)
<223> NM_006644 WT, CDS 323-2899
<400> 69
gggtcggtag ttcagcgccg gcgccggtgt gcgagccgcg gcagagtgag gcaggcaacc 60
cgaggtgcgg agcgacctgc ggaggctgag ccccgctttc tcccagggtt tcttatcagc 120
cagccgccgc tgtccccggg ggagtaggag gctcctgaca ggccgcggct gtctgtgtgt 180
ccttctgagt gtcagaggaa cggccagacc ccgcgggccg gagcagaacg cggccagggc 240
agaaagcggc ggcaggagaa gcaggcaggg ggccggagga cgcagaccga gacccgaggc 300
ggaggcggac cgcgagccgg cc atg tcg gtg gtg ggg ttg gac gtg ggc tcg 352
Met Ser Val Val Gly Leu Asp Val Gly Ser
1 5 10
cag agc tgc tac atc gcg gta gcc cgg gcc ggg ggc atc gag acc atc 400
Gln Ser Cys Tyr Ile Ala Val Ala Arg Ala Gly Gly Ile Glu Thr Ile
15 20 25
gcc aat gag ttc agc gac cgg tgc acc ccg tca gtc ata tca ttt gga 448
Ala Asn Glu Phe Ser Asp Arg Cys Thr Pro Ser Val Ile Ser Phe Gly
30 35 40
tca aaa aat aga aca atc gga gtt gca gcc aaa aat cag caa atc act 496
Ser Lys Asn Arg Thr Ile Gly Val Ala Ala Lys Asn Gln Gln Ile Thr
45 50 55
cat gca aac aat acg gtg tct aac ttc aaa aga ttt cat ggc cga gca 544
His Ala Asn Asn Thr Val Ser Asn Phe Lys Arg Phe His Gly Arg Ala
60 65 70
ttc aat gac ccc ttc att caa aag gag aag gaa aac ttg agt tac gat 592
Phe Asn Asp Pro Phe Ile Gln Lys Glu Lys Glu Asn Leu Ser Tyr Asp
75 80 85 90
ttg gtt cca ttg aaa aat ggt gga gtt gga ata aag gta atg tac atg 640
Leu Val Pro Leu Lys Asn Gly Gly Val Gly Ile Lys Val Met Tyr Met
95 100 105
ggt gaa gaa cat cta ttt agt gtg gag cag ata aca gcc atg ttg ttg 688
Gly Glu Glu His Leu Phe Ser Val Glu Gln Ile Thr Ala Met Leu Leu
110 115 120
act aag ctg aag gaa act gct gaa aac agc ctc aag aaa cca gta aca 736
Thr Lys Leu Lys Glu Thr Ala Glu Asn Ser Leu Lys Lys Pro Val Thr
125 130 135
gat tgt gtt att tca gtc ccc tcc ttc ttt aca gat gct gag agg cga 784
Asp Cys Val Ile Ser Val Pro Ser Phe Phe Thr Asp Ala Glu Arg Arg
140 145 150
tct gtg tta gat gct gca cag att gtt ggc cta aac tgt tta aga ctt 832
Ser Val Leu Asp Ala Ala Gln Ile Val Gly Leu Asn Cys Leu Arg Leu
155 160 165 170
atg aat gac atg aca gct gtt gct ttg aat tac gga att tat aag cag 880
Met Asn Asp Met Thr Ala Val Ala Leu Asn Tyr Gly Ile Tyr Lys Gln
175 180 185
gat ctc cca agc ctg gat gag aaa cct cgg ata gtg gtt ttt gtt gat 928
Asp Leu Pro Ser Leu Asp Glu Lys Pro Arg Ile Val Val Phe Val Asp
190 195 200
atg gga cat tca gct ttt caa gtg tct gct tgt gct ttt aac aag gga 976
Met Gly His Ser Ala Phe Gln Val Ser Ala Cys Ala Phe Asn Lys Gly
205 210 215
aaa ttg aag gta ctg gga aca gct ttt gat cct ttc tta gga gga aaa 1024
Lys Leu Lys Val Leu Gly Thr Ala Phe Asp Pro Phe Leu Gly Gly Lys
220 225 230
aac ttc gat gaa aag tta gtg gaa cat ttt tgt gca gaa ttt aaa act 1072
Asn Phe Asp Glu Lys Leu Val Glu His Phe Cys Ala Glu Phe Lys Thr
235 240 245 250
aag tac aag ttg gat gca aaa tcc aaa ata cga gca ctc cta cgt ctg 1120
Lys Tyr Lys Leu Asp Ala Lys Ser Lys Ile Arg Ala Leu Leu Arg Leu
255 260 265
tat cag gaa tgt gaa aaa ctg aaa aag cta atg agc tct aac agc aca 1168
Tyr Gln Glu Cys Glu Lys Leu Lys Lys Leu Met Ser Ser Asn Ser Thr
270 275 280
gac ctt cca ctg aat atc gaa tgc ttt atg aat gat aaa gat gtt tcc 1216
Asp Leu Pro Leu Asn Ile Glu Cys Phe Met Asn Asp Lys Asp Val Ser
285 290 295
gga aag atg aac agg tca caa ttt gaa gaa ctc tgt gct gaa ctt ctg 1264
Gly Lys Met Asn Arg Ser Gln Phe Glu Glu Leu Cys Ala Glu Leu Leu
300 305 310
caa aag ata gaa gta ccc ctt tat tca ctg ttg gaa caa act cat ctc 1312
Gln Lys Ile Glu Val Pro Leu Tyr Ser Leu Leu Glu Gln Thr His Leu
315 320 325 330
aaa gta gaa gat gtg agt gca gtt gag att gtt gga ggc gct aca cga 1360
Lys Val Glu Asp Val Ser Ala Val Glu Ile Val Gly Gly Ala Thr Arg
