CN114901802A - 重组cdkl5蛋白、基因疗法和生产方法 - Google Patents

重组cdkl5蛋白、基因疗法和生产方法 Download PDF

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CN114901802A
CN114901802A CN202080091287.7A CN202080091287A CN114901802A CN 114901802 A CN114901802 A CN 114901802A CN 202080091287 A CN202080091287 A CN 202080091287A CN 114901802 A CN114901802 A CN 114901802A
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肖恩·克拉克
肖恩·沙利文
希拉里·格雷
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Abstract

提供了用于CDKL5基因疗法的组合物，以及重组CDKL5蛋白。此类CDKL5基因疗法组合物和/或重组CDKL5蛋白可以掺入细胞穿透多肽和/或前导信号多肽。还提供了生产此类基因疗法组合物和重组CDKL5蛋白的方法，以及所述基因疗法组合物和重组CDKL5蛋白的药物组合物、治疗方法和用途。

Description

重组CDKL5蛋白、基因疗法和生产方法
技术领域
本发明总体上涉及激酶缺乏障碍的治疗，尤其是用于治疗涉及CDKL5缺乏的障碍的新型重组蛋白和基因疗法。
背景技术
CDKL5是丝氨酸/苏氨酸激酶，以前称为STK9。最近，该基因的突变被发现与许多神经性障碍有关，例如智力迟钝、沟通和运动能力丧失、婴儿痉挛和癫痫发作、非典型雷特综合征和X连锁韦斯特综合征。X连锁基因细胞周期蛋白依赖性激酶样5(CDKL5)的突变或缺失已被证明会导致癫痫性脑病，伴有早期发作的严重神经损伤和顽固性癫痫发作。
目前，医学文献中描述的年龄最大的患有CDKL5缺乏的患者已经达到41岁。许多其他患者年龄为十几岁和二十几岁，但是由于所述疾病仅在最近15年才被发现，因此，大多数新诊断的患者是婴幼儿。被诊断出患有CDKL5缺乏障碍的个体通常会出现神经发育延迟，并有癫痫发作的高风险，中位发病年龄为6周。一项针对111位受试者的研究发现，癫痫病患者中有85.6％的个体每天都会癫痫发作，平均每天发作6次。
目前的治疗方法包括癫痫发作药物、生酮饮食、迷走神经刺激和手术。通常施用的抗癫痫药物包括氯巴占、丙戊酸和托吡酯，在许多情况下，同时使用两种或更多种药物治疗方案。个体似乎有一个“蜜月期”，在这期间，他们在开始使用新类型药物后的一段时间内无癫痫发作，但最终会再次癫痫发作。观察到的蜜月持续时间为2个月至7年，中位数为6个月。例如，所述研究发现，111名受试者中目前有16名没有癫痫发作，并且一名个体从未有过癫痫发作。
病理表现的确切机制尚不清楚。一些实验数据表明，C端的某些无义突变会导致所述蛋白组成性地定位于细胞核，而其他错义突变在细胞质中高度存在。核定位信号和核输出信号均已在所述蛋白的C端被鉴定出。
一些突变酶变体导致磷酸化功能的部分或全部丧失，而其他突变和截短导致磷酸化能力的增加，表明功能丧失和功能获得均可能是致病的。由酶活性丧失/功能获得以及酶核定位与在细胞质中的停留所引起的相互作用和致病作用尚不清楚。对具有广泛CDKL5突变并表现出临床症状的患者进行的分析表明，引起临床症状的突变更可能在C端或激酶活性结构域中发现，这表明CDKL5的激酶活性和蛋白转运能力可能影响症状的临床表现。
发明内容
因此，本发明的各个方面涉及新的重组CDKL5蛋白和基因疗法组合物，所述蛋白和组合物可用于治疗CDKL5介导的神经性障碍，例如CDKL5缺乏或者由CDKL5突变或缺乏引起的非典型雷特综合征。本发明的其他方面涉及生产此类重组CDKL5蛋白和基因疗法组合物的方法，以及此类重组蛋白和基因疗法组合物的药物组合物、治疗方法、以及用途。
本发明的一个方面涉及包含基因疗法递送系统和编码CDKL5多肽的CDKL5多核苷酸的组合物。在各种实施例中，所述CDKL5多肽与SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26具有至少98％的序列同一性。
在一个或多个实施例中，所述CDKL5多肽与SEQ ID NO:1或SEQ ID NO:26具有至少98％的序列同一性。在一个或多个实施例中，所述CDKL5多核苷酸与SEQ ID NO:123具有至少90％的序列同一性。
在一个或多个实施例中，所述CDKL5多肽与SEQ ID NO:2、SEQ ID NO:3、SEQ IDNO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11或SEQ ID NO:12具有至少98％的序列同一性。
在一个或多个实施例中，所述CDKL5多肽与SEQ ID NO:13、SEQ ID NO:14、SEQ IDNO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ IDNO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24或SEQ ID NO:25具有至少98％的序列同一性。在一个或多个实施例中，所述CDKL5多核苷酸与SEQ ID NO:125、SEQ ID NO:127、SEQ ID NO:129、SEQ ID NO:131、SEQ ID NO:133、SEQ ID NO:135、SEQ ID NO:137、SEQ IDNO:139、SEQ ID NO:141、SEQ ID NO:143、SEQ ID NO:145、SEQ ID NO:147或1SEQ ID NO:149具有至少90％的序列同一性。
在一个或多个实施例中，所述基因疗法递送系统包含病毒载体、脂质体、脂质-核酸纳米粒子、外来体和基因编辑系统中的一项或多项。在一个或多个实施例中，所述基因编辑系统包含规律间隔成簇短回文重复(CRISPR)相关蛋白9(CRISPR-Cas-9)、转录激活因子样效应核酸酶(TALEN)或ZNF(锌指蛋白)中的一项或多项。
在一个或多个实施例中，所述基因疗法递送系统包含病毒载体。在一个或多个实施例中，所述病毒载体包含腺病毒载体、腺相关病毒载体、慢病毒载体、逆转录病毒载体、痘病毒载体或单纯疱疹病毒载体中的一项或多项。在一个或多个实施例中，所述病毒载体包含与CDKL5多核苷酸可操作地连接的病毒多核苷酸。在一个或多个实施例中，所述病毒载体包含至少一个反向末端重复(ITR)。
在一个或多个实施例中，所述组合物进一步包含SV40内含子、聚腺苷酸化信号或稳定化元件中的一项或多项。
在一个或多个实施例中，所述方法进一步包括启动子。在一个或多个实施例中，所述启动子与SEQ ID NO:29或SEQ ID NO:30具有至少90％的序列同一性。
在一个或多个实施例中，所述组合物进一步包含编码细胞穿透多肽的多核苷酸。在一个或多个实施例中，所述细胞穿透多肽与SEQ ID NO:32、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37或SEQ ID NO:167具有至少90％的序列同一性。在一个或多个实施例中，编码所述细胞穿透肽的多核苷酸与SEQ ID NO:150、SEQ ID NO:151、SEQ IDNO:152、SEQ ID NO:153、SEQ ID NO:154、SEQ ID NO:170、SEQ ID NO:171、SEQ ID NO:172或SEQ ID NO:173具有至少90％的序列同一性。
在一个或多个实施例中，所述组合物进一步包含编码前导信号多肽的多核苷酸。在一个或多个实施例中，所述前导信号多肽与SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:156、SEQ ID NO:157、SEQ ID NO:158、SEQ IDNO:159、SEQ ID NO:160、SEQ ID NO:161、SEQ ID NO:162、SEQ ID NO:163、SEQ ID NO:164、SEQ ID NO:165、SEQ ID NO:166或SEQ ID NO:168具有至少90％的序列同一性。在一个或多个实施例中，编码所述前导信号多肽的多核苷酸与SEQ ID NO:155具有至少90％的序列同一性。在一个或多个实施例中，编码所述前导信号多肽的多核苷酸与SEQ ID NO:169具有至少90％的序列同一性。
本发明的另一个方面涉及包含如本文所述的组合物和药学上可接受的载剂的药物配制品。
本发明的另一个方面涉及治疗CDKL5介导的神经性障碍的方法，所述方法包括将如本文所述的组合物或配制品施用至对其有需要的患者。在一个或多个实施例中，所述组合物或配制品是鞘内、静脉内、脑池内、脑室内或实质内施用的。在一个或多个实施例中，所述CDKL5介导的神经性障碍是CDKL5缺乏或者由CDKL5突变或缺乏引起的非典型雷特综合征中的一项或多项。
本发明的另一个方面涉及一种治疗CDKL5介导的神经性障碍的方法，所述方法包括将本文所述的组合物或配制品施用至离体细胞，并将离体细胞施用至对其有需要的患者。在一个或多个实施例中，离体细胞是鞘内、静脉内、脑池内、脑室内或实质内施用的。在一个或多个实施例中，所述CDKL5介导的神经性障碍是CDKL5缺乏或者由CDKL5突变或缺乏引起的非典型雷特综合征中的一项或多项。
本发明的另一个方面涉及新型CDKL5多肽。在各种实施例中，所述CDKL5多肽包含与SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ IDNO:24或SEQ ID NO:25具有至少99％的序列同一性的序列。在一个或多个实施例中，所述CDKL5多肽包含SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ IDNO:23、SEQ ID NO:24或SEQ ID NO:25的序列。在一个或多个实施例中，所述CDKL5多肽包含SEQ ID NO:13的序列。在一个或多个实施例中，所述CDKL5多肽包含SEQ ID NO:14的序列。在一个或多个实施例中，所述CDKL5多肽包含SEQ ID NO:15的序列。在一个或多个实施例中，所述CDKL5多肽包含SEQ ID NO:16的序列。在一个或多个实施例中，所述CDKL5多肽包含SEQ ID NO:17的序列。在一个或多个实施例中，所述CDKL5多肽包含SEQ ID NO:18的序列。在一个或多个实施例中，所述CDKL5多肽包含SEQ ID NO:19的序列。在一个或多个实施例中，所述CDKL5多肽包含SEQ ID NO:20的序列。在一个或多个实施例中，所述CDKL5多肽包含SEQ ID NO:21的序列。在一个或多个实施例中，所述CDKL5多肽包含SEQ ID NO:22的序列。在一个或多个实施例中，所述CDKL5多肽包含SEQ ID NO:23的序列。在一个或多个实施例中，所述CDKL5多肽包含SEQ ID NO:24的序列。在一个或多个实施例中，所述CDKL5多肽包含SEQ ID NO:25的序列。
本发明的另一个方面涉及一种融合蛋白，所述融合蛋白包含如本文所述的CDKL5多肽和可操作地偶联至CDKL5多肽的前导信号多肽。在一个或多个实施例中，所述前导信号多肽与SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42或SEQID NO:168具有至少90％的序列同一性。在一个或多个实施例中，所述前导信号多肽包含SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42或SEQ ID NO:168的序列。
本发明的另一个方面涉及一种融合蛋白，所述融合蛋白包含如本文所述的CDKL5多肽和可操作地偶联至CDKL5多肽的细胞穿透多肽。在一个或多个实施例中，所述细胞穿透多肽与SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ IDNO:36、SEQ ID NO:37或SEQ ID NO:167具有至少90％的序列同一性。在一个或多个实施例中，所述细胞穿透多肽包含SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37或SEQ ID NO:167的序列。在一个或多个实施例中，所述融合蛋白进一步包含前导信号多肽。在一个或多个实施例中，所述前导信号多肽与SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42或SEQ IDNO:168具有至少90％的序列同一性。在一个或多个实施例中，所述前导信号多肽包含SEQID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42或SEQ ID NO:168的序列。
在一个或多个实施例中，所述融合蛋白进一步包含一个或多个亲和标签、一个或多个蛋白酶切割位点或其组合。在一些实施例中，所述亲和标签包含MYC、HA、V5、NE、StrepII、Twin-Strep
Figure BDA0003721100640000061
谷胱甘肽S-转移酶(GST)、麦芽糖结合蛋白(MBP)、钙调蛋白结合肽(CBP)、
Figure BDA0003721100640000062
多组氨酸(His)、HPC4或其组合中的一项或多项。在一些实施例中，所述蛋白酶切割位点对凝血酶、弗林蛋白酶、因子Xa、金属蛋白酶、肠激酶、组织蛋白酶、HRV3C、TEV或其组合中的一项或多项敏感。
本发明的另一个方面涉及一种药物配制品，所述药物配制品包含如本文所述的CDKL5多肽或融合蛋白和药学上可接受的载剂。
本发明的另一个方面涉及治疗CDKL5介导的神经性障碍的方法，所述方法包括将如本文所述的CDKL5多肽或融合蛋白或配制品施用至对其有需要的患者。在一个或多个实施例中，所述多肽或融合蛋白或配制品是鞘内、静脉内、脑池内、脑室内或实质内施用的。在一个或多个实施例中，所述CDKL5介导的神经性障碍是CDKL5缺乏或者由CDKL5突变或缺乏引起的非典型雷特综合征中的一项或多项。
本发明的另一个方面涉及生产如本文所述的CDKL5多肽或融合蛋白的方法。在各种实施例中，所述方法包括表达CDKL5多肽或融合蛋白并纯化CDKL5多肽或融合蛋白。在一个或多个实施例中，所述CDKL5多肽或融合蛋白在中国仓鼠卵巢(CHO)细胞、HeLa细胞、人胚肾(HEK)细胞或大肠杆菌(Escherichia coli)细胞中表达。
本发明的另一个方面涉及生产包含CDKL5多肽的蛋白的方法，所述方法包括在昆虫细胞中表达所述蛋白并从所述昆虫细胞中纯化所述蛋白。在一个或多个实施例中，所述昆虫细胞是Sf9细胞或BTI-Tn-5B1-4细胞。
在一个或多个实施例中，所述蛋白包括含有所述CDKL5多肽和可操作地偶联至所述CDKL5多肽的细胞穿透多肽的融合蛋白。在一个或多个实施例中，所述细胞穿透多肽可操作地偶联至所述CDKL5多肽的N端。在一个或多个实施例中，所述细胞穿透多肽可操作地偶联至所述CDKL5多肽的C端。在一个或多个实施例中，所述融合蛋白进一步包含前导信号多肽。
在一个或多个实施例中，所述融合蛋白进一步包含一个或多个亲和标签、一个或多个蛋白酶切割位点或其组合。在一些实施例中，所述亲和标签包含MYC、HA、V5、NE、StrepII、Twin-Strep
Figure BDA0003721100640000071
谷胱甘肽S-转移酶(GST)、麦芽糖结合蛋白(MBP)、钙调蛋白结合肽(CBP)、
Figure BDA0003721100640000072
多组氨酸(His)、HPC4或其组合。在一些实施例中，所述蛋白酶切割位点对凝血酶、弗林蛋白酶、因子Xa、金属蛋白酶、肠激酶、组织蛋白酶、HRV3C、TEV或其组合中的一项或多项敏感。
在一个或多个实施例中，所述CDKL5多肽与SEQ ID NO:1、SEQ ID NO:2、SEQ IDNO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ IDNO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26具有至少98％的序列同一性。在一个或多个实施例中，所述CDKL5多肽与SEQ ID NO:1或SEQ IDNO:26具有至少98％的序列同一性。在一个或多个实施例中，所述CDKL5多肽与SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQID NO:9、SEQ ID NO:10、SEQ ID NO:11或SEQ ID NO:12具有至少98％的序列同一性。
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图1A显示了CDKL5107的多肽图谱。所述图谱鉴定了多肽的重要特征，包括ATP结合位点、激酶结构域和激酶活性位点、两个核定位信号和核输出信号。
图1B和1C显示了如下的图，其描绘合成的CDKL5构建体变体(1B)，并且图例描述了多肽的长度；连同相关氨基酸缺失信息，以描述如何合成构建体(1C)。
图2A-2BK显示用于在诸如CHO细胞、HEK细胞、Sf9或大肠杆菌细胞中表达各种CDKL5多肽和融合蛋白的示例性质粒。
图3A和3B显示了在大肠杆菌细胞中表达的各种CDKL5融合蛋白的Western印迹。图4A和4B分别显示了在CHO和HEK细胞中表达的各种CDKL5融合蛋白的Western印迹。
图4A显示了CDKL5变体在CHO细胞中的表达。图4B显示了CDKL5变体在HEK293F细胞中的表达。
图5显示了展示在CHO细胞中各种CDKL5融合蛋白的氨甲蝶呤扩增的Western印迹。
图6A和6B分别显示了展示培养基和细胞裂解物中各种CDKL5融合蛋白的表达和分泌的Western印迹。
图7显示了在HEK293F的细胞质中与几种潜在的底物共表达的CDKL5融合蛋白的Western印迹。
图8显示了在基于HeLa的体外转录/翻译系统中表达的各种CDKL5融合蛋白的Western印迹。
图9A和9B分别显示了展示在CHO和HEK细胞中表达的各种CDKL5融合蛋白的糖基化的Western印迹。
图10显示了CDKL5蛋白在细菌、哺乳动物和昆虫细胞表达系统中的相对表达和产量的定量分析。
图11A和11B显示了在Sf9昆虫细胞中表达的各种CDKL5融合蛋白的Sypro宝石红染色凝胶。
图12A显示了细胞裂解物中CDKL5融合蛋白和纯化的融合蛋白的Sypro宝石红染色凝胶。
图12B显示了展示图11A的CDKL5融合蛋白的HRV3C蛋白酶切割的Sypro宝石红染色凝胶。
图13显示了展示CDKL5融合蛋白在各种盐和赋形剂系统中的溶解度的考马斯染色凝胶。
图14A显示了TwinStrep-HRV3C-TATκ28-CDKL5-HRV3C-FLAG-His-HPC4蛋白的示意图。
图14B显示了TwinStrep-HRV3C-TATκ28-CDKL5-HRV3C-FLAG-His-HPC4蛋白的纯化和切割。
图15显示了TwinStrep-HRV3C-TATκ28-CDKL5-HRV3C-FLAG-His-HPC4蛋白纯化和切割的Western印迹分析。图15A显示了使用抗strepII抗体的Western印迹分析。图15B显示了使用抗HPC4抗体的Western印迹分析。
图16显示了TwinStrep-HRV3C-TATκ28-CDKL5-HRV3C-FLAG-His-HPC4蛋白的IMAC纯化。
图17显示了TwinStrep-HRV3C-TATκ28-CDKL5-HRV3C-FLAG-His-TwinStrep蛋白的示意图。
图18A显示了TwinStrep-HRV3C-TATκ28-CDKL5-HRV3C-FLAG-His-TwinStrep蛋白的纯化和切割。图18B显示了TwinStrep-HRV3C-TATκ28-CDKL5-HRV3C-FLAG-His-TwinStrep蛋白纯化和切割的Western印迹分析。
图19显示了TwinStrep-HRV3C-TATκ28-CDKL5-HRV3C-FLAG-His-TwinStrep蛋白的阳离子交换色谱纯化。
图20显示了大鼠DIV14胚胎原代皮层神经元中TATκ28-CDKL5蛋白的摄取。
图21显示了大鼠DIV7胚胎原代皮层神经元中TATκ28-CDKL5蛋白的摄取。
图22显示了大鼠DIV14胚胎原代皮层神经元中TATκ28-CDKL5蛋白的摄取。
图23显示了DIV14胚胎原代皮层神经元中TATκ28-CDKL5蛋白的时间依赖性摄取。
图24显示了DIV14胚胎原代皮层神经元中TATκ28-CDKL5蛋白摄取随时间的统计分析。
图25A显示了TATκ28-CDKL5蛋白与PSD95的共定位。图25B显示了TATκ28-CDKL5蛋白与突触蛋白1的共定位。
图26A-26E显示了通过慢病毒递送各种CDKL5融合蛋白处理的大鼠神经元。
图27A-27I显示了纹状体中BIP-TATκ28-CDKL5诱导的交叉校正。
图28A-27I显示了丘脑中BIP-TATκ28-CDKL5诱导的交叉校正。
图29A-29I显示了海马结构中BIP-TATκ28-CDKL5诱导的交叉校正。
图30A-30D显示了DAPI染色细胞、神经元、具有BIP-TATκ28-CDKL5mRNA和BIP-TATκ28-CDKL5蛋白的神经元、仅具有BIP-TATκ28-CDKL5 mRNA的神经元、交叉校正的神经元和交叉校正的非神经元的原始图像和重叠图像。
图31A-31B显示了使用visioopharm量化交叉校正的细胞。
图32A显示了矢状切面中交叉校正的神经元的统计分析。图32B显示了在包括新皮层、纹状体、丘脑和海马结构的特定脑区中的交叉校正的神经元的统计分析。
图33显示了用于转染如本文所述的融合蛋白的示例性质粒。
具体实施方式
在描述本发明的若干示例性实施例之前，应当理解，本发明不限于以下描述中列出的构建或方法步骤的细节。本发明能够有其他的实施例，并且能够以不同的方式实施或进行。
令人惊讶地发现，当在各种宿主细胞系统中表达和分泌时，包含野生型CDKL5序列的蛋白具有显著的N-连接糖基化。由于折叠和/或与结合伴侣的相互作用的改变，这种N-连接糖基化可能对酶功能产生负面影响。因此，本发明的各个方面涉及包含具有一个或多个突变以去除N-连接糖基化位点的CDKL5多肽的重组蛋白。
此外，在不希望受到任何特定理论约束的情况下，据信保留功能活性的较短的CDKL5变体可提供相对于全长野生型CDKL5多肽的益处，特别是当掺入包含CDKL5多肽的融合蛋白中时。在一个或多个实施例中，这样的益处可包括在蛋白生产过程中宿主细胞的分泌改善、溶解度提高、跨越血脑屏障(BBB)的能力增强和/或穿透靶细胞的能力增强。
本发明的其他方面涉及用于表达和分泌包含CDKL5多肽(例如，野生型CDKL5多肽，去除了一个或多个N-连接糖基化位点的CDKL5变体和/或较短的CDKL5变体)的重组蛋白的新细胞系统。
本发明的其他方面涉及利用如本文所述的编码CDKL5多肽的CDKL5多核苷酸以及基因疗法递送系统的基因疗法组合物和方法。
定义
如本文所用，术语“CDKL5介导的神经性障碍”是指可通过表达或过表达CDKL5蛋白来治疗的任何疾病或障碍。
如本文所用，术语“CDKL5缺乏”是指蛋白的生物学功能的任何缺乏。所述缺乏可以产生自编码蛋白的DNA或DNA相关调节区中的任何DNA突变，或由于表观遗传DNA修饰的任何变化导致的蛋白功能的任何变化，包括但不限于DNA甲基化或组蛋白修饰，CDKL5蛋白的二级、三级或四级结构的任何变化，或CDKL5蛋白相比于野生型或正常受试者执行其生物学功能的能力的任何变化。所述缺乏也可能包括CDKL5蛋白的缺少，例如功能完全的蛋白的无效突变或表达不足。
如本文所用，术语“由CDKL5突变或缺乏引起的非典型雷特综合征”是指具有与雷特综合征相似的临床体征但由CDKL5突变或缺乏引起的雷特综合征的非典型形式。
CDKL5缺乏、雷特综合征或非典型雷特综合征的症状或标志物包括但不限于癫痫发作、认知障碍、张力减退，以及自主神经、睡眠和胃肠道紊乱。
如本文所用，术语“基因疗法递送系统”是指可用于将外源目的基因递送至靶细胞从而将在靶细胞中表达或过表达目的基因的任何系统。在一个或多个实施例中，所述靶细胞是患者体内细胞。在一个或多个实施例中，所述靶细胞是离体细胞，并且然后将所述细胞施用至患者。
如本文中所使用，术语“载剂”旨在是指与化合物一起施用的稀释剂、助剂、赋形剂、或媒介物。适合的药物载剂是本领域已知的，并且在至少一个实施例中，其描述于“雷明顿药物科学”("Remington's Pharmaceutical Sciences")，E.W.马丁(E.W.Martin)著，第18版，或其他版本。
如本文中所使用，术语“酶替代疗法”或“ERT”旨在指代将外源的、经纯化的酶引入具有这种酶缺乏的个体中。施用的蛋白可以从自然来源或通过重组表达而获得。所述术语也指将经纯化的酶引入个体，所述个体在其他情况下需要或受益于施用的经纯化的酶。在至少一个实施例中，这样的个体患有酶缺乏。所述引入的酶可以是在体外产生的经纯化的重组酶，或从离体组织或体液例如像胎盘或动物奶，或从植物纯化的蛋白。
如本文中所使用，术语“受试者”或“患者”旨在是指人或非人动物。在至少一个实施例中，所述受试者是哺乳动物。在至少一个实施例中，所述受试者是人。
如本文中所使用，所述“治疗有效剂量”和“有效量”旨在是指足够导致受试者治疗应答的基因疗法组合物(例如，包含CDKL5多核苷酸的组合物)或重组蛋白(例如，CDKL5变体或融合蛋白)的量。治疗应答可以是使用者(例如，临床医生)将会识别为对疗法的有效响应的任何应答，包括本文所述和本领域已知的任何替代性临床标记物或症状。因此，在至少一个实施例中，治疗应答可以是CDKL5缺乏、雷特综合征或非典型雷特综合征(例如本领域已知的那些)的一个或多个症状或标志物的改善或抑制。
CDKL5蛋白的功能
人CDKL5基因由24个外显子组成，其中前三个(外显子1、1a和1b)未翻译。
最初发现的人CDKL5变体是1030个氨基酸，分子量为115kDa(CDKL5115)。另一个突出的变体CDKL5107包含改变的C端区域，因为可变剪接组合了与CDKL5115变体不同的外显子。CDKL5107(107kDa)较短，因为它包含外显子19的替代版本，并且不包含CDKL5115变体中存在的外显子20-21。已经发现hCDKL5107 mRNA在人脑中的丰度是hCDKL5115转录本的37倍，而鼠CDKL5107在鼠脑中的丰度是鼠CDKL5105变体的160倍。与人CDKL5115变体相比，人和鼠CDKL5107同工型均展示更长的半衰期和抗降解性。
已使用Lox-Cre重组系统生成了CDKL5基因敲除小鼠模型，这些小鼠表现出社交互动中的自闭症样缺陷、运动控制受损和恐惧记忆丧失的症状(Wang等人,Proc Natl AcadSci USA [美国国家科学院院刊],109(52),21516-21521)。例如，基因敲除CDKL5小鼠具有运动协调能力降低的症状，并在反复受到刺激时展示出记忆力减退和恐惧应答。这些变化使科学家们推测CDKL5激酶活性的丧失会导致神经元网络发育受损。以前的数据表明，CDKL5使甲基-CpG结合蛋白2(MeCP2)磷酸化，并且MeCP2中独立的功能丧失突变导致雷特综合征表型。CDKL5的其他底物包括Netrin G1配体(NGL-1)、Shootin1(SHTN1)、Mindbomb 1(MIB1)、DNA (胞嘧啶5)-甲基转移酶1(DNMT1)、双亲蛋白1(AMPH1)、末端结合蛋白EB2、微管相关蛋白1S(MAP1S)和组蛋白脱乙酰基酶4(HDAC4)。尽管尚未确定CDKL5的确切作用，但这些数据表明CDKL5在下游靶标的磷酸化中起着作用，这些下游靶标对正确的神经元发育(包括MeCP2)至关重要。在人中，CDKL5中的突变与一种表型有关，该表型与雷特综合征重叠，并且另外表现出早发性癫痫发作。虽然CDKL5 KO小鼠没有表现出任何早发性癫痫发作症状，但它们确实表现出运动缺陷、社交能力下降以及学习和记忆受损(Chen等人,a proteinassociated with Rett Syndrome,regulates neuronal morphogenesis via Rac1signaling[与雷特综合征相关的蛋白CDKL5通过Rac1信号传导调控神经元形态发生],JNeurosci[神经科学杂志]30:12777-12786)。
在大鼠中发现两种CDKL5同工型，一种标记为CDKL5a，另一种标记为CDKL5b。(Chen等人)。通常，除C端附近的最后100-150个氨基酸外，物种人、大鼠和小鼠的CDKL5基因均具有高度的序列保守性。westernblot数据显示，这两种变体在大鼠发育过程中都存在，而成年大鼠显现主要表达一种变体。此外，CDKL5以可鉴定出的量存在于脑、肝和肺中。
CDKL5在细胞核中起作用，但也在培养的神经元树突中被发现，表明可能存在替代细胞质作用。在培养的皮层神经元中，RNAi(RNA干扰)对CDKL5表达的下调抑制了神经突生长和树突状分枝化(分支)，而CDKL5的过表达则具有相反的作用(Chen等人)。为了表征CDKL5的细胞核和细胞质作用，在培养的皮层神经元RNAi模型中表达了具有核输出序列(NES)的CDKL5a变体。该NES-CDKL5a变体对用于使野生型基因表达沉默的RNAi具有抗性，因此当仅在细胞质中表达时，可用于建模CDKL5a。在使用GFP标签确认该CDKL5变体仅存在于细胞质中后，神经突的长度和神经突分支的数量均增加。当使用RNAi敲除内源性CDKL5表达时，观察到的NES-GFP-CDKL5a部分挽救疾病表型的能力表明，CDKL5在细胞质中的表达是神经突发育和生长的重要因素。
CDKL5中的人突变与类似于雷特综合征的表型有关，并且具有CDKL5突变的个体也出现早发性癫痫发作。这种癫痫发作不同于经典雷特综合征表型，后者在Rett症状发作之前有一个早期正常发育期。患有经典雷特综合征(RTT)的患者直到6-18个月大时显现都能正常发育，然后开始出现神经性症状，包括语言和运动能力丧失。RTT大脑的尸体解剖显示较小、较密集的神经元，运动和额叶皮层中的树突较短，表明神经元发育受到损害。大多数经典RTT病例归因于MECP2基因的突变，所述基因是X连锁基因，编码与哺乳动物基因组中的CpG二核苷酸选择性结合并通过募集复合物调节转录的核蛋白。尽管所知甚少，但通常认为由MECP2中的突变引起的基因表达失调是雷特综合征的根本原因。大约20％的经典雷特综合征病例和60％-80％的其他雷特综合征变体在MECP2中不携带突变，表明发病机理的另一种遗传原因。最近，已在具有某些RTT变体和其他严重脑病的患者中鉴定出一些CDKL5突变，并且已证明CDKL5在体内和体外均可与MeCP2相互作用。除MeCP2以外，已显示CDKL5与许多下游靶标(包括NGL-1)相互作用并使其磷酸化。磷酸化后，NGL-1与PSD95相互作用，并且对于树突棘的正确起源和发育以及突触形成至关重要(Ricciardi S等人“CDKL5 ensuresexcitatory synapse stability by reinforcing NGL-1-PSD95 interaction in thepostsynaptic compartment and is impaired in patient iPSC-derived neurons.[CDKL5通过增强突触后室中NGL-1-PSD95的相互作用确保兴奋性突触的稳定性，并在患者iPSC衍生的神经元中受损]”Nat Cell Biol[自然细胞生物学]14(9):911-923)。
还已经证明CDKL5可以使蛋白DNA甲基转移酶1(DNMT1)磷酸化(Kameshita I等人,“Cyclin-dependent kinase-like 5binds and phosphorylates DNA methyltransferase1.[细胞周期蛋白依赖性激酶样5结合并磷酸化DNA甲基转移酶1]”.Biochem Biophys ResCommun[生物化学与生物物理研究通讯]377:1162-1167)。这种磷酸化导致DNMT1的激活，DNMT1是一种维持型甲基化蛋白，优先甲基化半甲基化的DNA。此过程可用于在DNA复制过程中维持DNA甲基化模式，以便新合成的子代DNA链能够维持其所替换的亲本链的甲基化模式。由于通常认为DNA甲基化是用以使基因表达沉默的表观遗传机制，因此DNMT1的这种维持功能对于跨细胞世代保存基因表达模式至关重要。
现有模型表明，CDKL5激酶结构域使GSK-3β磷酸化，并且GSK-3β的磷酸化导致其失活。因此，缺乏CDKL5活性的个体似乎表现出增加的GSK-3β活性。先前的研究已显示，GSK-3β调节海马神经发生，并且增加的GSK-3β活性严重损害了新生海马神经元的树突形态。此外，GSK-3β似乎充当着诸如神经元存活和成熟等关键发育事件的负调节因子。使用CDKL5 KO小鼠进行的一项研究展示，用GSK-3β抑制剂治疗几乎可以完全挽救CDKL5活性不足的小鼠的海马发育和行为缺陷(Fuchs等人,“Inhibition of GSK3βRescues HippocampalDevelopment and Learning in a Mouse Model of CDKL5 Disorder.[抑制GSK3β可以挽救CDKL5障碍小鼠模型的海马发育和学习]”Neurobiology of Disease[疾病的神经生物学]82:298-310。这种发育挽救似乎还持续到治疗之后。
CDKL5107多肽构建体
图1A展示了CDKL5107的多肽图谱。SEQ ID NO:1提供了野生型全长人CDKL5107同工型的氨基酸序列。CDKL5107蛋白由960个氨基酸组成，激酶结构域包含在前约300个氨基酸中。960中的残基42是位于激酶结构域内的关键赖氨酸残基，在磷酸化反应过程中参与ATP结合，并且该残基的突变通常导致激酶活性丧失(“激酶失活”)。另外，存在跨越残基312-315(NLS1)和784-789(NLS2)的两个核定位信号，并且存在跨越残基836-845的核输出信号(NES)。C端从残基905跨越到960的氨基酸是CDKL5107所特有的氨基酸，在CDKL5115中不存在。CDKL5115和CDKL5107之间氨基酸残基1-904是相同的。SEQ ID NO:26提供了野生型全长人CDKL5115同工型的氨基酸序列。
本发明的各种实施例提供了新颖的CDKL5变体。图1B和1C显示了全长人CDKL5107同工型(构建体1)和新型CDKL5构建体(命名为构建体2-12)的多肽。这些CDKL5构建体通常归为两类：C端缺失一些氨基酸的构建体(构建体2-7)和多肽链的中间缺失一些氨基酸的构建体(构建体8-12)。此外，在CDKL5在C端与另外的N端氨基酸序列融合的那些构建体中，CDKL5的初始甲硫氨酸被去除。在这些构建体中，所述CDKL5多肽以第二个氨基酸赖氨酸开始。构建体1包含全长人CDKL5107同工型的所有960个氨基酸。包含完整960个氨基酸链的前851个氨基酸的构建体2代表缩短的CDKL5多肽，其中去除了CDKL5107和CDKL5115之间不同的尾序列，但激酶结构域、核定位信号(NLS1和NLS2)和核输出信号(NES)保持完整。构建体3进一步缩短，其中另外去除了核定位信号(NLS2)和核输出信号(NES)。如图1B和1C所示，构建体4-7甚至进一步缩短。构建体2-7均包含活性激酶结构域，而构建体3-7不包含所述NLS2或NES序列。构建体7进一步缩短至NLS1序列。其余的构建体(构建体8-12)在多肽链的中间部分均有缺失，同时保留了CDKL5107特有的C端氨基酸。在这些构建体中，构建体12缺失NES和NLS2序列。SEQ ID NO:1-12分别提供了构建体1-12的氨基酸序列。
在一个或多个实施例中，所述CDKL5多肽与SEQ ID NO:2、SEQ ID NO:3、SEQ IDNO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11或SEQ ID NO:12具有至少98％、至少98.5％、至少99％或至少99.5％的序列同一性。所述CDKL5多肽可能含有相对于SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ IDNO:11或SEQ ID NO:12的缺失、取代和/或插入，如具有相对于SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQID NO:10、SEQ ID NO:11或SEQ ID NO:12所描述的氨基酸序列的1、2、3、4、5、6、7、8、9、10、11、12、13、14、15或更多个缺失、取代和/或插入。
在一个或多个实施例中，所述CDKL5多肽序列与SEQ ID NO:1或SEQ ID NO:26具有至少98％、至少98.5％、至少99％或至少99.5％的序列同一性。所述CDKL5多肽可能包含相对于SEQ ID NO:1或SEQ ID NO:26的缺失、取代和/或插入，如具有相对于SEQ ID NO:1或SEQ ID NO:26所描述的氨基酸序列的1、2、3、4、5、6、7、8、9、10、11、12、13、14、15或更多个缺失、取代和/或插入。
在一个或多个实施例中，所述CDKL5多肽包含一个或多个亲和标签。在一个或多个实施例中，所述亲和标签位于CDKL5多肽的N端或C端的一个或多个上。可添加到融合蛋白的标签的实例包括但不限于表位标签(例如MYC、HA、V5、NE、StrepII、Twin-Strep
Figure BDA0003721100640000161
HPC4)、谷胱甘肽S-转移酶(GST)、麦芽糖结合蛋白(MBP)、钙调蛋白结合肽(CBP)、
Figure BDA0003721100640000162
多组氨酸(His)及其组合。
在一个或多个实施例中，所述CDKL5多肽包含一个或多个蛋白酶切割位点。在一些实施例中，所述蛋白酶切割位点位于CDKL5多肽的N端或C端的一个或多个上。示例性蛋白酶切割位点包括但不限于对凝血酶、弗林蛋白酶、因子Xa、金属蛋白酶、肠激酶、组织蛋白酶、HRV3C、TEV及其组合敏感的切割位点。
可以使用不同比对算法和/或程序来计算两个序列之间的同一性，包括可用作GCG序列分析包(威斯康辛大学，麦迪逊市，威斯康辛州)的一部分的FASTA或BLAST，并且可以与例如，默认设置一起使用。例如，考虑与本文所述的特定多肽具有至少98％、98.5％、99％或99.5％同一性，并且优选地表现出基本相同功能的多肽，以及编码此类多肽的多核苷酸。除非另有说明，相似性分数将基于BLOSUM62的使用。当使用BLASTP时，相似性百分比是基于BLASTP阳性得分，并且序列同一性百分比是基于BLASTP同一性得分。BLASTP“身份”显示了高得分序列对中相同的总残基的数量和分数；BLASTP“正”表示比对得分为正值并且彼此相似的残基的数量和分数。本披露考虑和涵盖具有与本文披露的氨基酸序列具有这些程度的同一性或相似性或任何中间程度的同一性或相似性的氨基酸序列。使用遗传密码推导出的相似多肽的多核苷酸序列，并且可以通过常规手段(具体地通过使用遗传密码来逆转录其氨基酸序列)获得。
本领域技术人员可以容易地获得编码特定多肽序列的多核苷酸序列。可以使用市售产品，例如使用OptimumGeneTM密码子优化工具(金斯瑞公司(GenScript)，皮斯卡塔韦，新泽西州)，对此类多核苷酸序列进行密码子优化以在靶细胞中表达。
CDKL5107 N-连接糖基化变体
本发明的各种实施例提供具有一个或多个突变以从CDKL5多肽去除一个或多个N-连接糖基化位点的新型CDKL5变体。野生型人同工型CDKL5107包含10个潜在的N-连接糖基化位点，而野生型人同工型CDKL5115包含8个潜在的N-连接糖基化位点。这些糖基化位点之一包括TEY(Thr-Glu-Tyr)基序：NYTEY(Asn-Tyr-Thr-Glu-Tyr)，因此糖基化位点之一位于激酶结构域中。这样，Asn-Tyr-Thr-Glu-Tyr位点处的糖基化很可能会干扰Thr-Glu-Tyr基序的磷酸化。通常，除了X不能是His或Pro以外，在蛋白氨基酸序列中的Asn-X-Ser或Asn-X-Thr序列指示潜在的糖基化位点。因此，本发明的各种实施例提供了具有被不同氨基酸例如谷氨酰胺(亦称Gln或Q)残基取代的一个或多个天冬酰胺(亦称Asn或N)残基的CDKL5多肽。选择谷氨酰胺进行取代的一个潜在优势是，这种氨基酸在结构上类似于天冬酰胺，而谷氨酰胺残基中只存在一个额外的亚甲基单元。然而，其他氨基酸也可以用作所述一个或多个天冬酰胺残基的取代。可替代地，可以通过将Asn-X-Ser或Asn-X-Thr序列中的第三个氨基酸改变为不是丝氨酸(亦称S或Ser)或苏氨酸(亦称T或Thr)的另一个氨基酸和/或将第二个氨基酸改变为组氨酸(亦称H或His)或脯氨酸(亦称P或Pro)来改变糖基化位点。
本发明的实施例还提供了编码一个或多个Asn残基被另一个氨基酸(例如Gln残基)取代的CDKL5多肽的CDKL5多核苷酸。例如，一个或多个AAC、AAT或AAU序列(编码Asn)可以被一个或多个CAA或CAG序列(编码Gln)取代。再次，CDKL5多核苷酸中的其他改变可编码糖基化位点的其他改变，例如用His或Pro取代第二个氨基酸和/或将第三氨基酸改变为非Ser或Thr的另一个氨基酸。
在一个或多个实施例中，所述CDKL5多肽与SEQ ID NO:13、SEQ ID NO:14、SEQ IDNO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ IDNO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24或SEQ ID NO:25具有至少98％、至少98.5％、至少99％或至少99.5％的序列同一性。所述CDKL5多肽可能含有相对于SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ IDNO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24或SEQID NO:25的缺失、取代和/或插入，如具有相对于SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ IDNO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24或SEQ ID NO:25所描述的氨基酸序列的1、2、3、4、5、6、7、8、9、10、11、12、13、14、15或更多个缺失、取代和/或插入。
在一个或多个实施例中，所述CDKL5多肽包含一个或多个亲和标签。在一个或多个实施例中，所述亲和标签位于CDKL5多肽的N端或C端的一个或多个上。可添加到融合蛋白的标签的实例包括但不限于表位标签(例如MYC、HA、V5、NE、StrepII、Twin-Strep
Figure BDA0003721100640000181
HPC4)、谷胱甘肽S-转移酶(GST)、麦芽糖结合蛋白(MBP)、钙调蛋白结合肽(CBP)、
Figure BDA0003721100640000182
多组氨酸(His)及其组合。
在一个或多个实施例中，所述CDKL5多肽包含一个或多个蛋白酶切割位点。在一些实施例中，所述蛋白酶切割位点位于CDKL5多肽的N端或C端的一个或多个上。示例性蛋白酶切割位点包括但不限于对凝血酶、弗林蛋白酶、因子Xa、金属蛋白酶、肠激酶、组织蛋白酶、HRV3C、TEV及其组合敏感的切割位点。
细胞穿透肽(CPP)
多种病毒和细胞蛋白具有介导跨细胞膜转运的碱性多肽序列。跨细胞膜转运的能力已成为跨膜递送高分子量多肽的重要工具。短语“蛋白转导结构域”(PTD)和“细胞穿透肽”(CPP)通常用于指可以穿越许多(如果不是全部)哺乳动物细胞的质膜的短肽(<30个氨基酸)。在研究确定允许它们共同跨越质膜的结构域的特定特性之后，研究人员观察到这些结构域含有大量的碱性氨基酸残基，例如赖氨酸和精氨酸。因此，细胞穿透肽分为两类：第一类由含有赖氨酸残基的两亲螺旋肽组成，其中赖氨酸残基带有正电荷，而第二类是富含精氨酸的肽。如果与难以递送至细胞内靶标的其他蛋白组合使用，这些肽可能具有治疗潜力。PTD的最常见实验用途是TAT、穿膜肽(Antp)和其他多精氨酸肽。
迄今为止，TAT一直是PTD中最佳表征的一种，已被成功地用于将短肽和寡核苷酸等小分子物质递送到细胞间靶点。HIV-TAT(HIV转录反式激活因子)是含有86个氨基酸的蛋白，参与人1型免疫缺陷病毒(HIV-1)的复制，许多研究显示TAT能够通过质膜转运并到达细胞核以激活病毒基因组的转录。研究还显示，当与几种不同的蛋白偶联时，TAT保留了其穿透特性。为了理解TAT蛋白的哪些区域对于转运特性至关重要，已经进行了实验，其中合成了不同长度的TAT肽片段，并评估了它们的穿透能力。(Lebleu等人“A Truncated HIV-1TAT Protein Basic Domain Rapidly Translocates through the Plasma Membrane andAccumulates in the Cell Nucleus.[截短HIV-1TAT蛋白碱性结构域通过质膜快速转运并在细胞核中积聚]”J.Biol.Chem.[生物化学杂志]1997,272:16010-16017)。碱性氨基酸区域已被确定为保留穿透特性的TAT的方面，并且进行了实验，其中不含该碱性氨基酸簇的TAT蛋白无法穿透细胞质膜。在某些情况下，较短序列的细胞穿透肽经过修饰，以防止在分泌过程中被内切蛋白酶(如弗林蛋白酶)切割。这些修饰将缩短的细胞穿透TAT氨基酸序列从YGRKKRRQRRR改变为YARKAARQARA，这种短肽称为TATκ。
TAT跨质膜转运的确切机制尚不确定。最近的研究探索了一种特殊类型的内吞作用参与TAT摄取的可能性，并且已经鉴定出一些对TAT穿透具有抗性的细胞系。由TAT递送的特定货物也可能在递送效率中发挥作用。先前的研究数据表明，在变性条件下制备时，TAT融合蛋白具有更好的细胞摄取能力，因为由于结构上的限制，正确折叠的蛋白货物可能需要更多的能量(Δ-G)才能跨越质膜。
细胞内蛋白伴侣重新折叠TAT货物的能力可能会因要重新折叠的蛋白货物的身份和大小而不同。在某些情况下，TAT融合蛋白在置于水性环境中时会沉淀，因此无法以变性方式制备，也无法在天然构象中保持很长时间的稳定。TAT融合蛋白的设计还必须针对要递送的特定货物进行定制。如果货物蛋白在N端紧密结合并且TAT结构域也在N端发现，则TAT转运结构域可能被埋在货物蛋白中，并且转导可能很差。
许多TAT货物变体已成功地递送到多种细胞类型中，包括原代培养细胞、转化细胞和小鼠组织中存在的细胞。在培养物中，TAT融合蛋白通常容易扩散到细胞内外，导致非常迅速地建立均匀浓度。
许多药物，例如酶、抗体、其他蛋白，或甚至载有药物的载剂颗粒，都需要在细胞内递送，以在细胞质、细胞核或其他特定细胞器内部发挥其治疗作用。因此，这些不同类型的大分子的递送代表了生物制剂发展中的重大挑战。现有数据表明，TAT可以通过多种机制跨越质膜。
也已将TAT转导结构域与酶超氧化物歧化酶(SOD)融合。(Torchilin,“Intracellular delivery of protein and peptide therapeutics.[蛋白和肽治疗剂的细胞内递送]”Protein Therapeutics.[蛋白治疗学杂志]2008.5(2-3):e95-e103)。这种融合蛋白被用来展示它可以跨细胞膜转运，以便将SOD酶递送到细胞内环境，因此，这种融合蛋白在治疗酶缺乏障碍方面具有治疗潜力，这种酶的缺乏会导致宿主细胞上活性氧类的大量积累和氧化应激。
TAT融合蛋白还被证明可以跨血脑屏障进行转导。与神经保护蛋白Bcl-xL融合的TAT结构域能够在培养中快速穿透细胞，当施用至患有脑缺血的小鼠时，融合蛋白在1-2小时内转导脑细胞。转导后，脑梗塞的大小呈剂量依赖性式减小(Cao,G.等人,“In VivoDelivery of a Bcl-xL Fusion Protein Containing the TAT Protein TransductionDomain Protects against Ischemic Brain Injury and Neuronal Apoptosis.[含TAT蛋白转导结构域的Bcl-xL融合蛋白的体内递送保护免于缺血性脑损伤和神经元凋亡]”J.Neurosci.[神经科学杂志]22,5423,2002)。
在各种实施例中，本文所述的CDKL5变体可操作地连接至CPP，例如TAT、修饰的TAT(TATκ)、转运肽、穿膜肽或P97。如本文所用，TAT可以指具有11个氨基酸的原始TAT肽(命名为TAT11)或可以指具有衍生自用于克隆的质粒的多接头的另外16个N端氨基酸的TAT肽(命名为TAT28)。类似地，TATκ可以指代TAT11的修饰版本(命名为TATκ11)或TAT28的修饰版本(命名为TATκ28)。TATκ28可以进一步修饰(命名为TATκκ28)以去除潜在的其他弱弗林蛋白酶位点。CPP(TAT28、TATκ28、TAT11、TATκ11、转运肽、穿膜肽、P97和TATκκ28)的氨基酸序列分别在SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ IDNO:36、SEQ ID NO:37和SEQ ID NO:167中提供。
在一些实施例中，所述CPP与SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ IDNO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37或SEQ ID NO:167具有至少90％的序列同一性。在一些实施例中，所述CPP与SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ IDNO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37或SEQ ID NO:167具有至少95％的序列同一性。在一些实施例中，所述CPP与SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ IDNO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37或SEQ ID NO:167具有100％的序列同一性。在一些实施例中，所述CPP与SEQ ID NO:32、SEQ ID NO:34、SEQ ID NO:35、SEQ IDNO:36、SEQ ID NO:37或SEQ ID NO:167具有至少90％的序列同一性。在一些实施例中，所述CPP与SEQ ID NO:32、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37或SEQ IDNO:167具有至少95％的序列同一性。在一些实施例中，所述CPP与SEQ ID NO:32、SEQ IDNO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37或SEQ ID NO:167具有100％的序列同一性。在各种实施例中，所述CPP不具有SEQ ID NO:34的序列。
在各种实施例中，所述CPP可具有添加的N端甘氨酸。例如，如不添加，TATκ28和TAT28将具有稳定性较低的N端天冬氨酸残基。向所述序列添加N端甘氨酸可通过N端规则增加蛋白稳定性。因此，在一些实施例中，具有先导信号多肽的任何融合蛋白可具有添加在先导信号多肽的C端的甘氨酸，使得在切割先导信号多肽时，融合蛋白的新N端将以甘氨酸开始。以类似的方式，缺少前导信号多肽的那些融合蛋白也可以在N端甲硫氨酸和融合蛋白的其余部分之间添加甘氨酸。同样以类似的方式，具有除TAT28或TATκ28以外的CPP的那些融合蛋白也可以在前导信号多肽和CPP之间添加甘氨酸。
在一个或多个实施例中，所述CPP可操作地偶联至CDKL5多肽的N端。在一个或多个实施例中，所述CPP可操作地偶联至CDKL5多肽的C端。
在一个或多个实施例中，所述CPP包含一个或多个亲和标签。在一个或多个实施例中，所述亲和标签位于CPP的N端或C端的一个或多个上。可添加到CPP的标签的实例包括但不限于表位标签(例如MYC、HA、V5、NE、StrepII、Twin-Strep
Figure BDA0003721100640000221
HPC4)、谷胱甘肽S-转移酶(GST)、麦芽糖结合蛋白(MBP)、钙调蛋白结合肽(CBP)、
Figure BDA0003721100640000222
多组氨酸(His)及其组合。
在一个或多个实施例中，所述CPP包含一个或多个蛋白酶切割位点。在一些实施例中，所述蛋白酶切割位点位于CPP的N端或C端中的一个或多个上。示例性蛋白酶切割位点包括但不限于对凝血酶、弗林蛋白酶、因子Xa、金属蛋白酶、肠激酶、组织蛋白酶、HRV3C、TEV及其组合敏感的切割位点。
包含CDKL5变体的融合蛋白
如上所述，CDKL5变体可用于融合蛋白，如同样含有CPP的蛋白。其他多肽也可掺入此类融合蛋白中，如用于增强蛋白分泌的先导信号多肽或用于检测和/或纯化所述融合蛋白的亲和标签，以及可用于连接功能性多肽的接头多肽。
前导信号多肽的实例包括但不限于人免疫球蛋白重链结合蛋白的修饰片段(修饰的BiP，例如SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41或SEQ ID NO:168)、鼠Igκ链前导多肽(SEQ ID NO:42，例如来自赛默飞世尔公司载体的pSecTag2)或胰岛素生长因子肽(IGF2)如野生型IFG2(SEQ ID NO:156)或其变体(例如SEQ ID NO:157-166)。修饰的BiP信号多肽的实例包括美国专利号9,279,007中描述的那些，该专利通过引用以其整体并入本文。修饰的BiP信号多肽的其他实例包括mvBIP，其具有在mBiP中在赖氨酸之前添加的缬氨酸，如SEQ ID NO:168中所示。
在一个或多个实施例中，所述融合蛋白包含具有N端CPP的CDKL5多肽，任选地在N端CPP之前具有前导信号多肽。在一个或多个实施例中，所述融合蛋白包含具有C端CPP的CDKL5多肽，任选地在CDKL5多肽之前具有前导信号多肽。在一个或多个实施例中，所述融合蛋白包含前导信号肽和不含CPP的CDKL5多肽。
可添加到融合蛋白的亲和标签的实例包括但不限于表位标签(例如MYC、HA、V5、NE、StrepII、Twin-Strep
Figure BDA0003721100640000231
HPC4)、谷胱甘肽S-转移酶(GST)、麦芽糖结合蛋白(MBP)、钙调蛋白结合肽(CBP)、
Figure BDA0003721100640000232
多组氨酸(His)及其组合。
融合蛋白的一些实施例还可包含蛋白酶切割位点。在一些实施例中，所述蛋白酶切割位点位于亲和标签的N端。在一些实施例中，所述蛋白酶切割位点位于亲和标签的C端。示例性蛋白酶切割位点包括但不限于对凝血酶、弗林蛋白酶、因子Xa、金属蛋白酶、肠激酶、组织蛋白酶、HRV3C、TEV及其组合敏感的切割位点。
蛋白生产方法
重组蛋白(例如CDKL5变体或融合蛋白)可以使用合适的载体在宿主细胞中表达和分泌。例如，可以使用哺乳动物细胞(例如，CHO、HeLa或HEK细胞)、昆虫细胞(例如，Sf9或BTI-Tn-5B1-4)或细菌细胞(例如，大肠杆菌或游海假交替单胞菌(P.haloplanktis)TAC125细胞)。示例性质粒在以下实施例中描述，并在图2A-2BK中显示。本领域技术人员可选择适于转化、转染或转导细胞的替代载体以生产本文所述的CDKL5变体和融合蛋白。图10显示了在细菌、哺乳动物和昆虫细胞表达系统中的相对CDKL5表达和产量。
表达和分泌后，可以使用标准技术从周围细胞培养基中回收和纯化重组蛋白。可替代地，可以直接从细胞而不是培养基中分离和纯化重组蛋白。
在一些实施例中，将所述BTI-Tn-5B1-4细胞用于表达和纯化CDKL5变体或融合蛋白。
为了裂解，可以将表达所述CDKL变体或融合蛋白的细胞沉淀，随后重悬于裂解缓冲液中。然后可以将重悬的细胞在空化室(cavitation chamber)中孵育，所述空化室中充入约100 PSI至约2000 PSI的氮气。可将重悬的细胞在充气的空化室中孵育约5分钟至约60分钟。在一些实施例中，所述重悬的细胞可以在用氮气充至750 PSI的空化室中孵育。在一些实施例中，所述重悬的细胞可以在充气的空化室中孵育15分钟。孵育后，来自空化室的流出物然后可转移到冰上。可以在废水中加入洗涤剂，随后在冰上孵育约5分钟至约60分钟。在一些实施例中，所述洗涤剂以约0.1％(w/v)至约5％(w/v)的量添加。在一些实施例中，所述洗涤剂是Triton X-100。然后将含有洗涤剂的流出物超声处理以裂解细胞。裂解后，可将可溶级分和不可溶级分分离。在一些实施例中，所述可溶级分和不可溶级分可通过离心分离。可对可溶材料进行过滤。在一些实施例中，所述可溶材料可通过0.45μm过滤器过滤。
为了纯化所述CDKL5变体或融合蛋白，然后对过滤的可溶物质进行纯化。在一些实施例中，所述CDKL5变体或融合蛋白通过色谱技术纯化。在一些实施例中，所述色谱技术是亲和色谱。在一些实施例中，所述CDKL5变体或融合蛋白包含一个或多个亲和标签。在一些实施例中，所述亲和标签包括但不限于表位标签(例如MYC、HA、V5、NE、StrepII、Twin-Strep
Figure BDA0003721100640000241
HPC4)、谷胱甘肽S-转移酶(GST)、麦芽糖结合蛋白(MBP)、钙调蛋白结合肽(CBP)、
Figure BDA0003721100640000242
多组氨酸(His)及其组合。在一些实施例中，所述CDKL5变体或融合蛋白具有标签Twin-Strep-
Figure BDA0003721100640000245
。在一些实施例中，将所述具有亲和标签的CDKL5变体或融合蛋白在纯化树脂上纯化。在所述CDKL5变体或具有Twin-Strep-
Figure BDA0003721100640000243
标签的融合蛋白的一些实施例中，所述纯化树脂是strep-tactin树脂。
所述CDKL5变体或融合蛋白的一些实施例还可包括一个或多个蛋白酶切割位点。在一些实施例中，所述蛋白酶切割位点位于CDKL5变体或融合蛋白的N端。在一些实施例中，所述蛋白酶切割位点位于CDKL5变体或融合蛋白的C端。在一些实施例中，所述蛋白酶切割位点位于CDKL5变体或融合蛋白的N端和C端。在一些实施例中，当CDKL5变体或融合蛋白与纯化树脂结合时进行切割。在一些实施例中，当CDKL5变体或具有Twin-Strep-
Figure BDA0003721100640000244
标签的融合蛋白与strep-tactin树脂结合时进行切割。
蛋白替代疗法
在一个或多个实施例中，可以向受试者施用CDKL5蛋白或变体或融合蛋白。在一些实施例中，所述受试者可以是人、家畜和农场动物，以及实验室、动物园动物、体育运动动物或宠物动物，如狗、马、猫、乳牛、绵羊、山羊、猪、小鼠、大鼠、兔、豚鼠、猴等。在一些实施例中，所述受试者是人。
在一个或多个实施例中，在从受试者分离的细胞中确定CDKL5蛋白或变体或融合蛋白的细胞摄取。在一些实施例中，所述细胞可以从大鼠分离。在一些实施例中，所述细胞可以是神经元细胞。在一些实施例中，所述细胞可以是胚胎原代皮层神经元。在一些实施例中，所述胚胎原代皮层神经元可以从大鼠中分离。在一些实施例中，所述细胞可以进行培养并与CDKL5蛋白或变体一起孵育一个持续时间。所述持续时间可以是至少5分钟、至少10分钟、至少15分钟、至少20分钟、至少25分钟、至少30分钟、至少40分钟、至少50分钟或至少60分钟。在一些实施例中，所述持续时间可以是5分钟到24小时、15分钟到24小时、30分钟到24小时、1小时到24小时、4小时到24小时、8小时到24小时、12小时到24小时、5分钟到12小时、15分钟到12小时、30分钟到12小时、1小时到12小时、2小时到12小时、4小时到12小时、6小时到12小时、8小时到12小时、10小时到12小时、5分钟到6小时、15分钟到6小时、30分钟到6小时、1小时到6小时、1.5小时到6小时、2小时到6小时、2.5小时到6小时、3小时到6小时、4小时到6小时、5小时到6小时、5分钟到4小时、15分钟到4小时、30分钟到4小时、1小时到4小时、1.5小时到4小时、2小时到4小时、2.5小时到4小时、3小时到4小时、5分钟到2小时、15分钟到2小时、30分钟到2小时、1小时到2小时、1.5小时到2小时、5分钟到1小时、15分钟到1小时或30分钟到1小时。
基因疗法
本文所述的任何CDKL5多肽和/或融合蛋白可经由编码所需CDKL5多肽和/或融合蛋白的适当多核苷酸(例如DNA或RNA)用于基因疗法。
在各种实施例中，通过使用包含基因疗法递送系统和CDKL5多核苷酸的组合物来提供基因疗法。示例性基因疗法递送系统包括但不限于病毒载体、脂质体、脂质-核酸纳米粒子、外来体和基因编辑系统。例如，可以使用诸如规律间隔成簇短回文重复(CRISPR)相关蛋白9(CRISPR-Cas-9)、转录激活因子样效应物核酸酶(TALEN)或ZNF(锌指蛋白)之类的基因编辑系统将CDKL5多核苷酸插入宿主细胞的DNA中。
病毒载体包括但不限于腺病毒载体、腺相关病毒(AAV)载体、慢病毒载体、逆转录病毒载体、痘病毒载体或单纯疱疹病毒载体。病毒载体通常利用病毒颗粒(病毒粒子)，病毒颗粒包括外壳蛋白(衣壳)和包裹在衣壳中的一个或多个DNA或RNA序列(病毒多核苷酸)。例如，AAV载体通常包括一个或多个反向端重复(ITR)序列、复制(Rep)基因序列和衣壳(Cap)基因序列。ITR、Rep和Cap序列可以包括在同一质粒中(顺式)，或者可以在单独的质粒中提供(反式)。衣壳可以衍生自与ITR序列相同的血清型，或者所述AAV载体可以是利用ITR序列和衍生自不同AAV血清型的衣壳的杂合载体。示例性AAV血清型包括AAV1、AAV2、AAV3、AAV4、AAV5、AAV6、AAV7、AAV8、AAV9、AAV10、AAV11、杂交血清型和合成血清型。SEQ ID NO:27(L-ITR)和SEQ ID NO:28(R-ITR)提供了一组示例性的ITR，这些ITR衍生自AAV2。
所述病毒载体还可包括用于增加表达和/或稳定载体的其他元件，如启动子(例如杂合CBA启动子(CBh)和人突触蛋白1启动子(hSyn1)、聚腺苷酸化信号(例如牛生长激素聚腺苷酸化信号(bGHpolyA))、稳定元件(例如，土拨鼠肝炎病毒(WHP)转录后调控元件(WPRE))和/或SV40内含子。CBh和hSyn1的DNA序列分别在SEQ ID NO:29和SEQ ID NO:30中提供。
所述基因疗法递送系统可以用于将CDKL5多核苷酸递送至靶细胞，从而可以在靶细胞中表达CDKL5多肽(或包含所述多肽的融合蛋白)。在各种实施例中，所述CDKL5多肽(例如野生型CDKL5多肽，去除了一个或多个N-连接糖基化位点的CDKL5变体和/或较短的CDKL5变体)(或包含所述多肽的融合蛋白)在靶细胞中表达并在同一细胞中利用。在其他实施例中，所述CDKL5多肽(或包含所述多肽的融合蛋白)在第一细胞中表达、分泌，然后穿透到第二细胞中。在此类实施例中，可使用前导信号多肽和/或细胞穿透来增强CDKL5多肽的分泌和/或穿透。在不希望受到任何特定理论约束的情况下，据信CDKL5多肽的分泌和穿透可用于增强基因疗法相对于传统基因疗法方法的效果，而传统的基因疗法方法仅将DNA和RNA引入患者体内，因为基因疗法中的转导可能仅限于患者细胞的某一部分(例如，10％的靶标患者细胞成功地被DNA/RNA转导)。通过这种方式，成功转导的细胞可用于针对转导细胞和未成功转导的相邻细胞表达CDKL5多肽(或包含所述多肽的融合蛋白)。
交叉校正
本发明的另一个方面可以包括交叉校正。基因疗法可能无法有效地成功转染所有缺陷细胞。在一个或多个实施例中，可以通过相邻的成功转染的细胞校正未转染的细胞中的遗传缺陷。例如，所述CDKL5多肽或融合蛋白可以在成功转染的细胞中表达，从所述细胞分泌，并被未成功转染的相邻细胞吸收。所述缺陷可由本文所述的任何基因疗法方法，通过合适的编码所需的CDKL5多肽和/或融合蛋白的多核苷酸(例如DNA或RNA)进行交叉校正。本文所述的任何CDKL5多肽和/或融合蛋白均可用于交叉校正CDKL5相关的缺陷。
在一个或多个实施例中，将CDKL5无效受试者用于确定融合蛋白诱导的交叉校正。在一些实施例中，所述受试者是小鼠。在一些实施例中，可使用病毒载体校正CDKL5缺陷。在一个特定的实施例中，使用AAV载体来校正CDKL5缺陷。在一个特定的实施例中，所述AAV载体包含AAV-PHP.B.CBH.BIP-TATκ28-CDKL5.SV40。在一个特定的实施例中，包含校正基因的病毒载体以足以校正遗传缺陷的剂量施用。在一些实施例中，小鼠中足以校正遗传缺陷的剂量在10×e2GC/小鼠至10×e15GC/小鼠的范围内。在一些实施例中，小鼠中足以校正遗传缺陷的剂量可以是10xe2GC/小鼠、10xe3GC/小鼠、10xe4GC/小鼠、10xe5GC/小鼠、10xe6GC/小鼠、10xe7GC/小鼠、10xe8GC/小鼠、10xe9GC/小鼠、10xe10GC/小鼠、10xe11GC/小鼠、10xe12GC/小鼠、10xe13GC/小鼠、10xe14GC/小鼠或10xe15GC/小鼠。示例性施用途径包括但不限于鞘内、静脉内、脑池内、眶后、腹腔内、脑室内或脑实质内施用。
在一个或多个实施例中，可将所述CDKL5无效小鼠分为治疗组和对照组。根据施用途径，每个组(治疗组和对照组)可以进一步分为两个亚组。如果需要，可以同时使用多于一种途径。在一个或多个实施例中，可以通过脑室内(ICV)或眶后(RO)施用途径对每个亚组施用AAV-PHP.B.CBH.BIP-TATκ28-CDKL5.SV40剂量。每个亚组接受的AAV-PHP.B.CBH.BIP-TATκ28-CDKL5.SV40剂量的量为10xe8GC/小鼠、10xe9GC/小鼠或10xe10GC/小鼠。施用后三个月，可以评估载体对行为终点的影响，并且可以对小鼠实施安乐死以进行转基因表达分析。
对小鼠实施安乐死后，可以采集大脑的各个切面，包括但不限于矢状切面。切片可以用DAPI、抗NeuN抗体、抗CDKL5 RNA抗体和抗CDKL5蛋白抗体进行免疫染色。这些切片可取自大脑新皮层、纹状体、丘脑和海马结构切片。
免疫染色图像可使用Visiopharm软件进行分析。免疫染色的细胞可分为六：组(1)DAPI染色以鉴定细胞；(2)NeuN染色以鉴定神经元；(3)具有CDKL5 mRNA和CDKL5蛋白的神经元；(4)具有CDKL5 mRNA的神经元；(5)交叉校正的神经元；以及(6)交叉校正的非神经元。图像分析的结果可进一步进行交叉校正的神经元和非神经元的统计分析。
配制品、治疗方法和使用
可以根据常规程序将基因疗法组合物(例如，包含CDKL5多核苷酸)或蛋白替代疗法组合物(例如，包含含有CDKL5变体或融合蛋白的重组蛋白)配制成适于向人施用的药物组合物。例如，在一个或多个实施例中，用于静脉内施用的组合物是在无菌等渗水缓冲液中的溶液。必要时，所述组合物还可以包括增溶剂和局部麻醉剂以缓解注射部位的疼痛。通常，成分以单位剂型分开或混合在一起提供，例如，作为在气密容器中的干燥冻干粉或无水浓缩物，气密容器如指明活性剂的量的安瓿或小药囊。在通过输注施用组合物时，可以用包含无菌药用级的水、盐水或右旋糖/水的输液瓶进行分配。在通过注射施用组合物时，可以提供无菌注射用水或盐水的安瓿，这样使得可以在施用前将这些成分混合。
基因疗法组合物(例如，包含CDKL5多核苷酸)或蛋白替代疗法组合物(例如，包含含有CDKL5变体或融合蛋白的重组蛋白)(或包含基因疗法组合物或蛋白替代疗法组合物的组合物或药物)通过适当的途径施用。在一个或多个实施例中，所述基因疗法组合物或蛋白替代疗法组合物是静脉内施用的。在其他实施例中，所述基因疗法组合物或蛋白替代疗法组合物通过直接施用于靶组织来施用，例如施用于心脏或骨骼肌(例如，肌肉内；脑室内)或神经系统(例如，鞘内递送-向脑或脊髓蛛网膜下的空间递送)。如果需要，可以同时使用多于一种途径。示例性施用途径包括但不限于鞘内、静脉内、脑池内、脑室内或脑实质内施用。
所述基因疗法组合物(例如，包含CDKL5多核苷酸)或蛋白替代疗法组合物(例如，包含含有CDKL5变体或融合蛋白的重组蛋白)(或包含此类基因疗法组合物或蛋白替代疗法的组合物或药物)以治疗有效量施用(例如，当以固定间隔施用时，足以治疗疾病的剂量，如通过改善与疾病相关的症状、预防或延迟疾病的发生和/或减轻疾病症状的严重性或降低频率)。在治疗疾病中治疗有效量将取决于疾病影响的性质和程度。另外，可以任选地采用体外或体内测定来帮助鉴定最佳剂量范围。待采用的确切剂量还取决于施用途径和疾病的严重程度，并且应根据从业者的判断和每个患者的情况来决定。有效剂量可以从源自体外或动物模型测试系统的剂量-应答曲线推算。
治疗有效量的基因疗法组合物(例如，包含CDKL5多核苷酸)或蛋白替代疗法组合物(例如，包含含有CDKL5变体或融合蛋白的重组蛋白)(或包含此类基因疗法组合物或蛋白替代疗法的组合物或药物)可以是根据疾病影响的性质和程度以固定间隔施用和/或持续施用。如本文中所使用，以“规律的间隔”施用表示，将所述治疗有效量定期地施用(如区别于一次性剂量)。单个个体的施用间隔不需要是固定的间隔，但是可以是随时间变化的，其取决于所述个体的需要。
基因疗法组合物(例如，包含CDKL5多核苷酸)或蛋白替代疗法组合物(例如，包含含有CDKL5变体或融合蛋白的重组蛋白)(或包含此类基因疗法组合物或蛋白替代疗法组合物的组合物或药物)可制备以供以后使用，例如制备于单位剂量的小瓶或注射器中，或用于静脉注射的瓶子或袋子中。可以将包含基因疗法组合物(例如，包含CDKL5多核苷酸)或蛋白替代疗法组合物(例如，包含含有CDKL5变体或融合蛋白的重组蛋白)(或包含此类基因疗法组合物或蛋白替代疗法组合物的组合物或药剂)以及任选赋形剂或其他活性成分如其他药物的试剂盒封装在包装材料中，并且伴随着用于治疗需要治疗的受试者(例如患有CDKL5缺乏、雷特综合征或雷特综合征变体的患者)的关于重组、稀释或剂量的说明书。
实例
实例1-12-CDKL5融合蛋白
图2A-2BK显示用于在适当细胞中表达融合蛋白的质粒，例如哺乳动物细胞(例如，CHO细胞或HEK细胞)、昆虫细胞(例如，Sf9细胞)或细菌细胞(例如，大肠杆菌细胞)。这些蛋白具有SEQ ID NO:43-105所示的氨基酸序列。包含CDKL5截短变体的SEQ ID NO:49-59的融合蛋白的缺失或截短的编号相对于全长CDKL5107多肽(1-960)。包含CDKL5糖基化变体的SEQID NO:93-105的融合蛋白具有通过Asn取代为Gln而改变的特定N-连接糖基化位点，例如“1-10NQ”表示所有10个N-连接糖基化位点都通过Asn取代为Gln而改变，“2NQ”表示只有第二个N-连接糖基化位点通过Asn取代为Gln而改变。另外，据预测某些N-连接糖基化位点比其他位点具有更高的糖基化可能性，因此首先研究了这些位点。基于此，所研究的前7个N-连接糖基化位点标记为位点1-7，并在氨基酸序列中以粗体表示，接下来所研究的3个N-连接糖基化位点标记为位点8-10，在氨基酸序列中以粗体和下划线表示。因此，从N端到C端的N-连接糖基化位点的顺序是1、2、3、8、4、9、10、5、6和7。相对于全长CDKL5-107多肽(1-960)的N-连接糖基化位点编号和基序序列如下：1＝Asn159，NLS；2＝Asn167，NYT；3＝Asn348，NLS；4＝Asn500，NLS；5＝Asn764，NIS；6＝Asn942，NRT；7＝Asn945，NRS；8＝Asn363，NES；9＝Asn731，NVS；10＝Asn748，NHS。
在CDKL5在C端与另外的N端氨基酸序列融合的那些构建体中，CDKL5的初始甲硫氨酸(氨基酸1)被去除。在这些构建体中，所述CDKL5多肽以第二个氨基酸赖氨酸开始。尽管特别提及了N端氨基酸序列(例如N端CPP)，但是本披露还涵盖了C端氨基酸序列(例如C端CPP)。
下表1汇总了图2A-2BK和SEQ ID NO:43-105中使用的缩写：
表1
Figure BDA0003721100640000301
Figure BDA0003721100640000311
Figure BDA0003721100640000321
图2A显示了用于在CHO细胞中表达SEQ ID NO:43的融合蛋白的示例性质粒。该融合蛋白包含修饰的BiP前导信号多肽、TATκ28和全长人CDKL5107同工型。
图2B显示了用于在CHO细胞中表达SEQ ID NO:44的融合蛋白的示例性质粒。该融合蛋白包含鼠Igκ链前导多肽、TATκ28和全长人CDKL5107同工型。
图2C显示了用于在CHO细胞中表达SEQ ID NO:45的融合蛋白的示例性质粒。该融合蛋白包含修饰的BiP前导信号多肽、TATκ28和全长人CDKL5115同工型。
图2D显示了用于在CHO细胞中表达SEQ ID NO:46的融合蛋白的示例性质粒。该融合蛋白包含鼠Igκ链前导多肽、TATκ28和全长人CDKL5115同工型。
图2E显示了用于在CHO细胞中表达SEQ ID NO:47的融合蛋白的示例性质粒。该融合蛋白包含TATκ28和全长人CDKL5107同工型。
图2F显示了用于在大肠杆菌细胞中表达SEQ ID NO:48的融合蛋白的示例性质粒。该融合蛋白包含TATκ28和全长人CDKL5107同工型。
图2G显示了用于在大肠杆菌细胞中表达SEQ ID NO:49的融合蛋白的示例性质粒。该融合蛋白包含TATκ28和构建体2的CDKL5107变体。
图2H显示了用于在大肠杆菌细胞中表达SEQ ID NO:50的融合蛋白的示例性质粒。该融合蛋白包含TATκ28和构建体3的CDKL5107变体。
图2I显示了用于在大肠杆菌细胞中表达SEQ ID NO:51的融合蛋白的示例性质粒。该融合蛋白包含TATκ28和构建体4的CDKL5107变体。
图2J显示了用于在大肠杆菌细胞中表达SEQ ID NO:52的融合蛋白的示例性质粒。该融合蛋白包含TATκ28和构建体5的CDKL5107变体。
图2K显示了用于在大肠杆菌细胞中表达SEQ ID NO:53的融合蛋白的示例性质粒。该融合蛋白包含TATκ28和构建体6的CDKL5107变体。
图2L显示了用于在大肠杆菌细胞中表达SEQ ID NO:54的融合蛋白的示例性质粒。该融合蛋白包含TATκ28和构建体7的CDKL5107变体。
图2M显示了用于在大肠杆菌细胞中表达SEQ ID NO:55的融合蛋白的示例性质粒。该融合蛋白包含TATκ28和构建体8的CDKL5107变体。
图2N显示了用于在大肠杆菌细胞中表达SEQ ID NO:56的融合蛋白的示例性质粒。该融合蛋白包含TATκ28和构建体9的CDKL5107变体。
图2O显示了用于在大肠杆菌细胞中表达SEQ ID NO:57的融合蛋白的示例性质粒。该融合蛋白包含TATκ28和构建体10的CDKL5107变体。
图2P显示了用于在大肠杆菌细胞中表达SEQ ID NO:58的融合蛋白的示例性质粒。该融合蛋白包含TATκ28和构建体11的CDKL5107变体。
图2Q显示了用于在大肠杆菌细胞中表达SEQ ID NO:59的融合蛋白的示例性质粒。该融合蛋白包含TATκ28和构建体12的CDKL5107变体。
图2R显示了用于在大肠杆菌细胞中表达SEQ ID NO:60的融合蛋白的示例性质粒。该融合蛋白包含TAT28和全长人CDKL5107同工型。
图2S显示了用于在大肠杆菌细胞中表达SEQ ID NO:61的融合蛋白的示例性质粒。该融合蛋白包含TATκ28和增强型绿色荧光蛋白(eGFP)。
图2T显示了用于在大肠杆菌细胞中表达SEQ ID NO:62的融合蛋白的示例性质粒。该融合蛋白包含无CPP的eGFP。
图2U显示了用于在大肠杆菌细胞中表达SEQ ID NO:63的融合蛋白的示例性质粒。该融合蛋白包含人双载蛋白1(AMPH1)。
图2V显示了用于在CHO细胞中表达SEQ ID NO:64的融合蛋白的示例性质粒。该融合蛋白包含人双载蛋白1(AMPH1)。
图2W显示了用于在CHO细胞中表达SEQ ID NO:65的融合蛋白的示例性质粒。该融合蛋白包含修饰的BiP前导信号多肽、TATκ11和全长人CDKL5107同工型。
图2X显示了用于在CHO细胞中表达SEQ ID NO:66的融合蛋白的示例性质粒。该融合蛋白包含鼠Igκ链前导多肽、TATκ11和全长人CDKL5107同工型。
图2Y显示了用于在CHO细胞中表达SEQ ID NO:67的融合蛋白的示例性质粒。该融合蛋白包含TATκ11和无前导信号多肽的全长人CDKL5107同工型。
图2Z显示了用于在大肠杆菌细胞中表达SEQ ID NO:68的融合蛋白的示例性质粒。该融合蛋白包含TATκ11和无前导信号多肽的全长人CDKL5107同工型。
图2AA显示了用于在大肠杆菌细胞中表达SEQ ID NO:69的融合蛋白的示例性质粒。该融合蛋白包含TAT11和没有前导信号多肽的全长人CDKL5107同工型。
图2AB显示了用于在CHO细胞中表达SEQ ID NO:70的融合蛋白的示例性质粒。该融合蛋白包含TAT11和没有前导信号多肽的全长人CDKL5107同工型。
图2AC显示了用于在CHO细胞中表达SEQ ID NO:71的融合蛋白的示例性质粒。该融合蛋白包含穿膜肽CPP和没有前导信号多肽的全长人CDKL5107同工型。
图2AD显示了用于在CHO细胞中表达SEQ ID NO:72的融合蛋白的示例性质粒。该融合蛋白包含转运肽CPP和没有前导信号多肽的全长人CDKL5107同工型。
图2AE显示了用于在CHO细胞中表达SEQ ID NO:73的融合蛋白的示例性质粒。该融合蛋白包含TAT28和不含前导信号多肽的全长人CDKL5107同工型。
图2AF显示了用于在CHO细胞中表达SEQ ID NO:74的融合蛋白的示例性质粒。该融合蛋白包含修饰的BiP前导信号多肽、P97 CPP和全长人CDKL5107同工型。
图2AG显示了用于在人细胞中表达SEQ ID NO:75的融合蛋白的示例性质粒。该融合蛋白包含P97 CPP和没有前导信号多肽的全长人CDKL5107同工型。
图2AH显示了用于在人细胞中表达SEQ ID NO:76的融合蛋白的示例性质粒。该融合蛋白包含TATκ28和没有前导信号多肽的全长人CDKL5107同工型。
图2AI显示了用于在人细胞中表达SEQ ID NO:77的融合蛋白的示例性质粒。该融合蛋白包含TATκ11和无前导信号多肽的全长人CDKL5107同工型。
图2AJ显示了用于在人细胞中表达SEQ ID NO:78的融合蛋白的示例性质粒。该融合蛋白包含TAT28和不含前导信号多肽的全长人CDKL5107同工型。
图2AK显示了用于在人细胞中表达SEQ ID NO:79的融合蛋白的示例性质粒。该融合蛋白包含TAT11和没有前导信号多肽的全长人CDKL5107同工型。
图2AL显示了用于在人细胞中表达SEQ ID NO:80的融合蛋白的示例性质粒。该融合蛋白包含穿膜肽CPP和没有前导信号多肽的全长人CDKL5107同工型。
图2AM显示了用于在人细胞中表达SEQ ID NO:81的融合蛋白的示例性质粒。该融合蛋白包含转运肽CPP和没有前导信号多肽的全长人CDKL5107同工型。
图2AN显示了用于在人细胞中表达SEQ ID NO:82的融合蛋白的示例性质粒。该融合蛋白包含修饰的BiP前导信号多肽、TATκ28和全长人CDKL5115同工型。
图2AO显示了用于在昆虫细胞中表达SEQ ID NO:83的融合蛋白的示例性质粒。该融合蛋白包含TATκ28和没有前导信号多肽的全长人CDKL5107同工型。
图2AP显示了用于在昆虫细胞中表达SEQ ID NO:84的融合蛋白的示例性质粒。该融合蛋白包含TATκ11和无前导信号多肽的全长人CDKL5107同工型。
图2AQ显示了用于在昆虫细胞中表达SEQ ID NO:85的融合蛋白的示例性质粒。该融合蛋白包含TAT28和不含前导信号多肽的全长人CDKL5107同工型。
图2AR显示了用于在昆虫细胞中表达SEQ ID NO:86的融合蛋白的示例性质粒。该融合蛋白包含TAT11和没有前导信号多肽的全长人CDKL5107同工型。
图2AS显示了用于在昆虫细胞中表达SEQ ID NO:87的融合蛋白的示例性质粒。该融合蛋白包含穿膜肽CPP和没有前导信号多肽的全长人CDKL5107同工型。
图2AT显示了用于在昆虫细胞中表达SEQ ID NO:88的融合蛋白的示例性质粒。该融合蛋白包含转运肽CPP和没有前导信号多肽的全长人CDKL5107同工型。
图2AU显示了用于在昆虫细胞中表达SEQ ID NO:89的融合蛋白的示例性质粒。该融合蛋白包含P97 CPP和没有前导信号多肽的全长人CDKL5107同工型。
图2AV显示了用于在昆虫细胞中表达SEQ ID NO:90的融合蛋白的示例性质粒。该融合蛋白包含无CPP的eGFP。
图2AW显示了用于在昆虫细胞中表达SEQ ID NO:91的融合蛋白的示例性质粒。该融合蛋白包含TATκ28和eGFP。
图2AX显示了用于在昆虫细胞中表达SEQ ID NO:92的融合蛋白的示例性质粒。该融合蛋白包含没有前导信号多肽或CPP的全长人CDKL5107同工型。
图2AY显示了用于在CHO细胞中表达SEQ ID NO:93的融合蛋白的示例性质粒。该融合蛋白包含修饰的BiP前导信号多肽、TATκ28和1-7NQ CDKL5107糖基化变体。
图2AZ显示了用于在CHO细胞中表达SEQ ID NO:94的融合蛋白的示例性质粒。该融合蛋白包含修饰的BiP前导信号多肽、TATκ28和2-7NQ CDKL5107糖基化变体。
图2BA显示了用于在CHO细胞中表达SEQ ID NO:95的融合蛋白的示例性质粒。该融合蛋白包含修饰的BiP前导信号多肽、TATκ28和1,3-7NQ CDKL5107糖基化变体。
图2BB显示了用于在CHO细胞中表达SEQ ID NO:96的融合蛋白的示例性质粒。该融合蛋白包含修饰的BiP前导信号多肽、TATκ28和1-2,4-7NQ CDKL5107糖基化变体。
图2BC显示了用于在CHO细胞中表达SEQ ID NO:97的融合蛋白的示例性质粒。该融合蛋白包含修饰的BiP前导信号多肽、TATκ28和1-3,5-7NQ CDKL5107糖基化变体。
图2BD显示了用于在CHO细胞中表达SEQ ID NO:98的融合蛋白的示例性质粒。该融合蛋白包含修饰的BiP前导信号多肽、TATκ28和1-4,6-7NQ CDKL5107糖基化变体。
图2BE显示了用于在CHO细胞中表达SEQ ID NO:99的融合蛋白的示例性质粒。该融合蛋白包含修饰的BiP前导信号多肽、TATκ28和1-5,7NQ CDKL5107糖基化变体。
图2BF显示了用于在CHO细胞中表达SEQ ID NO:100的融合蛋白的示例性质粒。该融合蛋白包含修饰的BiP前导信号多肽、TATκ28和1-6NQ CDKL5107糖基化变体。
图2BG显示了用于在CHO细胞中表达SEQ ID NO:101的融合蛋白的示例性质粒。该融合蛋白包含修饰的BiP前导信号多肽、TATκ28和2NQ CDKL5107糖基化变体。
图2BH显示了用于在CHO细胞中表达SEQ ID NO:102的融合蛋白的示例性质粒。该融合蛋白包含修饰的BiP前导信号多肽、TATκ28和1-10NQ CDKL5107糖基化变体。
图2BI显示了用于在CHO细胞中表达SEQ ID NO:103的融合蛋白的示例性质粒。该融合蛋白包含修饰的BiP前导信号多肽、TATκ28和1-7,9-10NQ CDKL5107糖基化变体。
图2BJ显示了用于在CHO细胞中表达SEQ ID NO:104的融合蛋白的示例性质粒。该融合蛋白包含修饰的BiP前导信号多肽、TATκ28和1-8,10NQ CDKL5107糖基化变体。
图2BK显示了用于在CHO细胞中表达SEQ ID NO:105的融合蛋白的示例性质粒。该融合蛋白包含修饰的BiP前导信号多肽、TATκ28和1-9NQ CDKL5107糖基化变体。
各种CDKL5融合蛋白在大肠杆菌、CHO、HEK和昆虫细胞中表达，并使用HeLa细胞裂解物进行体外转录/翻译，如下所进一步描述。
实例1-CDKL5截短变体在大肠杆菌细胞中的表达
将TATκ28-CDKL5_107-FH的全长和截短克隆到pET载体pEX-1中，并转化到大肠杆菌BL21(DE3)中。将菌落纯化的转化体在LB+100μg/mL氨苄青霉素中于37℃培养至指数期。然后将培养物冷却至20℃，并在有(或没有)1mM IPTG的情况下诱导16小时。收集细胞沉淀并在补充有1X完全蛋白酶抑制剂复合物(罗氏公司(Roche))的B-Per完全细菌蛋白提取液(赛默公司(Thermo))中裂解。在室温下让裂解进行30分钟。通过在4℃下以16,000xg离心15分钟，从裂解物中制备可溶级分。蛋白在SDS-PAGE上解析，转移到硝酸纤维素膜上，用兔抗多组氨酸抗体(赛默公司)探测，并用荧光二抗检测。
图3A和3B所示的印迹证实了CDKL5截短变体的表达。在图3A和3B中，无IPTG诱导的培养物是奇数泳道，有IPTG诱导的培养物是偶数泳道，在无IPTG诱导的泳道中没有CDKL5融合蛋白表达，而在有IPTG诱导的泳道中有CDKL5融合蛋白表达。