335 340 345
att cca gct gtg aag gaa aga att gcc aaa ttc ttt gga aaa gat att 1408
Ile Pro Ala Val Lys Glu Arg Ile Ala Lys Phe Phe Gly Lys Asp Ile
350 355 360
agc aca aca ctc aat gca gat gaa gca gta gcc aga gga tgt gca tta 1456
Ser Thr Thr Leu Asn Ala Asp Glu Ala Val Ala Arg Gly Cys Ala Leu
365 370 375
cag tgt gca ata ctt tcc ccg gca ttt aaa gtt aga gaa ttt tcc gtc 1504
Gln Cys Ala Ile Leu Ser Pro Ala Phe Lys Val Arg Glu Phe Ser Val
380 385 390
aca gat gca gtt cct ttt cca ata tct ctg atc tgg aac cat gat tca 1552
Thr Asp Ala Val Pro Phe Pro Ile Ser Leu Ile Trp Asn His Asp Ser
395 400 405 410
gaa gat act gaa ggt gtt cat gaa gtc ttt agt cga aac cat gct gct 1600
Glu Asp Thr Glu Gly Val His Glu Val Phe Ser Arg Asn His Ala Ala
415 420 425
cct ttc tcc aaa gtt ctc acc ttt ctg aga agg ggg cct ttt gag cta 1648
Pro Phe Ser Lys Val Leu Thr Phe Leu Arg Arg Gly Pro Phe Glu Leu
430 435 440
gaa gct ttc tat tct gat ccc caa gga gtt cca tat cca gaa gca aaa 1696
Glu Ala Phe Tyr Ser Asp Pro Gln Gly Val Pro Tyr Pro Glu Ala Lys
445 450 455
ata ggc cgc ttt gta gtt cag aat gtt tct gca cag aaa gat gga gaa 1744
Ile Gly Arg Phe Val Val Gln Asn Val Ser Ala Gln Lys Asp Gly Glu
460 465 470
aaa tct aga gta aaa gtc aaa gtg cga gtc aac acc cat ggc att ttc 1792
Lys Ser Arg Val Lys Val Lys Val Arg Val Asn Thr His Gly Ile Phe
475 480 485 490
acc atc tct acg gca tct atg gtg gag aaa gtc cca act gag gag aat 1840
Thr Ile Ser Thr Ala Ser Met Val Glu Lys Val Pro Thr Glu Glu Asn
495 500 505
gaa atg tct tct gaa gct gac atg gag tgt ctg aat cag aga cca cca 1888
Glu Met Ser Ser Glu Ala Asp Met Glu Cys Leu Asn Gln Arg Pro Pro
510 515 520
gaa aac cca gac act gat aaa aat gtc cag caa gac aac agt gaa gct 1936
Glu Asn Pro Asp Thr Asp Lys Asn Val Gln Gln Asp Asn Ser Glu Ala
525 530 535
gga aca cag ccc cag gta caa act gat gct caa caa acc tca cag tct 1984
Gly Thr Gln Pro Gln Val Gln Thr Asp Ala Gln Gln Thr Ser Gln Ser
540 545 550
ccc cct tca cct gaa ctt acc tca gaa gaa aac aaa atc cca gat gct 2032
Pro Pro Ser Pro Glu Leu Thr Ser Glu Glu Asn Lys Ile Pro Asp Ala
555 560 565 570
gac aaa gca aat gaa aaa aaa gtt gac cag cct cca gaa gct aaa aag 2080
Asp Lys Ala Asn Glu Lys Lys Val Asp Gln Pro Pro Glu Ala Lys Lys
575 580 585
ccc aaa ata aag gtg gtg aat gtt gag ctg cct att gaa gcc aac ttg 2128
Pro Lys Ile Lys Val Val Asn Val Glu Leu Pro Ile Glu Ala Asn Leu
590 595 600
gtc tgg cag tta ggg aaa gac ctt ctt aac atg tat att gag aca gag 2176
Val Trp Gln Leu Gly Lys Asp Leu Leu Asn Met Tyr Ile Glu Thr Glu
605 610 615
ggt aag atg ata atg caa gat aaa ttg gaa aaa gaa agg aat gat gct 2224
Gly Lys Met Ile Met Gln Asp Lys Leu Glu Lys Glu Arg Asn Asp Ala
620 625 630
aaa aat gca gtt gag gaa tat gtg tat gag ttc aga gac aag ctg tgt 2272
Lys Asn Ala Val Glu Glu Tyr Val Tyr Glu Phe Arg Asp Lys Leu Cys
635 640 645 650
gga cca tat gaa aaa ttt ata tgt gag cag gat cat caa aat ttt ttg 2320
Gly Pro Tyr Glu Lys Phe Ile Cys Glu Gln Asp His Gln Asn Phe Leu
655 660 665
aga ctc ctc aca gaa act gaa gac tgg ctg tat gaa gaa gga gag gac 2368
Arg Leu Leu Thr Glu Thr Glu Asp Trp Leu Tyr Glu Glu Gly Glu Asp
670 675 680
caa gct aaa caa gca tat gtt gac aag ttg gaa gaa tta atg aaa att 2416
Gln Ala Lys Gln Ala Tyr Val Asp Lys Leu Glu Glu Leu Met Lys Ile
685 690 695
ggc act cca gtt aaa gtt cgg ttt cag gaa gct gaa gaa cgg cca aaa 2464
Gly Thr Pro Val Lys Val Arg Phe Gln Glu Ala Glu Glu Arg Pro Lys
700 705 710
atg ttt gaa gaa cta gga cag agg ctg cag cat tat gcc aag ata gca 2512
Met Phe Glu Glu Leu Gly Gln Arg Leu Gln His Tyr Ala Lys Ile Ala
715 720 725 730
gct gac ttc aga aat aag gat gag aaa tac aac cat att gat gag tct 2560
Ala Asp Phe Arg Asn Lys Asp Glu Lys Tyr Asn His Ile Asp Glu Ser
735 740 745
gaa atg aaa aaa gtg gag aag tct gtt aat gaa gtg atg gaa tgg atg 2608
Glu Met Lys Lys Val Glu Lys Ser Val Asn Glu Val Met Glu Trp Met
750 755 760
aat aat gtc atg aat gct cag gct aaa aag agt ctt gat cag gat cca 2656
Asn Asn Val Met Asn Ala Gln Ala Lys Lys Ser Leu Asp Gln Asp Pro
765 770 775
gtt gta cgt gct cag gaa att aaa aca aaa atc aag gaa ttg aac aac 2704
Val Val Arg Ala Gln Glu Ile Lys Thr Lys Ile Lys Glu Leu Asn Asn
780 785 790
aca tgt gaa ccc gtt gta aca caa ccg aaa cca aaa att gaa tca ccc 2752
Thr Cys Glu Pro Val Val Thr Gln Pro Lys Pro Lys Ile Glu Ser Pro
795 800 805 810
aaa ctg gaa aga act cca aat ggc cca aat att gat aaa aag gaa gaa 2800
Lys Leu Glu Arg Thr Pro Asn Gly Pro Asn Ile Asp Lys Lys Glu Glu
815 820 825
gat tta gaa gac aaa aac aat ttt ggt gct gaa cct cca cat cag aat 2848
Asp Leu Glu Asp Lys Asn Asn Phe Gly Ala Glu Pro Pro His Gln Asn
830 835 840
ggt gaa tgt tac cct aat gag aaa aat tct gtt aat atg gac ttg gac 2896
Gly Glu Cys Tyr Pro Asn Glu Lys Asn Ser Val Asn Met Asp Leu Asp
845 850 855
tag ataaccttaa attggcctat tccttcaatt aataaaatat ttttgccata 2949
gtatgtgact ctacataaca tactgaaact atttatattt tcttttttaa ggatatttag 3009
aaattttgtg tattatatgg aaaaagaaaa aaagcttaag tctgtagtct ttatgatcct 3069
aaaagggaaa attgccttgg taactttcag attcctgtgg aattgtgaat tcatactaag 3129
ctttctgtgc agtctcacca tttgcatcac tgaggatgaa actgactttt gtcttttgga 3189
gaaaaaaaac tgtactgctt gttcaagagg gctgtgatta aaatctttaa gcatttgttc 3249
ctgccaaggt agttttcttg cattttgctc tccattcagc atgtgtgtgg gtgtggatgt 3309
ttataaacaa gactaagtct gacttcataa gggctttcta aaaccatttc tgtccaagag 3369
aaaatgactt tttgctttga tattaaaaat tcaatgagta aaacaaaagc tagtcaaatg 3429
tgttagcagc atgcagaaca aaaactttaa actttctctc tcactataca gtatattgtc 3489
atgtgaaagt gtggaatgga agaaatgtcg atcctgttgt aactgattgt gaacactttt 3549
atgagcttta aaataaagtt catcttatgg tgtcatttct aaactgttga ttttgtcact 3609
aatttaaaaa atgagatgag ggagaatatg aattattcta gcagaaatga agttagtgtc 3669
cagtttttct tttttactgc ttatgttctc tcttttctaa gtgaaaatgt ttttctcctg 3729
acagaaaaat agcatatgtt tattacatta aagcatttta aaaatactat aaagtgaata 3789
aaacttaaaa tcttgccacc cagaagaaaa cattgttaac acttcgttat acatccttgg 3849
agccttttac ccctaatgat gggggtatat ttgtgtgagt gtctatgtta tagtgctgta 3909
ggctgttttt aaaaactctg tgccagggaa attagtaaat acagtcaagt gttgtaactg 3969
cataaatgta gtgagttcat tataaagacg tacttaaaaa taccaatctt gctattggta 4029
gatttaggtg tttctcattt ttgctgttct aaataatgct gcaatgaatc tatctggttg 4089
ttttgtaagc acaaaattga agtagtgttg gaggtagggg agaagacaca tgcacttagg 4149
ataggtgaca accagctcct cactagggtg caacagttta ttcttttttt ttttttggta 4209
gagctggggt ttcgctatgt tgcccaagtt cgtcttgaac tcctgggctc aagcaatctg 4269
tctgcctcag cctcccaaag tgctgggatt acatggtgtg agccaccatg cccagccatt 4329
tatgatcttg atgagggcca actttccctc ttccacaagg gattaatctt agaactatag 4389
ccaatttatt ataagtacta tttagctact ctgtgctcca cacatcacgg agtaatatct 4449
tcaaactatg aggtttagta acacttgact gctgaggttt atttcctcag ctctgatgct 4509
tcctgggtga agatgtaagt tattaaatta actcaaattt taaagctaac acttcattcc 4569
atctagacca ggtagctcgt catttgtacg tctgataggt gcttcaacat ctcagaattg 4629
gcttattttt catgcattgc atattgtact catttgtaat attggaatgt aaaatgttct 4689
tactaagaat ctttatgtca gctattcaac atttccctac tttataattt ctagctgctt 4749
taccatttag caactttaaa tttttatgca gttaatatgt ttctttggtt tttatgtttt 4809