对于图3A，泳道鉴定如下：
表2-图3A的泳道鉴定
Figure BDA0003721100640000381
Figure BDA0003721100640000391
对于图3B，泳道鉴定如下：
表3-图3B的泳道鉴定
# 样品名称 AA大小(差值) 泳道
7 Δ529-960 -432 1,2
8 Δ421-960 -540 3,4
9 Δ315-960 -646 5,6
10 Δ315-420 -106 7,8
11 Δ315-528 -214 9,10
12 Δ315-636 -322 11,12
实例2-CDKL5融合蛋白在CHO细胞中的表达
使用8个质粒用Maxcyte STX电穿孔CHO-S细胞(20x10^6个细胞)：(1)pOptiVec空载体；2)TATκ28-CDKL5-107-3xFlagHis；3)TATκ11-CDKL5-107-3xFlagHis；4)TAT11-CDKL5-107-3xFlagHis；5)TAT28-CDKL5-107-3xFlagHis；6)ANTP-CDKL5-107-3xFlagHis；7)TRANSP-CDKL5-107-3xFlagHis和8)MBiP-TATκ28-CDKL5-107-3xFlagHis(编码序列经过CHO密码子优化)。在培养基中回收细胞，并培养一天。收获细胞并裂解。对于每次转染，将20μg裂解物进行4％-12％BisTris SDS-PAGE，并使用iBlot2系统转移到硝酸纤维素印迹上。将印迹在1xTBS-T中的5％牛奶中封闭。通过与1:2000稀释的兔抗His抗体一起孵育过夜，对印迹进行Western印迹分析。经过一系列洗涤后，将印迹与1:10000的抗兔IgG DyaLight 680二抗一起孵育。进行另外的洗涤。将印迹在Licor Odyssey扫描仪上成像。图4A所示的印迹证实了CDKL5融合蛋白的表达。
实例3-CDKL5融合蛋白在HEK细胞中的表达
用FuGeneHD(24μl FuGeneHD:8μg DNA比)和7个质粒转染HEK293F细胞(8x10^6个细胞)：1)空pOptiVec；2)TATκ11-CDKL5_107-3xFlagHis；3)TAT11-CDKL5_107-3xFlagHis；4)TAT28-CDKL5_107-3xFlagHis；5)ANTP-CDKL5_107-3xFlagHis；6)TRANSP-CDKL5_107-3xFlagHis和7)TATκ28-CDKL5_107-3xFlagHis(编码序列经过人密码子优化)。孵育细胞并在转染后2天收获。裂解细胞，并对20μg裂解物进行4％-12％BisTris SDS-PAGE，并使用iBlot2系统转移到硝酸纤维素印迹上。将印迹在1xTBS-T中的5％牛奶中封闭。通过与1:2000稀释的兔抗His抗体一起孵育过夜，对印迹进行Western印迹分析。经过一系列洗涤后，将印迹与1:10000的抗兔IgG DyaLight 680二抗一起孵育。进行另外的洗涤。将印迹在Licor Odyssey扫描仪上成像。图4B所示的印迹证实了CDKL5融合蛋白的表达。
实例4-CDKL5融合蛋白在CHO细胞中的甲氨蝶呤扩增
用甲氨蝶呤扩增法来扩增CDKL5融合蛋白在CHO-DG44细胞中的表达。将TATκ28-CDKL5_107-FH(无信号序列)、Igκ-TATκ28-CDKL5_107-FH和mBiP-TATκ28-CDKL5_107-FH克隆到pOptiVec载体中，该载体提供了甲氨蝶呤抗性的DHFR基因。将这些质粒转染到DG44细胞(缺乏dhfr)中，并通过在缺乏次黄嘌呤和胸苷的培养基中生长进行选择。通过依次在0.1、0.25、0.5和1μM甲氨蝶呤(MTX)中培养细胞，可以获得抗甲氨蝶呤的继代培养物，使细胞在步骤之间恢复至70％的活力。将细胞沉淀在含75mM NaCl，1％Triton X-100和1.5X蛋白酶抑制剂混合物(不含EDTA)(pH 7.4)的50mM Tris-HCl中裂解。在LDS-PAGE上解析40μg的总蛋白，将其转移到硝酸纤维素膜上，用兔抗多组氨酸抗体(赛默公司)探测，并用荧光二抗检测。
图5所示的印迹展示，为了选择更高拷贝数的DHFR变体::CDKL5，随着甲氨蝶呤浓度的增加，出现了基因重排的证据(除了mBiP构建体)，并且只有mBiP版本的CDKL5水平升高。用107kDa(CDKL5_107)和115kDa(CDKL5_115)版本的CDKL5复制了该模式。此外，只有在mBiP构建体的情况下，显现的CDKL5的形式才稍微更大。在不希望受到任何特定理论约束的情况下，据信TATκ28-CDKL5的胞质表达对细胞有毒性或减少细胞增殖。当缺少信号序列或使用Igκ序列时，只有那些重排CDKL5序列、消除其表达的细胞才能被高水平的甲氨蝶呤选择。由mBiP信号序列产生的较高质量形式与在分泌途径中N-连接聚糖的添加相一致，而缺少这种具有Igκ信号序列的较大形式则表明转运效率较低。
实例5-分泌到培养基中和细胞裂解物中的CDKL5表达的比较
除了上面提到的DG44转染的细胞系(无信号序列的TATκ28-CDKL5_107-FH、Igκ-TATκ28-CDKL5_107-FH和mBiP-TATκ28-CDKL5_107-FH)之外，还比较了在粘附HEK293T细胞中稳定转染的Igκ-TATκ28-eGFP-CDKL5_107-MH质粒在培养基中和在细胞裂解物中的CDKL5融合蛋白分泌。mBiP-TATκ28-CDKL5_107-FH细胞系以0mM MTX和0.5μM MTX继代培养物二者为代表。在无血清生长两天后，收集条件培养基并浓缩200倍。
将细胞沉淀在含75mM NaCl，1％Triton X-100和1.5X蛋白酶抑制剂混合物(不含EDTA)(pH 7.4)的50mM Tris-HCl中裂解。在LDS-PAGE上解析细胞裂解物或浓缩条件培养基，将其转移到硝酸纤维素膜上，用兔抗多组氨酸抗体(赛默公司)探测，并用荧光二抗检测。
图6A和6B所示的印迹分别比较了各种信号序列构建体中CDKL5的分泌和内部贮存。甲氨蝶呤扩增的继代培养物以星号指出-Bip-TATκ-CDKL5*。甲氨蝶呤扩增的mBiP构建体大大提高了表达的CDKL5的水平，并且大多数蛋白陷在细胞内。TATκ28-eGFP-CDKL5构建体仅提供约0.1μg/L的CDKL5融合蛋白分泌量，而mBiP TATκ28-CDKL5构建体实现了约15μg/L的CDKL5融合蛋白分泌量(增加150倍)。在相同的表达mBiP-TATκ28-CDKL5的细胞内，CDKL5融合蛋白占总蛋白的0.1％(1mg/g)。
实例6-CDKL5融合蛋白和潜在底物的共表达
将同时含有TATκ28-CDKL5-FH(无信号序列)和若干假定CDKL5底物(HOMER1、HDAC4、ARHGEF2、MAPRE2、AMPH1或SHANK1)之一或无蛋白伴侣的单一质粒(pCHO 1.0)瞬时转染到HEK293F细胞中。在培养5天后，收获细胞并在50mM磷酸钠、150mM氯化钠、0.5％Triton-X100、1X完全蛋白酶抑制剂复合物、无EDTA(pH为7)中于4℃裂解30分钟。通过将裂解物在4℃下以16,000xg离心15分钟获得可溶级分。通过BCA测定确定可溶蛋白，并在SDS-PAGE上解析等量的样品，转移到硝酸纤维素膜上，用兔抗多组氨酸(赛默飞世尔公司)和小鼠抗CDKL5抗体(EMD密理博公司(EMD Millipore))进行探测，并用近红外荧光二抗、抗兔IgGDyaLight 680和抗小鼠IgG DyaLight 800(细胞信号传导技术公司(Cell SignalingTechnology))检测。如图7的印迹所示，AMPH1的共表达增加了可溶TATκ28-CDKL5的量，而ARHGEF2的共表达减少了可溶TATκ28-CDKL5的量。后者表明消除ARHGEF2表达可能会增加可溶TATκ28-CDKL5的量。
实例7-CDKL5蛋白的体外转录/翻译
将以下蛋白克隆到T7/EMCV-IRES质粒(pT7CFE1)中：eGFP、CDKL5_115和TAT28-CDKL5_107-FH。将纯化的质粒DNA引入基于HeLa细胞的IVT试剂盒(赛默公司)中，以在30℃下进行5小时的非CAP依赖性联合体外转录/翻译。蛋白样品在SDS-PAGE上解析，转移到硝酸纤维素膜上，用兔抗多组氨酸(His)抗体(赛默公司)探测，并用荧光检测二抗。图8所示的印迹证实了CDKL5融合蛋白的表达。
实例8-CDKL5蛋白的糖基化
对MBiP-TATκ28-CDKL5-107-3xFlagHis的进一步分析揭示，该融合蛋白在CHO-DG44和HEK293F细胞中表达时被糖基化。通过电穿孔将质粒瞬时转染到CHO-DG44和HEK293F细胞中。裂解细胞沉淀，并通过离心获得可溶级分。将可溶级分在PNGase F缓冲液中变性，并与PNGase F一起孵育以除去N-连接聚糖。消化的样品通过SDS-PAGE解析，转移到硝酸纤维素膜上，并用抗多组氨酸抗体进行免疫印迹。图4A中的印迹展示，在用PNGase F处理之前在CHO-DG44细胞中表达时，包含野生型CDKL5107同工型的融合蛋白被高度糖基化，而当在CHO-DG44细胞中表达时，N-连接糖基化位点的7个Asn残基被Gln取代(1-7NQ)产生很少或没有被糖基化的融合蛋白。另外的包含CDKL5糖基化变体1-4,6-7NQ；1-5,7NQ；1-6NQ；2NQ；2-7NQ；1,3-7NQ；1-2,4-7NQ和1-3,5-7NQ的融合蛋白在HEK293F细胞中表达，不处理或用PNGase F处理，如图4B所示。这些包含其他糖基化变体的融合蛋白具有不同程度的糖基化，并且均比包含野生型CDKL5107同工型的融合蛋白的糖基化程度低，因此显示各种N-连接糖基化位点可以单独进行糖基化。还发现包含野生型CDKL5115同工型的融合蛋白被糖基化。
实例9-CDKL5融合蛋白在昆虫细胞中的表达
还研究了其他表达系统以改善表达，减少糖基化和/或增强纯化。一种此种系统利用昆虫细胞Sf9。为了保护TATκ28-CDKL5和其他CDKL5融合蛋白的N端，将GST标签与N端基因融合，并通过HRV3C蛋白酶位点与CDKL5融合蛋白的其余部分分开。将另一个HRV3C蛋白酶位点添加到CDKL5蛋白的C端，以分离FLAG和多组氨酸(His)亲和标签。将Sf9细胞与线性化杆状病毒(BV)DNA共转染并转移质粒：1)GST-P-TATκ28-eGFP-P-FH；2)GST-P-eGFP-P-FH；3)GST-P-TAT28-CDKL5_107-P-FH；4)GST-P-TATκ28-CDKL5_107-P-FH；5)GST-P-p97p-CDKL5_107-P-FH；6)GST-P-Antp-CDKL5_107-P-FH；7)GST-P-TAT11-CDKL5_107-P-FH和GST-P-Transp-CDKL5_107-P-FH(编码序列经Sf9密码子优化)。1μg蛋白在复制的4％-12％的10孔NuPage凝胶上运行完。凝胶在175V下运行90分钟。使用iBLOT在20v下将蛋白转移到硝酸纤维素中，持续7分钟。如图5所示，用Sypro宝石红总蛋白染色分析CDKL5融合蛋白的表达。
实例10-GST-P-TATκ28-CDKL5蛋白的纯化和切割
还纯化了来自昆虫细胞的CDKL5融合蛋白，以从细胞裂解物中分离出CDKL5蛋白。GST-P-TATκ28-CDKL5_107-P-FH蛋白在Sf900II培养基中作为悬浮培养物维持的High Five(BTI-Tn-5B1-4)细胞中表达。感染的细胞沉淀用补充有不含EDTA的1X HALT蛋白酶抑制剂混合物(赛默公司，78437)、1mM三2-羧乙基-膦(TCEP)和5mM EDTA的50mM NaPO4、500mMNaCl、10％甘油(pH为6)裂解，比率为每1亿个细胞10ml裂解缓冲液。使用Parr 4639细胞破碎仪在750PSI下通过氮气空化作用裂解15分钟后，添加Triton X-100至0.5％。通过以31,000×g离心20分钟使裂解物澄清。将可溶材料调节至350mM NaCl，并施加到HiTrap SPFast Flow树脂(GE医疗集团(GE Healthcare)，17-5157-01)上。用10个柱体积(CV)NaCl梯度350-2000mM洗脱结合的蛋白。将CDKL5蛋白峰(525-1225mM NaCl)用缓冲液交换至缓冲液B(50mM NaPO4、500mM NaCl、10％甘油、无EDTA的1X HALT蛋白酶抑制剂混合物、1mM TCEP，pH为8)中。将蛋白施加到已填充硫酸镍并用缓冲液B预平衡的IMAC琼脂糖凝胶6FF树脂(GE医疗集团，17-0921-09)上。用缓冲液B+60mM咪唑洗涤所述树脂。将所述树脂与40U的HRV3C蛋白酶(密理博公司(Millipore)，71493)一起在4℃下孵育过夜，以去除GST、FLAG和多组氨酸(His)亲和标签。在3小时和过夜后检查裂解材料的等分试样。用50mM NaPO4、500mMNaCl、10％甘油、1mM TCEP+1X HALT PI-EDTA+0.5％Triton X-100+500mM咪唑洗涤所述树脂以洗脱CDKL5。洗脱的蛋白缺少亲和标签，并且迁移通过SDS-PAGE更快。
图10A和10B显示了Sypro宝石红总蛋白染色的凝胶分析。图11A显示了与未感染的对照细胞相比，昆虫细胞中GST-P-TATκ28-CDKL5_107-P-FH的表达以及IMAC树脂上加标签蛋白的回收。图11B显示了从IMAC树脂上洗脱的蛋白切割前后的加标签CDKL5蛋白。类似地，图12A显示了细胞裂解物中CDKL5融合蛋白和纯化的融合蛋白的Sypro宝石红染色凝胶。图12B显示了展示图11A的CDKL5融合蛋白的HRV3C蛋白酶切割的Sypro宝石红染色凝胶
实例11-CDKL5蛋白在盐溶液中的溶解度
通过在50mM磷酸钠、500mM NaCl、10％甘油、1mM TCEP、1mM EDTA、1x HALT蛋白酶抑制剂混合物(pH 6.0)中在室温下使用氮气空化裂解15分钟，释放在HighFive细胞中通过感染杆状病毒表达的GST-P-TATκ28-CDKL5_107-P-FH。细胞破裂后，添加Triton X-100至0.5％，并在4℃下孵育30分钟。通过在室温下以15,000x g离心15分钟，将裂解物分为可溶和不可溶级分。然后将可溶级分在以下条件下通过稀释至相同的最终体积进行进一步修饰：
·维持在500mM NaCl
·降低至350mM NaCl
·降低至250mM NaCl
·(A)补充2％聚山梨醇酯-80，并降低至350mM NaCl
·(B)补充50mM精氨酸/50mM谷氨酰胺，并降至350mM NaCl
·(C)补充100mM甜菜碱，并降低至350mM NaCl
·(D)补充100mM甘氨酸，并降低至350mM NaCl
在所述条件下于室温下孵育1小时后，通过离心将溶液再次分离为可溶和不可溶级分。将不可溶级分重悬于等于可溶级分的体积中，并且在LDS-PAGE上解析可溶级分和不可溶级分，然后通过考马斯亮蓝染色进行检测。
图13显示CDKL5融合蛋白在高盐浓度(例如，至少500mM NaCl)下可溶，并且低于500mM的NaCl水平导致不可溶的CDKL5蛋白。CDKL5蛋白可以短暂暴露于低至350mM的NaCl浓度，但会造成一定的损失。因此，本文所述的大多数纯化步骤都是在高盐水平下进行的，但是这种高盐水平可能与体内施用不相容。
实例12-TwinStrep-HRV3C-TATκ28-CDKL5-HRV3C-FLAG-His-HPC4蛋白的纯化和切割
在本实例中，表达并纯化了融合蛋白TwinStrep-HRV3C-TATκ28-CDKL5-HRV3C-FLAG-His-HPC4。图14A显示了所述融合蛋白的示意图。所述融合蛋白具有根据SEQ ID NO:174的氨基酸序列。类似地，所述融合蛋白具有根据SEQ ID NO:175的核苷酸序列。图14B显示了融合蛋白表达、纯化、通过HRV3C蛋白酶的柱上消化以及回收的融合蛋白。图15显示了纯化过程的Western印迹分析。在图15A中，用抗strep抗体进行了Western印迹分析，结果表明在N端完全消化。相反，图15B显示了使用抗HPC4抗体的Western印迹分析，表明在C端消化不完全。图16显示了融合蛋白和His-HRV3C蛋白酶的IMAC/Ni树脂纯化。
实例13-TwinStrep-HRV3C-TATκ28-CDKL5-HRV3C-FLAG-His-TwinStrep蛋白的纯化和切割
纯化来自昆虫细胞的CDKL5融合蛋白以从细胞裂解物中分离CDKL5蛋白。
在本实例中，所述融合蛋白是TwinStrep-HRV3C-TATκ28-CDKL5-HRV3C-FLAG-His-TwinStrep蛋白。所述融合蛋白具有根据SEQ ID NO:176的氨基酸序列。类似地，所述融合蛋白具有根据SEQ ID NO:177的核苷酸序列。图17显示了所述融合蛋白的示意图。所述融合蛋白在High Five(BTI-Tn-5B1-4)细胞中表达。感染的细胞沉淀并贮存在-80℃下。
为了裂解，将细胞沉淀重悬于补充有不含EDTA的1X HALT蛋白酶抑制剂混合物(赛默公司，78437)的裂解缓冲液(50mM Tris HCl、500mM NaCl、10％甘油、1mM EDTA，pH为8)中。使用Parr 4639细胞破碎仪在750PSI下通过氮气空化作用裂解15分钟后，添加TritonX-100至0.5％。通过以31,000×g离心20分钟使裂解物澄清。将澄清的裂解物收集到可溶级分中。
用裂解缓冲液洗涤不可溶沉淀。然后将洗涤的不可溶沉淀物重悬于2ml的裂解缓冲液中并进行超声处理。超声处理后的可溶级分用于蛋白分析。使用BCA测定来测量蛋白浓度。使用NuPAGE来分析昆虫细胞中的蛋白表达。在图18中，开始和上样分别显示了总细胞蛋白和可溶级分。
为了从其他可溶蛋白中纯化融合蛋白，使用了Strep-Tectin树脂。将可溶级分上样到预先平衡的Strep-Tectin柱上。使用His-HRV3C蛋白酶在Strep-Tectin柱上切割亲和标签。为了进行切割，将与Strep-Tectin结合的融合蛋白与His-HRV3C蛋白酶一起孵育约1小时。消化后，收集流通液和洗涤液。在图18中，洗涤-2显示了消化的融合蛋白。再重复一次消化过程。在图18中，洗涤-3显示了重复消化的融合蛋白。从重复的消化过程中收集流通液。将流通液和洗涤液一起汇集在裂解池中。在图18中，脱硫生物素洗脱的级分显示无未消化的融合蛋白。图18A中的帝国蓝染色凝胶分析和使用图18B的抗strep抗体的Western印迹分析表明，融合蛋白在N端和C端被完全消化。
为了对消化的融合蛋白和His-HRV3C蛋白酶进行缓冲液交换，使用了HiPrep 26/20脱盐柱(Cytiva 17-5087-01)。用缓冲液A(50mM Bis-Tris、350mM NaCl、10％(v/v)甘油，pH为6)预平衡色谱柱。将含有His-HRV3C蛋白酶的融合蛋白上样至柱中，并将各级分汇集到脱盐池中。
为了从His-HRV3C蛋白酶中纯化融合蛋白，使用了SP琼脂糖凝胶捕获柱。将脱盐池应用于SP琼脂糖凝胶捕获物，所述捕获物已用缓冲液A预先平衡。将TATκ28-CDKL5蛋白用55％的缓冲液A和45％的缓冲液B(50mM Bis-Tris、2000mM NaCl、10％(v/v)甘油，pH为6)洗脱，以从纯化的TATκ28-CDKL5蛋白级分中去除His-HVRc3。图19显示了使用SP琼脂糖凝胶捕获柱进行的纯化过程。
实例14-DIV14胚胎原代皮层神经元中纯化的TATκ28-CDKL5蛋白的摄取
在本实例中，确定了在胚胎原代皮层神经元中CDKL5融合蛋白的摄取。从E15健康大鼠胚胎中分离出胚胎原代皮层神经元。将胚胎原代皮层神经元接种在聚-l-赖氨酸包被的玻璃盖玻片上，并在体外维持14天(DIV14)。通过亲和标签色谱分析从杆状病毒/昆虫细胞表达系统中纯化重组TATκ28-CDKL5。通过蛋白酶切割除去亲和标签，并进一步分离全长蛋白，并通过阳离子交换色谱浓缩。用10μg/ml重组TATκ28-CDKL5处理培养的胚胎原代皮层神经元6小时。未处理的培养胚胎原代皮层神经元被用作阴性对照。将经处理或未处理的每个样品在4％PFA中固定，在0.1％皂苷中透化，并使用抗MAP2、抗CDKL5和/或抗磷酸化(S222)EB2抗体染色。用DAPI对细胞进行复染色，并在Prolong Diamond抗褪色固定介质下固定在玻璃显微镜载玻片上。使用具有63倍油浸物镜的Leica SP8点扫描激光共聚焦显微镜对样品成像。使用Leica Lightning软件处理图像，并使用ImageJ软件进行合并和着色。使用ImageJ软件对磷酸(S222)EB2信号进行分析，并使用GraphPad Prism软件进行绘图。图20A-20F显示了DIV14胚胎原代皮层神经元中TATκ28-CDKL5的摄取。图20A-20C显示了用等体积的盐水处理的阴性对照的图像。图20A显示了在荧光显微镜下用抗DAPI和抗MAP2染色的大鼠DIV14胚胎原代皮层神经元的图像。图20B是图20A的部分放大。图20C显示了图20B，但是仅针对抗CDKL5蛋白荧光。图20D-20F显示了摄取实验的结果，其中细胞用TATκ28-CDKL5处理。图20D显示了在荧光显微镜下用抗DAPI和抗MAP2染色的大鼠DIV14胚胎原代皮层神经元的图像。图20E是图20D的部分放大。图20F显示了图20E，但是仅针对抗CDKL5荧光。
在大鼠DIV7胚胎原代皮层神经元中也进行了类似的实验，以将结果与大鼠DIV14胚胎原代皮层神经元进行比较。
图21A-21F显示了大鼠DIV7胚胎原代皮层神经元中TATκ28-CDKL5的摄取。图21A-21C是用等体积的盐水处理的阴性对照。图21A显示了在荧光显微镜下用抗DAPI、抗MAP2和抗CDKL5蛋白染色的大鼠DIV7胚胎原代皮层神经元的图像。图21B是图21A的部分放大。图21C显示了图21B，但是仅针对DAPI和抗CDKL5蛋白荧光。图21D-21F显示了摄取实验的结果，其中细胞用TATκ28-CDKL5处理。图21D显示了在荧光显微镜下用抗DAPI、抗MAP2和抗CDKL5蛋白染色的大鼠DIV7胚胎原代皮层神经元的图像。图21E是图21D的部分放大。图21F显示了图21E，但是仅针对DAPI和抗CDKL5蛋白荧光。
类似地，图22A-22F显示了大鼠DIV14胚胎原代皮层神经元中TATκ28-CDKL5的摄取。图22A-22C代表阴性对照的图像。图22A显示了在荧光显微镜下用抗DAPI、抗MAP2和抗CDKL5蛋白染色的胚胎原代皮层神经元的图像，图22B是图22A的部分放大。图22C显示了图22B，但仅针对DAPI和抗CDKL5蛋白荧光。图22D-22F显示了摄取实验的结果，其中细胞用TATκ28-CDKL5蛋白处理。图22D显示了在荧光显微镜下用抗DAPI、抗MAP2和抗CDKL5蛋白染色的大鼠DIV14胚胎原代皮层神经元的图像。图22E是图22D的部分放大。图22F显示了图22E，但仅针对DAPI和抗CDKL5蛋白荧光。
实例15-DIV14胚胎原代皮层神经元中纯化的TATκ28-CDKL5蛋白的时间依赖性摄取
为了进一步随时间确定TATκ28-CDKL5，将培养的胚胎原代皮层神经元用10μg/ml重组TATκ28-CDKL5处理15分钟、30分钟、2小时、6小时或24小时。在每个时间点，将处理过的盖玻片在4％PFA中固定，在0.1％皂苷中透化，并使用抗MAP2、抗CDKL5和/或抗磷酸化(S222)EB2抗体染色。用DAPI对细胞进行复染色，并在Prolong Diamond抗褪色固定介质下固定在玻璃显微镜载玻片上。使用具有63倍油浸物镜的Leica SP8点扫描激光共聚焦显微镜对样品成像。使用Leica Lightning软件处理图像，并使用ImageJ软件进行合并和着色。图23A-23J显示了培养的胚胎原代皮层神经元对TATκ28-CDKL5蛋白的快速摄取。图23A显示了用抗DAPI、抗MAP2和抗CDKL5的阴性对照。图23B-23E显示分别在15、30、120和360分钟用抗DAPI、抗MAP2和抗CDKL5染色的皮质神经元。图23F显示了图23A的图像，但是对抗CDKL5进行了过滤。同样，图23G-23J显示了分别针对抗CDKL5过滤的图23B-23E图像。对图23A-23J的分析表明，在皮层神经元中的TATκ28-CDKL5蛋白积累在至少6小时的时间段内逐渐增加了信号强度的增加。使用ImageJ软件对磷酸(S222)EB2信号进行分析，并使用GraphPad Prism软件进行绘图。图24观察到摄取后磷酸(S222)EB2信号强度的增加，这表明TATκ28-CDKL5在细胞内具有活性。
CDKL5蛋白被报道与PSD95在神经元中共定位。在一个特定的实施例中，用15μg/ml的TATκ28-CDKL5处理DIV14神经元2小时。然后将神经元用抗PSD95和抗CDKL5染色。图25A和图25B分别显示了CDKL5与PSD95和突触蛋白1的共定位。
实例16-CDKL5向大鼠神经元的慢病毒递送
图26A-26E显示以下病毒对原代cdkl5Δ大鼠神经元的慢病毒递送：未处理的(13A)、mBiP(12B)、p97(13C)、TATκ28(13D)和穿膜肽(13E)。用200μl CPP-CKDL5慢病毒上清液处理细胞，并孵育24小时，感染复数(MOI)约为0.03。用ViraPowerTM慢病毒包装混合物Invitrogen K487500完成慢病毒递送的封装。转导后，将细胞在PFA中固定，在皂苷中透化，并用Ms抗βIII微管蛋白(红色)、Shp抗CKDL5(绿色)和DAPI(蓝色)标记；用63倍油镜成像。这些图像显示了CDKL5融合蛋白沿神经突的定位。
实例17-CDKL5 AAV构建体
SEQ ID NO:106-121提供了CDKL5 AAV载体的示例性序列。
SEQ ID NO:106提供了使用CBh启动子以及SEQ ID NO:27的L-ITR和SEQ ID NO:28的R-ITR来表达全长人CDKL5107同工型的质粒的示例性序列。DNA序列经密码子优化以在小鼠中表达。
SEQ ID NO:107提供了使用CBh启动子以及SEQ ID NO:27的L-ITR和SEQ ID NO:28的R-ITR来表达全长人CDKL5107同工型的激酶失活版本的质粒的示例性序列。DNA序列经密码子优化以在小鼠中表达。
SEQ ID NO:108提供了使用CBh启动子以及SEQ ID NO:27的L-ITR和SEQ ID NO:28的R-ITR来表达eGFP的质粒的示例性序列。DNA序列经密码子优化以在小鼠中表达。
SEQ ID NO:109提供了使用CBh启动子以及SEQ ID NO:27的L-ITR和SEQ ID NO:28的R-ITR来表达包含NLS和eGFP的融合蛋白的质粒的示例性序列。DNA序列经密码子优化以在小鼠中表达。
SEQ ID NO:110提供了使用CBh启动子和SEQ ID NO:27的L-ITR和SEQ ID NO:28的R-ITR来表达包含修饰的BiP前导信号多肽、TATκ28和全长人CDKL5107同工型的融合蛋白的质粒的示例性序列。DNA序列经密码子优化以在小鼠中表达。
SEQ ID NO:111提供了使用CBh启动子以及SEQ ID NO:27的L-ITR和SEQ ID NO:28的R-ITR来表达包含修饰的BiP前导信号多肽、TATκ28和全长人CDKL5107同工型的激酶失活版本的融合蛋白的质粒的示例性序列。DNA序列经密码子优化以在小鼠中表达。
SEQ ID NO:112提供了使用CBh启动子以及SEQ ID NO:27的L-ITR和SEQ ID NO:28的R-ITR来表达包含修饰的BiP前导信号多肽、TATκ28和eGFP的融合蛋白的质粒的示例性序列。DNA序列经密码子优化以在小鼠中表达。
SEQ ID NO:113提供了使用CBh启动子以及SEQ ID NO:27的L-ITR和SEQ ID NO:28的R-ITR来表达包含修饰的BiP前导信号多肽、TATκ28、NLS和eGFP的融合蛋白的质粒的示例性序列。DNA序列经密码子优化以在小鼠中表达。
SEQ ID NO:114提供了使用hSyn1启动子以及SEQ ID NO:27的L-ITR和SEQ ID NO:28的R-ITR来表达全长人CDKL5107同工型的质粒的示例性序列。DNA序列经密码子优化以在小鼠中表达。
SEQ ID NO:115提供了使用hSyn1启动子以及SEQ ID NO:27的L-ITR和SEQ ID NO:28的R-ITR来表达全长人CDKL5107同工型的激酶失活版本的质粒的示例性序列。DNA序列经密码子优化以在小鼠中表达。
SEQ ID NO:116提供了使用hSyn1启动子以及SEQ ID NO:27的L-ITR和SEQ ID NO:28的R-ITR来表达eGFP的质粒的示例性序列。DNA序列经密码子优化以在小鼠中表达。
SEQ ID NO:117提供了使用hSyn1启动子以及SEQ ID NO:27的L-ITR和SEQ ID NO:28的R-ITR来表达包含NLS和eGFP的融合蛋白的质粒的示例性序列。DNA序列经密码子优化以在小鼠中表达。
SEQ ID NO:118提供了使用hSyn1启动子以及SEQ ID NO:27的L-ITR和SEQ ID NO:28的R-ITR来表达包含修饰的BiP前导信号多肽、TATκ28和全长人CDKL5107同工型的融合蛋白的质粒的示例性序列。DNA序列经密码子优化以在小鼠中表达。
SEQ ID NO:119提供了使用hSyn1启动子以及SEQ ID NO:27的L-ITR和SEQ ID NO:28的R-ITR来表达包含修饰的BiP前导信号多肽、TATκ28和全长人CDKL5107同工型的激酶失活版本的融合蛋白的质粒的示例性序列。DNA序列经密码子优化以在小鼠中表达。
SEQ ID NO:120提供了使用hSyn1启动子以及SEQ ID NO:27的L-ITR和SEQ ID NO:28的R-ITR来表达包含修饰的BiP前导信号多肽、TATκ28和eGFP的融合蛋白的质粒的示例性序列。DNA序列经密码子优化以在小鼠中表达。
SEQ ID NO:121提供了使用hSyn1启动子以及SEQ ID NO:27的L-ITR和SEQ ID NO:28的R-ITR来表达包含修饰的BiP前导信号多肽、TATκ28、NLS和eGFP的融合蛋白的质粒的示例性序列。DNA序列经密码子优化以在小鼠中表达。
将生成含有SEQ ID NO:SEQ ID NO:106-121的质粒并在小鼠中测试。将针对大鼠密码子优化的相似质粒在小鼠中进行测试。
SEQ ID NO:122提供了用于在人中表达融合蛋白而密码子优化的示例性DNA序列。SEQ ID NO:122编码的融合蛋白包含修饰的BiP前导信号多肽、TATκ28和全长人CDKL5107同工型。
SEQ ID NO:123中提供了用于在人中表达全长人CDKL5107同工型(但没有起始甲硫氨酸密码子或终止密码子)而密码子优化的示例性DNA序列。
本领域技术人员可以通过缺失全长CDKL5107同工型的DNA序列的相关部分来获得用于本文描述的CDKL5截短变体的在人中表达的示例性DNA序列。
SEQ ID NO:124、126、128、130、132、134、136、138、140、142、144、146和148中分别提供了用于在人中表达而密码子优化的SEQ ID NO:93-105的糖基化变体融合蛋白的示例性DNA序列。
SEQ ID NO:125、127、129、131、133、135、137、139、141、143、145、147和149中分别提供了用于在人中表达而密码子优化(但不含起始蛋氨酸密码子或终止密码子)的SEQ IDNO:13-25的糖基化变体CDKL5多肽的示例性DNA序列。
SEQ ID NO:150-154中分别提供了用于在人中表达而密码子优化(但没有起始甲硫氨酸密码子或终止密码子)的TATκ11、TATκ28、穿膜肽、转运肽和P97的示例性DNA序列。SEQ ID NO:170-173提供了使用不同密码子优化工具关于在人中表达而密码子优化(但没有起始甲硫氨酸密码子或终止密码子)的TATκκ28的示例性DNA序列
SEQ ID NO:155提供了用于在人中表达而密码子优化(包括起始甲硫氨酸密码子但无终止密码子)的mBIP的示例性DNA序列。SEQ ID NO:169提供了用于在人中表达而密码子优化(包括起始甲硫氨酸密码子但无终止密码子)的mvBIP的示例性DNA序列。
实例18-CDKL5交叉校正
在本实例中，将CDKL5无效小鼠用于确定BIP-TATκ28-CDKL5诱导的交叉校正。将CDKL5无效小鼠分为治疗组和对照组。通过脑室内(ICV)注射以10xe9GC/小鼠或10xe10GC/小鼠的剂量将AAV-PHP.B.CBH.BIP-TATκ28-CDKL5.SV40施用至治疗组。向对照组小鼠施用PBS。施用后三个月，评估载体对行为终点的影响，并对小鼠实施安乐死以进行转基因表达分析。
对小鼠实施安乐死后，取出大脑切片。将切片用DAPI、抗NeuN抗体、抗CDKL5 RNA核糖核酸探针和抗CDKL5蛋白抗体染色。图27-29分别显示了大脑纹状体、丘脑和海马结构区的抗NeuN抗体、抗CDKL5 RNA核糖核酸探针和抗CDKL5蛋白抗体染色的图像。
使用Visiopharm软件进行图像分析，并将细胞分为六组：(1)DAPI染色以鉴定细胞；(2)NeuN染色以鉴定神经元；(3)具有CDKL5 mRNA和CDKL5蛋白的神经元；(4)具有CDKL5mRNA的神经元；以及(5)交叉校正的神经元。图30显示了已鉴定的六个组的图像。图29A和29B代表来自对照组的免疫染色的脑切片的图像，而图29C和29D代表来自治疗组的免疫染色的脑切片的图像。图29A和29C代表用DAPI、抗NeuN和抗CDKL5蛋白染色的脑切片的图像。图29B和29D代表用DAPI和抗CDKL5mRNA标记的脑切片的图像。图31显示了已鉴定的交叉校正的细胞。图32A显示了矢状切面中交叉校正的神经元的统计分析。图32B显示了矢状切面的特定大脑区域(新皮层、纹状体、丘脑和海马结构)中交叉校正的神经元的统计分析。
实例19-N端和C端CPP的比较
用于表达各种融合蛋白的示例性质粒如图33所示。该质粒包含EF1a启动子、多克隆位点(MCS)、IRES，随后是嘌呤霉素抗性、核定位的GFP和纳米荧光素酶。IRES之后的蛋白由T2A跳跃肽分离。将针对表达下表4中提供的融合蛋白对质粒进行测试：
表4
Figure BDA0003721100640000531
Figure BDA0003721100640000541
Figure BDA0003721100640000551
在整个说明书中对“一个实施例”、“某些实施例”、“不同实施例”、“一个或多个实施例”或“实施例”的引用意味着与所述实施例相联系地描述的具体的特征、结构、材料或特性被包括在本披露内容的至少一个实施例中。因此，在整个说明书的多个位置中出现的短语如“在一个或多个实施例中”、“在某些实施例中”、“在不同实施例中”、“在一个实施例中”或“在实施例中”不一定是指本披露内容的同一实施例。此外，在一个或多个实施例中，具体的特征、结构、材料或特性能以任何合适的方式进行组合。
尽管本披露内容已经参照具体实施例提供了描述，但是应当理解这些实施例仅仅说明本披露内容的原理和应用。对本领域技术人员而言应当清楚的是，在不脱离本披露内容的精神和范围的情况下，可以对本披露内容进行多种修改和变化。因此，意图是本披露内容包括在所附权利要求及其等效物的范围内的修改和变化。
序列表
SEQ ID NO:1 CDKL5107同工型多肽1-960(全长)
MKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKFKDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNMLELLEEMPNGVPPEKVKSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGNNANYTEYVATRWYRSPELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKVLGPLPSEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGILNSVLLDLMKNLLKLDPADRYLTEQCLNHPTFQTQRLLDRSPSRSAKRKPYHVESSTLSNRNQAGKSTALQSHHRSNSKDIQNLSVGLPRADEGLPANESFLNGNLAGASLSPLHTKTYQASSQPGSTSKDLTNNNIPHLLSPKEAKSKTEFDFNIDPKPSEGPGTKYLKSNSRSQQNRHSFMESSQSKAGTLQPNEKQSRHSYIDTIPQSSRSPSYRTKAKSHGALSDSKSVSNLSEARAQIAEPSTSRYFPSSCLDLNSPTSPTPTRHSDTRTLLSPSGRNNRNEGTLDSRRTTTRHSKTMEELKLPEHMDSSHSHSLSAPHESFSYGLGYTSPFSSQQRPHRHSMYVTRDKVRAKGLDGSLSIGQGMAARANSLQLLSPQPGEQLPPEMTVARSSVKETSREGTSSFHTRQKSEGGVYHDPHSDDGTAPKENRHLYNDPVPRRVGSFYRVPSPRPDNSFHENNVSTRVSSLPSESSSGTNHSKRQPAFDPWKSPENISHSEQLKEKEKQGFFRSMKKKKKKSQTVPNSDSPDLLTLQKSIHSASTPSSRPKEWRPEKISDLQTQSQPLKSLRKLLHLSSASNHPASSDPRFQPLTAQQTKNSFSEIRIHPLSQASGGSSNIRQEPAPKGRPALQLPGQMDPGWHVSSVTRSATEGPSYSEQLGAKSGPNGHPYNRTNRSRMPNLNDLKETAL
SEQ ID NO:2 CDKL5107变体Δ853-960
MKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKFKDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNMLELLEEMPNGVPPEKVKSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGNNANYTEYVATRWYRSPELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKVLGPLPSEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGILNSVLLDLMKNLLKLDPADRYLTEQCLNHPTFQTQRLLDRSPSRSAKRKPYHVESSTLSNRNQAGKSTALQSHHRSNSKDIQNLSVGLPRADEGLPANESFLNGNLAGASLSPLHTKTYQASSQPGSTSKDLTNNNIPHLLSPKEAKSKTEFDFNIDPKPSEGPGTKYLKSNSRSQQNRHSFMESSQSKAGTLQPNEKQSRHSYIDTIPQSSRSPSYRTKAKSHGALSDSKSVSNLSEARAQIAEPSTSRYFPSSCLDLNSPTSPTPTRHSDTRTLLSPSGRNNRNEGTLDSRRTTTRHSKTMEELKLPEHMDSSHSHSLSAPHESFSYGLGYTSPFSSQQRPHRHSMYVTRDKVRAKGLDGSLSIGQGMAARANSLQLLSPQPGEQLPPEMTVARSSVKETSREGTSSFHTRQKSEGGVYHDPHSDDGTAPKENRHLYNDPVPRRVGSFYRVPSPRPDNSFHENNVSTRVSSLPSESSSGTNHSKRQPAFDPWKSPENISHSEQLKEKEKQGFFRSMKKKKKKSQTVPNSDSPDLLTLQKSIHSASTPSSRPKEWRPEKISDLQTQSQPLKSLRKLLHLSSASNHP
SEQ ID NO:3 CDKL5107变体Δ745-960
MKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKFKDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNMLELLEEMPNGVPPEKVKSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGNNANYTEYVATRWYRSPELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKVLGPLPSEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGILNSVLLDLMKNLLKLDPADRYLTEQCLNHPTFQTQRLLDRSPSRSAKRKPYHVESSTLSNRNQAGKSTALQSHHRSNSKDIQNLSVGLPRADEGLPANESFLNGNLAGASLSPLHTKTYQASSQPGSTSKDLTNNNIPHLLSPKEAKSKTEFDFNIDPKPSEGPGTKYLKSNSRSQQNRHSFMESSQSKAGTLQPNEKQSRHSYIDTIPQSSRSPSYRTKAKSHGALSDSKSVSNLSEARAQIAEPSTSRYFPSSCLDLNSPTSPTPTRHSDTRTLLSPSGRNNRNEGTLDSRRTTTRHSKTMEELKLPEHMDSSHSHSLSAPHESFSYGLGYTSPFSSQQRPHRHSMYVTRDKVRAKGLDGSLSIGQGMAARANSLQLLSPQPGEQLPPEMTVARSSVKETSREGTSSFHTRQKSEGGVYHDPHSDDGTAPKENRHLYNDPVPRRVGSFYRVPSPRPDNSFHENNVSTRVSSLPSESS
SEQ ID NO:4 CDKL5107变体Δ637-960
MKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKFKDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNMLELLEEMPNGVPPEKVKSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGNNANYTEYVATRWYRSPELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKVLGPLPSEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGILNSVLLDLMKNLLKLDPADRYLTEQCLNHPTFQTQRLLDRSPSRSAKRKPYHVESSTLSNRNQAGKSTALQSHHRSNSKDIQNLSVGLPRADEGLPANESFLNGNLAGASLSPLHTKTYQASSQPGSTSKDLTNNNIPHLLSPKEAKSKTEFDFNIDPKPSEGPGTKYLKSNSRSQQNRHSFMESSQSKAGTLQPNEKQSRHSYIDTIPQSSRSPSYRTKAKSHGALSDSKSVSNLSEARAQIAEPSTSRYFPSSCLDLNSPTSPTPTRHSDTRTLLSPSGRNNRNEGTLDSRRTTTRHSKTMEELKLPEHMDSSHSHSLSAPHESFSYGLGYTSPFSSQQRPHRHSMYVTRDKVRAKGLDGSLSIGQGMA
SEQ ID NO:5 CDKL5107变体Δ529-960
MKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKFKDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNMLELLEEMPNGVPPEKVKSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGNNANYTEYVATRWYRSPELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKVLGPLPSEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGILNSVLLDLMKNLLKLDPADRYLTEQCLNHPTFQTQRLLDRSPSRSAKRKPYHVESSTLSNRNQAGKSTALQSHHRSNSKDIQNLSVGLPRADEGLPANESFLNGNLAGASLSPLHTKTYQASSQPGSTSKDLTNNNIPHLLSPKEAKSKTEFDFNIDPKPSEGPGTKYLKSNSRSQQNRHSFMESSQSKAGTLQPNEKQSRHSYIDTIPQSSRSPSYRTKAKSHGALSDSKSVSNLSEARAQIAEPSTSRYFPSSCLDLNSPT
SEQ ID NO:6 CDKL5107变体Δ421-960
MKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKFKDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNMLELLEEMPNGVPPEKVKSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGNNANYTEYVATRWYRSPELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKVLGPLPSEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGILNSVLLDLMKNLLKLDPADRYLTEQCLNHPTFQTQRLLDRSPSRSAKRKPYHVESSTLSNRNQAGKSTALQSHHRSNSKDIQNLSVGLPRADEGLPANESFLNGNLAGASLSPLHTKTYQASSQPGSTSKDLTNNNIPHLLSPKEAKSKTEFDFN
SEQ ID NO:7 CDKL5107变体Δ315-960
MKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKFKDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNMLELLEEMPNGVPPEKVKSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGNNANYTEYVATRWYRSPELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKVLGPLPSEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGILNSVLLDLMKNLLKLDPADRYLTEQCLNHPTFQTQRLLDRSPSRSAKRK
SEQ ID NO:8 CDKL5107变体Δ315-420
MKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKFKDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNMLELLEEMPNGVPPEKVKSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGNNANYTEYVATRWYRSPELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKVLGPLPSEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGILNSVLLDLMKNLLKLDPADRYLTEQCLNHPTFQTQRLLDRSPSRSAKRKIDPKPSEGPGTKYLKSNSRSQQNRHSFMESSQSKAGTLQPNEKQSRHSYIDTIPQSSRSPSYRTKAKSHGALSDSKSVSNLSEARAQIAEPSTSRYFPSSCLDLNSPTSPTPTRHSDTRTLLSPSGRNNRNEGTLDSRRTTTRHSKTMEELKLPEHMDSSHSHSLSAPHESFSYGLGYTSPFSSQQRPHRHSMYVTRDKVRAKGLDGSLSIGQGMAARANSLQLLSPQPGEQLPPEMTVARSSVKETSREGTSSFHTRQKSEGGVYHDPHSDDGTAPKENRHLYNDPVPRRVGSFYRVPSPRPDNSFHENNVSTRVSSLPSESSSGTNHSKRQPAFDPWKSPENISHSEQLKEKEKQGFFRSMKKKKKKSQTVPNSDSPDLLTLQKSIHSASTPSSRPKEWRPEKISDLQTQSQPLKSLRKLLHLSSASNHPASSDPRFQPLTAQQTKNSFSEIRIHPLSQASGGSSNIRQEPAPKGRPALQLPGQMDPGWHVSSVTRSATEGPSYSEQLGAKSGPNGHPYNRTNRSRMPNLNDLKETAL
SEQ ID NO:9 CDKL5107变体Δ315-528
MKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKFKDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNMLELLEEMPNGVPPEKVKSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGNNANYTEYVATRWYRSPELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKVLGPLPSEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGILNSVLLDLMKNLLKLDPADRYLTEQCLNHPTFQTQRLLDRSPSRSAKRKSPTPTRHSDTRTLLSPSGRNNRNEGTLDSRRTTTRHSKTMEELKLPEHMDSSHSHSLSAPHESFSYGLGYTSPFSSQQRPHRHSMYVTRDKVRAKGLDGSLSIGQGMAARANSLQLLSPQPGEQLPPEMTVARSSVKETSREGTSSFHTRQKSEGGVYHDPHSDDGTAPKENRHLYNDPVPRRVGSFYRVPSPRPDNSFHENNVSTRVSSLPSESSSGTNHSKRQPAFDPWKSPENISHSEQLKEKEKQGFFRSMKKKKKKSQTVPNSDSPDLLTLQKSIHSASTPSSRPKEWRPEKISDLQTQSQPLKSLRKLLHLSSASNHPASSDPRFQPLTAQQTKNSFSEIRIHPLSQASGGSSNIRQEPAPKGRPALQLPGQMDPGWHVSSVTRSATEGPSYSEQLGAKSGPNGHPYNRTNRSRMPNLNDLKETAL
SEQ ID NO:10 CDKL5107变体Δ315-636
MKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKFKDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNMLELLEEMPNGVPPEKVKSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGNNANYTEYVATRWYRSPELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKVLGPLPSEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGILNSVLLDLMKNLLKLDPADRYLTEQCLNHPTFQTQRLLDRSPSRSAKRKARANSLQLLSPQPGEQLPPEMTVARSSVKETSREGTSSFHTRQKSEGGVYHDPHSDDGTAPKENRHLYNDPVPRRVGSFYRVPSPRPDNSFHENNVSTRVSSLPSESSSGTNHSKRQPAFDPWKSPENISHSEQLKEKEKQGFFRSMKKKKKKSQTVPNSDSPDLLTLQKSIHSASTPSSRPKEWRPEKISDLQTQSQPLKSLRKLLHLSSASNHPASSDPRFQPLTAQQTKNSFSEIRIHPLSQASGGSSNIRQEPAPKGRPALQLPGQMDPGWHVSSVTRSATEGPSYSEQLGAKSGPNGHPYNRTNRSRMPNLNDLKETAL
SEQ ID NO:11 CDKL5107变体Δ315-744
MKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKFKDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNMLELLEEMPNGVPPEKVKSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGNNANYTEYVATRWYRSPELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKVLGPLPSEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGILNSVLLDLMKNLLKLDPADRYLTEQCLNHPTFQTQRLLDRSPSRSAKRKSGTNHSKRQPAFDPWKSPENISHSEQLKEKEKQGFFRSMKKKKKKSQTVPNSDSPDLLTLQKSIHSASTPSSRPKEWRPEKISDLQTQSQPLKSLRKLLHLSSASNHPASSDPRFQPLTAQQTKNSFSEIRIHPLSQASGGSSNIRQEPAPKGRPALQLPGQMDPGWHVSSVTRSATEGPSYSEQLGAKSGPNGHPYNRTNRSRMPNLNDLKETAL
SEQ ID NO:12 CDKL5107变体Δ315-852
MKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKFKDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNMLELLEEMPNGVPPEKVKSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGNNANYTEYVATRWYRSPELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKVLGPLPSEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGILNSVLLDLMKNLLKLDPADRYLTEQCLNHPTFQTQRLLDRSPSRSAKRKASSDPRFQPLTAQQTKNSFSEIRIHPLSQASGGSSNIRQEPAPKGRPALQLPGQMDPGWHVSSVTRSATEGPSYSEQLGAKSGPNGHPYNRTNRSRMPNLNDLKETAL
SEQ ID NO:13 CDKL5107变体1-7NQ
Figure BDA0003721100640000591
SEQ ID NO:14CDKL5107变体2-7NQ
Figure BDA0003721100640000592
SEQ ID NO:15 CDKL5107变体1,3-7NQ
Figure BDA0003721100640000601
SEQ ID NO:16 CDKL5107变体1-2,4-7NQ
Figure BDA0003721100640000602
SEQ ID NO:17 CDKL5107变体1-3,5-7NQ
Figure BDA0003721100640000603
Figure BDA0003721100640000611
SEQ ID NO:18 CDKL5107变体1-4,6-7NQ
Figure BDA0003721100640000612
SEQ ID NO:19 CDKL5107变体1-5,7NQ
Figure BDA0003721100640000613
SEQ ID NO:20 CDKL5107变体1-6NQ
Figure BDA0003721100640000614
Figure BDA0003721100640000621
SEQ ID NO:21 CDKL5107变体2NQ
Figure BDA0003721100640000622
SEQ ID NO:22CDKL5107变体1-10NQ
Figure BDA0003721100640000623
SEQ ID NO:23 CDKL5107变体1-7,9-10NQ
Figure BDA0003721100640000624
Figure BDA0003721100640000631
SEQ ID NO:24 CDKL5107变体1-8,10NQ
Figure BDA0003721100640000632
SEQ ID NO:25 CDKL5107变体1-9NQ
Figure BDA0003721100640000633
SEQ ID NO:26 CDKL5115同工型多肽1-1030(全长)
MKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKFKDSEENEEVKETTLRELKM
LRTLKQENIVELKEAFRRRGKLYLVFEYVEKNMLELLEEMPNGVPPEKVKSYIYQLIKAIHWCHKNDIVHRDIKPENLLI SHNDVLKLCDFGFARNLSEGNNANYTEYVATRWYRSPELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKVLGPLPSEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGILNSVLLDLMKNLLKLDPADRYLTEQCLNHPTFQTQRLLDRSPSRSAKRKPYHVESSTLSNRNQAGKSTALQSHHRSNSKDIQNLSVGLPRADEGLPANESFLNGNLAGASLSPLHTKTYQASSQPGSTSKDLTNNNIPHLLSPKEAKSKTEFDFNIDPKPSEGPGTKYLKSNSRSQQNRHSFMESSQSKAGTLQPNEKQSRHSYIDTIPQSSRSPSYRTKAKSHGALSDSKSVSNLSEARAQIAEPSTSRYFPSSCLDLNSPTSPTPTRHSDTRTLLSPSGRNNRNEGTLDSRRTTTRHSKTMEELKLPEHMDSSHSHSLSAPHESFSYGLGYTSPFSSQQRPHRHSMYVTRDKVRAKGLDGSLSIGQGMAARANSLQLLSPQPGEQLPPEMTVARSSVKETSREGTSSFHTRQKSEGGVYHDPHSDDGTAPKENRHLYNDPVPRRVGSFYRVPSPRPDNSFHENNVSTRVSSLPSESSSGTNHSKRQPAFDPWKSPENISHSEQLKEKEKQGFFRSMKKKKKKSQTVPNSDSPDLLTLQKSIHSASTPSSRPKEWRPEKI SDLQTQSQPLKSLRKLLHLSSASNHPASSDPRFQPLTAQQTKNSFSEIRIHPLSQASGGSSNIRQEPAPKGRPALQLPDGGCDGRRQRHHSGPQDRRFMLRTTEQQGEYFCCGDPKKPHTPCVPNRALHRPISSPAPYPVLQVRGTSMCPTLQVRGTDAFSCPTQQSGFSFFVRHVMREALIHRAQVNQAALLTYHENAALTGK
SEQ ID NO:27 AAV2 L-ITR
CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCT
SEQ ID NO:28 AAV2 R-ITR
AGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGG
SEQ ID NO:29 CBh
TTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTACGGGACTTTCCTACTTGGCAGTACATCTCCACGTTCTGCTTCACTCTCCCCATCTCCCCCCCCTCCCCACCCCCAATTTTGTATTTATTTATTTTTTAATTATTTTGTGCAGCGATGGGGGCGGGGGGGGGGGGGGCGCGCGCCAGGCGGGGCGGGGCGGGGCGAGGGGCGGGGCGGGGCGAGGCGGAGAGGTGCGGCGGCAGCCAATCAGAGCGGCGCGCTCCGAAAGTTTCCTTTTATGGCGAGGCGGCGGCGGCGGCGGCCCTATAAAAAGCGAAGCGCGCGGCGGGGAGTCGCTGCGTTGCCTTCGCCCCGTGCCCCGCTCCGCGCCGCCTCGCGCCGCCCGCCCCGGCTCTGACTGACCGCGTTACTCCCACAGGTGAGCGGGCGGGACGGCCCTTCTCCTCCGGGCTGTAATTAGCAAGAGGTAAGGGTTTAAGGGATGGTTGGTTGGTGGGGTATTAATGTTTAATTACCTGTTTTACAGGCCTGAAATCACTTGGTTTTAGGTTGG
SEQ ID NO:30 hSyn1
ACTACAAACCGAGTATCTGCAGAGGGCCCTGCGTATGAGTGCAAGTGGGTTTTAGGACCAGGATGAGGCGGGGTGGGGGTGCCTACCTGACGACCGACCCCGACCCACTGGACAAGCACCCAACCCCCATTCCCCAAATTGCGCATCCCCTATCAGAGAGGGGGAGGGGAAACAGGATGCGGCGAGGCGCGTGCGCACTGCCAGCTTCAGCACCGCGGACAGTGCCTTCGCCCCCGCCTGGCGGCGCGCGCCACCGCCGCCTCAGCACTGAAGGCGCGCTGACGTCACTCGCCGGTCCCCCGCAAACTCCCCTTCCCGGCCACCTTGGTCGCGTCCGCGCCGCCGCCGGCCCAGCCGGACCGCACCACGCGAGGCGCGAGATAGGGGGGCACGGGCGCGACCATCTGCGCTGCGGCGCCGGCGACTCAGCGCTGCCTCAGTCTGCGGTGGGCAGCGGAGGAGTCGTGTCGTGCCTGAGAGCGCAGCTGTGCTCCTGGGCACCGCGCAGTCCGCCCCCGCGGCTCCTGGCCAGACCACCCCTAGGACCCCCTGCCCCAAGTCGCAGCCTTCGA
SEQ ID NO:31 TAT28 CPP
DAAQPARRARRTKLAAYGRKKRRQRRR
SEQ ID NO:32 TATκ28 CPP
DAAQPARRARRTKLAAYARKAARQARA
SEQ ID NO:33 TAT11 CPP
YGRKKRRQRRR
SEQ ID NO:34TATκ11 CPP
YARKAARQARA
SEQ ID NO:35转运肽CPP
AGYLLGKINLKALAALAKKIL
SEQ ID NO:36穿膜肽CPP
RQIKIWFQNRRMKWKK
SEQ ID NO:37 P97 CPP
DSSHAFTLDELR
SEQ ID NO:38 MBiP
MKLSLVAAMLLLLSLVAAMLLLLSAARA
SEQ ID NO:39 MBiP2
MKLSLVAAMLLLLWVALLLLSAARA
SEQ ID NO:40 MBiP3
MKLSLVAAMLLLLSLVALLLLSAARA
SEQ ID NO:41 MBiP4
MKLSLVAAMLLLLALVALLLLSAARA
SEQ ID NO:42鼠Igκ
METDTLLLWVLLLWVPGSTG
SEQ ID NO:43 pOptiVec中的MBip_Tκ28p_107_3xFlagHis_cho-opt
Figure BDA0003721100640000661
SEQ ID NO:44 pOptiVec中的Igκ_Tκ28p_107_3xFlagHis_cho-opt
Figure BDA0003721100640000662
SEQ ID NO:45 pOptiVec中的MBiP_Tκ28p_115_3xFlagHis_cho-opt
Figure BDA0003721100640000663
Figure BDA0003721100640000671
SEQ ID NO:46 pOptiVec中的Igκ_Tκ28p_115_3xFlagHis_cho-opt
Figure BDA0003721100640000672
SEQ ID NO:47 pOptiVec中的Tκ28p_107_3xFlagHis_cho-opt
Figure BDA0003721100640000673
Figure BDA0003721100640000681
SEQ ID NO:48 pEX-1中的Tκ28p_107_3xFlagHis_大肠杆菌-opt
Figure BDA0003721100640000682
SEQ ID NO:49 pEX-1中的Δ853-960
Figure BDA0003721100640000683
SEQ ID NO:50 pEX-1中的Δ745-960
Figure BDA0003721100640000684
Figure BDA0003721100640000691
SEQ ID NO:51 pEX-1中的Δ637-960
Figure BDA0003721100640000692
SEQ ID NO:52 pEX-1中的Δ529-960
Figure BDA0003721100640000693
SEQ ID NO:53 pEX-1中的Δ421-960
Figure BDA0003721100640000694
SEQ ID NO:54 pEX-1中的Δ315-960
Figure BDA0003721100640000701
SEQ ID NO:55 pEX-1中的Δ315-420
Figure BDA0003721100640000702
SEQ ID NO:56 pEX-1中的Δ315-528
Figure BDA0003721100640000703
SEQ ID NO:57 pEX-1中的Δ315-636
Figure BDA0003721100640000704
Figure BDA0003721100640000711
SEQ ID NO:58 pEX-1中的Δ315-744
Figure BDA0003721100640000712
SEQ ID NO:59 pEX-1中的Δ315-852
Figure BDA0003721100640000713
SEQ ID NO:60 pEX-1中的TT28p_107_3xFlagHis_大肠杆菌-opt
Figure BDA0003721100640000714
SEQ ID NO:61 pEX-1中的Tκ28p_eGFP_大肠杆菌-opt_3xFlagHis
Figure BDA0003721100640000721
SEQ ID NO:62 pEX-1中的eGFP_3xFlagHis_大肠杆菌-opt
Figure BDA0003721100640000722
SEQ ID NO:63 pEX-1中的AMPH1-3xFlagHis(大肠杆菌-opt)
Figure BDA0003721100640000723
SEQ ID NO:64 pOptiVec中的AMPH1-3xFlagHis cho-opt
Figure BDA0003721100640000724
SEQ ID NO:65 pOptiVec中的MBip_TATκ11_107_3xFlagHis_cho-opt
Figure BDA0003721100640000731
SEQ ID NO:66 pOptiVec中的Igκ_TATκ11_107_3xFlagHis_cho-opt
Figure BDA0003721100640000732
SEQ ID NO:67 pOptiVec中的TATκ11_107_3xFlagHis_cho-opt(无前导)
Figure BDA0003721100640000733
Figure BDA0003721100640000741
SEQ ID NO:68 pEX-1中的TATκ11_107_3xFlagHis_大肠杆菌-opt
Figure BDA0003721100640000742
SEQ ID NO:69 pEX-1中的TAT11_107_3xFlagHis_大肠杆菌-opt
Figure BDA0003721100640000743
SEQ ID NO:70 pOptiVec中的TAT11_107_3xFlagHis_cho-opt(无前导)
Figure BDA0003721100640000744
Figure BDA0003721100640000751
SEQ ID NO:71 pOptiVec中的ANTP_107_3xFlagHis_cho-opt
Figure BDA0003721100640000752
SEQ ID NO:72 pOptiVec中的TRANSP_107_3xFlagHis_cho-opt
Figure BDA0003721100640000753
Figure BDA0003721100640000761
SEQ ID NO:73 pOptiVec中的TAT28_107_3xFlagHis_cho-opt
Figure BDA0003721100640000762
SEQ ID NO:74 pOptiVec中的MBIP_P97_107_3xFlagHis_cho-opt
Figure BDA0003721100640000763
SEQ ID NO:75 pT7CFE1中的P97_107_3xFlagHis_人-opt
Figure BDA0003721100640000764
Figure BDA0003721100640000771
SEQ ID NO:76 pOptiVec中的Tκ28p_107_3xFlagHis_人-opt
Figure BDA0003721100640000772
SEQ ID NO:77 pOptiVec中的TATκ11_107_3xFlagHis_人-opt
Figure BDA0003721100640000773
SEQ ID NO:78 pOptiVec中的TAT28_107_3xFlagHis_人-opt
Figure BDA0003721100640000781
SEQ ID NO:79 pOptiVec中的TAT11_107_3xFlagHis_人-opt
Figure BDA0003721100640000782
SEQ ID NO:80 pOptiVec中的ANTP_107_3xFlagHis_人-opt
Figure BDA0003721100640000783
Figure BDA0003721100640000791
SEQ ID NO:81 pOptiVec中的TRANSP_107_3xFlagHis_人-opt
Figure BDA0003721100640000792
SEQ ID NO:82 pOptiVec中的MBip_Tκ28p_107_3xFlagHis_人-opt
Figure BDA0003721100640000793
SEQ ID NO:83-GST-P-TATκ28-CDKL5_107-P-FH_pVL1393(昆虫)
Figure BDA0003721100640000794
Figure BDA0003721100640000801
SEQ ID NO:84-GST-P-TATκ11-CDKL5_107-P-FH_pVL1393(昆虫)
Figure BDA0003721100640000802
SEQ ID NO:85-GST-P-TAT28-CDKL5_107-P-FH_pVL1393(昆虫)
Figure BDA0003721100640000803
Figure BDA0003721100640000811
SEQ ID NO:86-GST-P-TAT11-CDKL5_107-P-FH_pVL1393(昆虫)
Figure BDA0003721100640000812
SEQ ID NO:87-GST-P-ANTP-CDKL5_107-P-FH_pVL1393(昆虫)
Figure BDA0003721100640000813
Figure BDA0003721100640000821
SEQ ID NO:88-GST-P-TRANSP-CDKL5_107-P-FH_pVL1393(昆虫)
Figure BDA0003721100640000822
SEQ ID NO:89-GST-P-P97P-CDKL5_107-P-FH_pVL1393(昆虫)
Figure BDA0003721100640000823
Figure BDA0003721100640000831
SEQ ID NO:90-GST-P-eGFP-P-FH_pVL1393(昆虫)
Figure BDA0003721100640000832
SEQ ID NO:91-GST-P-TATκ28-eGFP-P-FH_pVL1393(昆虫)
Figure BDA0003721100640000833
SEQ ID NO:92-GST-P-CDKL5_107-P-FH_pVL1393(昆虫)
Figure BDA0003721100640000834
SEQ ID NO:93 MBip-TATκ28-CDKL5_107-FH_cho[1-7NQ]
Figure BDA0003721100640000841
SEQ ID NO:94 MBip-TATκ28-CDKL5_107-FH_cho[2-7NQ]
Figure BDA0003721100640000842
SEQ ID NO:95 MBip-TATκ28-CDKL5_107-FH_cho[1,3-7NQ]
Figure BDA0003721100640000843
Figure BDA0003721100640000851
SEQ ID NO:96 MBip-TATκ28-CDKL5_107-FH_cho[1-2,4-7NQ]
Figure BDA0003721100640000852
SEQ ID NO:97 MBip-TATκ28-CDKL5_107-FH_cho[1-3,5-7NQ]
Figure BDA0003721100640000853
SEQ ID NO:98 MBip-TATκ28-CDKL5_107-FH_cho[1-4,6-7NQ]
Figure BDA0003721100640000854
Figure BDA0003721100640000861
SEQ ID NO:99 MBip-TATκ28-CDKL5_107-FH_cho[1-5,7NQ]
Figure BDA0003721100640000862
SEQ ID NO:100 MBip-TATκ28-CDKL5_107-FH_cho[1-6NQ]
Figure BDA0003721100640000863
Figure BDA0003721100640000871
SEQ ID NO:101 MBip-TATκ28-CDKL5_107-FH_cho[2NQ]
Figure BDA0003721100640000872
SEQ ID NO:102 MBip-TATκ28-CDKL5_107-FH_cho[1-10NQ]
Figure BDA0003721100640000873
SEQ ID NO:103 MBip-TATκ28-CDKL5_107-FH_cho[1-7,9-10NQ]
Figure BDA0003721100640000874
Figure BDA0003721100640000883
SEQ ID NO:104 MBip-TATκ28-CDKL5_107-FH_cho[1-8,10NQ]
Figure BDA0003721100640000881
SEQ ID NO:105 MBip-TATκ28-CDKL5_107-FH_cho[1-9NQ]
Figure BDA0003721100640000882
SEQ ID NO:106 AAVC-CBh-hCDKL5-107
L-ITR:1-141
CBh启动子：159-976
hCDKL5-107 ORF:1000-2885
bGHp(A):3910-4137
R-ITR:4149-4289
Amp(R):5206-6063
pUC起点：6214-6881
Figure BDA0003721100640000891
Figure BDA0003721100640000901
Figure BDA0003721100640000911
SEQ ID NO:107 AAVC-CBh-hCDKL5-107(失活激酶)
L-ITR:1-141
CBh启动子:159-976
hCDKL5-107(失活激酶)ORF：1000-2885
bGHp(A):3910-4137
R-ITR:4149-4289
Amp(R):5206-6063
pUC起点：6214-6881
Figure BDA0003721100640000921
Figure BDA0003721100640000931
Figure BDA0003721100640000941
SEQ ID NO:108 AAVC-CBh-eGFP
L-ITR:1-141
CBh启动子:159-976
EGFP ORF：1000-1722
bGHp(A):1747-1974
R-ITR:1986-2126
Amp(R):3043-3900
pUC起点：4051-4718
Figure BDA0003721100640000942
Figure BDA0003721100640000951
Figure BDA0003721100640000961
SEQ ID NO:109 AAVC-CBh-NLS-eGFP
L-ITR:1-141
CBh启动子:159-976
NLS-eGFP：1000-1782
bGHp(A):1807-2034
R-ITR:2046-2186
Amp(R):3103-3960
pUC起点：4111-4778
Figure BDA0003721100640000962
Figure BDA0003721100640000971
Figure BDA0003721100640000981
SEQ ID NO:110 AAVC-CBh-mBPIP-TATκ28-hCDKL5-107
L-ITR:1-141
CBh启动子:159-976
Bip-TATκ28-hCDKL5-107：1000-4065
bGHp(A):4090-4317
R-ITR:4329-4469
Amp(R):5386-6243
pUC起点：6394-7061
Figure BDA0003721100640000991
Figure BDA0003721100640001001
Figure BDA0003721100640001011
SEQ ID NO:111 AAVC-CBh-mBPIP-TATκ28-hCDKL5-107(失活激酶)
L-ITR:1-141
CBh启动子:159-976
Bip-TATκ28-hCDKL5-107(激酶失活)：1000-4065
bGHp(A):4090-4317
R-ITR:4329-4469
Amp(R):5386-6243
pUC起点：6394-7061
Figure BDA0003721100640001012
Figure BDA0003721100640001021
Figure BDA0003721100640001031
Figure BDA0003721100640001041
SEQ ID NO:112 AAVC-CBh-mBPIP-TATκ28-eGFP
L-ITR:1-141
CBh启动子:159-976
Bip-TATκ28-EGFP：1000-1905
bGHp(A):1930-2157
R-ITR:2169-2309
Amp(R):3226-4083
pUC起点：4234-4901
Figure BDA0003721100640001042
Figure BDA0003721100640001051
Figure BDA0003721100640001061
SEQ ID NO:113 AAVC-CBh-mBPIP-TATκ28-NLS-eGFP
L-ITR:1-141
CBh启动子:159-976
BIp-TATκ28-NLS-eGFP：1000-1965
bGHp(A):1990-2217
R-ITR:2229-2369
Amp(R):3286-4143
pUC起点：4294-4961
Figure BDA0003721100640001071
Figure BDA0003721100640001081
SEQ ID NO:114 AAVC-Syn-hCDKL5-107
L-ITR:1-141
Syn-1启动子：159-730
hCDKL5-107 ORF:754-3639
bGHp(A):3664-3891
R-ITR:3903-4043
Amp(R):4960-5817
pUC起点：5968-6635
Figure BDA0003721100640001091
Figure BDA0003721100640001101
Figure BDA0003721100640001111
SEQ ID NO:115 AAVC-Syn-hCDKL5-107(失活激酶)
L-ITR:1-141
Syn-1启动子：159-730
hCDKL5-107 ORF(激酶失活)：754-3639
bGHp(A):3664-3891
R-ITR:3903-4043
Amp(R):4960-5817
pUC起点：5968-6635
Figure BDA0003721100640001112
Figure BDA0003721100640001121
Figure BDA0003721100640001131
Figure BDA0003721100640001141
SEQ ID NO:116 AAVC-Syn-eGFP
L-ITR:1-141
Syn-1启动子：159-730
EGFP ORF：754-1476
bGHp(A):1501-1728
R-ITR:1740-1880
Amp(R):2797-3654
pUC起点：3805-4472
Figure BDA0003721100640001142
Figure BDA0003721100640001151
Figure BDA0003721100640001161
SEQ ID NO:117 AAVC-Syn-NLS-eGFP
L-ITR:1-141
Syn-1启动子：159-730
NLS-eGFP：754-1536
bGHp(A):1561-1788
R-ITR:1800-1940
Amp(R):2857-3714
pUC起点：3865-4532
Figure BDA0003721100640001162
Figure BDA0003721100640001171
Figure BDA0003721100640001181
SEQ ID NO:118 AAVC-Syn-mBPIP-TATκ28-hCDKL5-107
L-ITR:1-141
Syn-1启动子：159-730
Bip-TATκ28-hCDKL5-107:754-3819
bGHp(A):3844-4071
R-ITR:4083-4223
Amp(R):5140-5997
pUC起点：6148-6815
Figure BDA0003721100640001182
Figure BDA0003721100640001191
Figure BDA0003721100640001201
Figure BDA0003721100640001211
SEQ ID NO:119 AAVC-Syn-mBPIP-TATκ28-hCDKL5-107(失活激酶)
L-ITR:1-141
Syn-1启动子：159-730
Bip-TATκ28-hCDKL5-107(激酶失活)：754-3819
bGHp(A):3844-4071
R-ITR:4083-4223
Amp(R):5140-5997
pUC起点：6148-6815
Figure BDA0003721100640001212
Figure BDA0003721100640001221
Figure BDA0003721100640001231
Figure BDA0003721100640001241
SEQ ID NO:120 AAVC-Syn-mBPIP-TATκ28-eGFP