ctgaatgtct ttaatgcaca ttaatgtata cttagtagat acacatttac acattgagaa 4869
gtgaagatag gtttgtgttc tgtgtacaat taggacatcc attaaaaaag atttttaaaa 4929
actgtgaatg ggaaaacatg tttttcctcc tgtcctaaaa tagaacctga tgacgggagg 4989
gagcatcagt cagtctggcc taaatcagtg tactgcgctt ttggatgcgg gcaaaagtat 5049
tgtcatgttg attactttat aataacgtat taatatcatt ggctcaaaca gttgtgatat 5109
atacctagta atcatcgagg atctcaaaga tatgcaccag tttgaataaa tgctgtttaa 5169
agattaaatt ttacaattca ttttaaattg tcattttgtg acaatatttc taaacaacgt 5229
ccatttttaa taaca 5244
<210> 70
<211> 858
<212> PRT
<213> 智人
<400> 70
Met Ser Val Val Gly Leu Asp Val Gly Ser Gln Ser Cys Tyr Ile Ala
1 5 10 15
Val Ala Arg Ala Gly Gly Ile Glu Thr Ile Ala Asn Glu Phe Ser Asp
20 25 30
Arg Cys Thr Pro Ser Val Ile Ser Phe Gly Ser Lys Asn Arg Thr Ile
35 40 45
Gly Val Ala Ala Lys Asn Gln Gln Ile Thr His Ala Asn Asn Thr Val
50 55 60
Ser Asn Phe Lys Arg Phe His Gly Arg Ala Phe Asn Asp Pro Phe Ile
65 70 75 80
Gln Lys Glu Lys Glu Asn Leu Ser Tyr Asp Leu Val Pro Leu Lys Asn
85 90 95
Gly Gly Val Gly Ile Lys Val Met Tyr Met Gly Glu Glu His Leu Phe
100 105 110
Ser Val Glu Gln Ile Thr Ala Met Leu Leu Thr Lys Leu Lys Glu Thr
115 120 125
Ala Glu Asn Ser Leu Lys Lys Pro Val Thr Asp Cys Val Ile Ser Val
130 135 140
Pro Ser Phe Phe Thr Asp Ala Glu Arg Arg Ser Val Leu Asp Ala Ala
145 150 155 160
Gln Ile Val Gly Leu Asn Cys Leu Arg Leu Met Asn Asp Met Thr Ala
165 170 175
Val Ala Leu Asn Tyr Gly Ile Tyr Lys Gln Asp Leu Pro Ser Leu Asp
180 185 190
Glu Lys Pro Arg Ile Val Val Phe Val Asp Met Gly His Ser Ala Phe
195 200 205
Gln Val Ser Ala Cys Ala Phe Asn Lys Gly Lys Leu Lys Val Leu Gly
210 215 220
Thr Ala Phe Asp Pro Phe Leu Gly Gly Lys Asn Phe Asp Glu Lys Leu
225 230 235 240
Val Glu His Phe Cys Ala Glu Phe Lys Thr Lys Tyr Lys Leu Asp Ala
245 250 255
Lys Ser Lys Ile Arg Ala Leu Leu Arg Leu Tyr Gln Glu Cys Glu Lys
260 265 270
Leu Lys Lys Leu Met Ser Ser Asn Ser Thr Asp Leu Pro Leu Asn Ile
275 280 285
Glu Cys Phe Met Asn Asp Lys Asp Val Ser Gly Lys Met Asn Arg Ser
290 295 300
Gln Phe Glu Glu Leu Cys Ala Glu Leu Leu Gln Lys Ile Glu Val Pro
305 310 315 320
Leu Tyr Ser Leu Leu Glu Gln Thr His Leu Lys Val Glu Asp Val Ser
325 330 335
Ala Val Glu Ile Val Gly Gly Ala Thr Arg Ile Pro Ala Val Lys Glu
340 345 350
Arg Ile Ala Lys Phe Phe Gly Lys Asp Ile Ser Thr Thr Leu Asn Ala
355 360 365
Asp Glu Ala Val Ala Arg Gly Cys Ala Leu Gln Cys Ala Ile Leu Ser
370 375 380
Pro Ala Phe Lys Val Arg Glu Phe Ser Val Thr Asp Ala Val Pro Phe
385 390 395 400
Pro Ile Ser Leu Ile Trp Asn His Asp Ser Glu Asp Thr Glu Gly Val
405 410 415
His Glu Val Phe Ser Arg Asn His Ala Ala Pro Phe Ser Lys Val Leu
420 425 430
Thr Phe Leu Arg Arg Gly Pro Phe Glu Leu Glu Ala Phe Tyr Ser Asp
435 440 445
Pro Gln Gly Val Pro Tyr Pro Glu Ala Lys Ile Gly Arg Phe Val Val
450 455 460
Gln Asn Val Ser Ala Gln Lys Asp Gly Glu Lys Ser Arg Val Lys Val
465 470 475 480
Lys Val Arg Val Asn Thr His Gly Ile Phe Thr Ile Ser Thr Ala Ser
485 490 495
Met Val Glu Lys Val Pro Thr Glu Glu Asn Glu Met Ser Ser Glu Ala
500 505 510
Asp Met Glu Cys Leu Asn Gln Arg Pro Pro Glu Asn Pro Asp Thr Asp
515 520 525
Lys Asn Val Gln Gln Asp Asn Ser Glu Ala Gly Thr Gln Pro Gln Val
530 535 540
Gln Thr Asp Ala Gln Gln Thr Ser Gln Ser Pro Pro Ser Pro Glu Leu
545 550 555 560
Thr Ser Glu Glu Asn Lys Ile Pro Asp Ala Asp Lys Ala Asn Glu Lys
565 570 575
Lys Val Asp Gln Pro Pro Glu Ala Lys Lys Pro Lys Ile Lys Val Val
580 585 590
Asn Val Glu Leu Pro Ile Glu Ala Asn Leu Val Trp Gln Leu Gly Lys
595 600 605
Asp Leu Leu Asn Met Tyr Ile Glu Thr Glu Gly Lys Met Ile Met Gln