L-ITR:1-141
Syn-1启动子：159-730
Bip-TATκ28-EGFP：754-1659
bGHp(A):1684-1911
R-ITR:1923-2063
Amp(R):2980-3837
pUC起点：3988-4655
Figure BDA0003721100640001242
Figure BDA0003721100640001251
Figure BDA0003721100640001261
SEQ ID NO:121 AAVC-Syn-mBPIP-TATκ28-NLS-eGFP
L-ITR:1-141
Syn-1启动子：159-730
Bip-TATκ28-NLS-eGFP：754-1719
bGHp(A):1744-1971
R-ITR:1983-2123
Amp(R):3040-3897
pUC起点：4048-4715
Figure BDA0003721100640001262
Figure BDA0003721100640001271
Figure BDA0003721100640001281
SEQ ID NO:122 mBPIP-TATκ28-CDKL5-107的DNA序列(人优化)
Figure BDA0003721100640001282
Figure BDA0003721100640001291
SEQ ID NO:123 CDKL5-107的DNA序列(人优化)
AAGATCCCCAATATCGGCAACGTGATGAATAAGTTCGAGATCCTGGGAGTGGTGGGAGAGGGAGCCTACGGCGTGGTGCTGAAGTGCAGACACAAGGAGACACACGAGATCGTGGCCATCAAGAAGTTTAAGGACAGCGAGGAGAATGAGGAGGTGAAGGAGACAACCCTGCGCGAGCTGAAGATGCTGCGGACACTGAAGCAGGAGAACATCGTGGAGCTGAAGGAGGCCTTCCGGAGAAGGGGCAAGCTGTACCTGGTGTTTGAGTATGTGGAGAAGAACATGCTGGAGCTGCTGGAGGAGATGCCTAATGGCGTGCCCCCTGAGAAGGTGAAGTCCTACATCTATCAGCTGATCAAGGCCATCCACTGGTGCCACAAGAACGATATCGTGCACCGCGACATCAAGCCCGAGAACCTGCTGATCTCCCACAATGACGTGCTGAAGCTGTGCGACTTCGGCTTTGCCCGGAACCTGAGCGAGGGCAACAATGCCAATTACACAGAGTATGTGGCCACCCGCTGGTACAGAAGCCCCGAGCTGCTGCTGGGCGCCCCCTATGGCAAGAGCGTGGATATGTGGTCCGTGGGCTGCATCCTGGGCGAGCTGTCTGATGGCCAGCCTCTGTTCCCAGGCGAGAGCGAGATCGACCAGCTGTTTACCATCCAGAAGGTGCTGGGCCCTCTGCCAAGCGAGCAGATGAAGCTGTTCTACTCCAACCCAAGGTTCCACGGCCTGAGGTTTCCAGCCGTGAATCACCCTCAGAGCCTGGAGCGCCGGTATCTGGGCATCCTGAACTCCGTGCTGCTGGACCTGATGAAGAACCTGCTGAAGCTGGACCCCGCCGACAGATACCTGACCGAGCAGTGTCTGAATCACCCTACATTTCAGACCCAGAGACTGCTGGATAGGAGCCCTTCCCGCTCTGCCAAGCGGAAGCCATATCACGTGGAGAGCAGCACCCTGTCCAATCGCAACCAGGCCGGCAAGTCTACAGCCCTGCAGAGCCACCACCGGAGCAACTCCAAGGATATCCAGAATCTGTCCGTGGGCCTGCCTAGGGCCGACGAGGGCCTGCCAGCAAACGAGAGCTTCCTGAATGGAAACCTGGCAGGAGCCTCTCTGAGCCCACTGCACACAAAGACCTACCAGGCCTCTAGCCAGCCCGGCTCCACATCTAAGGACCTGACCAACAATAACATCCCACACCTGCTGTCTCCCAAGGAGGCCAAGAGCAAGACCGAGTTCGACTTCAACATCGACCCAAAGCCTAGCGAGGGACCTGGCACAAAGTATCTGAAGAGCAACAGCCGGAGCCAGCAGAATAGGCACTCCTTCATGGAGTCCTCTCAGTCTAAGGCCGGCACCCTGCAGCCAAACGAGAAGCAGAGCAGGCACTCCTACATCGACACCATCCCACAGAGCAGCCGGAGCCCCTCCTATCGGACAAAGGCCAAGTCTCACGGCGCCCTGTCTGATAGCAAGTCCGTGTCTAATCTGAGCGAGGCCAGAGCCCAGATCGCAGAGCCCAGCACCTCCAGGTACTTTCCTTCTAGCTGTCTGGATCTGAACTCTCCTACAAGCCCAACACCCACCAGACACAGCGACACAAGGACCCTGCTGTCTCCAAGCGGCAGAAATAACAGGAACGAGGGCACCCTGGACAGCCGGCGGACCACAACCAGGCACAGCAAGACAATGGAGGAGCTGAAGCTGCCAGAGCACATGGATTCCTCTCACTCCCACTCTCTGAGCGCCCCCCACGAGTCCTTCTCTTACGGCCTGGGCTATACCTCCCCCTTCAGCAGCCAGCAGCGCCCCCACCGGCACTCTATGTACGTGACAAGAGATAAGGTGAGGGCAAAGGGCCTGGACGGCAGCCTGTCCATCGGACAGGGAATGGCAGCCCGGGCCAACTCCCTGCAGCTGCTGTCTCCTCAGCCAGGAGAGCAGCTGCCACCAGAGATGACCGTGGCACGGAGCAGCGTGAAGGAGACAAGCAGGGAGGGCACCTCCTCTTTCCACACAAGACAGAAGTCCGAGGGCGGCGTGTATCACGATCCCCACTCTGACGATGGCACAGCCCCTAAGGAGAACAGGCACCTGTACAATGACCCCGTGCCTAGGAGGGTGGGCTCCTTCTATCGCGTGCCATCTCCCCGGCCTGATAATAGCTTTCACGAGAATAACGTGAGCACCCGGGTGAGCAGCCTGCCATCTGAGTCTAGCTCCGGCACAAACCACTCTAAGAGGCAGCCCGCCTTTGACCCTTGGAAGAGCCCAGAGAATATCTCTCACAGCGAGCAGCTGAAGGAGAAGGAGAAGCAGGGCTTCTTTCGCAGCATGAAGAAGAAGAAGAAGAAGAGCCAGACCGTGCCTAACTCCGATTCTCCAGACCTGCTGACCCTGCAGAAGTCCATCCACAGCGCCTCCACACCCTCTAGCAGACCTAAGGAGTGGAGGCCTGAGAAGATCAGCGACCTGCAGACCCAGAGCCAGCCACTGAAGTCCCTGCGGAAGCTGCTGCACCTGTCCTCTGCCAGCAACCACCCAGCCAGCTCCGATCCAAGGTTCCAGCCCCTGACAGCCCAGCAGACCAAGAACAGCTTCAGCGAGATCAGAATCCACCCTCTGTCCCAGGCCTCTGGAGGCTCTAGCAACATCAGGCAGGAGCCAGCACCAAAGGGCCGGCCCGCCCTGCAGCTGCCTGGCCAGATGGACCCAGGCTGGCACGTGTCCTCTGTGACAAGATCCGCCACCGAGGGCCCATCCTACTCTGAGCAGCTGGGAGCAAAGAGCGGACCTAATGGACACCCATATAACAGGACCAATAGATCCAGGATGCCCAATCTGAACGATCTGAAGGAGACAGCCCTG
SEQ ID NO:124MBIP-TATκ28-CDKL5_107-FH[1-7NQ]的DNA序列(人优化)
Figure BDA0003721100640001301
Figure BDA0003721100640001311
SEQ ID NO:125 CDKL5_107[1-7NQ]的DNA序列(人优化)
Figure BDA0003721100640001312
Figure BDA0003721100640001321
SEQ ID NO:126 MBIP-TATκ28-CDKL5_107-FH[2-7NQ]的DNA序列(人优化)
Figure BDA0003721100640001322
Figure BDA0003721100640001331
SEQ ID NO:127 CDKL5_107[2-7NQ]的DNA序列(人优化)
Figure BDA0003721100640001332
Figure BDA0003721100640001341
SEQ ID NO:128 MBIP-TATκ28-CDKL5_107-FH[1,3-7NQ]的DNA序列(人优化)
Figure BDA0003721100640001342
Figure BDA0003721100640001351
SEQ ID NO:129 CDKL5_107[1,3-7NQ]的DNA序列(人优化)
Figure BDA0003721100640001352
Figure BDA0003721100640001361
SEQ ID NO:130 MBIP-TATκ28-CDKL5_107-FH[1-2,4-7NQ]的DNA序列(人优化)
Figure BDA0003721100640001362
Figure BDA0003721100640001371
SEQ ID NO:131 CDKL5_107[1-2,4-7NQ]的DNA序列(人优化)
Figure BDA0003721100640001372
Figure BDA0003721100640001381
SEQ ID NO:132 MBIP-TATκ28-CDKL5_107-FH[1-3,5-7NQ]的DNA序列(人优化)
Figure BDA0003721100640001382
Figure BDA0003721100640001391
SEQ ID NO:133 CDKL5_107[1-3,5-7NQ]的DNA序列(人优化)
Figure BDA0003721100640001392
Figure BDA0003721100640001401
SEQ ID NO:134 MBIP-TATκ28-CDKL5_107-FH[1-4,6-7NQ]的DNA序列(人优化)
Figure BDA0003721100640001402
Figure BDA0003721100640001411
SEQ ID NO:135 CDKL5_107[1-4,6-7NQ]的DNA序列(人优化)
Figure BDA0003721100640001412
Figure BDA0003721100640001421
SEQ ID NO:136 MBIP-TATκ28-CDKL5_107-FH[1-5,7NQ]的DNA序列(人优化)
Figure BDA0003721100640001422
Figure BDA0003721100640001431
SEQ ID NO:137 CDKL5_107[1-5,7NQ]的DNA序列(人优化)
Figure BDA0003721100640001432
Figure BDA0003721100640001441
SEQ ID NO:138 MBIP-TATκ28-CDKL5_107-FH[1-6NQ]的DNA序列(人优化)
Figure BDA0003721100640001442
Figure BDA0003721100640001451
SEQ ID NO:139 CDKL5_107[1-6NQ]的DNA序列(人优化)
Figure BDA0003721100640001452
Figure BDA0003721100640001461
SEQ ID NO:140 MBIP-TATκ28-CDKL5_107-FH[2NQ]的DNA序列(人优化)
Figure BDA0003721100640001462
Figure BDA0003721100640001471
SEQ ID NO:141 CDKL5_107[2NQ]的DNA序列(人优化)
Figure BDA0003721100640001472
Figure BDA0003721100640001481
SEQ ID NO:142 MBIP-TATκ28-CDKL5_107-FH[1-10NQ]的DNA序列(人优化)
Figure BDA0003721100640001482
Figure BDA0003721100640001491
SEQ ID NO:143 CDKL5_107[1-10NQ]的DNA序列(人优化)
Figure BDA0003721100640001492
Figure BDA0003721100640001501
SEQ ID NO:144 MBIP-TATκ28-CDKL5_107-FH[1-7,9-10NQ]的DNA序列(人优化)
Figure BDA0003721100640001502
Figure BDA0003721100640001511
SEQ ID NO:145 CDKL5_107[1-7,9-10NQ]的DNA序列(人优化)
Figure BDA0003721100640001512
Figure BDA0003721100640001521
SEQ ID NO:146 MBIP-TATκ28-CDKL5_107-FH[1-8,10NQ]的DNA序列(人优化)
Figure BDA0003721100640001522
Figure BDA0003721100640001531
SEQ ID NO:147 CDKL5_107[1-8,10NQ]的DNA序列(人优化)
Figure BDA0003721100640001532
Figure BDA0003721100640001541
SEQ ID NO:148 MBIP-TATκ28-CDKL5_107-FH[1-9NQ]的DNA序列(人优化)
Figure BDA0003721100640001542
Figure BDA0003721100640001551
SEQ ID NO:149 CDKL5_107[1-9NQ]的DNA序列(人优化)
Figure BDA0003721100640001552
Figure BDA0003721100640001561
SEQ ID NO:150 TATκ11的DNA序列(人优化)
TACGCCCGGAAGGCCGCCCGGCAGGCCAGAGCC
SEQ ID NO:151 TATκ28的DNA序列(人优化)
GACGCAGCACAGCCCGCAAGAAGAGCAAGAAGAACTAAACTGGCCGCTTACGCAAGGAAGGCAGCAAGACAGGCAAGAGCA
SEQ ID NO:152穿膜肽CPP的DNA序列(人优化)
CGGCAGATCAAGATTTGGTTCCAGAACCGGAGAATGAAGTGGAAGAAG
SEQ ID NO:153转运肽CPP的DNA序列(人优化)
GCCGGCTACCTGCTGGGCAAGATCAACCTGAAGGCCCTGGCCGCCCTGGCCAAGAAGATCCTG
SEQ ID NO:154 P97 CPP的DNA序列(人优化)
GACAGCTCCCACGCCTTCACCCTGGATGAGCTGCGG
SEQ ID NO:155 mBIP的DNA序列(人优化)
ATGAAGCTGTCCCTGGTGGCCGCTATGCTGCTGCTGCTGTCTCTGGTCGCTGCCATGTTATTACTGCTGTCTGCCGCTAGGGCC
SEQ ID NO:156 IGF
AYRPSETLCGGELVDTLQFVCGDRGFYFSRPASRVSRRSRGIVEECCFRSCDLALLETYCATPAKSE
SEQ ID NO:157 IGF F26S
Figure BDA0003721100640001562
SEQ ID NO:158 IGF Y27L
Figure BDA0003721100640001563
SEQ ID NO:159 IGF V43L
Figure BDA0003721100640001564
SEQ ID NO:160 IGF F48T
Figure BDA0003721100640001571
SEQ ID NO:161 IGF R49S
Figure BDA0003721100640001572
SEQ ID NO:162 IGF S50I
Figure BDA0003721100640001573
SEQ ID NO:163 IGF A54R
Figure BDA0003721100640001574
SEQ ID NO:164 IGF L55R
Figure BDA0003721100640001575
SEQ ID NO:165 IGF F26S、Y27L、V43L、F48T、R49S、S50I、A54R、L55R
Figure BDA0003721100640001576
SEQ ID NO:166 IGFΔl-7、Y27L、K65R
Figure BDA0003721100640001577
SEQ ID NO:167 TATκκ28 CPP
Figure BDA0003721100640001578
SEQ ID NO:168 mvBIP
Figure BDA0003721100640001579
SEQ ID NO:169 mvBIP的示例性DNA序列
ATGAAGCTGTCCCTGGTGGCCGCTATGCTGCTGCTGCTGTCTCTGGTCGCTGCCATGTTATTACTGCTGTCTGCCGCTAGGGCC
SEQ ID NO:170 TATκκ28的示例性DNA序列
TCTGATGCTGCCCAGCCTGCTAGAAGGGCCGCCAGGACAAAACTGGCCGCCTATGCCAGAAAAGCCGCCAGACAGGCCAGAGCC
SEQ ID NO:171 TATκκ28的示例性DNA序列
AGCGACGCCGCTCAACCAGCTCGACGCGCCGCCAGAACCAAGCTGGCCGCCTACGCCCGGAAGGCCGCCAGACAGGCCAGAGCC
SEQ ID NO:172 TATκκ28的示例性DNA序列
AGCGACGCCGCCCAGCCCGCCAGAAGAGCCGCCAGAACCAAGCTGGCCGCCTACGCCAGAAAGGCCGCCAGACAGGCCAGAGCC
SEQ ID NO:173 TATκκ28的示例性DNA序列
TCTGATGCCGCCCAGCCTGCCAGACGGGCTGCACGGACGAAGCTGGCCGCCTACGCCAGAAAGGCGGCCAGACAGGCCAGAGCC
SEQ ID NO:174 TwinStrep-3cV2-TATκ28-hCDKL5-Flag-His-HPC4(氨基酸序列)
MSAWSHPQFEKGGGSGGGSGGSAWSHPQFEKGSLEVLFQGPDAAQPARRARRTKLAAYARKAARQARAGGGGSKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKFKDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNMLELLEEMPNGVPPEKVKSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGNNANYTEYVATRWYRSPELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKVLGPLPSEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGILNSVLLDLMKNLLKLDPADRYLTEQCLNHPTFQTQRLLDRSPSRSAKRKPYHVESSTLSNRNQAGKSTALQSHHRSNSKDIQNLSVGLPRADEGLPANESFLNGNLAGASLSPLHTKTYQASSQPGSTSKDLTNNNIPHLLSPKEAKSKTEFDFNIDPKPSEGPGTKYLKSNSRSQQNRHSFMESSQSKAGTLQPNEKQSRHSYIDTIPQSSRSPSYRTKAKSHGALSDSKSVSNLSEARAQIAEPSTSRYFPSSCLDLNSPTSPTPTRHSDTRTLLSPSGRNNRNEGTLDSRRTTTRHSKTMEELKLPEHMDSSHSHSLSAPHESFSYGLGYTSPFSSQQRPHRHSMYVTRDKVRAKGLDGSLSIGQGMAARANSLQLLSPQPGEQLPPEMTVARSSVKETSREGTSSFHTRQKSEGGVYHDPHSDDGTAPKENRHLYNDPVPRRVGSFYRVPSPRPDNSFHENNVSTRVSSLPSESSSGTNHSKRQPAFDPWKSPENISHSEQLKEKEKQGFFRSMKKKKKKSQTVPNSDSPDLLTLQKSIHSASTPSSRPKEWRPEKISDLQTQSQPLKSLRKLLHLSSASNHPASSDPRFQPLTAQQTKNSFSEIRIHPLSQASGGSSNIRQEPAPKGRPALQLPGQMDPGWHVSSVTRSATEGPSYSEQLGAKSGPNGHPYNRTNRSRMPNLNDLKETALGAGGGGSLEVLFQGPDYKDHDGDYKDHDIDYKDDDDKDGAPHHHHHHEDQVDPRLIDGK
SEQ ID NO:175 TwinStrep-3cV2-TATκ28-hCDKL5-Flag-His-HPC4(DNA序列)
ATGTCAGCGTGGTCGCATCCTCAATTCGAAAAGGGCGGCGGTTCGGGTGGAGGAAGTGGCGGATCGGCCTGGTCTCACCCGCAATTCGAAAAGGGTTCCCTcGAgGTcCTTTTtCAAGGTCCcGACGCTGCTCAGCCTGCTCGCCGTGCCAGGAGAACCAAGCTGGCTGCCTACGCTCGTAAGGCTGCTAGACAAGCTAGGGCCGGTGGCGGAGGTAGCAAGATCCCAAACATCGGTAACGTGATGAACAAGTTCGAGATCCTGGGCGTGGTCGGTGAAGGCGCTTACGGAGTGGTCCTGAAGTGCAGGCACAAGGAGACCCACGAAATCGTGGCCATCAAGAAGTTCAAGGACTCTGAGGAAAACGAGGAAGTCAAAGAGACCACTCTGCGTGAACTGAAGATGCTGAGGACTCTGAAGCAGGAGAACATCGTCGAGCTGAAGGAAGCTTTCCGCCGTAGGGGAAAGCTGTACCTGGTGTTCGAGTACGTCGAAAAGAACATGCTGGAGCTGCTGGAGGAAATGCCAAACGGTGTGCCTCCCGAAAAGGTCAAGAGCTACATCTACCAGCTGATCAAGGCCATCCACTGGTGCCACAAGAACGACATCGTGCACCGTGACATCAAGCCTGAGAACCTGCTGATCAGCCACAACGACGTCCTGAAGCTGTGCGACTTCGGTTTCGCTAGGAACCTGTCTGAGGGCAACAACGCTAACTACACTGAATACGTGGCCACCCGTTGGTACAGGTCTCCAGAGCTGCTGCTGGGTGCCCCTTACGGCAAGTCTGTGGACATGTGGTCTGTCGGATGCATCCTGGGTGAACTGAGCGACGGACAGCCCCTGTTCCCAGGAGAGTCTGAAATCGACCAGCTGTTCACCATCCAGAAGGTCCTGGGCCCCCTGCCAAGCGAGCAGATGAAGCTGTTCTACTCTAACCCCCGTTTCCACGGACTGAGGTTCCCTGCTGTGAACCACCCCCAGAGCCTGGAAAGACGCTACCTGGGTATCCTGAACTCTGTCCTGCTGGACCTGATGAAGAACCTGCTGAAGCTGGACCCTGCTGACCGCTACCTGACCGAGCAGTGCCTGAACCACCCCACTTTCCAGACCCAGAGACTGCTGGACCGCAGCCCCTCTCGTTCAGCCAAGAGGAAGCCATACCACGTGGAATCCAGCACCCTGAGCAACCGTAACCAGGCTGGCAAGTCCACTGCCCTGCAGAGCCACCACAGGTCCAACAGCAAGGACATCCAAAACCTGTCAGTGGGACTGCCAAGGGCTGACGAGGGACTGCCAGCCAACGAATCCTTCCTGAACGGCAACCTGGCTGGAGCCTCTCTGTCACCACTGCACACTAAGACCTACCAGGCTTCTTCACAGCCTGGTTCCACTAGCAAGGACCTGACCAACAACAACATCCCACACCTGCTGTCTCCTAAGGAAGCTAAATCAAAGACCGAGTTCGACTTCAACATCGACCCTAAGCCCTCCGAGGGACCTGGTACTAAGTACCTGAAGTCTAACTCAAGATCCCAGCAGAACCGCCACTCATTCATGGAGTCCAGCCAGTCCAAGGCTGGTACCCTGCAGCCCAACGAAAAGCAGTCCCGCCACAGCTACATCGACACCATCCCTCAGTCTTCACGTAGCCCCTCTTACAGGACTAAGGCTAAGAGCCACGGCGCCCTGTCAGACTCCAAGAGCGTGTCTAACCTGTCTGAGGCTAGAGCCCAGATCGCCGAACCTTCAACCTCCCGCTACTTCCCCTCCAGCTGCCTGGACCTGAACTCTCCCACTTCACCAACTCCTACCAGACACTCCGACACTCGCACCCTGCTGAGCCCATCTGGTAGAAACAACCGCAACGAGGGCACCCTGGACTCACGTAGGACCACTACCCGTCACTCCAAGACTATGGAGGAACTGAAGCTGCCAGAGCACATGGACTCTTCACACTCACACTCCCTGAGCGCTCCTCACGAATCTTTCTCATACGGCCTGGGATACACCAGCCCATTCTCCAGCCAGCAGCGTCCTCACAGGCACTCTATGTACGTGACTAGAGACAAGGTCCGCGCTAAGGGACTGGACGGTTCCCTGTCTATCGGTCAGGGAATGGCTGCTAGGGCCAACTCTCTGCAGCTGCTGTCACCCCAGCCAGGAGAGCAGCTGCCACCTGAAATGACCGTGGCTAGATCTTCAGTCAAGGAGACTTCCCGCGAAGGCACCTCCAGCTTCCACACTAGACAGAAGTCAGAGGGCGGAGTGTACCACGACCCTCACTCTGACGACGGAACTGCTCCCAAGGAAAACCGCCACCTGTACAACGACCCTGTGCCCAGACGCGTCGGATCCTTCTACCGTGTCCCAAGCCCTAGGCCCGACAACTCTTTCCACGAGAACAACGTGAGCACCAGAGTCTCTTCACTGCCCTCTGAATCCAGCTCTGGCACTAACCACTCAAAGCGCCAGCCTGCTTTCGACCCCTGGAAGTCCCCAGAGAACATCTCTCACTCAGAACAGCTGAAGGAGAAGGAAAAGCAGGGATTCTTCCGCTCAATGAAGAAGAAGAAGAAGAAGTCCCAGACCGTGCCCAACTCCGACAGCCCAGACCTGCTGACCCTGCAGAAGTCAATCCACTCTGCCTCAACTCCTTCATCCAGACCCAAGGAGTGGCGCCCCGAAAAGATCTCCGACCTGCAGACTCAGTCCCAGCCACTGAAGAGCCTGCGTAAGCTGCTGCACCTGAGCTCTGCTTCCAACCACCCTGCCTCATCCGACCCACGTTTCCAGCCTCTGACTGCTCAGCAGACCAAGAACTCCTTCAGCGAGATCAGGATCCACCCACTGTCCCAGGCTAGCGGTGGCAGCTCTAACATCCGTCAGGAACCAGCTCCTAAGGGACGTCCAGCTCTGCAGCTGCCTGGTCAGATGGACCCAGGCTGGCACGTGTCATCCGTCACTAGATCAGCTACCGAGGGACCATCTTACTCAGAACAGCTGGGTGCCAAGTCAGGCCCCAACGGACACCCATACAACCGCACCAACCGTTCCAGGATGCCTAACCTGAACGACCTGAAGGAGACTGCTCTGGGgGCCGGAGGTGGCGGATCCCTgGAaGTgCTgTTcCAgGGcCCTGACTACAAGGACCACGACGGTGACTACAAAGATCACGACATCGACTACAAGGACGACGACGACAAGGACGGTGCCCCACACCACCACCACCACCACGAAGATCAGGTGGATCCTCGCCTGATCGATGGCAAGTAA
SEQ ID NO:176 TwinStrep-3cV2-TATκ28-hCDKL5-Flag-His-TwinStrep(氨基酸序列)
MSAWSHPQFEKGGGSGGGSGGSAWSHPQFEKGSLEVLFQGPDAAQPARRARRTKLAAYARKAARQARAGGGGSKIPNIGNVMNKFEILGVVGEGAYGVVLKCRHKETHEIVAIKKFKDSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNMLELLEEMPNGVPPEKVKSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGNNANYTEYVATRWYRSPELLLGAPYGKSVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQKVLGPLPSEQMKLFYSNPRFHGLRFPAVNHPQSLERRYLGILNSVLLDLMKNLLKLDPADRYLTEQCLNHPTFQTQRLLDRSPSRSAKRKPYHVESSTLSNRNQAGKSTALQSHHRSNSKDIQNLSVGLPRADEGLPANESFLNGNLAGASLSPLHTKTYQASSQPGSTSKDLTNNNIPHLLSPKEAKSKTEFDFNIDPKPSEGPGTKYLKSNSRSQQNRHSFMESSQSKAGTLQPNEKQSRHSYIDTIPQSSRSPSYRTKAKSHGALSDSKSVSNLSEARAQIAEPSTSRYFPSSCLDLNSPTSPTPTRHSDTRTLLSPSGRNNRNEGTLDSRRTTTRHSKTMEELKLPEHMDSSHSHSLSAPHESFSYGLGYTSPFSSQQRPHRHSMYVTRDKVRAKGLDGSLSIGQGMAARANSLQLLSPQPGEQLPPEMTVARSSVKETSREGTSSFHTRQKSEGGVYHDPHSDDGTAPKENRHLYNDPVPRRVGSFYRVPSPRPDNSFHENNVSTRVSSLPSESSSGTNHSKRQPAFDPWKSPENISHSEQLKEKEKQGFFRSMKKKKKKSQTVPNSDSPDLLTLQKSIHSASTPSSRPKEWRPEKISDLQTQSQPLKSLRKLLHLSSASNHPASSDPRFQPLTAQQTKNSFSEIRIHPLSQASGGSSNIRQEPAPKGRPALQLPGQMDPGWHVSSVTRSATEGPSYSEQLGAKSGPNGHPYNRTNRSRMPNLNDLKETALGAGGGGSLEVLFQGPDYKDHDGDYKDHDIDYKDDDDKDGAPHHHHHHSAWSHPQFEKGGGSGGGSGGSAWSHPQFEK*
SEQ ID NO:177 TwinStrep-3cV2-TATκ28-hCDKL5-Flag-His-TwinStrep(DNA序列)
ATGTCAGCGTGGTCGCATCCTCAATTCGAAAAGGGCGGCGGTTCGGGTGGAGGAAGTGGCGGATCGGCCTGGTCTCACCCGCAATTCGAAAAGGGTTCCCTcGAgGTcCTgTTtCAgGGcCCcGACGCTGCTCAGCCTGCTCGCCGTGCCAGGAGAACCAAGCTGGCTGCCTACGCTCGTAAGGCTGCTAGACAAGCTAGGGCCGGTGGCGGAGGTAGCAAGATCCCAAACATCGGTAACGTGATGAACAAGTTCGAGATCCTGGGCGTGGTCGGTGAAGGCGCTTACGGAGTGGTCCTGAAGTGCAGGCACAAGGAGACCCACGAAATCGTGGCCATCAAGAAGTTCAAGGACTCTGAGGAAAACGAGGAAGTCAAAGAGACCACTCTGCGTGAACTGAAGATGCTGAGGACTCTGAAGCAGGAGAACATCGTCGAGCTGAAGGAAGCTTTCCGCCGTAGGGGAAAGCTGTACCTGGTGTTCGAGTACGTCGAAAAGAACATGCTGGAGCTGCTGGAGGAAATGCCAAACGGTGTGCCTCCCGAAAAGGTCAAGAGCTACATCTACCAGCTGATCAAGGCCATCCACTGGTGCCACAAGAACGACATCGTGCACCGTGACATCAAGCCTGAGAACCTGCTGATCAGCCACAACGACGTCCTGAAGCTGTGCGACTTCGGTTTCGCTAGGAACCTGTCTGAGGGCAACAACGCTAACTACACTGAATACGTGGCCACCCGTTGGTACAGGTCTCCAGAGCTGCTGCTGGGTGCCCCTTACGGCAAGTCTGTGGACATGTGGTCTGTCGGATGCATCCTGGGTGAACTGAGCGACGGACAGCCCCTGTTCCCAGGAGAGTCTGAAATCGACCAGCTGTTCACCATCCAGAAGGTCCTGGGCCCCCTGCCAAGCGAGCAGATGAAGCTGTTCTACTCTAACCCCCGTTTCCACGGACTGAGGTTCCCTGCTGTGAACCACCCCCAGAGCCTGGAAAGACGCTACCTGGGTATCCTGAACTCTGTCCTGCTGGACCTGATGAAGAACCTGCTGAAGCTGGACCCTGCTGACCGCTACCTGACCGAGCAGTGCCTGAACCACCCCACTTTCCAGACCCAGAGACTGCTGGACCGCAGCCCCTCTCGTTCAGCCAAGAGGAAGCCATACCACGTGGAATCCAGCACCCTGAGCAACCGTAACCAGGCTGGCAAGTCCACTGCCCTGCAGAGCCACCACAGGTCCAACAGCAAGGACATCCAAAACCTGTCAGTGGGACTGCCAAGGGCTGACGAGGGACTGCCAGCCAACGAATCCTTCCTGAACGGCAACCTGGCTGGAGCCTCTCTGTCACCACTGCACACTAAGACCTACCAGGCTTCTTCACAGCCTGGTTCCACTAGCAAGGACCTGACCAACAACAACATCCCACACCTGCTGTCTCCTAAGGAAGCTAAATCAAAGACCGAGTTCGACTTCAACATCGACCCTAAGCCCTCCGAGGGACCTGGTACTAAGTACCTGAAGTCTAACTCAAGATCCCAGCAGAACCGCCACTCATTCATGGAGTCCAGCCAGTCCAAGGCTGGTACCCTGCAGCCCAACGAAAAGCAGTCCCGCCACAGCTACATCGACACCATCCCTCAGTCTTCACGTAGCCCCTCTTACAGGACTAAGGCTAAGAGCCACGGCGCCCTGTCAGACTCCAAGAGCGTGTCTAACCTGTCTGAGGCTAGAGCCCAGATCGCCGAACCTTCAACCTCCCGCTACTTCCCCTCCAGCTGCCTGGACCTGAACTCTCCCACTTCACCAACTCCTACCAGACACTCCGACACTCGCACCCTGCTGAGCCCATCTGGTAGAAACAACCGCAACGAGGGCACCCTGGACTCACGTAGGACCACTACCCGTCACTCCAAGACTATGGAGGAACTGAAGCTGCCAGAGCACATGGACTCTTCACACTCACACTCCCTGAGCGCTCCTCACGAATCTTTCTCATACGGCCTGGGATACACCAGCCCATTCTCCAGCCAGCAGCGTCCTCACAGGCACTCTATGTACGTGACTAGAGACAAGGTCCGCGCTAAGGGACTGGACGGTTCCCTGTCTATCGGTCAGGGAATGGCTGCTAGGGCCAACTCTCTGCAGCTGCTGTCACCCCAGCCAGGAGAGCAGCTGCCACCTGAAATGACCGTGGCTAGATCTTCAGTCAAGGAGACTTCCCGCGAAGGCACCTCCAGCTTCCACACTAGACAGAAGTCAGAGGGCGGAGTGTACCACGACCCTCACTCTGACGACGGAACTGCTCCCAAGGAAAACCGCCACCTGTACAACGACCCTGTGCCCAGACGCGTCGGATCCTTCTACCGTGTCCCAAGCCCTAGGCCCGACAACTCTTTCCACGAGAACAACGTGAGCACCAGAGTCTCTTCACTGCCCTCTGAATCCAGCTCTGGCACTAACCACTCAAAGCGCCAGCCTGCTTTCGACCCCTGGAAGTCCCCAGAGAACATCTCTCACTCAGAACAGCTGAAGGAGAAGGAAAAGCAGGGATTCTTCCGCTCAATGAAGAAGAAGAAGAAGAAGTCCCAGACCGTGCCCAACTCCGACAGCCCAGACCTGCTGACCCTGCAGAAGTCAATCCACTCTGCCTCAACTCCTTCATCCAGACCCAAGGAGTGGCGCCCCGAAAAGATCTCCGACCTGCAGACTCAGTCCCAGCCACTGAAGAGCCTGCGTAAGCTGCTGCACCTGAGCTCTGCTTCCAACCACCCTGCCTCATCCGACCCACGTTTCCAGCCTCTGACTGCTCAGCAGACCAAGAACTCCTTCAGCGAGATCAGGATCCACCCACTGTCCCAGGCTAGCGGTGGCAGCTCTAACATCCGTCAGGAACCAGCTCCTAAGGGACGTCCAGCTCTGCAGCTGCCTGGTCAGATGGACCCAGGCTGGCACGTGTCATCCGTCACTAGATCAGCTACCGAGGGACCATCTTACTCAGAACAGCTGGGTGCCAAGTCAGGCCCCAACGGACACCCATACAACCGCACCAACCGTTCCAGGATGCCTAACCTGAACGACCTGAAGGAGACTGCTCTGGGgGCCGGAGGTGGCGGATCCCTGGAAGTGCTTTTCCAAGGTCCcGACTACAAGGACCACGACGGTGACTACAAAGATCACGACATCGACTACAAGGACGACGACGACAAGGACGGTGCCCCACACCACCACCACCACCACTCTGCATGGTCGCATCCTCAATTCGAGAAGGGGGGTGGCAGCGGAGGGGGTTCCGGCGGATCAGCCTGGAGTCACCCACAGTTTGAAAAATAA
序列表
<110> 阿米库斯治疗学公司（Amicus Therapeutics, Inc.）
<120> 重组CDKL5蛋白、基因疗法和生产方法
<130> AT18-008-PCT
<160> 177
<170> PatentIn 3.5版
<210> 1
<211> 960
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107同工型多肽1-960 (全长)
<400> 1
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro
530 535 540
Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr
545 550 555 560
Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His
565 570 575
Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe
580 585 590
Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro
595 600 605
His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly
610 615 620
Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn
625 630 635 640
Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu
645 650 655
Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr
660 665 670
Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp
675 680 685
Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr
690 695 700
Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser
705 710 715 720
Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val
725 730 735
Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg
740 745 750
Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His Ser
755 760 765
Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys
770 775 780
Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp
785 790 795 800
Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser
805 810 815
Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln
820 825 830
Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala
835 840 845
Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala
850 855 860
Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser
865 870 875 880
Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys
885 890 895
Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His
900 905 910
Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu
915 920 925
Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg Thr
930 935 940
Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu
945 950 955 960
<210> 2
<211> 852
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体Δ853-960
<400> 2
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro
530 535 540
Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr
545 550 555 560
Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His
565 570 575
Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe
580 585 590
Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro
595 600 605
His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly
610 615 620
Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn
625 630 635 640
Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu
645 650 655
Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr
660 665 670
Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp
675 680 685
Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr
690 695 700
Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser
705 710 715 720
Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val
725 730 735
Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg
740 745 750
Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His Ser
755 760 765
Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys
770 775 780
Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp
785 790 795 800
Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser
805 810 815
Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln
820 825 830
Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala
835 840 845
Ser Asn His Pro
850
<210> 3
<211> 744
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体Δ745-960
<400> 3
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro
530 535 540
Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr
545 550 555 560
Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His
565 570 575
Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe
580 585 590
Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro
595 600 605
His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly
610 615 620
Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn
625 630 635 640
Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu
645 650 655
Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr
660 665 670
Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp
675 680 685
Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr
690 695 700
Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser
705 710 715 720
Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val
725 730 735
Ser Ser Leu Pro Ser Glu Ser Ser
740
<210> 4
<211> 636
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体Δ637-960
<400> 4
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro
530 535 540
Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr
545 550 555 560
Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His
565 570 575
Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe
580 585 590
Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro
595 600 605
His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly
610 615 620
Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala
625 630 635
<210> 5
<211> 528
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体Δ529-960
<400> 5
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
<210> 6
<211> 420
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体Δ421-960
<400> 6
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn
420
<210> 7
<211> 314
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体Δ315-960
<400> 7
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys
305 310
<210> 8
<211> 854
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体Δ315-420
<400> 8
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Ile Asp Pro Lys Pro Ser
305 310 315 320
Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln
325 330 335
Asn Arg His Ser Phe Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu
340 345 350
Gln Pro Asn Glu Lys Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro
355 360 365
Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly
370 375 380
Ala Leu Ser Asp Ser Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala
385 390 395 400
Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu
405 410 415
Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr
420 425 430
Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr
435 440 445
Leu Asp Ser Arg Arg Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu
450 455 460
Leu Lys Leu Pro Glu His Met Asp Ser Ser His Ser His Ser Leu Ser
465 470 475 480
Ala Pro His Glu Ser Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe
485 490 495
Ser Ser Gln Gln Arg Pro His Arg His Ser Met Tyr Val Thr Arg Asp
500 505 510
Lys Val Arg Ala Lys Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly
515 520 525
Met Ala Ala Arg Ala Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly
530 535 540
Glu Gln Leu Pro Pro Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu
545 550 555 560
Thr Ser Arg Glu Gly Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu
565 570 575
Gly Gly Val Tyr His Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys
580 585 590
Glu Asn Arg His Leu Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser
595 600 605
Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn
610 615 620
Asn Val Ser Thr Arg Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly
625 630 635 640
Thr Asn His Ser Lys Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro
645 650 655
Glu Asn Ile Ser His Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly
660 665 670
Phe Phe Arg Ser Met Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro
675 680 685
Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser
690 695 700
Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile
705 710 715 720
Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu
725 730 735
Leu His Leu Ser Ser Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg
740 745 750
Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile
755 760 765
Arg Ile His Pro Leu Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg
770 775 780
Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln
785 790 795 800
Met Asp Pro Gly Trp His Val Ser Ser Val Thr Arg Ser Ala Thr Glu
805 810 815
Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly
820 825 830
His Pro Tyr Asn Arg Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp
835 840 845
Leu Lys Glu Thr Ala Leu
850
<210> 9
<211> 746
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体Δ315-528
<400> 9
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Ser Pro Thr Pro Thr Arg
305 310 315 320
His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn Asn Arg
325 330 335
Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His Ser Lys
340 345 350
Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser His Ser
355 360 365
His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu Gly Tyr
370 375 380
Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser Met Tyr
385 390 395 400
Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser Leu Ser
405 410 415
Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu Leu Ser
420 425 430
Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala Arg Ser
435 440 445
Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His Thr Arg
450 455 460
Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp Asp Gly
465 470 475 480
Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val Pro Arg
485 490 495
Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp Asn Ser
500 505 510
Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro Ser Glu
515 520 525
Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe Asp Pro
530 535 540
Trp Lys Ser Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys Glu Lys
545 550 555 560
Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys Lys Ser
565 570 575
Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu Gln Lys
580 585 590
Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu Trp Arg
595 600 605
Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu Lys Ser
610 615 620
Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro Ala Ser
625 630 635 640
Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys Asn Ser
645 650 655
Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly Gly Ser
660 665 670
Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala Leu Gln
675 680 685
Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val Thr Arg
690 695 700
Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala Lys Ser
705 710 715 720
Gly Pro Asn Gly His Pro Tyr Asn Arg Thr Asn Arg Ser Arg Met Pro
725 730 735
Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu
740 745
<210> 10
<211> 638
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体Δ315-636
<400> 10
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Ala Arg Ala Asn Ser Leu
305 310 315 320
Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr
325 330 335
Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser
340 345 350
Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His
355 360 365
Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp
370 375 380
Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg
385 390 395 400
Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser
405 410 415
Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro
420 425 430
Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His Ser Glu Gln
435 440 445
Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys
450 455 460
Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu
465 470 475 480
Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro
485 490 495
Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln
500 505 510
Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn
515 520 525
His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln
530 535 540
Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala
545 550 555 560
Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg
565 570 575
Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser
580 585 590
Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu
595 600 605
Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg Thr Asn Arg
610 615 620
Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu
625 630 635
<210> 11
<211> 530
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体Δ315-744
<400> 11
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Ser Gly Thr Asn His Ser
305 310 315 320
Lys Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser
325 330 335
His Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser
340 345 350
Met Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser
355 360 365
Pro Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro
370 375 380
Ser Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln
385 390 395 400
Thr Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser
405 410 415
Ser Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu
420 425 430
Thr Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro
435 440 445
Leu Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala
450 455 460
Pro Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly
465 470 475 480
Trp His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr
485 490 495
Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn
500 505 510
Arg Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr
515 520 525
Ala Leu
530
<210> 12
<211> 422
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体Δ315-852
<400> 12
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Ala Ser Ser Asp Pro Arg
305 310 315 320
Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile
325 330 335
Arg Ile His Pro Leu Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg
340 345 350
Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln
355 360 365
Met Asp Pro Gly Trp His Val Ser Ser Val Thr Arg Ser Ala Thr Glu
370 375 380
Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly
385 390 395 400
His Pro Tyr Asn Arg Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp
405 410 415
Leu Lys Glu Thr Ala Leu
420
<210> 13
<211> 960
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体1-7NQ
<400> 13
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Gln Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro
530 535 540
Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr
545 550 555 560
Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His
565 570 575
Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe
580 585 590
Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro
595 600 605
His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly
610 615 620
Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn
625 630 635 640
Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu
645 650 655
Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr
660 665 670
Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp
675 680 685
Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr
690 695 700
Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser
705 710 715 720
Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val
725 730 735
Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg
740 745 750
Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser
755 760 765
Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys
770 775 780
Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp
785 790 795 800
Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser
805 810 815
Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln
820 825 830
Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala
835 840 845
Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala
850 855 860
Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser
865 870 875 880
Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys
885 890 895
Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His
900 905 910
Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu
915 920 925
Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr
930 935 940
Gln Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu
945 950 955 960
<210> 14
<211> 960
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体2-7NQ
<400> 14
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Gln Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro
530 535 540
Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr
545 550 555 560
Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His
565 570 575
Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe
580 585 590
Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro
595 600 605
His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly
610 615 620
Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn
625 630 635 640
Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu
645 650 655
Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr
660 665 670
Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp
675 680 685
Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr
690 695 700
Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser
705 710 715 720
Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val
725 730 735
Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg
740 745 750
Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser
755 760 765
Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys
770 775 780
Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp
785 790 795 800
Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser
805 810 815
Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln
820 825 830
Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala
835 840 845
Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala
850 855 860
Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser
865 870 875 880
Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys
885 890 895
Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His
900 905 910
Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu
915 920 925
Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr
930 935 940
Gln Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu
945 950 955 960
<210> 15
<211> 960
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体1,3-7NQ
<400> 15
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Gln Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro
530 535 540
Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr
545 550 555 560
Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His
565 570 575
Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe
580 585 590
Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro
595 600 605
His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly
610 615 620
Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn
625 630 635 640
Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu
645 650 655
Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr
660 665 670
Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp
675 680 685
Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr
690 695 700
Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser
705 710 715 720
Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val
725 730 735
Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg
740 745 750
Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser
755 760 765
Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys
770 775 780
Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp
785 790 795 800
Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser
805 810 815
Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln
820 825 830
Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala
835 840 845
Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala
850 855 860
Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser
865 870 875 880
Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys
885 890 895
Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His
900 905 910
Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu
915 920 925
Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr
930 935 940
Gln Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu
945 950 955 960
<210> 16
<211> 960
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体1-2,4-7NQ
<400> 16
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Gln Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro
530 535 540
Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr
545 550 555 560
Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His
565 570 575
Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe
580 585 590
Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro
595 600 605
His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly
610 615 620
Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn
625 630 635 640
Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu
645 650 655
Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr
660 665 670
Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp
675 680 685
Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr
690 695 700
Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser
705 710 715 720
Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val
725 730 735
Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg
740 745 750
Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser
755 760 765
Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys
770 775 780
Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp
785 790 795 800
Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser
805 810 815
Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln
820 825 830
Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala
835 840 845
Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala
850 855 860
Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser
865 870 875 880
Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys
885 890 895
Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His
900 905 910
Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu
915 920 925
Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr
930 935 940
Gln Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu
945 950 955 960
<210> 17
<211> 960
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体1-3,5-7NQ
<400> 17
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro
530 535 540
Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr
545 550 555 560
Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His
565 570 575
Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe
580 585 590
Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro
595 600 605
His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly
610 615 620
Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn
625 630 635 640
Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu
645 650 655
Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr
660 665 670
Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp
675 680 685
Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr
690 695 700
Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser
705 710 715 720
Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val
725 730 735
Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg
740 745 750
Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser
755 760 765
Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys
770 775 780
Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp
785 790 795 800
Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser
805 810 815
Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln
820 825 830
Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala
835 840 845
Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala
850 855 860
Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser
865 870 875 880
Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys
885 890 895
Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His
900 905 910
Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu
915 920 925
Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr
930 935 940
Gln Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu
945 950 955 960
<210> 18
<211> 960
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体1-4,6-7NQ
<400> 18
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Gln Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro
530 535 540
Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr
545 550 555 560
Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His
565 570 575
Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe
580 585 590
Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro
595 600 605
His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly
610 615 620
Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn
625 630 635 640
Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu
645 650 655
Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr
660 665 670
Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp
675 680 685
Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr
690 695 700
Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser
705 710 715 720
Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val
725 730 735
Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg
740 745 750
Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His Ser
755 760 765
Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys
770 775 780
Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp
785 790 795 800
Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser
805 810 815
Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln
820 825 830
Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala
835 840 845
Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala
850 855 860
Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser
865 870 875 880
Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys
885 890 895
Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His
900 905 910
Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu
915 920 925
Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr
930 935 940
Gln Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu
945 950 955 960
<210> 19
<211> 960
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体1-5,7NQ
<400> 19
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Gln Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro
530 535 540
Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr
545 550 555 560
Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His
565 570 575
Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe
580 585 590
Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro
595 600 605
His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly
610 615 620
Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn
625 630 635 640
Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu
645 650 655
Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr
660 665 670
Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp
675 680 685
Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr
690 695 700
Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser
705 710 715 720
Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val
725 730 735
Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg
740 745 750
Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser
755 760 765
Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys
770 775 780
Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp
785 790 795 800
Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser
805 810 815
Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln
820 825 830
Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala
835 840 845
Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala
850 855 860
Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser
865 870 875 880
Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys
885 890 895
Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His
900 905 910
Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu
915 920 925
Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg Thr
930 935 940
Gln Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu
945 950 955 960
<210> 20
<211> 960
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体1-6NQ
<400> 20
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Gln Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro
530 535 540
Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr
545 550 555 560
Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His
565 570 575
Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe
580 585 590
Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro
595 600 605
His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly
610 615 620
Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn
625 630 635 640
Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu
645 650 655
Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr
660 665 670
Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp
675 680 685
Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr
690 695 700
Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser
705 710 715 720
Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val
725 730 735
Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg
740 745 750
Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser
755 760 765
Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys
770 775 780
Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp
785 790 795 800
Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser
805 810 815
Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln
820 825 830
Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala
835 840 845
Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala
850 855 860
Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser
865 870 875 880
Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys
885 890 895
Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His
900 905 910
Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu
915 920 925
Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr
930 935 940
Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu
945 950 955 960
<210> 21
<211> 960
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体2NQ
<400> 21
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro
530 535 540
Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr
545 550 555 560
Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His
565 570 575
Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe
580 585 590
Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro
595 600 605
His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly
610 615 620
Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn
625 630 635 640
Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu
645 650 655
Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr
660 665 670
Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp
675 680 685
Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr
690 695 700
Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser
705 710 715 720
Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val
725 730 735
Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg
740 745 750
Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His Ser
755 760 765
Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys
770 775 780
Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp
785 790 795 800
Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser
805 810 815
Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln
820 825 830
Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala
835 840 845
Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala
850 855 860
Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser
865 870 875 880
Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys
885 890 895
Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His
900 905 910
Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu
915 920 925
Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg Thr
930 935 940
Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu
945 950 955 960
<210> 22
<211> 960
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体1-10NQ
<400> 22
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Gln Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Gln Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro
530 535 540
Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr
545 550 555 560
Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His
565 570 575
Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe
580 585 590
Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro
595 600 605
His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly
610 615 620
Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn
625 630 635 640
Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu
645 650 655
Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr
660 665 670
Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp
675 680 685
Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr
690 695 700
Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser
705 710 715 720
Pro Arg Pro Asp Asn Ser Phe His Glu Asn Gln Val Ser Thr Arg Val
725 730 735
Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Gln His Ser Lys Arg
740 745 750
Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser
755 760 765
Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys
770 775 780
Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp
785 790 795 800
Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser
805 810 815
Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln
820 825 830
Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala
835 840 845
Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala
850 855 860
Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser
865 870 875 880
Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys
885 890 895
Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His
900 905 910
Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu
915 920 925
Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr
930 935 940
Gln Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu
945 950 955 960
<210> 23
<211> 960
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体1-7, 9-10NQ
<400> 23
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Gln Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro
530 535 540
Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr
545 550 555 560
Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His
565 570 575
Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe
580 585 590
Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro
595 600 605
His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly
610 615 620
Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn
625 630 635 640
Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu
645 650 655
Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr
660 665 670
Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp
675 680 685
Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr
690 695 700
Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser
705 710 715 720
Pro Arg Pro Asp Asn Ser Phe His Glu Asn Gln Val Ser Thr Arg Val
725 730 735
Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Gln His Ser Lys Arg
740 745 750
Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser
755 760 765
Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys
770 775 780
Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp
785 790 795 800
Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser
805 810 815
Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln
820 825 830
Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala
835 840 845
Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala
850 855 860
Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser
865 870 875 880
Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys
885 890 895
Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His
900 905 910
Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu
915 920 925
Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr
930 935 940
Gln Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu
945 950 955 960
<210> 24
<211> 960
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体1-8, 10NQ
<400> 24
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Gln Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Gln Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro
530 535 540
Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr
545 550 555 560
Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His
565 570 575
Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe
580 585 590
Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro
595 600 605
His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly
610 615 620
Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn
625 630 635 640
Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu
645 650 655
Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr
660 665 670
Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp
675 680 685
Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr
690 695 700
Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser
705 710 715 720
Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val
725 730 735
Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Gln His Ser Lys Arg
740 745 750
Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser
755 760 765
Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys
770 775 780
Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp
785 790 795 800
Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser
805 810 815
Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln
820 825 830
Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala
835 840 845
Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala
850 855 860
Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser
865 870 875 880
Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys
885 890 895
Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His
900 905 910
Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu
915 920 925
Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr
930 935 940
Gln Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu
945 950 955 960
<210> 25
<211> 960
<212> PRT
<213> 人工序列
<220>
<223> CDKL5107变体1-9NQ
<400> 25
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Gln Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Gln Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro
530 535 540
Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr
545 550 555 560
Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His
565 570 575
Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe
580 585 590
Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro
595 600 605
His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly
610 615 620
Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn
625 630 635 640
Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu
645 650 655
Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr
660 665 670
Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp
675 680 685
Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr
690 695 700
Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser
705 710 715 720
Pro Arg Pro Asp Asn Ser Phe His Glu Asn Gln Val Ser Thr Arg Val
725 730 735
Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg
740 745 750
Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser
755 760 765
Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys
770 775 780
Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp
785 790 795 800
Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser
805 810 815
Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln
820 825 830
Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala
835 840 845
Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala
850 855 860
Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser
865 870 875 880
Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys
885 890 895
Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His
900 905 910
Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu
915 920 925
Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr
930 935 940
Gln Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu
945 950 955 960
<210> 26
<211> 1030
<212> PRT
<213> 人工序列
<220>
<223> CDKL5115同工型多肽1-1030 (全长)
<400> 26
Met Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu
1 5 10 15
Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His
20 25 30
Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu
35 40 45
Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu
50 55 60
Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg
65 70 75 80
Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met
85 90 95
Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val
100 105 110
Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys
115 120 125
Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser
130 135 140
His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu
145 150 155 160
Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp
165 170 175
Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val
180 185 190
Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln
195 200 205
Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln
210 215 220
Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser
225 230 235 240
Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln
245 250 255
Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp
260 265 270
Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr
275 280 285
Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp
290 295 300
Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser
305 310 315 320
Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln
325 330 335
Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly
340 345 350
Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn
355 360 365
Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr
370 375 380
Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn
385 390 395 400
Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu
405 410 415
Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys
420 425 430
Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met
435 440 445
Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln
450 455 460
Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro
465 470 475 480
Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys
485 490 495
Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser
500 505 510
Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr
515 520 525
Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro
530 535 540
Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr
545 550 555 560
Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His
565 570 575
Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe
580 585 590
Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro
595 600 605
His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly
610 615 620
Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn
625 630 635 640
Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu
645 650 655
Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr
660 665 670
Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp
675 680 685
Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr
690 695 700
Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser
705 710 715 720
Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val
725 730 735
Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg
740 745 750
Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His Ser
755 760 765
Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys
770 775 780
Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp
785 790 795 800
Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser
805 810 815
Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln
820 825 830
Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala
835 840 845
Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala
850 855 860
Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser
865 870 875 880
Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys
885 890 895
Gly Arg Pro Ala Leu Gln Leu Pro Asp Gly Gly Cys Asp Gly Arg Arg
900 905 910
Gln Arg His His Ser Gly Pro Gln Asp Arg Arg Phe Met Leu Arg Thr
915 920 925
Thr Glu Gln Gln Gly Glu Tyr Phe Cys Cys Gly Asp Pro Lys Lys Pro
930 935 940
His Thr Pro Cys Val Pro Asn Arg Ala Leu His Arg Pro Ile Ser Ser
945 950 955 960
Pro Ala Pro Tyr Pro Val Leu Gln Val Arg Gly Thr Ser Met Cys Pro
965 970 975
Thr Leu Gln Val Arg Gly Thr Asp Ala Phe Ser Cys Pro Thr Gln Gln
980 985 990
Ser Gly Phe Ser Phe Phe Val Arg His Val Met Arg Glu Ala Leu Ile
995 1000 1005
His Arg Ala Gln Val Asn Gln Ala Ala Leu Leu Thr Tyr His Glu
1010 1015 1020
Asn Ala Ala Leu Thr Gly Lys
1025 1030
<210> 27
<211> 141
<212> DNA
<213> 人工序列
<220>
<223> AAV2 L-ITR
<400> 27
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc t 141
<210> 28
<211> 141
<212> DNA
<213> 人工序列
<220>
<223> AAV2 R-ITR
<400> 28
aggaacccct agtgatggag ttggccactc cctctctgcg cgctcgctcg ctcactgagg 60
ccgggcgacc aaaggtcgcc cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc 120
gagcgcgcag ctgcctgcag g 141
<210> 29
<211> 818
<212> DNA
<213> 人工序列
<220>
<223> CBh
<400> 29
ttaatagtaa tcaattacgg ggtcattagt tcatagccca tatatggagt tccgcgttac 60
ataacttacg gtaaatggcc cgcctggctg accgcccaac gacccccgcc cattgacgtc 120
aataatgacg tatgttccca tagtaacgcc aatagggact ttccattgac gtcaatgggt 180
ggagtattta cggtaaactg cccacttggc agtacatcaa gtgtatcata tgccaagtac 240
gccccctatt gacgtcaatg acggtaaatg gcccgcctgg cattatgccc agtacatgac 300
cttacgggac tttcctactt ggcagtacat ctccacgttc tgcttcactc tccccatctc 360
ccccccctcc ccacccccaa ttttgtattt atttattttt taattatttt gtgcagcgat 420
gggggcgggg gggggggggg cgcgcgccag gcggggcggg gcggggcgag gggcggggcg 480
gggcgaggcg gagaggtgcg gcggcagcca atcagagcgg cgcgctccga aagtttcctt 540
ttatggcgag gcggcggcgg cggcggccct ataaaaagcg aagcgcgcgg cggggagtcg 600
ctgcgttgcc ttcgccccgt gccccgctcc gcgccgcctc gcgccgcccg ccccggctct 660
gactgaccgc gttactccca caggtgagcg ggcgggacgg cccttctcct ccgggctgta 720
attagcaaga ggtaagggtt taagggatgg ttggttggtg gggtattaat gtttaattac 780
ctgttttaca ggcctgaaat cacttggttt taggttgg 818
<210> 30
<211> 572
<212> DNA
<213> 人工序列
<220>
<223> hSyn1
<400> 30
actacaaacc gagtatctgc agagggccct gcgtatgagt gcaagtgggt tttaggacca 60
ggatgaggcg gggtgggggt gcctacctga cgaccgaccc cgacccactg gacaagcacc 120
caacccccat tccccaaatt gcgcatcccc tatcagagag ggggagggga aacaggatgc 180
ggcgaggcgc gtgcgcactg ccagcttcag caccgcggac agtgccttcg cccccgcctg 240
gcggcgcgcg ccaccgccgc ctcagcactg aaggcgcgct gacgtcactc gccggtcccc 300
cgcaaactcc ccttcccggc caccttggtc gcgtccgcgc cgccgccggc ccagccggac 360
cgcaccacgc gaggcgcgag ataggggggc acgggcgcga ccatctgcgc tgcggcgccg 420
gcgactcagc gctgcctcag tctgcggtgg gcagcggagg agtcgtgtcg tgcctgagag 480
cgcagctgtg ctcctgggca ccgcgcagtc cgcccccgcg gctcctggcc agaccacccc 540
taggaccccc tgccccaagt cgcagccttc ga 572
<210> 31
<211> 27
<212> PRT
<213> 人工序列
<220>
<223> TAT28 CPP
<400> 31
Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu Ala Ala
1 5 10 15
Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg
20 25
<210> 32
<211> 27
<212> PRT
<213> 人工序列
<220>
<223> TATκ28 CPP
<400> 32
Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu Ala Ala
1 5 10 15
Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala
20 25
<210> 33
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> TAT11 CPP
<400> 33
Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg
1 5 10
<210> 34
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> TATκ11 CPP
<400> 34
Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala
1 5 10
<210> 35
<211> 21
<212> PRT
<213> 人工序列
<220>
<223> 转运肽CPP
<400> 35
Ala Gly Tyr Leu Leu Gly Lys Ile Asn Leu Lys Ala Leu Ala Ala Leu
1 5 10 15
Ala Lys Lys Ile Leu
20
<210> 36
<211> 16
<212> PRT
<213> 人工序列
<220>
<223> 穿膜肽CPP
<400> 36
Arg Gln Ile Lys Ile Trp Phe Gln Asn Arg Arg Met Lys Trp Lys Lys
1 5 10 15
<210> 37
<211> 12
<212> PRT
<213> 人工序列
<220>
<223> P97 CPP
<400> 37
Asp Ser Ser His Ala Phe Thr Leu Asp Glu Leu Arg
1 5 10
<210> 38
<211> 28
<212> PRT
<213> 人工序列
<220>
<223> MBiP
<400> 38
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala
20 25
<210> 39
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> MBiP2
<400> 39
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Trp Val Ala
1 5 10 15
Leu Leu Leu Leu Ser Ala Ala Arg Ala
20 25
<210> 40
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> MBiP3
<400> 40
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Leu Leu Leu Leu Ser Ala Ala Arg Ala
20 25
<210> 41
<211> 26
<212> PRT
<213> 人工序列
<220>
<223> MBiP4
<400> 41
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ala Leu Val
1 5 10 15
Ala Leu Leu Leu Leu Ser Ala Ala Arg Ala
20 25
<210> 42
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 鼠Igκ
<400> 42
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly
20
<210> 43
<211> 1064
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的MBip_Tκ28p_107_3xFlagHis_cho-opt
<400> 43
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala Gly Asp Ala Ala
20 25 30
Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg
35 40 45
Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro
50 55 60
Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly
65 70 75 80
Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His
85 90 95
Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu
100 105 110
Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys
115 120 125
Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys
130 135 140
Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu
145 150 155 160
Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile
165 170 175
Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val
180 185 190
His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val
195 200 205
Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn
210 215 220
Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro
225 230 235 240
Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser
245 250 255
Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro
260 265 270
Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly
275 280 285
Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe
290 295 300
His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg
305 310 315 320
Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn
325 330 335
Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu
340 345 350
Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser
355 360 365
Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser
370 375 380
Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg
385 390 395 400
Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly Leu Pro Arg Ala
405 410 415
Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala
420 425 430
Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser
435 440 445
Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His
450 455 460
Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn
465 470 475 480
Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser
485 490 495
Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln
500 505 510
Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser
515 520 525
Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr
530 535 540
Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Asn
545 550 555 560
Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr
565 570 575
Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro
580 585 590
Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn
595 600 605
Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His
610 615 620
Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser
625 630 635 640
His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu
645 650 655
Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser
660 665 670
Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser
675 680 685
Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu
690 695 700
Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala
705 710 715 720
Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His
725 730 735
Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp
740 745 750
Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val
755 760 765
Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp
770 775 780
Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro
785 790 795 800
Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe
805 810 815
Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys
820 825 830
Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys
835 840 845
Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu
850 855 860
Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
865 870 875 880
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
885 890 895
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro
900 905 910
Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys
915 920 925
Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly
930 935 940
Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala
945 950 955 960
Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val
965 970 975
Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala
980 985 990
Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg Thr Asn Arg Ser Arg
995 1000 1005
Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly
1010 1015 1020
Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp
1025 1030 1035
Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
1040 1045 1050
Lys Asp Gly Ala Pro His His His His His His
1055 1060
<210> 44
<211> 1056
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的Igκ_Tκ28p_107_3xFlagHis_cho-opt
<400> 44
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg
20 25 30
Thr Lys Leu Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala
35 40 45
Gly Gly Gly Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys
50 55 60
Phe Glu Ile Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu
65 70 75 80
Lys Cys Arg His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe
85 90 95
Lys Asp Ser Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu
100 105 110
Leu Lys Met Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys
115 120 125
Glu Ala Phe Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val
130 135 140
Glu Lys Asn Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro
145 150 155 160
Pro Glu Lys Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His
165 170 175
Trp Cys His Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn
180 185 190
Leu Leu Ile Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe
195 200 205
Ala Arg Asn Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val
210 215 220
Ala Thr Arg Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr
225 230 235 240
Gly Lys Ser Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu
245 250 255
Ser Asp Gly Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu
260 265 270
Phe Thr Ile Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys
275 280 285
Leu Phe Tyr Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val
290 295 300
Asn His Pro Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser
305 310 315 320
Val Leu Leu Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp
325 330 335
Arg Tyr Leu Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln
340 345 350
Arg Leu Leu Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr
355 360 365
His Val Glu Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser
370 375 380
Thr Ala Leu Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn
385 390 395 400
Leu Ser Val Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu
405 410 415
Ser Phe Leu Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His
420 425 430
Thr Lys Thr Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp
435 440 445
Leu Thr Asn Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys
450 455 460
Ser Lys Thr Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly
465 470 475 480
Pro Gly Thr Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg
485 490 495