610 615 620
Asp Lys Leu Glu Lys Glu Arg Asn Asp Ala Lys Asn Ala Val Glu Glu
625 630 635 640
Tyr Val Tyr Glu Phe Arg Asp Lys Leu Cys Gly Pro Tyr Glu Lys Phe
645 650 655
Ile Cys Glu Gln Asp His Gln Asn Phe Leu Arg Leu Leu Thr Glu Thr
660 665 670
Glu Asp Trp Leu Tyr Glu Glu Gly Glu Asp Gln Ala Lys Gln Ala Tyr
675 680 685
Val Asp Lys Leu Glu Glu Leu Met Lys Ile Gly Thr Pro Val Lys Val
690 695 700
Arg Phe Gln Glu Ala Glu Glu Arg Pro Lys Met Phe Glu Glu Leu Gly
705 710 715 720
Gln Arg Leu Gln His Tyr Ala Lys Ile Ala Ala Asp Phe Arg Asn Lys
725 730 735
Asp Glu Lys Tyr Asn His Ile Asp Glu Ser Glu Met Lys Lys Val Glu
740 745 750
Lys Ser Val Asn Glu Val Met Glu Trp Met Asn Asn Val Met Asn Ala
755 760 765
Gln Ala Lys Lys Ser Leu Asp Gln Asp Pro Val Val Arg Ala Gln Glu
770 775 780
Ile Lys Thr Lys Ile Lys Glu Leu Asn Asn Thr Cys Glu Pro Val Val
785 790 795 800
Thr Gln Pro Lys Pro Lys Ile Glu Ser Pro Lys Leu Glu Arg Thr Pro
805 810 815
Asn Gly Pro Asn Ile Asp Lys Lys Glu Glu Asp Leu Glu Asp Lys Asn
820 825 830
Asn Phe Gly Ala Glu Pro Pro His Gln Asn Gly Glu Cys Tyr Pro Asn
835 840 845
Glu Lys Asn Ser Val Asn Met Asp Leu Asp
850 855
<210> 71
<211> 4766
<212> DNA
<213> 智人
<220>
<221> CDS
<222> (1095)..(1838)
<223> NM_170735.6 WT, CDS 1095-1838
<400> 71
gcgcgcgcgc acacacacac acacacacag agagaacatc tctagtaaaa agaaaagttg 60
agctttctta gctagatgtg tgtattagcc agaaaaagcc aaggagtgaa gggttttaga 120
gaactggagg agataaagtg gagtctgcat atgggaggca tttgaaatgg acttaaatgt 180
ctttttaatg ctgacttttt cagttttctc cttaccagac acattgtttt catgacatta 240
gccccaggca tagacacatc attaaaatga acatgtcaaa aaatgatttc tgtttagaaa 300
taagcaaaac attttcagtt gtgaccaccc aggtgtagaa taaagaacag tggaattggg 360
agccctgagt tctaacataa actttcttca tgacataagg caagtcttct atggcctttg 420
gtttccttac ctgtaaaaca ggatggctca atgaaattat ctttcttctt tgctataata 480
gagtatctct gtgggaagag gaaaaaaaaa gtcaatttaa aggctcctta tagttcccca 540
actgctgttt tattgtgcta ttcatgccta gacatcacat agctagaaag gcccatcaga 600
cccctcaggc cactgctgtt cctgtcacac attcctgcaa aggaccatgt tgctaacttg 660
aaaaaaatta ctattaatta cacttgcagt tgttgcttag taacatttat gattttgtgt 720
ttctcgtgac agcatgagca gagatcatta aaaattaaac ttacaaagct gctaaagtgg 780
gaagaaggag aacttgaagc cacaattttt gcacttgctt agaagccatc taatctcagg 840
tttatatgct agatcttggg ggaaacactg catgtctctg gtttatatta aaccacatac 900
agcacactac tgacactgat ttgtgtctgg tgcagctgga gtttatcacc aagacataaa 960
aaaaccttga ccctgcagaa tggcctggaa ttacaatcag atgggccaca tggcatcccg 1020
gtgaaagaaa gccctaacca gttttctgtc ttgtttctgc tttctcccta cagttccacc 1080
aggtgagaag agtg atg acc atc ctt ttc ctt act atg gtt att tca tac 1130
Met Thr Ile Leu Phe Leu Thr Met Val Ile Ser Tyr
1 5 10
ttt ggt tgc atg aag gct gcc ccc atg aaa gaa gca aac atc cga gga 1178
Phe Gly Cys Met Lys Ala Ala Pro Met Lys Glu Ala Asn Ile Arg Gly
15 20 25
caa ggt ggc ttg gcc tac cca ggt gtg cgg acc cat ggg act ctg gag 1226
Gln Gly Gly Leu Ala Tyr Pro Gly Val Arg Thr His Gly Thr Leu Glu
30 35 40
agc gtg aat ggg ccc aag gca ggt tca aga ggc ttg aca tca ttg gct 1274
Ser Val Asn Gly Pro Lys Ala Gly Ser Arg Gly Leu Thr Ser Leu Ala
45 50 55 60
gac act ttc gaa cac gtg ata gaa gag ctg ttg gat gag gac cag aaa 1322
Asp Thr Phe Glu His Val Ile Glu Glu Leu Leu Asp Glu Asp Gln Lys
65 70 75
gtt cgg ccc aat gaa gaa aac aat aag gac gca gac ttg tac acg tcc 1370
Val Arg Pro Asn Glu Glu Asn Asn Lys Asp Ala Asp Leu Tyr Thr Ser
80 85 90
agg gtg atg ctc agt agt caa gtg cct ttg gag cct cct ctt ctc ttt 1418
Arg Val Met Leu Ser Ser Gln Val Pro Leu Glu Pro Pro Leu Leu Phe
95 100 105
ctg ctg gag gaa tac aaa aat tac cta gat gct gca aac atg tcc atg 1466
Leu Leu Glu Glu Tyr Lys Asn Tyr Leu Asp Ala Ala Asn Met Ser Met
110 115 120
agg gtc cgg cgc cac tct gac cct gcc cgc cga ggg gag ctg agc gtg 1514
Arg Val Arg Arg His Ser Asp Pro Ala Arg Arg Gly Glu Leu Ser Val
125 130 135 140
tgt gac agt att agt gag tgg gta acg gcg gca gac aaa aag act gca 1562
Cys Asp Ser Ile Ser Glu Trp Val Thr Ala Ala Asp Lys Lys Thr Ala
145 150 155
gtg gac atg tcg ggc ggg acg gtc aca gtc ctt gaa aag gtc cct gta 1610
Val Asp Met Ser Gly Gly Thr Val Thr Val Leu Glu Lys Val Pro Val
160 165 170
tca aaa ggc caa ctg aag caa tac ttc tac gag acc aag tgc aat ccc 1658
Ser Lys Gly Gln Leu Lys Gln Tyr Phe Tyr Glu Thr Lys Cys Asn Pro
175 180 185
atg ggt tac aca aaa gaa ggc tgc agg ggc ata gac aaa agg cat tgg 1706
Met Gly Tyr Thr Lys Glu Gly Cys Arg Gly Ile Asp Lys Arg His Trp
190 195 200
aac tcc cag tgc cga act acc cag tcg tac gtg cgg gcc ctt acc atg 1754
Asn Ser Gln Cys Arg Thr Thr Gln Ser Tyr Val Arg Ala Leu Thr Met
205 210 215 220
gat agc aaa aag aga att ggc tgg cga ttc ata agg ata gac act tct 1802
Asp Ser Lys Lys Arg Ile Gly Trp Arg Phe Ile Arg Ile Asp Thr Ser
225 230 235
tgt gta tgt aca ttg acc att aaa agg gga aga tag tggatttatg 1848
Cys Val Cys Thr Leu Thr Ile Lys Arg Gly Arg
240 245
ttgtatagat tagattatat tgagacaaaa attatctatt tgtatatata cataacaggg 1908
taaattattc agttaagaaa aaaataattt tatgaactgc atgtataaat gaagtttata 1968
cagtacagtg gttctacaat ctatttattg gacatgtcca tgaccagaag ggaaacagtc 2028
atttgcgcac aacttaaaaa gtctgcatta cattccttga taatgttgtg gtttgttgcc 2088
gttgccaaga actgaaaaca taaaaagtta aaaaaaataa taaattgcat gctgctttaa 2148
ttgtgaattg ataataaact gtcctctttc agaaaacaga aaaaaaacac acacacacac 2208
aacaaaaatt tgaaccaaaa cattccgttt acattttaga cagtaagtat cttcgttctt 2268
gttagtacta tatctgtttt actgctttta acttctgata gcgttggaat taaaacaatg 2328
tcaaggtgct gttgtcattg ctttactggc ttaggggatg ggggatgggg ggtatatttt 2388
tgtttgtttt gtgttttttt ttcgtttgtt tgttttgttt tttagttccc acagggagta 2448
gagatgggga aagaattcct acaatatata ttctggctga taaaagatac atttgtatgt 2508
tgtgaagatg tttgcaatat cgatcagatg actagaaagt gaataaaaat taaggcaact 2568
gaacaaaaaa atgctcacac tccacatccc gtgatgcacc tcccaggccc cgctcattct 2628
ttgggcgttg gtcagagtaa gctgcttttg acggaaggac ctatgtttgc tcagaacaca 2688
ttctttcccc ccctccccct ctggtctcct ctttgttttg ttttaaggaa gaaaaatcag 2748
ttgcgcgttc tgaaatattt taccactgct gtgaacaagt gaacacattg tgtcacatca 2808
tgacactcgt ataagcatgg agaacagtga ttttttttta gaacagaaaa caacaaaaaa 2868
taaccccaaa atgaagatta ttttttatga ggagtgaaca tttgggtaaa tcatggctaa 2928
gcttaaaaaa aactcatggt gaggcttaac aatgtcttgt aagcaaaagg tagagccctg 2988
tatcaaccca gaaacaccta gatcagaaca ggaatccaca ttgccagtga catgagactg 3048
aacagccaaa tggaggctat gtggagttgg cattgcattt accggcagtg cgggaggaat 3108
ttctgagtgg ccatcccaag gtctaggtgg aggtggggca tggtatttga gacattccaa 3168
aacgaaggcc tctgaaggac ccttcagagg tggctctgga atgacatgtg tcaagctgct 3228
tggacctcgt gctttaagtg cctacattat ctaactgtgc tcaagaggtt ctcgactgga 3288
ggaccacact caagccgact tatgcccacc atcccacctc tggataattt tgcataaaat 3348
tggattagcc tggagcaggt tgggagccaa atgtggcatt tgtgatcatg agattgatgc 3408
aatgagatag aagatgtttg ctacctgaac acttattgct ttgaaactag acttgaggaa 3468
accagggttt atcttttgag aacttttggt aagggaaaag ggaacaggaa aagaaacccc 3528
aaactcaggc cgaatgatca aggggaccca taggaaatct tgtccagaga caagacttcg 3588
ggaaggtgtc tggacattca gaacaccaag acttgaaggt gccttgctca atggaagagg 3648
ccaggacaga gctgacaaaa ttttgctccc cagtgaaggc cacagcaacc ttctgcccat 3708