His Ser Phe Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro
500 505 510
Asn Glu Lys Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser
515 520 525
Ser Arg Ser Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu
530 535 540
Ser Asp Ser Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile
545 550 555 560
Ala Glu Pro Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu
565 570 575
Asn Ser Pro Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr
580 585 590
Leu Leu Ser Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp
595 600 605
Ser Arg Arg Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys
610 615 620
Leu Pro Glu His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro
625 630 635 640
His Glu Ser Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser
645 650 655
Gln Gln Arg Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val
660 665 670
Arg Ala Lys Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala
675 680 685
Ala Arg Ala Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln
690 695 700
Leu Pro Pro Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser
705 710 715 720
Arg Glu Gly Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly
725 730 735
Val Tyr His Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn
740 745 750
Arg His Leu Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr
755 760 765
Arg Val Pro Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val
770 775 780
Ser Thr Arg Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn
785 790 795 800
His Ser Lys Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn
805 810 815
Ile Ser His Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe
820 825 830
Arg Ser Met Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser
835 840 845
Asp Ser Pro Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser
850 855 860
Thr Pro Ser Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp
865 870 875 880
Leu Gln Thr Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His
885 890 895
Leu Ser Ser Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln
900 905 910
Pro Leu Thr Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile
915 920 925
His Pro Leu Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu
930 935 940
Pro Ala Pro Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp
945 950 955 960
Pro Gly Trp His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro
965 970 975
Ser Tyr Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro
980 985 990
Tyr Asn Arg Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys
995 1000 1005
Glu Thr Ala Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln
1010 1015 1020
Gly Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile
1025 1030 1035
Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His His His
1040 1045 1050
His His His
1055
<210> 45
<211> 1134
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的MBiP_Tκ28p_115_3xFlagHis_cho-opt
<400> 45
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala Gly Asp Ala Ala
20 25 30
Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg
35 40 45
Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro
50 55 60
Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly
65 70 75 80
Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His
85 90 95
Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu
100 105 110
Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys
115 120 125
Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys
130 135 140
Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu
145 150 155 160
Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile
165 170 175
Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val
180 185 190
His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val
195 200 205
Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn
210 215 220
Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro
225 230 235 240
Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser
245 250 255
Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro
260 265 270
Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly
275 280 285
Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe
290 295 300
His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg
305 310 315 320
Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn
325 330 335
Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu
340 345 350
Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser
355 360 365
Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser
370 375 380
Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg
385 390 395 400
Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly Leu Pro Arg Ala
405 410 415
Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala
420 425 430
Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser
435 440 445
Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His
450 455 460
Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn
465 470 475 480
Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser
485 490 495
Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln
500 505 510
Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser
515 520 525
Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr
530 535 540
Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Asn
545 550 555 560
Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr
565 570 575
Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro
580 585 590
Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn
595 600 605
Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His
610 615 620
Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser
625 630 635 640
His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu
645 650 655
Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser
660 665 670
Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser
675 680 685
Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu
690 695 700
Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala
705 710 715 720
Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His
725 730 735
Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp
740 745 750
Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val
755 760 765
Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp
770 775 780
Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro
785 790 795 800
Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe
805 810 815
Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys
820 825 830
Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys
835 840 845
Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu
850 855 860
Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
865 870 875 880
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
885 890 895
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro
900 905 910
Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys
915 920 925
Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly
930 935 940
Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala
945 950 955 960
Leu Gln Leu Pro Asp Gly Gly Cys Asp Gly Arg Arg Gln Arg His His
965 970 975
Ser Gly Pro Gln Asp Arg Arg Phe Met Leu Arg Thr Thr Glu Gln Gln
980 985 990
Gly Glu Tyr Phe Cys Cys Gly Asp Pro Lys Lys Pro His Thr Pro Cys
995 1000 1005
Val Pro Asn Arg Ala Leu His Arg Pro Ile Ser Ser Pro Ala Pro
1010 1015 1020
Tyr Pro Val Leu Gln Val Arg Gly Thr Ser Met Cys Pro Thr Leu
1025 1030 1035
Gln Val Arg Gly Thr Asp Ala Phe Ser Cys Pro Thr Gln Gln Ser
1040 1045 1050
Gly Phe Ser Phe Phe Val Arg His Val Met Arg Glu Ala Leu Ile
1055 1060 1065
His Arg Ala Gln Val Asn Gln Ala Ala Leu Leu Thr Tyr His Glu
1070 1075 1080
Asn Ala Ala Leu Thr Gly Lys Gly Gly Gly Gly Ser Glu Asn Leu
1085 1090 1095
Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp
1100 1105 1110
His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro
1115 1120 1125
His His His His His His
1130
<210> 46
<211> 1126
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的Igκ_Tκ28p_115_3xFlagHis_cho-opt
<400> 46
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg
20 25 30
Thr Lys Leu Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala
35 40 45
Gly Gly Gly Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys
50 55 60
Phe Glu Ile Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu
65 70 75 80
Lys Cys Arg His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe
85 90 95
Lys Asp Ser Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu
100 105 110
Leu Lys Met Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys
115 120 125
Glu Ala Phe Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val
130 135 140
Glu Lys Asn Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro
145 150 155 160
Pro Glu Lys Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His
165 170 175
Trp Cys His Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn
180 185 190
Leu Leu Ile Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe
195 200 205
Ala Arg Asn Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val
210 215 220
Ala Thr Arg Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr
225 230 235 240
Gly Lys Ser Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu
245 250 255
Ser Asp Gly Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu
260 265 270
Phe Thr Ile Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys
275 280 285
Leu Phe Tyr Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val
290 295 300
Asn His Pro Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser
305 310 315 320
Val Leu Leu Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp
325 330 335
Arg Tyr Leu Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln
340 345 350
Arg Leu Leu Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr
355 360 365
His Val Glu Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser
370 375 380
Thr Ala Leu Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn
385 390 395 400
Leu Ser Val Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu
405 410 415
Ser Phe Leu Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His
420 425 430
Thr Lys Thr Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp
435 440 445
Leu Thr Asn Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys
450 455 460
Ser Lys Thr Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly
465 470 475 480
Pro Gly Thr Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg
485 490 495
His Ser Phe Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro
500 505 510
Asn Glu Lys Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser
515 520 525
Ser Arg Ser Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu
530 535 540
Ser Asp Ser Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile
545 550 555 560
Ala Glu Pro Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu
565 570 575
Asn Ser Pro Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr
580 585 590
Leu Leu Ser Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp
595 600 605
Ser Arg Arg Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys
610 615 620
Leu Pro Glu His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro
625 630 635 640
His Glu Ser Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser
645 650 655
Gln Gln Arg Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val
660 665 670
Arg Ala Lys Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala
675 680 685
Ala Arg Ala Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln
690 695 700
Leu Pro Pro Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser
705 710 715 720
Arg Glu Gly Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly
725 730 735
Val Tyr His Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn
740 745 750
Arg His Leu Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr
755 760 765
Arg Val Pro Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val
770 775 780
Ser Thr Arg Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn
785 790 795 800
His Ser Lys Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn
805 810 815
Ile Ser His Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe
820 825 830
Arg Ser Met Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser
835 840 845
Asp Ser Pro Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser
850 855 860
Thr Pro Ser Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp
865 870 875 880
Leu Gln Thr Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His
885 890 895
Leu Ser Ser Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln
900 905 910
Pro Leu Thr Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile
915 920 925
His Pro Leu Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu
930 935 940
Pro Ala Pro Lys Gly Arg Pro Ala Leu Gln Leu Pro Asp Gly Gly Cys
945 950 955 960
Asp Gly Arg Arg Gln Arg His His Ser Gly Pro Gln Asp Arg Arg Phe
965 970 975
Met Leu Arg Thr Thr Glu Gln Gln Gly Glu Tyr Phe Cys Cys Gly Asp
980 985 990
Pro Lys Lys Pro His Thr Pro Cys Val Pro Asn Arg Ala Leu His Arg
995 1000 1005
Pro Ile Ser Ser Pro Ala Pro Tyr Pro Val Leu Gln Val Arg Gly
1010 1015 1020
Thr Ser Met Cys Pro Thr Leu Gln Val Arg Gly Thr Asp Ala Phe
1025 1030 1035
Ser Cys Pro Thr Gln Gln Ser Gly Phe Ser Phe Phe Val Arg His
1040 1045 1050
Val Met Arg Glu Ala Leu Ile His Arg Ala Gln Val Asn Gln Ala
1055 1060 1065
Ala Leu Leu Thr Tyr His Glu Asn Ala Ala Leu Thr Gly Lys Gly
1070 1075 1080
Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp
1085 1090 1095
His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp
1100 1105 1110
Asp Asp Lys Asp Gly Ala Pro His His His His His His
1115 1120 1125
<210> 47
<211> 1037
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的Tκ28p_107_3xFlagHis_cho-opt
<400> 47
Met Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu
1 5 10 15
Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly
20 25 30
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
35 40 45
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
50 55 60
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
65 70 75 80
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
85 90 95
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
100 105 110
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
115 120 125
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
130 135 140
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
145 150 155 160
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
165 170 175
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
180 185 190
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
195 200 205
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
210 215 220
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
225 230 235 240
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
245 250 255
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
260 265 270
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
275 280 285
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
290 295 300
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
305 310 315 320
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
325 330 335
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu
340 345 350
Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu
355 360 365
Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val
370 375 380
Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu
385 390 395 400
Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr
405 410 415
Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn
420 425 430
Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr
435 440 445
Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr
450 455 460
Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe
465 470 475 480
Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys
485 490 495
Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser
500 505 510
Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser
515 520 525
Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro
530 535 540
Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro
545 550 555 560
Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser
565 570 575
Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg
580 585 590
Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu
595 600 605
His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser
610 615 620
Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg
625 630 635 640
Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys
645 650 655
Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala
660 665 670
Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro
675 680 685
Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly
690 695 700
Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His
705 710 715 720
Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu
725 730 735
Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro
740 745 750
Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg
755 760 765
Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys
770 775 780
Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His
785 790 795 800
Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met
805 810 815
Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro
820 825 830
Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser
835 840 845
Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr
850 855 860
Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser
865 870 875 880
Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr
885 890 895
Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu
900 905 910
Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro
915 920 925
Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp
930 935 940
His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser
945 950 955 960
Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg
965 970 975
Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala
980 985 990
Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys
995 1000 1005
Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp
1010 1015 1020
Asp Asp Asp Lys Asp Gly Ala Pro His His His His His His
1025 1030 1035
<210> 48
<211> 1037
<212> PRT
<213> 人工序列
<220>
<223> pEX-1中的Tκ28p_107_3xFlagHis_大肠杆菌-opt
<400> 48
Met Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu
1 5 10 15
Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly
20 25 30
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
35 40 45
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
50 55 60
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
65 70 75 80
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
85 90 95
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
100 105 110
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
115 120 125
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
130 135 140
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
145 150 155 160
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
165 170 175
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
180 185 190
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
195 200 205
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
210 215 220
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
225 230 235 240
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
245 250 255
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
260 265 270
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
275 280 285
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
290 295 300
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
305 310 315 320
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
325 330 335
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu
340 345 350
Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu
355 360 365
Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val
370 375 380
Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu
385 390 395 400
Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr
405 410 415
Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn
420 425 430
Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr
435 440 445
Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr
450 455 460
Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe
465 470 475 480
Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys
485 490 495
Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser
500 505 510
Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser
515 520 525
Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro
530 535 540
Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro
545 550 555 560
Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser
565 570 575
Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg
580 585 590
Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu
595 600 605
His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser
610 615 620
Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg
625 630 635 640
Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys
645 650 655
Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala
660 665 670
Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro
675 680 685
Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly
690 695 700
Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His
705 710 715 720
Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu
725 730 735
Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro
740 745 750
Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg
755 760 765
Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys
770 775 780
Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His
785 790 795 800
Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met
805 810 815
Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro
820 825 830
Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser
835 840 845
Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr
850 855 860
Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser
865 870 875 880
Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr
885 890 895
Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu
900 905 910
Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro
915 920 925
Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp
930 935 940
His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser
945 950 955 960
Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg
965 970 975
Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala
980 985 990
Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys
995 1000 1005
Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp
1010 1015 1020
Asp Asp Asp Lys Asp Gly Ala Pro His His His His His His
1025 1030 1035
<210> 49
<211> 929
<212> PRT
<213> 人工序列
<220>
<223> pEX-1中的Δ853-960
<400> 49
Met Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu
1 5 10 15
Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly
20 25 30
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
35 40 45
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
50 55 60
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
65 70 75 80
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
85 90 95
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
100 105 110
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
115 120 125
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
130 135 140
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
145 150 155 160
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
165 170 175
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
180 185 190
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
195 200 205
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
210 215 220
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
225 230 235 240
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
245 250 255
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
260 265 270
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
275 280 285
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
290 295 300
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
305 310 315 320
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
325 330 335
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu
340 345 350
Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu
355 360 365
Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val
370 375 380
Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu
385 390 395 400
Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr
405 410 415
Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn
420 425 430
Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr
435 440 445
Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr
450 455 460
Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe
465 470 475 480
Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys
485 490 495
Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser
500 505 510
Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser
515 520 525
Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro
530 535 540
Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro
545 550 555 560
Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser
565 570 575
Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg
580 585 590
Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu
595 600 605
His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser
610 615 620
Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg
625 630 635 640
Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys
645 650 655
Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala
660 665 670
Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro
675 680 685
Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly
690 695 700
Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His
705 710 715 720
Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu
725 730 735
Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro
740 745 750
Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg
755 760 765
Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys
770 775 780
Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His
785 790 795 800
Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met
805 810 815
Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro
820 825 830
Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser
835 840 845
Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr
850 855 860
Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser
865 870 875 880
Ala Ser Asn His Pro Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln
885 890 895
Gly Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp
900 905 910
Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His His His His His
915 920 925
His
<210> 50
<211> 821
<212> PRT
<213> 人工序列
<220>
<223> pEX-1中的Δ745-960
<400> 50
Met Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu
1 5 10 15
Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly
20 25 30
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
35 40 45
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
50 55 60
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
65 70 75 80
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
85 90 95
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
100 105 110
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
115 120 125
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
130 135 140
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
145 150 155 160
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
165 170 175
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
180 185 190
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
195 200 205
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
210 215 220
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
225 230 235 240
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
245 250 255
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
260 265 270
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
275 280 285
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
290 295 300
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
305 310 315 320
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
325 330 335
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu
340 345 350
Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu
355 360 365
Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val
370 375 380
Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu
385 390 395 400
Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr
405 410 415
Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn
420 425 430
Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr
435 440 445
Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr
450 455 460
Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe
465 470 475 480
Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys
485 490 495
Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser
500 505 510
Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser
515 520 525
Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro
530 535 540
Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro
545 550 555 560
Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser
565 570 575
Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg
580 585 590
Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu
595 600 605
His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser
610 615 620
Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg
625 630 635 640
Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys
645 650 655
Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala
660 665 670
Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro
675 680 685
Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly
690 695 700
Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His
705 710 715 720
Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu
725 730 735
Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro
740 745 750
Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg
755 760 765
Val Ser Ser Leu Pro Ser Glu Ser Ser Gly Gly Gly Gly Ser Glu Asn
770 775 780
Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp
785 790 795 800
His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His
805 810 815
His His His His His
820
<210> 51
<211> 713
<212> PRT
<213> 人工序列
<220>
<223> pEX-1中的Δ637-960
<400> 51
Met Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu
1 5 10 15
Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly
20 25 30
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
35 40 45
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
50 55 60
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
65 70 75 80
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
85 90 95
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
100 105 110
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
115 120 125
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
130 135 140
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
145 150 155 160
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
165 170 175
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
180 185 190
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
195 200 205
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
210 215 220
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
225 230 235 240
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
245 250 255
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
260 265 270
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
275 280 285
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
290 295 300
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
305 310 315 320
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
325 330 335
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu
340 345 350
Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu
355 360 365
Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val
370 375 380
Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu
385 390 395 400
Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr
405 410 415
Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn
420 425 430
Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr
435 440 445
Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr
450 455 460
Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe
465 470 475 480
Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys
485 490 495
Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser
500 505 510
Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser
515 520 525
Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro
530 535 540
Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro
545 550 555 560
Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser
565 570 575
Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg
580 585 590
Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu
595 600 605
His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser
610 615 620
Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg
625 630 635 640
Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys
645 650 655
Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Gly Gly Gly
660 665 670
Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp Gly
675 680 685
Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp
690 695 700
Gly Ala Pro His His His His His His
705 710
<210> 52
<211> 605
<212> PRT
<213> 人工序列
<220>
<223> pEX-1中的Δ529-960
<400> 52
Met Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu
1 5 10 15
Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly
20 25 30
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
35 40 45
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
50 55 60
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
65 70 75 80
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
85 90 95
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
100 105 110
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
115 120 125
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
130 135 140
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
145 150 155 160
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
165 170 175
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
180 185 190
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
195 200 205
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
210 215 220
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
225 230 235 240
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
245 250 255
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
260 265 270
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
275 280 285
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
290 295 300
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
305 310 315 320
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
325 330 335
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu
340 345 350
Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu
355 360 365
Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val
370 375 380
Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu
385 390 395 400
Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr
405 410 415
Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn
420 425 430
Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr
435 440 445
Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr
450 455 460
Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe
465 470 475 480
Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys
485 490 495
Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser
500 505 510
Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser
515 520 525
Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro
530 535 540
Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro
545 550 555 560
Thr Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys
565 570 575
Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp
580 585 590
Asp Asp Lys Asp Gly Ala Pro His His His His His His
595 600 605
<210> 53
<211> 497
<212> PRT
<213> 人工序列
<220>
<223> pEX-1中的Δ421-960
<400> 53
Met Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu
1 5 10 15
Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly
20 25 30
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
35 40 45
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
50 55 60
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
65 70 75 80
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
85 90 95
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
100 105 110
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
115 120 125
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
130 135 140
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
145 150 155 160
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
165 170 175
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
180 185 190
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
195 200 205
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