cctgtctgtt catggagagg gtccctgcct cacctctgcc attttgggtt aggagaagtc 3768
aagttgggag cctgaaatag tggttcttgg aaaaatggat ccccagtgaa aactagagct 3828
ctaagcccat tcagcccatt tcacacctga aaatgttagt gatcaccact tggaccagca 3888
tccttaagta tcagaaagcc ccaagcaatt gctgcatctt agtagggtga gggataagca 3948
aaagaggatg ttcaccataa cccaggaatg aagataccat cagcaaagaa tttcaatttg 4008
ttcagtcttt catttagagc tagtctttca cagtaccatc tgaatacctc tttgaaagaa 4068
ggaagacttt acgtagtgta gatttgtttt gtgttgtttg aaaatattat ctttgtaatt 4128
atttttaata tgtaaggaat gcttggaata tctgctgtat gtcaacttta tgcagcttcc 4188
ttttgaggga caaatttaaa acaaacaacc ccccatcaca aacttaaagg attgcaaggg 4248
ccagatctgt taagtggttt cataggagac acatccagca attgtgtggt cagtggctct 4308
tttacccaat aagatacatc acagtcacat gcttgatggt ttatgttgac ctaagattta 4368
ttttgttaaa atctctctct gttgtgttcg ttcttgttct gttttgtttt gttttttaaa 4428
gtcttgctgt ggtctctttg tggcagaagt gtttcatgca tggcagcagg cctgttgctt 4488
ttttatggcg attcccattg aaaatgtaag taaatgtctg tggccttgtt ctctctatgg 4548
taaagatatt attcaccatg taaaacaaaa aacaatattt attgtatttt agtatattta 4608
tataattatg ttattgaaaa aaattggcat taaaacttaa ccgcatcaga agcctattgt 4668
aaatacaagt tctatttaag tgtactaatt aacatataat atatgtttta aatatagaat 4728
ttttaatgtt tttaaatata ttttcaaagt acataaaa 4766
<210> 72
<211> 247
<212> PRT
<213> 智人
<400> 72
Met Thr Ile Leu Phe Leu Thr Met Val Ile Ser Tyr Phe Gly Cys Met
1 5 10 15
Lys Ala Ala Pro Met Lys Glu Ala Asn Ile Arg Gly Gln Gly Gly Leu
20 25 30
Ala Tyr Pro Gly Val Arg Thr His Gly Thr Leu Glu Ser Val Asn Gly
35 40 45
Pro Lys Ala Gly Ser Arg Gly Leu Thr Ser Leu Ala Asp Thr Phe Glu
50 55 60
His Val Ile Glu Glu Leu Leu Asp Glu Asp Gln Lys Val Arg Pro Asn
65 70 75 80
Glu Glu Asn Asn Lys Asp Ala Asp Leu Tyr Thr Ser Arg Val Met Leu
85 90 95
Ser Ser Gln Val Pro Leu Glu Pro Pro Leu Leu Phe Leu Leu Glu Glu
100 105 110
Tyr Lys Asn Tyr Leu Asp Ala Ala Asn Met Ser Met Arg Val Arg Arg
115 120 125
His Ser Asp Pro Ala Arg Arg Gly Glu Leu Ser Val Cys Asp Ser Ile
130 135 140
Ser Glu Trp Val Thr Ala Ala Asp Lys Lys Thr Ala Val Asp Met Ser
145 150 155 160
Gly Gly Thr Val Thr Val Leu Glu Lys Val Pro Val Ser Lys Gly Gln
165 170 175
Leu Lys Gln Tyr Phe Tyr Glu Thr Lys Cys Asn Pro Met Gly Tyr Thr
180 185 190
Lys Glu Gly Cys Arg Gly Ile Asp Lys Arg His Trp Asn Ser Gln Cys
195 200 205
Arg Thr Thr Gln Ser Tyr Val Arg Ala Leu Thr Met Asp Ser Lys Lys
210 215 220
Arg Ile Gly Trp Arg Phe Ile Arg Ile Asp Thr Ser Cys Val Cys Thr
225 230 235 240
Leu Thr Ile Lys Arg Gly Arg
245
<210> 73
<211> 357
<212> DNA
<213> 人工序列
<220>
<223> 成熟BDNF WT
<220>
<221> CDS
<222> (1)..(357)
<400> 73
cac agc gac cca gct aga agg gga gag ctg tcc gtg tgc gat tcc atc 48
His Ser Asp Pro Ala Arg Arg Gly Glu Leu Ser Val Cys Asp Ser Ile
1 5 10 15
agc gag tgg gtg acc gcc gct gac aag aag aca gct gtg gat atg agc 96
Ser Glu Trp Val Thr Ala Ala Asp Lys Lys Thr Ala Val Asp Met Ser
20 25 30
ggc ggc acc gtg aca gtg ctg gag aag gtg ccc gtg tct aag ggc cag 144
Gly Gly Thr Val Thr Val Leu Glu Lys Val Pro Val Ser Lys Gly Gln
35 40 45
ctg aag cag tat ttc tac gag acc aag tgc aac cct atg ggc tac aca 192
Leu Lys Gln Tyr Phe Tyr Glu Thr Lys Cys Asn Pro Met Gly Tyr Thr
50 55 60
aag gag ggc tgt agg ggc atc gac aag cgg cat tgg aac tcc cag tgt 240
Lys Glu Gly Cys Arg Gly Ile Asp Lys Arg His Trp Asn Ser Gln Cys
65 70 75 80
aga acc aca cag tcc tat gtg cgc gcc ctg acc atg gac tcc aag aag 288
Arg Thr Thr Gln Ser Tyr Val Arg Ala Leu Thr Met Asp Ser Lys Lys
85 90 95
agg atc ggc tgg agg ttc atc cgc atc gat aca agc tgc gtg tgc acc 336
Arg Ile Gly Trp Arg Phe Ile Arg Ile Asp Thr Ser Cys Val Cys Thr
100 105 110
ctg aca atc aag agg ggc cgg 357
Leu Thr Ile Lys Arg Gly Arg
115
<210> 74
<211> 119
<212> PRT
<213> 人工序列
<220>
<223> 合成结构
<400> 74
His Ser Asp Pro Ala Arg Arg Gly Glu Leu Ser Val Cys Asp Ser Ile
1 5 10 15
Ser Glu Trp Val Thr Ala Ala Asp Lys Lys Thr Ala Val Asp Met Ser
20 25 30
Gly Gly Thr Val Thr Val Leu Glu Lys Val Pro Val Ser Lys Gly Gln
35 40 45
Leu Lys Gln Tyr Phe Tyr Glu Thr Lys Cys Asn Pro Met Gly Tyr Thr
50 55 60
Lys Glu Gly Cys Arg Gly Ile Asp Lys Arg His Trp Asn Ser Gln Cys
65 70 75 80
Arg Thr Thr Gln Ser Tyr Val Arg Ala Leu Thr Met Asp Ser Lys Lys
85 90 95
Arg Ile Gly Trp Arg Phe Ile Arg Ile Asp Thr Ser Cys Val Cys Thr
100 105 110
Leu Thr Ile Lys Arg Gly Arg
115
<210> 75
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 连接肽
<400> 75
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly Ser Gly Gly Gly Gly Ser
20 25
<210> 76
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> GS 连接子
<400> 76
Gly Gly Gly Gly Ser
1 5
<210> 77
<211> 6
<212> PRT
<213> 人工序列
<220>
<223> H4 连接子
<400> 77
Glu Ala Ala Ala Ala Lys
1 5

Claims (14)

1.一种融合蛋白的制造方法,其中,所述融合蛋白包含BDNF以及抗转铁蛋白受体抗体或其片段,
所述融合蛋白的制造方法包括以下工序:
在蛋白质生产用培养基中培养含有编码所述融合蛋白的基因和编码外源性伴侣蛋白的基因的经转化的哺乳动物细胞,来生产所述融合蛋白;以及
对所生产的所述融合蛋白进行回收,
其中,编码所述融合蛋白的基因包含编码所述BDNF的基因的碱基序列和编码所述抗转铁蛋白受体抗体或其片段的基因的碱基序列,
所述伴侣蛋白包含选自由HSP90α、HSP90β、CDC37、HSP70、HSP40、HSP60、HSP10、HSP110以及HSP27构成的组中的一种以上。
2.根据权利要求1所述的融合蛋白的制造方法,其中,所述融合蛋白包含所述BDNF以及所述抗转铁蛋白受体抗体或其片段,
所述融合蛋白的制造方法包括以下工序:
准备哺乳动物细胞;
使用编码所述融合蛋白的基因和编码所述伴侣蛋白的基因,对所述哺乳动物细胞进行转化;
在蛋白质生产用培养基中培养经转化的所述哺乳动物细胞,来生产所述融合蛋白;以及
对所生产的所述融合蛋白进行回收,
其中,编码所述融合蛋白的基因包含编码所述BDNF的基因的碱基序列和编码所述抗转铁蛋白受体抗体或其片段的基因的碱基序列,
所述伴侣蛋白包含选自由HSP90α、HSP90β、CDC37、HSP70、HSP40、HSP60、HSP10、HSP110以及HSP27构成的组中的一种以上。
3.根据权利要求2所述的融合蛋白的制造方法,其中,
对所述哺乳动物细胞进行转化的工序使用含有编码所述融合蛋白的基因和编码所述伴侣蛋白的基因的一种以上重组蛋白表达载体来实施。
4.根据权利要求2所述的融合蛋白的制造方法,其中,
对所述哺乳动物细胞进行转化的工序通过使含有编码所述融合蛋白的基因的一种以上重组蛋白表达载体、以及含有编码所述伴侣蛋白的基因的一种以上表达增强载体同时或分别与所述哺乳动物细胞接触来实施。
5.根据权利要求1所述的融合蛋白的制造方法,其中,所述融合蛋白包含所述BDNF以及所述抗转铁蛋白受体抗体或其片段,
所述融合蛋白的制造方法包括以下工序:
准备哺乳动物细胞,所述哺乳动物细胞包含含有编码所述融合蛋白的基因的一种以上重组蛋白表达载体;
使用含有编码所述伴侣蛋白的基因的至少一种表达增强载体,对所述哺乳动物细胞进行转化;
在蛋白质生产用培养基中培养经转化的所述哺乳动物细胞,来生产所述融合蛋白;以及
对所生产的所述融合蛋白进行回收,
其中,编码所述融合蛋白的基因包含编码所述BDNF的基因的碱基序列和编码所述抗转铁蛋白受体抗体或其片段的基因的碱基序列,
所述伴侣蛋白包含选自由HSP90α、HSP90β、CDC37、HSP70、HSP40、HSP60、HSP10、HSP110以及HSP27构成的组中的一种以上。
6.根据权利要求5所述的融合蛋白的制造方法,其中,
所述表达增强载体包含:第一表达增强载体,含有编码第一伴侣蛋白的基因;以及第二表达增强载体,含有编码第二伴侣蛋白的基因,
所述第一伴侣蛋白与所述第二伴侣蛋白不同。
7.根据权利要求1至6中任一项所述的融合蛋白的制造方法,其中,
所述伴侣蛋白包含HSP90α和CDC37中的任一者或两者。
8.根据权利要求1至7中任一项所述的融合蛋白的制造方法,其中,
所述BDNF直接或借助连接肽与所述抗转铁蛋白受体抗体或其片段结合。
9.根据权利要求8所述的融合蛋白的制造方法,其中,
所述连接肽包含选自由Gly、Ser、Gly-Ser、Gly-Gly-Ser、Gly-Gly-Gly-Gly-Ser、Gly-Gly-Gly-Gly-Gly-Ser、Ser-Gly-Gly-Gly-Gly、以及这些氨基酸序列1~10个连续而成的氨基酸序列构成的组中的氨基酸序列。
10.根据权利要求1至9中任一项所述的融合蛋白的制造方法,其中,
所述BDNF包含相对于序列号32的氨基酸序列具有至少90%的序列一致性的氨基酸序列。
11.根据权利要求1至10中任一项所述的融合蛋白的制造方法,其中,
所述抗转铁蛋白受体抗体的片段为Fab片段、F(ab’)2片段、或F(ab’)片段。
12.根据权利要求1至11中任一项所述的融合蛋白的制造方法,其中,
所述哺乳动物细胞包含选自由CHO细胞、COS细胞、BHK细胞、HeLa细胞、HEK293细胞、NS0细胞以及Sp2/0细胞构成的组中的一种以上。
13.一种重组蛋白生产用哺乳动物细胞,其包含:含有编码融合蛋白的基因的一种以上重组蛋白表达载体,
所述融合蛋白包含BDNF以及抗转铁蛋白受体抗体或其片段,
编码所述融合蛋白的基因包含编码所述BDNF的基因的碱基序列和编码所述抗转铁蛋白受体抗体或其片段的基因的碱基序列,
所述重组蛋白生产用哺乳动物细胞还包含:含有编码伴侣蛋白的基因的一种以上表达增强载体,
所述伴侣蛋白包含选自由HSP90α、HSP90β、CDC37、HSP70、HSP40、HSP60、HSP10、HSP110以及HSP27构成的组中的一种以上。
14.一种试剂盒,其用于增强哺乳动物细胞中的、包含BDNF以及抗转铁蛋白受体抗体或其片段的融合蛋白的生产量,
所述试剂盒包含:含有编码伴侣蛋白的基因的一种以上表达增强载体,
所述伴侣蛋白包含选自由HSP90α、HSP90β、CDC37、HSP70、HSP40、HSP60、HSP10、HSP110以及HSP27构成的组中的至少一种。
CN202280019883.3A 2021-03-10 2022-03-09 融合蛋白的制造方法 Pending CN116964213A (zh)

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