210 215 220
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
225 230 235 240
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
245 250 255
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
260 265 270
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
275 280 285
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
290 295 300
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
305 310 315 320
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
325 330 335
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu
340 345 350
Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu
355 360 365
Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val
370 375 380
Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu
385 390 395 400
Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr
405 410 415
Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn
420 425 430
Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr
435 440 445
Glu Phe Asp Phe Asn Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln
450 455 460
Gly Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp
465 470 475 480
Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His His His His His
485 490 495
His
<210> 54
<211> 391
<212> PRT
<213> 人工序列
<220>
<223> pEX-1中的Δ315-960
<400> 54
Met Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu
1 5 10 15
Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly
20 25 30
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
35 40 45
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
50 55 60
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
65 70 75 80
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
85 90 95
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
100 105 110
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
115 120 125
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
130 135 140
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
145 150 155 160
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
165 170 175
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
180 185 190
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
195 200 205
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
210 215 220
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
225 230 235 240
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
245 250 255
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
260 265 270
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
275 280 285
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
290 295 300
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
305 310 315 320
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
325 330 335
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Gly Gly Gly Gly Ser
340 345 350
Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp Gly Asp Tyr
355 360 365
Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala
370 375 380
Pro His His His His His His
385 390
<210> 55
<211> 931
<212> PRT
<213> 人工序列
<220>
<223> pEX-1中的Δ315-420
<400> 55
Met Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu
1 5 10 15
Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly
20 25 30
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
35 40 45
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
50 55 60
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
65 70 75 80
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
85 90 95
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
100 105 110
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
115 120 125
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
130 135 140
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
145 150 155 160
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
165 170 175
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
180 185 190
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
195 200 205
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
210 215 220
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
225 230 235 240
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
245 250 255
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
260 265 270
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
275 280 285
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
290 295 300
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
305 310 315 320
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
325 330 335
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Ile Asp Pro Lys Pro
340 345 350
Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln
355 360 365
Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln Ser Lys Ala Gly Thr
370 375 380
Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser Tyr Ile Asp Thr Ile
385 390 395 400
Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr Lys Ala Lys Ser His
405 410 415
Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Asn Leu Ser Glu Ala Arg
420 425 430
Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys
435 440 445
Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro Thr Arg His Ser Asp
450 455 460
Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly
465 470 475 480
Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His Ser Lys Thr Met Glu
485 490 495
Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser His Ser His Ser Leu
500 505 510
Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro
515 520 525
Phe Ser Ser Gln Gln Arg Pro His Arg His Ser Met Tyr Val Thr Arg
530 535 540
Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln
545 550 555 560
Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro
565 570 575
Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala Arg Ser Ser Val Lys
580 585 590
Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His Thr Arg Gln Lys Ser
595 600 605
Glu Gly Gly Val Tyr His Asp Pro His Ser Asp Asp Gly Thr Ala Pro
610 615 620
Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val Pro Arg Arg Val Gly
625 630 635 640
Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp Asn Ser Phe His Glu
645 650 655
Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro Ser Glu Ser Ser Ser
660 665 670
Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser
675 680 685
Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln
690 695 700
Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys Lys Ser Gln Thr Val
705 710 715 720
Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu Gln Lys Ser Ile His
725 730 735
Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys
740 745 750
Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys
755 760 765
Leu Leu His Leu Ser Ser Ala Ser Asn His Pro Ala Ser Ser Asp Pro
770 775 780
Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu
785 790 795 800
Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile
805 810 815
Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly
820 825 830
Gln Met Asp Pro Gly Trp His Val Ser Ser Val Thr Arg Ser Ala Thr
835 840 845
Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn
850 855 860
Gly His Pro Tyr Asn Arg Thr Asn Arg Ser Arg Met Pro Asn Leu Asn
865 870 875 880
Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr
885 890 895
Phe Gln Gly Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp
900 905 910
Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His His His
915 920 925
His His His
930
<210> 56
<211> 823
<212> PRT
<213> 人工序列
<220>
<223> pEX-1中的Δ315-528
<400> 56
Met Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu
1 5 10 15
Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly
20 25 30
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
35 40 45
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
50 55 60
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
65 70 75 80
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
85 90 95
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
100 105 110
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
115 120 125
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
130 135 140
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
145 150 155 160
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
165 170 175
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
180 185 190
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
195 200 205
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
210 215 220
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
225 230 235 240
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
245 250 255
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
260 265 270
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
275 280 285
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
290 295 300
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
305 310 315 320
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
325 330 335
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Ser Pro Thr Pro Thr
340 345 350
Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn Asn
355 360 365
Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His Ser
370 375 380
Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser His
385 390 395 400
Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu Gly
405 410 415
Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser Met
420 425 430
Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser Leu
435 440 445
Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu Leu
450 455 460
Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala Arg
465 470 475 480
Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His Thr
485 490 495
Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp Asp
500 505 510
Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val Pro
515 520 525
Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp Asn
530 535 540
Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro Ser
545 550 555 560
Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe Asp
565 570 575
Pro Trp Lys Ser Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys Glu
580 585 590
Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys Lys
595 600 605
Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu Gln
610 615 620
Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu Trp
625 630 635 640
Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu Lys
645 650 655
Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro Ala
660 665 670
Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys Asn
675 680 685
Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly Gly
690 695 700
Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala Leu
705 710 715 720
Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val Thr
725 730 735
Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala Lys
740 745 750
Ser Gly Pro Asn Gly His Pro Tyr Asn Arg Thr Asn Arg Ser Arg Met
755 760 765
Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly Gly Ser
770 775 780
Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp Gly Asp Tyr
785 790 795 800
Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala
805 810 815
Pro His His His His His His
820
<210> 57
<211> 715
<212> PRT
<213> 人工序列
<220>
<223> pEX-1中的Δ315-636
<400> 57
Met Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu
1 5 10 15
Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly
20 25 30
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
35 40 45
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
50 55 60
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
65 70 75 80
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
85 90 95
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
100 105 110
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
115 120 125
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
130 135 140
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
145 150 155 160
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
165 170 175
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
180 185 190
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
195 200 205
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
210 215 220
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
225 230 235 240
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
245 250 255
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
260 265 270
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
275 280 285
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
290 295 300
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
305 310 315 320
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
325 330 335
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Ala Arg Ala Asn Ser
340 345 350
Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met
355 360 365
Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser
370 375 380
Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro
385 390 395 400
His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn
405 410 415
Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro
420 425 430
Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser
435 440 445
Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln
450 455 460
Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His Ser Glu
465 470 475 480
Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys
485 490 495
Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu
500 505 510
Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg
515 520 525
Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser
530 535 540
Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser
545 550 555 560
Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln
565 570 575
Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln
580 585 590
Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly
595 600 605
Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val
610 615 620
Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln
625 630 635 640
Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg Thr Asn
645 650 655
Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly
660 665 670
Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His
675 680 685
Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
690 695 700
Lys Asp Gly Ala Pro His His His His His His
705 710 715
<210> 58
<211> 607
<212> PRT
<213> 人工序列
<220>
<223> pEX-1中的Δ315-744
<400> 58
Met Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu
1 5 10 15
Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly
20 25 30
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
35 40 45
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
50 55 60
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
65 70 75 80
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
85 90 95
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
100 105 110
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
115 120 125
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
130 135 140
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
145 150 155 160
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
165 170 175
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
180 185 190
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
195 200 205
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
210 215 220
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
225 230 235 240
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
245 250 255
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
260 265 270
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
275 280 285
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
290 295 300
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
305 310 315 320
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
325 330 335
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Ser Gly Thr Asn His
340 345 350
Ser Lys Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile
355 360 365
Ser His Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg
370 375 380
Ser Met Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp
385 390 395 400
Ser Pro Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr
405 410 415
Pro Ser Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu
420 425 430
Gln Thr Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu
435 440 445
Ser Ser Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro
450 455 460
Leu Thr Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His
465 470 475 480
Pro Leu Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro
485 490 495
Ala Pro Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro
500 505 510
Gly Trp His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser
515 520 525
Tyr Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr
530 535 540
Asn Arg Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu
545 550 555 560
Thr Ala Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp
565 570 575
Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys
580 585 590
Asp Asp Asp Asp Lys Asp Gly Ala Pro His His His His His His
595 600 605
<210> 59
<211> 499
<212> PRT
<213> 人工序列
<220>
<223> pEX-1中的Δ315-852
<400> 59
Met Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu
1 5 10 15
Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly
20 25 30
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
35 40 45
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
50 55 60
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
65 70 75 80
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
85 90 95
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
100 105 110
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
115 120 125
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
130 135 140
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
145 150 155 160
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
165 170 175
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
180 185 190
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
195 200 205
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
210 215 220
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
225 230 235 240
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
245 250 255
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
260 265 270
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
275 280 285
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
290 295 300
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
305 310 315 320
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
325 330 335
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Ala Ser Ser Asp Pro
340 345 350
Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu
355 360 365
Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile
370 375 380
Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly
385 390 395 400
Gln Met Asp Pro Gly Trp His Val Ser Ser Val Thr Arg Ser Ala Thr
405 410 415
Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn
420 425 430
Gly His Pro Tyr Asn Arg Thr Asn Arg Ser Arg Met Pro Asn Leu Asn
435 440 445
Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr
450 455 460
Phe Gln Gly Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp
465 470 475 480
Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His His His
485 490 495
His His His
<210> 60
<211> 1037
<212> PRT
<213> 人工序列
<220>
<223> pEX-1中的TT28p_107_3xFlagHis_大肠杆菌-opt
<400> 60
Met Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu
1 5 10 15
Ala Ala Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Gly Gly Gly
20 25 30
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
35 40 45
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
50 55 60
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
65 70 75 80
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
85 90 95
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
100 105 110
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
115 120 125
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
130 135 140
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
145 150 155 160
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
165 170 175
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
180 185 190
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
195 200 205
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
210 215 220
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
225 230 235 240
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
245 250 255
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
260 265 270
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
275 280 285
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
290 295 300
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
305 310 315 320
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
325 330 335
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu
340 345 350
Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu
355 360 365
Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val
370 375 380
Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu
385 390 395 400
Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr
405 410 415
Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn
420 425 430
Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr
435 440 445
Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr
450 455 460
Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe
465 470 475 480
Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys
485 490 495
Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser
500 505 510
Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser
515 520 525
Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro
530 535 540
Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro
545 550 555 560
Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser
565 570 575
Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg
580 585 590
Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu
595 600 605
His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser
610 615 620
Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg
625 630 635 640
Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys
645 650 655
Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala
660 665 670
Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro
675 680 685
Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly
690 695 700
Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His
705 710 715 720
Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu
725 730 735
Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro
740 745 750
Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg
755 760 765
Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys
770 775 780
Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His
785 790 795 800
Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met
805 810 815
Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro
820 825 830
Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser
835 840 845
Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr
850 855 860
Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser
865 870 875 880
Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr
885 890 895
Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu
900 905 910
Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro
915 920 925
Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp
930 935 940
His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser
945 950 955 960
Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg
965 970 975
Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala
980 985 990
Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys
995 1000 1005
Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp
1010 1015 1020
Asp Asp Asp Lys Asp Gly Ala Pro His His His His His His
1025 1030 1035
<210> 61
<211> 316
<212> PRT
<213> 人工序列
<220>
<223> pEX-1中的Tκ28p_eGFP_大肠杆菌-opt_3xFlagHis
<400> 61
Met Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu
1 5 10 15
Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly
20 25 30
Gly Ser Val Ser Lys Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile
35 40 45
Leu Val Glu Leu Asp Gly Asp Val Asn Gly His Lys Phe Ser Val Ser
50 55 60
Gly Glu Gly Glu Gly Asp Ala Thr Tyr Gly Lys Leu Thr Leu Lys Phe
65 70 75 80
Ile Cys Thr Thr Gly Lys Leu Pro Val Pro Trp Pro Thr Leu Val Thr
85 90 95
Thr Leu Thr Tyr Gly Val Gln Cys Phe Ser Arg Tyr Pro Asp His Met
100 105 110
Lys Gln His Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Val Gln
115 120 125
Glu Arg Thr Ile Phe Phe Lys Asp Asp Gly Asn Tyr Lys Thr Arg Ala
130 135 140
Glu Val Lys Phe Glu Gly Asp Thr Leu Val Asn Arg Ile Glu Leu Lys
145 150 155 160
Gly Ile Asp Phe Lys Glu Asp Gly Asn Ile Leu Gly His Lys Leu Glu
165 170 175
Tyr Asn Tyr Asn Ser His Asn Val Tyr Ile Met Ala Asp Lys Gln Lys
180 185 190
Asn Gly Ile Lys Val Asn Phe Lys Ile Arg His Asn Ile Glu Asp Gly
195 200 205
Ser Val Gln Leu Ala Asp His Tyr Gln Gln Asn Thr Pro Ile Gly Asp
210 215 220
Gly Pro Val Leu Leu Pro Asp Asn His Tyr Leu Ser Thr Gln Ser Ala
225 230 235 240
Leu Ser Lys Asp Pro Asn Glu Lys Arg Asp His Met Val Leu Leu Glu
245 250 255
Phe Val Thr Ala Ala Gly Ile Thr Leu Gly Met Asp Glu Leu Tyr Lys
260 265 270
Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp
275 280 285
His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp
290 295 300
Asp Lys Asp Gly Ala Pro His His His His His His
305 310 315
<210> 62
<211> 283
<212> PRT
<213> 人工序列
<220>
<223> pEX-1中的eGFP_3xFlagHis_大肠杆菌-opt
<400> 62
Met Val Ser Lys Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile Leu
1 5 10 15
Val Glu Leu Asp Gly Asp Val Asn Gly His Lys Phe Ser Val Ser Gly
20 25 30
Glu Gly Glu Gly Asp Ala Thr Tyr Gly Lys Leu Thr Leu Lys Phe Ile
35 40 45
Cys Thr Thr Gly Lys Leu Pro Val Pro Trp Pro Thr Leu Val Thr Thr
50 55 60
Leu Thr Tyr Gly Val Gln Cys Phe Ser Arg Tyr Pro Asp His Met Lys
65 70 75 80
Gln His Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Val Gln Glu
85 90 95
Arg Thr Ile Phe Phe Lys Asp Asp Gly Asn Tyr Lys Thr Arg Ala Glu
100 105 110
Val Lys Phe Glu Gly Asp Thr Leu Val Asn Arg Ile Glu Leu Lys Gly
115 120 125
Ile Asp Phe Lys Glu Asp Gly Asn Ile Leu Gly His Lys Leu Glu Tyr
130 135 140
Asn Tyr Asn Ser His Asn Val Tyr Ile Met Ala Asp Lys Gln Lys Asn
145 150 155 160
Gly Ile Lys Val Asn Phe Lys Ile Arg His Asn Ile Glu Asp Gly Ser
165 170 175
Val Gln Leu Ala Asp His Tyr Gln Gln Asn Thr Pro Ile Gly Asp Gly
180 185 190
Pro Val Leu Leu Pro Asp Asn His Tyr Leu Ser Thr Gln Ser Ala Leu
195 200 205
Ser Lys Asp Pro Asn Glu Lys Arg Asp His Met Val Leu Leu Glu Phe
210 215 220
Val Thr Ala Ala Gly Ile Thr Leu Gly Met Asp Glu Leu Tyr Lys Gly
225 230 235 240
Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His
245 250 255
Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
260 265 270
Lys Asp Gly Ala Pro His His His His His His
275 280
<210> 63
<211> 739
<212> PRT
<213> 人工序列
<220>
<223> pEX-1中的AMPH1-3xFlagHis (大肠杆菌-opt)
<400> 63
Met Ala Asp Ile Lys Thr Gly Ile Phe Ala Lys Asn Val Gln Lys Arg
1 5 10 15
Leu Asn Arg Ala Gln Glu Lys Val Leu Gln Lys Leu Gly Lys Ala Asp
20 25 30
Glu Thr Lys Asp Glu Gln Phe Glu Glu Tyr Val Gln Asn Phe Lys Arg
35 40 45
Gln Glu Ala Glu Gly Thr Arg Leu Gln Arg Glu Leu Arg Gly Tyr Leu
50 55 60
Ala Ala Ile Lys Gly Met Gln Glu Ala Ser Met Lys Leu Thr Glu Ser
65 70 75 80
Leu His Glu Val Tyr Glu Pro Asp Trp Tyr Gly Arg Glu Asp Val Lys
85 90 95
Met Val Gly Glu Lys Cys Asp Val Leu Trp Glu Asp Phe His Gln Lys
100 105 110
Leu Val Asp Gly Ser Leu Leu Thr Leu Asp Thr Tyr Leu Gly Gln Phe
115 120 125
Pro Asp Ile Lys Asn Arg Ile Ala Lys Arg Ser Arg Lys Leu Val Asp
130 135 140
Tyr Asp Ser Ala Arg His His Leu Glu Ala Leu Gln Ser Ser Lys Arg
145 150 155 160
Lys Asp Glu Ser Arg Ile Ser Lys Ala Glu Glu Glu Phe Gln Lys Ala
165 170 175
Gln Lys Val Phe Glu Glu Phe Asn Val Asp Leu Gln Glu Glu Leu Pro
180 185 190
Ser Leu Trp Ser Arg Arg Val Gly Phe Tyr Val Asn Thr Phe Lys Asn
195 200 205
Val Ser Ser Leu Glu Ala Lys Phe His Lys Glu Ile Ala Val Leu Cys
210 215 220
His Lys Leu Tyr Glu Val Met Thr Lys Leu Gly Asp Gln His Ala Asp
225 230 235 240
Lys Ala Phe Thr Ile Gln Gly Ala Pro Ser Asp Ser Gly Pro Leu Arg
245 250 255
Ile Ala Lys Thr Pro Ser Pro Pro Glu Glu Pro Ser Pro Leu Pro Ser
260 265 270
Pro Thr Ala Ser Pro Asn His Thr Leu Ala Pro Ala Ser Pro Ala Pro
275 280 285
Ala Arg Pro Arg Ser Pro Ser Gln Thr Arg Lys Gly Pro Pro Val Pro
290 295 300
Pro Leu Pro Lys Val Thr Pro Thr Lys Glu Leu Gln Gln Glu Asn Ile
305 310 315 320
Ile Ser Phe Phe Glu Asp Asn Phe Val Pro Glu Ile Ser Val Thr Thr
325 330 335
Pro Ser Gln Asn Glu Val Pro Glu Val Lys Lys Glu Glu Thr Leu Leu
340 345 350
Asp Leu Asp Phe Asp Pro Phe Lys Pro Glu Val Thr Pro Ala Gly Ser
355 360 365
Ala Gly Val Thr His Ser Pro Met Ser Gln Thr Leu Pro Trp Asp Leu
370 375 380
Trp Thr Thr Ser Thr Asp Leu Val Gln Pro Ala Ser Gly Gly Ser Phe
385 390 395 400
Asn Gly Phe Thr Gln Pro Gln Asp Thr Ser Leu Phe Thr Met Gln Thr
405 410 415
Asp Gln Ser Met Ile Cys Asn Leu Ala Glu Ser Glu Gln Ala Pro Pro
420 425 430
Thr Glu Pro Lys Ala Glu Glu Pro Leu Ala Ala Val Thr Pro Ala Val
435 440 445
Gly Leu Asp Leu Gly Met Asp Thr Arg Ala Glu Glu Pro Val Glu Glu
450 455 460
Ala Val Ile Ile Pro Gly Ala Asp Ala Asp Ala Ala Val Gly Thr Leu
465 470 475 480
Val Ser Ala Ala Glu Gly Ala Pro Gly Glu Glu Ala Glu Ala Glu Lys
485 490 495
Ala Thr Val Pro Ala Gly Glu Gly Val Ser Leu Glu Glu Ala Lys Ile
500 505 510
Gly Thr Glu Thr Thr Glu Gly Ala Glu Ser Ala Gln Pro Glu Ala Glu
515 520 525
Glu Leu Glu Ala Thr Val Pro Gln Glu Lys Val Ile Pro Ser Val Val
530 535 540
Ile Glu Pro Ala Ser Asn His Glu Glu Glu Gly Glu Asn Glu Ile Thr
545 550 555 560
Ile Gly Ala Glu Pro Lys Glu Thr Thr Glu Asp Ala Ala Pro Pro Gly
565 570 575
Pro Thr Ser Glu Thr Pro Glu Leu Ala Thr Glu Gln Lys Pro Ile Gln
580 585 590
Asp Pro Gln Pro Thr Pro Ser Ala Pro Ala Met Gly Ala Ala Asp Gln
595 600 605
Leu Ala Ser Ala Arg Glu Ala Ser Gln Glu Leu Pro Pro Gly Phe Leu
610 615 620
Tyr Lys Val Glu Thr Leu His Asp Phe Glu Ala Ala Asn Ser Asp Glu
625 630 635 640
Leu Thr Leu Gln Arg Gly Asp Val Val Leu Val Val Pro Ser Asp Ser
645 650 655
Glu Ala Asp Gln Asp Ala Gly Trp Leu Val Gly Val Lys Glu Ser Asp
660 665 670
Trp Leu Gln Tyr Arg Asp Leu Ala Thr Tyr Lys Gly Leu Phe Pro Glu
675 680 685
Asn Phe Thr Arg Arg Leu Asp Glu Asn Leu Tyr Phe Gln Gly Gly Gly
690 695 700
Gly Gly Ser Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp
705 710 715 720
Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His His His
725 730 735
His His His
<210> 64
<211> 739
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的AMPH1-3xFlagHis cho-opt
<400> 64
Met Ala Asp Ile Lys Thr Gly Ile Phe Ala Lys Asn Val Gln Lys Arg
1 5 10 15
Leu Asn Arg Ala Gln Glu Lys Val Leu Gln Lys Leu Gly Lys Ala Asp
20 25 30
Glu Thr Lys Asp Glu Gln Phe Glu Glu Tyr Val Gln Asn Phe Lys Arg
35 40 45
Gln Glu Ala Glu Gly Thr Arg Leu Gln Arg Glu Leu Arg Gly Tyr Leu
50 55 60
Ala Ala Ile Lys Gly Met Gln Glu Ala Ser Met Lys Leu Thr Glu Ser
65 70 75 80
Leu His Glu Val Tyr Glu Pro Asp Trp Tyr Gly Arg Glu Asp Val Lys
85 90 95
Met Val Gly Glu Lys Cys Asp Val Leu Trp Glu Asp Phe His Gln Lys
100 105 110
Leu Val Asp Gly Ser Leu Leu Thr Leu Asp Thr Tyr Leu Gly Gln Phe
115 120 125
Pro Asp Ile Lys Asn Arg Ile Ala Lys Arg Ser Arg Lys Leu Val Asp
130 135 140
Tyr Asp Ser Ala Arg His His Leu Glu Ala Leu Gln Ser Ser Lys Arg
145 150 155 160
Lys Asp Glu Ser Arg Ile Ser Lys Ala Glu Glu Glu Phe Gln Lys Ala
165 170 175
Gln Lys Val Phe Glu Glu Phe Asn Val Asp Leu Gln Glu Glu Leu Pro
180 185 190
Ser Leu Trp Ser Arg Arg Val Gly Phe Tyr Val Asn Thr Phe Lys Asn
195 200 205
Val Ser Ser Leu Glu Ala Lys Phe His Lys Glu Ile Ala Val Leu Cys
210 215 220
His Lys Leu Tyr Glu Val Met Thr Lys Leu Gly Asp Gln His Ala Asp
225 230 235 240
Lys Ala Phe Thr Ile Gln Gly Ala Pro Ser Asp Ser Gly Pro Leu Arg
245 250 255
Ile Ala Lys Thr Pro Ser Pro Pro Glu Glu Pro Ser Pro Leu Pro Ser
260 265 270
Pro Thr Ala Ser Pro Asn His Thr Leu Ala Pro Ala Ser Pro Ala Pro
275 280 285
Ala Arg Pro Arg Ser Pro Ser Gln Thr Arg Lys Gly Pro Pro Val Pro
290 295 300
Pro Leu Pro Lys Val Thr Pro Thr Lys Glu Leu Gln Gln Glu Asn Ile
305 310 315 320
Ile Ser Phe Phe Glu Asp Asn Phe Val Pro Glu Ile Ser Val Thr Thr
325 330 335
Pro Ser Gln Asn Glu Val Pro Glu Val Lys Lys Glu Glu Thr Leu Leu
340 345 350
Asp Leu Asp Phe Asp Pro Phe Lys Pro Glu Val Thr Pro Ala Gly Ser
355 360 365
Ala Gly Val Thr His Ser Pro Met Ser Gln Thr Leu Pro Trp Asp Leu
370 375 380
Trp Thr Thr Ser Thr Asp Leu Val Gln Pro Ala Ser Gly Gly Ser Phe
385 390 395 400
Asn Gly Phe Thr Gln Pro Gln Asp Thr Ser Leu Phe Thr Met Gln Thr
405 410 415
Asp Gln Ser Met Ile Cys Asn Leu Ala Glu Ser Glu Gln Ala Pro Pro
420 425 430
Thr Glu Pro Lys Ala Glu Glu Pro Leu Ala Ala Val Thr Pro Ala Val
435 440 445
Gly Leu Asp Leu Gly Met Asp Thr Arg Ala Glu Glu Pro Val Glu Glu
450 455 460
Ala Val Ile Ile Pro Gly Ala Asp Ala Asp Ala Ala Val Gly Thr Leu
465 470 475 480
Val Ser Ala Ala Glu Gly Ala Pro Gly Glu Glu Ala Glu Ala Glu Lys
485 490 495
Ala Thr Val Pro Ala Gly Glu Gly Val Ser Leu Glu Glu Ala Lys Ile
500 505 510
Gly Thr Glu Thr Thr Glu Gly Ala Glu Ser Ala Gln Pro Glu Ala Glu
515 520 525
Glu Leu Glu Ala Thr Val Pro Gln Glu Lys Val Ile Pro Ser Val Val
530 535 540
Ile Glu Pro Ala Ser Asn His Glu Glu Glu Gly Glu Asn Glu Ile Thr
545 550 555 560
Ile Gly Ala Glu Pro Lys Glu Thr Thr Glu Asp Ala Ala Pro Pro Gly
565 570 575
Pro Thr Ser Glu Thr Pro Glu Leu Ala Thr Glu Gln Lys Pro Ile Gln
580 585 590
Asp Pro Gln Pro Thr Pro Ser Ala Pro Ala Met Gly Ala Ala Asp Gln
595 600 605
Leu Ala Ser Ala Arg Glu Ala Ser Gln Glu Leu Pro Pro Gly Phe Leu
610 615 620
Tyr Lys Val Glu Thr Leu His Asp Phe Glu Ala Ala Asn Ser Asp Glu
625 630 635 640
Leu Thr Leu Gln Arg Gly Asp Val Val Leu Val Val Pro Ser Asp Ser
645 650 655
Glu Ala Asp Gln Asp Ala Gly Trp Leu Val Gly Val Lys Glu Ser Asp
660 665 670
Trp Leu Gln Tyr Arg Asp Leu Ala Thr Tyr Lys Gly Leu Phe Pro Glu
675 680 685
Asn Phe Thr Arg Arg Leu Asp Glu Asn Leu Tyr Phe Gln Gly Gly Gly
690 695 700
Gly Gly Ser Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp
705 710 715 720
Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His His His
725 730 735
His His His
<210> 65
<211> 1048
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的MBip_TATκ11_107_3xFlagHis_cho-opt
<400> 65
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala Gly Tyr Ala Arg
20 25 30
Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro
35 40 45
Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly
50 55 60
Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His
65 70 75 80
Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu
85 90 95
Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys
100 105 110
Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys
115 120 125
Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu
130 135 140
Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile
145 150 155 160
Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val
165 170 175
His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val
180 185 190
Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn
195 200 205
Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro
210 215 220
Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser
225 230 235 240
Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro
245 250 255
Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly
260 265 270
Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe
275 280 285
His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg
290 295 300
Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn
305 310 315 320
Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu
325 330 335
Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser
340 345 350
Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser
355 360 365
Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg
370 375 380
Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly Leu Pro Arg Ala
385 390 395 400
Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala
405 410 415
Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser
420 425 430
Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His
435 440 445
Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn
450 455 460
Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser
465 470 475 480
Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln
485 490 495
Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser
500 505 510
Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr
515 520 525
Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Asn
530 535 540
Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr
545 550 555 560
Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro
565 570 575
Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn
580 585 590
Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His
595 600 605
Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser
610 615 620
His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu
625 630 635 640
Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser
645 650 655
Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser
660 665 670
Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu
675 680 685
Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala
690 695 700
Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His
705 710 715 720
Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp
725 730 735
Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val
740 745 750
Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp
755 760 765
Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro
770 775 780
Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe
785 790 795 800
Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys
805 810 815
Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys
820 825 830
Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu
835 840 845
Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
850 855 860
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
865 870 875 880
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro
885 890 895
Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys
900 905 910
Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly
915 920 925
Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala
930 935 940
Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val
945 950 955 960
Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala
965 970 975
Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg Thr Asn Arg Ser Arg
980 985 990
Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly Gly
995 1000 1005
Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp Gly
1010 1015 1020
Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys
1025 1030 1035
Asp Gly Ala Pro His His His His His His
1040 1045
<210> 66
<211> 1040
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的Igκ_TATκ11_107_3xFlagHis_cho-opt
<400> 66
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Gly Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala
20 25 30
Gly Gly Gly Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys
35 40 45
Phe Glu Ile Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu
50 55 60
Lys Cys Arg His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe
65 70 75 80
Lys Asp Ser Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu
85 90 95
Leu Lys Met Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys
100 105 110
Glu Ala Phe Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val
115 120 125
Glu Lys Asn Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro
130 135 140
Pro Glu Lys Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His
145 150 155 160
Trp Cys His Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn
165 170 175
Leu Leu Ile Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe
180 185 190
Ala Arg Asn Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val
195 200 205
Ala Thr Arg Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr
210 215 220
Gly Lys Ser Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu
225 230 235 240
Ser Asp Gly Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu
245 250 255
Phe Thr Ile Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys
260 265 270
Leu Phe Tyr Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val
275 280 285
Asn His Pro Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser
290 295 300
Val Leu Leu Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp
305 310 315 320
Arg Tyr Leu Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln
325 330 335
Arg Leu Leu Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr
340 345 350
His Val Glu Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser
355 360 365
Thr Ala Leu Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn
370 375 380
Leu Ser Val Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu
385 390 395 400
Ser Phe Leu Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His
405 410 415
Thr Lys Thr Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp
420 425 430
Leu Thr Asn Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys
435 440 445
Ser Lys Thr Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly
450 455 460
Pro Gly Thr Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg
465 470 475 480
His Ser Phe Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro
485 490 495
Asn Glu Lys Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser
500 505 510
Ser Arg Ser Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu
515 520 525
Ser Asp Ser Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile
530 535 540
Ala Glu Pro Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu
545 550 555 560
Asn Ser Pro Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr
565 570 575
Leu Leu Ser Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp
580 585 590
Ser Arg Arg Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys
595 600 605
Leu Pro Glu His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro
610 615 620
His Glu Ser Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser
625 630 635 640
Gln Gln Arg Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val
645 650 655
Arg Ala Lys Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala
660 665 670
Ala Arg Ala Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln
675 680 685
Leu Pro Pro Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser
690 695 700
Arg Glu Gly Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly
705 710 715 720
Val Tyr His Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn
725 730 735
Arg His Leu Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr
740 745 750
Arg Val Pro Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val
755 760 765
Ser Thr Arg Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn
770 775 780
His Ser Lys Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn
785 790 795 800
Ile Ser His Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe
805 810 815
Arg Ser Met Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser
820 825 830
Asp Ser Pro Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser
835 840 845
Thr Pro Ser Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp
850 855 860
Leu Gln Thr Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His
865 870 875 880
Leu Ser Ser Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln
885 890 895
Pro Leu Thr Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile
900 905 910
His Pro Leu Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu
915 920 925
Pro Ala Pro Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp
930 935 940
Pro Gly Trp His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro
945 950 955 960
Ser Tyr Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro
965 970 975
Tyr Asn Arg Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys
980 985 990
Glu Thr Ala Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly
995 1000 1005
Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp
1010 1015 1020
Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His His His His
1025 1030 1035
His His
1040
<210> 67
<211> 1021
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的TATκ11_107_3xFlagHis_cho-opt (无前导)
<400> 67
Met Gly Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly
1 5 10 15
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
20 25 30
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
35 40 45
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
50 55 60
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
65 70 75 80
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
85 90 95
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
100 105 110
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
115 120 125
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
130 135 140
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
145 150 155 160
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
165 170 175
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
180 185 190
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
195 200 205
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
210 215 220
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
225 230 235 240
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
245 250 255
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
260 265 270
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
275 280 285
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
290 295 300
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
305 310 315 320
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu
325 330 335
Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu
340 345 350
Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val
355 360 365
Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu
370 375 380
Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr
385 390 395 400
Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn
405 410 415
Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr
420 425 430
Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr
435 440 445
Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe
450 455 460
Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys
465 470 475 480
Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser
485 490 495
Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser
500 505 510
Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro
515 520 525
Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro
530 535 540
Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser
545 550 555 560
Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg
565 570 575
Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu
580 585 590
His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser
595 600 605
Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg
610 615 620
Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys
625 630 635 640
Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala
645 650 655
Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro
660 665 670
Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly
675 680 685
Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His
690 695 700
Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu
705 710 715 720
Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro
725 730 735
Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg
740 745 750
Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys
755 760 765
Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His
770 775 780
Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met
785 790 795 800
Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro
805 810 815
Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser
820 825 830
Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr
835 840 845
Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser
850 855 860
Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr
865 870 875 880
Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu
885 890 895
Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro
900 905 910
Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp
915 920 925
His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser
930 935 940
Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg
945 950 955 960
Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala
965 970 975
Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys
980 985 990
Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp
995 1000 1005
Asp Asp Lys Asp Gly Ala Pro His His His His His His
1010 1015 1020
<210> 68
<211> 1021
<212> PRT
<213> 人工序列
<220>
<223> pEX-1中的TATκ11_107_3xFlagHis_大肠杆菌-opt
<400> 68
Met Gly Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly
1 5 10 15
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
20 25 30
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
35 40 45
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
50 55 60
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
65 70 75 80
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
85 90 95
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
100 105 110
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
115 120 125
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
130 135 140
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
145 150 155 160
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
165 170 175
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
180 185 190
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
195 200 205
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
210 215 220
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
225 230 235 240
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
245 250 255
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
260 265 270
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
275 280 285
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
290 295 300
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
305 310 315 320
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu
325 330 335
Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu
340 345 350
Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val
355 360 365
Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu
370 375 380
Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr
385 390 395 400
Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn
405 410 415
Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr
420 425 430
Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr
435 440 445
Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe
450 455 460
Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys
465 470 475 480
Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser
485 490 495
Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser
500 505 510
Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro
515 520 525
Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro
530 535 540
Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser
545 550 555 560
Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg
565 570 575
Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu
580 585 590
His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser
595 600 605
Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg
610 615 620
Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys
625 630 635 640
Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala
645 650 655
Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro
660 665 670
Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly
675 680 685
Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His
690 695 700
Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu
705 710 715 720
Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro
725 730 735
Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg
740 745 750
Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys
755 760 765
Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His
770 775 780
Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met
785 790 795 800
Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro
805 810 815
Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser
820 825 830
Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr
835 840 845
Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser
850 855 860
Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr
865 870 875 880
Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu
885 890 895
Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro
900 905 910
Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp
915 920 925
His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser
930 935 940
Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg
945 950 955 960
Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala
965 970 975
Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys
980 985 990
Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp
995 1000 1005
Asp Asp Lys Asp Gly Ala Pro His His His His His His
1010 1015 1020
<210> 69
<211> 1021
<212> PRT
<213> 人工序列
<220>
<223> pEX-1中的TAT11_107_3xFlagHis_大肠杆菌-opt
<400> 69
Met Gly Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Gly Gly Gly
1 5 10 15
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
20 25 30
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
35 40 45
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
50 55 60
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
65 70 75 80
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
85 90 95
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
100 105 110
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
115 120 125
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
130 135 140
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
145 150 155 160
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
165 170 175
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
180 185 190
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
195 200 205
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
210 215 220
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
225 230 235 240
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
245 250 255
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
260 265 270
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
275 280 285
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
290 295 300
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
305 310 315 320
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu
325 330 335
Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu
340 345 350
Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val
355 360 365
Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu
370 375 380
Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr
385 390 395 400
Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn
405 410 415
Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr
420 425 430
Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr
435 440 445
Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe
450 455 460
Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys
465 470 475 480
Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser
485 490 495
Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser
500 505 510
Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro
515 520 525
Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro
530 535 540
Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser
545 550 555 560
Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg
565 570 575
Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu
580 585 590
His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser
595 600 605
Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg
610 615 620
Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys
625 630 635 640
Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala
645 650 655
Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro
660 665 670
Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly
675 680 685
Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His
690 695 700
Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu
705 710 715 720
Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro
725 730 735
Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg
740 745 750
Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys
755 760 765
Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His
770 775 780
Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met
785 790 795 800
Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro
805 810 815
Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser
820 825 830
Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr
835 840 845
Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser
850 855 860
Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr
865 870 875 880
Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu
885 890 895
Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro
900 905 910
Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp
915 920 925
His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser
930 935 940
Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg
945 950 955 960
Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala
965 970 975
Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys
980 985 990
Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp
995 1000 1005
Asp Asp Lys Asp Gly Ala Pro His His His His His His
1010 1015 1020
<210> 70
<211> 1021
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的TAT11_107_3xFlagHis_cho-opt (无前导)
<400> 70
Met Gly Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Gly Gly Gly
1 5 10 15
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
20 25 30
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
35 40 45
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
50 55 60
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
65 70 75 80
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
85 90 95
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
100 105 110
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
115 120 125
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
130 135 140
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
145 150 155 160
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
165 170 175
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
180 185 190
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
195 200 205
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
210 215 220
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
225 230 235 240
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
245 250 255
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
260 265 270
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
275 280 285
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
290 295 300
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
305 310 315 320
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu
325 330 335
Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu
340 345 350
Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val
355 360 365
Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu
370 375 380
Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr
385 390 395 400
Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn
405 410 415
Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr
420 425 430
Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr
435 440 445
Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe
450 455 460
Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys
465 470 475 480
Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser
485 490 495
Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser
500 505 510
Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro
515 520 525
Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro
530 535 540
Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser
545 550 555 560
Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg
565 570 575
Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu
580 585 590
His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser
595 600 605
Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg
610 615 620
Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys
625 630 635 640
Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala
645 650 655
Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro
660 665 670
Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly
675 680 685
Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His
690 695 700
Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu
705 710 715 720
Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro
725 730 735
Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg
740 745 750
Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys
755 760 765
Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His
770 775 780
Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met
785 790 795 800
Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro
805 810 815
Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser
820 825 830
Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr
835 840 845
Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser
850 855 860
Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr
865 870 875 880
Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu
885 890 895
Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro
900 905 910
Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp
915 920 925
His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser
930 935 940
Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg
945 950 955 960
Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala
965 970 975
Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys
980 985 990
Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp
995 1000 1005
Asp Asp Lys Asp Gly Ala Pro His His His His His His
1010 1015 1020
<210> 71
<211> 1026
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的ANTP_107_3xFlagHis_cho-opt
<400> 71
Met Gly Arg Gln Ile Lys Ile Trp Phe Gln Asn Arg Arg Met Lys Trp
1 5 10 15
Lys Lys Gly Gly Gly Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met
20 25 30
Asn Lys Phe Glu Ile Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val
35 40 45
Val Leu Lys Cys Arg His Lys Glu Thr His Glu Ile Val Ala Ile Lys
50 55 60
Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu
65 70 75 80
Arg Glu Leu Lys Met Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu
85 90 95
Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu
100 105 110
Tyr Val Glu Lys Asn Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly
115 120 125
Val Pro Pro Glu Lys Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala
130 135 140
Ile His Trp Cys His Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro
145 150 155 160
Glu Asn Leu Leu Ile Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe
165 170 175
Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu
180 185 190
Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala
195 200 205
Pro Tyr Gly Lys Ser Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly
210 215 220
Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp
225 230 235 240
Gln Leu Phe Thr Ile Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln
245 250 255
Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro
260 265 270
Ala Val Asn His Pro Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu
275 280 285
Asn Ser Val Leu Leu Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro
290 295 300
Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln
305 310 315 320
Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys
325 330 335
Pro Tyr His Val Glu Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly
340 345 350
Lys Ser Thr Ala Leu Gln Ser His His Arg Ser Asn Ser Lys Asp Ile
355 360 365
Gln Asn Leu Ser Val Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala
370 375 380
Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro
385 390 395 400
Leu His Thr Lys Thr Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser
405 410 415
Lys Asp Leu Thr Asn Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu
420 425 430
Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser
435 440 445
Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln
450 455 460
Asn Arg His Ser Phe Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu
465 470 475 480
Gln Pro Asn Glu Lys Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro
485 490 495
Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly
500 505 510
Ala Leu Ser Asp Ser Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala
515 520 525
Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu
530 535 540
Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr
545 550 555 560
Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr
565 570 575
Leu Asp Ser Arg Arg Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu
580 585 590
Leu Lys Leu Pro Glu His Met Asp Ser Ser His Ser His Ser Leu Ser
595 600 605
Ala Pro His Glu Ser Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe
610 615 620
Ser Ser Gln Gln Arg Pro His Arg His Ser Met Tyr Val Thr Arg Asp
625 630 635 640
Lys Val Arg Ala Lys Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly
645 650 655
Met Ala Ala Arg Ala Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly
660 665 670
Glu Gln Leu Pro Pro Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu
675 680 685
Thr Ser Arg Glu Gly Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu
690 695 700
Gly Gly Val Tyr His Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys
705 710 715 720
Glu Asn Arg His Leu Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser
725 730 735
Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn
740 745 750
Asn Val Ser Thr Arg Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly
755 760 765
Thr Asn His Ser Lys Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro
770 775 780
Glu Asn Ile Ser His Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly
785 790 795 800
Phe Phe Arg Ser Met Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro
805 810 815
Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser
820 825 830
Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile
835 840 845
Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu
850 855 860
Leu His Leu Ser Ser Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg
865 870 875 880
Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile
885 890 895
Arg Ile His Pro Leu Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg
900 905 910
Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln
915 920 925
Met Asp Pro Gly Trp His Val Ser Ser Val Thr Arg Ser Ala Thr Glu
930 935 940
Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly
945 950 955 960
His Pro Tyr Asn Arg Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp
965 970 975
Leu Lys Glu Thr Ala Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe
980 985 990
Gln Gly Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile
995 1000 1005
Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His His His
1010 1015 1020
His His His
1025
<210> 72
<211> 1031
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的TRANSP_107_3xFlagHis_cho-opt
<400> 72
Met Gly Ala Gly Tyr Leu Leu Gly Lys Ile Asn Leu Lys Ala Leu Ala
1 5 10 15
Ala Leu Ala Lys Lys Ile Leu Gly Gly Gly Gly Ser Lys Ile Pro Asn
20 25 30
Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly Glu
35 40 45
Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His Glu
50 55 60
Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu Val
65 70 75 80
Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys Gln
85 90 95
Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys Leu
100 105 110
Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu Glu
115 120 125
Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile Tyr
130 135 140
Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val His
145 150 155 160
Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val Leu
165 170 175
Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn Asn
180 185 190
Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro Glu
195 200 205
Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser Val
210 215 220
Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro Gly
225 230 235 240
Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly Pro
245 250 255
Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe His
260 265 270
Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg Arg
275 280 285
Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn Leu
290 295 300
Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu Asn
305 310 315 320
His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser Arg
325 330 335
Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser Asn
340 345 350
Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg Ser
355 360 365
Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly Leu Pro Arg Ala Asp
370 375 380
Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala Gly
385 390 395 400
Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser Gln
405 410 415
Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His Leu
420 425 430
Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn Ile
435 440 445
Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser Asn
450 455 460
Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln Ser
465 470 475 480
Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser Tyr
485 490 495
Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr Lys
500 505 510
Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Asn Leu
515 520 525
Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr Phe
530 535 540
Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro Thr
545 550 555 560
Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn Asn
565 570 575
Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His Ser
580 585 590
Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser His
595 600 605
Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu Gly
610 615 620
Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser Met
625 630 635 640
Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser Leu
645 650 655
Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu Leu
660 665 670
Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala Arg
675 680 685
Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His Thr
690 695 700
Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp Asp
705 710 715 720
Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val Pro
725 730 735
Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp Asn
740 745 750
Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro Ser
755 760 765
Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe Asp
770 775 780
Pro Trp Lys Ser Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys Glu
785 790 795 800
Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys Lys
805 810 815
Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu Gln
820 825 830
Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu Trp
835 840 845
Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu Lys
850 855 860
Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro Ala
865 870 875 880
Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys Asn
885 890 895
Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly Gly
900 905 910
Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala Leu
915 920 925
Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val Thr
930 935 940
Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala Lys
945 950 955 960
Ser Gly Pro Asn Gly His Pro Tyr Asn Arg Thr Asn Arg Ser Arg Met
965 970 975
Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly Gly Ser
980 985 990
Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp Gly Asp Tyr
995 1000 1005
Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly
1010 1015 1020
Ala Pro His His His His His His
1025 1030
<210> 73
<211> 1037
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的TAT28_107_3xFlagHis_cho-opt
<400> 73
Met Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu
1 5 10 15
Ala Ala Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Gly Gly Gly
20 25 30
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
35 40 45
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
50 55 60
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
65 70 75 80
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
85 90 95
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
100 105 110
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
115 120 125
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
130 135 140
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
145 150 155 160
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
165 170 175
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
180 185 190
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
195 200 205
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
210 215 220
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
225 230 235 240
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
245 250 255
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
260 265 270
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
275 280 285
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
290 295 300
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
305 310 315 320
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
325 330 335
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu
340 345 350
Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu
355 360 365
Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val
370 375 380
Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu
385 390 395 400
Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr
405 410 415
Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn
420 425 430
Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr
435 440 445
Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr
450 455 460
Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe
465 470 475 480
Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys
485 490 495
Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser
500 505 510
Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser
515 520 525
Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro
530 535 540
Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro
545 550 555 560
Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser
565 570 575
Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg
580 585 590
Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu
595 600 605
His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser
610 615 620
Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg
625 630 635 640
Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys
645 650 655
Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala
660 665 670
Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro
675 680 685
Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly
690 695 700
Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His
705 710 715 720
Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu
725 730 735
Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro
740 745 750
Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg
755 760 765
Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys
770 775 780
Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His
785 790 795 800
Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met
805 810 815
Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro
820 825 830
Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser
835 840 845
Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr
850 855 860
Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser
865 870 875 880
Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr
885 890 895
Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu
900 905 910
Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro
915 920 925
Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp
930 935 940
His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser
945 950 955 960
Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg
965 970 975
Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala
980 985 990
Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys
995 1000 1005
Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp
1010 1015 1020
Asp Asp Asp Lys Asp Gly Ala Pro His His His His His His
1025 1030 1035
<210> 74
<211> 1049
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的MBIP_P97_107_3xFlagHis_cho-opt
<400> 74
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala Gly Asp Ser Ser
20 25 30
His Ala Phe Thr Leu Asp Glu Leu Arg Gly Gly Gly Gly Ser Lys Ile
35 40 45
Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val
50 55 60
Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr
65 70 75 80
His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu
85 90 95
Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu
100 105 110
Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly
115 120 125
Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu
130 135 140
Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr
145 150 155 160
Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile
165 170 175
Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp
180 185 190
Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu Ser Glu Gly
195 200 205
Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser
210 215 220
Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp
225 230 235 240
Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe
245 250 255
Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu
260 265 270
Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg
275 280 285
Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu
290 295 300
Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys
305 310 315 320
Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys
325 330 335
Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro
340 345 350
Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu
355 360 365
Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His
370 375 380
Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly Leu Pro Arg
385 390 395 400
Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu
405 410 415
Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser
420 425 430
Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro
435 440 445
His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe
450 455 460
Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys
465 470 475 480
Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser
485 490 495
Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His
500 505 510
Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg
515 520 525
Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser
530 535 540
Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg
545 550 555 560
Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr
565 570 575
Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg
580 585 590
Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg
595 600 605
His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser
610 615 620
Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly
625 630 635 640
Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His
645 650 655
Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly
660 665 670
Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln
675 680 685
Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val
690 695 700
Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe
705 710 715 720
His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser
725 730 735
Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro
740 745 750
Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro
755 760 765
Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu
770 775 780
Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala
785 790 795 800
Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His Ser Glu Gln Leu
805 810 815
Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys
820 825 830
Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr
835 840 845
Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys
850 855 860
Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro
865 870 875 880
Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His
885 890 895
Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr
900 905 910
Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser
915 920 925
Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro
930 935 940
Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser
945 950 955 960
Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly
965 970 975
Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg Thr Asn Arg Ser
980 985 990
Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly
995 1000 1005
Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp
1010 1015 1020
Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
1025 1030 1035
Lys Asp Gly Ala Pro His His His His His His
1040 1045
<210> 75
<211> 1022
<212> PRT
<213> 人工序列
<220>
<223> pT7CFE1中的P97_107_3xFlagHis_人-opt
<400> 75
Met Gly Asp Ser Ser His Ala Phe Thr Leu Asp Glu Leu Arg Gly Gly
1 5 10 15
Gly Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu
20 25 30
Ile Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys
35 40 45
Arg His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp
50 55 60
Ser Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys
65 70 75 80
Met Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala
85 90 95
Phe Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys
100 105 110
Asn Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu
115 120 125
Lys Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys
130 135 140
His Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu
145 150 155 160
Ile Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg
165 170 175
Asn Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr
180 185 190
Arg Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys
195 200 205
Ser Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp
210 215 220
Gly Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr
225 230 235 240
Ile Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe
245 250 255
Tyr Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His
260 265 270
Pro Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu
275 280 285
Leu Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr
290 295 300
Leu Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu
305 310 315 320
Leu Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val
325 330 335
Glu Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala
340 345 350
Leu Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser
355 360 365
Val Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe
370 375 380
Leu Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys
385 390 395 400
Thr Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr
405 410 415
Asn Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys
420 425 430
Thr Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly
435 440 445
Thr Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser
450 455 460
Phe Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu
465 470 475 480
Lys Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg
485 490 495
Ser Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp
500 505 510
Ser Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu
515 520 525
Pro Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser
530 535 540
Pro Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu
545 550 555 560
Ser Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg
565 570 575
Arg Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro
580 585 590
Glu His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu
595 600 605
Ser Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln
610 615 620
Arg Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala
625 630 635 640
Lys Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg
645 650 655
Ala Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro
660 665 670
Pro Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu
675 680 685
Gly Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr
690 695 700
His Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His
705 710 715 720
Leu Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val
725 730 735
Pro Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr
740 745 750
Arg Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser
755 760 765
Lys Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser
770 775 780
His Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser
785 790 795 800
Met Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser
805 810 815
Pro Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro
820 825 830
Ser Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln
835 840 845
Thr Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser
850 855 860
Ser Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu
865 870 875 880
Thr Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro
885 890 895
Leu Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala
900 905 910
Pro Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly
915 920 925
Trp His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr
930 935 940
Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn
945 950 955 960
Arg Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr
965 970 975
Ala Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr
980 985 990
Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp
995 1000 1005
Asp Asp Asp Lys Asp Gly Ala Pro His His His His His His
1010 1015 1020
<210> 76
<211> 1037
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的Tκ28p_107_3xFlagHis_人-opt
<400> 76
Met Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu
1 5 10 15
Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly
20 25 30
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
35 40 45
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
50 55 60
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
65 70 75 80
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
85 90 95
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
100 105 110
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
115 120 125
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
130 135 140
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
145 150 155 160
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
165 170 175
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
180 185 190
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
195 200 205
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
210 215 220
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
225 230 235 240
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
245 250 255
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
260 265 270
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
275 280 285
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
290 295 300
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
305 310 315 320
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
325 330 335
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu
340 345 350
Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu
355 360 365
Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val
370 375 380
Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu
385 390 395 400
Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr
405 410 415
Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn
420 425 430
Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr
435 440 445
Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr
450 455 460
Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe
465 470 475 480
Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys
485 490 495
Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser
500 505 510
Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser
515 520 525
Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro
530 535 540
Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro
545 550 555 560
Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser
565 570 575
Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg
580 585 590
Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu
595 600 605
His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser
610 615 620
Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg
625 630 635 640
Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys
645 650 655
Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala
660 665 670
Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro
675 680 685
Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly
690 695 700
Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His
705 710 715 720
Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu
725 730 735
Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro
740 745 750
Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg
755 760 765
Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys
770 775 780
Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His
785 790 795 800
Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met
805 810 815
Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro
820 825 830
Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser
835 840 845
Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr
850 855 860
Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser
865 870 875 880
Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr
885 890 895
Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu
900 905 910
Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro
915 920 925
Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp
930 935 940
His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser
945 950 955 960
Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg
965 970 975
Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala
980 985 990
Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys
995 1000 1005
Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp
1010 1015 1020
Asp Asp Asp Lys Asp Gly Ala Pro His His His His His His
1025 1030 1035
<210> 77
<211> 1021
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的TATκ11_107_3xFlagHis_人-opt
<400> 77
Met Gly Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly
1 5 10 15
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
20 25 30
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
35 40 45
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
50 55 60
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
65 70 75 80
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
85 90 95
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
100 105 110
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
115 120 125
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
130 135 140
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
145 150 155 160
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
165 170 175
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
180 185 190
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
195 200 205
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
210 215 220
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
225 230 235 240
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
245 250 255
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
260 265 270
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
275 280 285
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
290 295 300
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
305 310 315 320
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu
325 330 335
Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu
340 345 350
Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val
355 360 365
Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu
370 375 380
Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr
385 390 395 400
Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn
405 410 415
Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr
420 425 430
Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr
435 440 445
Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe
450 455 460
Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys
465 470 475 480
Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser
485 490 495
Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser
500 505 510
Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro
515 520 525
Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro
530 535 540
Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser
545 550 555 560
Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg
565 570 575
Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu
580 585 590
His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser
595 600 605
Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg
610 615 620
Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys
625 630 635 640
Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala
645 650 655
Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro
660 665 670
Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly
675 680 685
Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His
690 695 700
Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu
705 710 715 720
Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro
725 730 735
Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg
740 745 750
Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys
755 760 765
Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His
770 775 780
Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met
785 790 795 800
Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro
805 810 815
Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser
820 825 830
Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr
835 840 845
Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser
850 855 860
Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr
865 870 875 880
Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu
885 890 895
Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro
900 905 910
Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp
915 920 925
His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser
930 935 940
Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg
945 950 955 960
Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala
965 970 975
Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys
980 985 990
Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp
995 1000 1005
Asp Asp Lys Asp Gly Ala Pro His His His His His His
1010 1015 1020
<210> 78
<211> 1037
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的TAT28_107_3xFlagHis_人-opt
<400> 78
Met Gly Asp Ala Ala Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu
1 5 10 15
Ala Ala Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Gly Gly Gly
20 25 30
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
35 40 45
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
50 55 60
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
65 70 75 80
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
85 90 95
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
100 105 110
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
115 120 125
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
130 135 140
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
145 150 155 160
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
165 170 175
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
180 185 190
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
195 200 205
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
210 215 220
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
225 230 235 240
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
245 250 255
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
260 265 270
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
275 280 285
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
290 295 300
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
305 310 315 320
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
325 330 335
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu
340 345 350
Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu
355 360 365
Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val
370 375 380
Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu
385 390 395 400
Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr
405 410 415
Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn
420 425 430
Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr
435 440 445
Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr
450 455 460
Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe
465 470 475 480
Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys
485 490 495
Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser
500 505 510
Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser
515 520 525
Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro
530 535 540
Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro
545 550 555 560
Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser
565 570 575
Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg
580 585 590
Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu
595 600 605
His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser
610 615 620
Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg
625 630 635 640
Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys
645 650 655
Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala
660 665 670
Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro
675 680 685
Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly
690 695 700
Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His
705 710 715 720
Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu
725 730 735
Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro
740 745 750
Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg
755 760 765
Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys
770 775 780
Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His
785 790 795 800
Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met
805 810 815
Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro
820 825 830
Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser
835 840 845
Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr
850 855 860
Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser
865 870 875 880
Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr
885 890 895
Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu
900 905 910
Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro
915 920 925
Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp
930 935 940
His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser
945 950 955 960
Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg
965 970 975
Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala
980 985 990
Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys
995 1000 1005
Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp
1010 1015 1020
Asp Asp Asp Lys Asp Gly Ala Pro His His His His His His
1025 1030 1035
<210> 79
<211> 1021
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的TAT11_107_3xFlagHis_人-opt
<400> 79
Met Gly Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Gly Gly Gly
1 5 10 15
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
20 25 30
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
35 40 45
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
50 55 60
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
65 70 75 80
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
85 90 95
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
100 105 110
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
115 120 125
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
130 135 140
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
145 150 155 160
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
165 170 175
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
180 185 190
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
195 200 205
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
210 215 220
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
225 230 235 240
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
245 250 255
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
260 265 270
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
275 280 285
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
290 295 300
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
305 310 315 320
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu
325 330 335
Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu
340 345 350
Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val
355 360 365
Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu
370 375 380
Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr
385 390 395 400
Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn
405 410 415
Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr
420 425 430
Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr
435 440 445
Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe
450 455 460
Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys
465 470 475 480
Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser
485 490 495
Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser
500 505 510
Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro
515 520 525
Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro
530 535 540
Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser
545 550 555 560
Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg
565 570 575
Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu
580 585 590
His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser
595 600 605
Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg
610 615 620
Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys
625 630 635 640
Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala
645 650 655
Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro
660 665 670
Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly
675 680 685
Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His
690 695 700
Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu
705 710 715 720
Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro
725 730 735
Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg
740 745 750
Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys
755 760 765
Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His
770 775 780
Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met
785 790 795 800
Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro
805 810 815
Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser
820 825 830
Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr
835 840 845
Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser
850 855 860
Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr
865 870 875 880
Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu
885 890 895
Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro
900 905 910
Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp
915 920 925
His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser
930 935 940
Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg
945 950 955 960
Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala
965 970 975
Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys
980 985 990
Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp
995 1000 1005
Asp Asp Lys Asp Gly Ala Pro His His His His His His
1010 1015 1020
<210> 80
<211> 1026
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的ANTP_107_3xFlagHis_人-opt
<400> 80
Met Gly Arg Gln Ile Lys Ile Trp Phe Gln Asn Arg Arg Met Lys Trp
1 5 10 15
Lys Lys Gly Gly Gly Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met
20 25 30
Asn Lys Phe Glu Ile Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val
35 40 45
Val Leu Lys Cys Arg His Lys Glu Thr His Glu Ile Val Ala Ile Lys
50 55 60
Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu
65 70 75 80
Arg Glu Leu Lys Met Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu
85 90 95
Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu
100 105 110
Tyr Val Glu Lys Asn Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly
115 120 125
Val Pro Pro Glu Lys Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala
130 135 140
Ile His Trp Cys His Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro
145 150 155 160
Glu Asn Leu Leu Ile Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe
165 170 175
Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu
180 185 190
Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala
195 200 205
Pro Tyr Gly Lys Ser Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly
210 215 220
Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp
225 230 235 240
Gln Leu Phe Thr Ile Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln
245 250 255
Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro
260 265 270
Ala Val Asn His Pro Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu
275 280 285
Asn Ser Val Leu Leu Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro
290 295 300
Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln
305 310 315 320
Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys
325 330 335
Pro Tyr His Val Glu Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly
340 345 350
Lys Ser Thr Ala Leu Gln Ser His His Arg Ser Asn Ser Lys Asp Ile
355 360 365
Gln Asn Leu Ser Val Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala
370 375 380
Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro
385 390 395 400
Leu His Thr Lys Thr Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser
405 410 415
Lys Asp Leu Thr Asn Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu
420 425 430
Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser
435 440 445
Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln
450 455 460
Asn Arg His Ser Phe Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu
465 470 475 480
Gln Pro Asn Glu Lys Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro
485 490 495
Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly
500 505 510
Ala Leu Ser Asp Ser Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala
515 520 525
Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu
530 535 540
Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr
545 550 555 560
Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr
565 570 575
Leu Asp Ser Arg Arg Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu
580 585 590
Leu Lys Leu Pro Glu His Met Asp Ser Ser His Ser His Ser Leu Ser
595 600 605
Ala Pro His Glu Ser Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe
610 615 620
Ser Ser Gln Gln Arg Pro His Arg His Ser Met Tyr Val Thr Arg Asp
625 630 635 640
Lys Val Arg Ala Lys Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly
645 650 655
Met Ala Ala Arg Ala Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly
660 665 670
Glu Gln Leu Pro Pro Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu
675 680 685
Thr Ser Arg Glu Gly Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu
690 695 700
Gly Gly Val Tyr His Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys
705 710 715 720
Glu Asn Arg His Leu Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser
725 730 735
Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn
740 745 750
Asn Val Ser Thr Arg Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly
755 760 765
Thr Asn His Ser Lys Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro
770 775 780
Glu Asn Ile Ser His Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly
785 790 795 800
Phe Phe Arg Ser Met Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro
805 810 815
Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser
820 825 830
Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile
835 840 845
Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu
850 855 860
Leu His Leu Ser Ser Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg
865 870 875 880
Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile
885 890 895
Arg Ile His Pro Leu Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg
900 905 910
Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln
915 920 925
Met Asp Pro Gly Trp His Val Ser Ser Val Thr Arg Ser Ala Thr Glu
930 935 940
Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly
945 950 955 960
His Pro Tyr Asn Arg Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp
965 970 975
Leu Lys Glu Thr Ala Leu Gly Gly Gly Gly Ser Glu Asn Leu Tyr Phe
980 985 990
Gln Gly Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile
995 1000 1005
Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His His His
1010 1015 1020
His His His
1025
<210> 81
<211> 1031
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的TRANSP_107_3xFlagHis_人-opt
<400> 81
Met Gly Ala Gly Tyr Leu Leu Gly Lys Ile Asn Leu Lys Ala Leu Ala
1 5 10 15
Ala Leu Ala Lys Lys Ile Leu Gly Gly Gly Gly Ser Lys Ile Pro Asn
20 25 30
Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly Glu
35 40 45
Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His Glu
50 55 60
Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu Val
65 70 75 80
Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys Gln
85 90 95
Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys Leu
100 105 110
Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu Glu
115 120 125
Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile Tyr
130 135 140
Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val His
145 150 155 160
Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val Leu
165 170 175
Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn Asn
180 185 190
Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro Glu
195 200 205
Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser Val
210 215 220
Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro Gly
225 230 235 240
Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly Pro
245 250 255
Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe His
260 265 270
Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg Arg
275 280 285
Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn Leu
290 295 300
Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu Asn
305 310 315 320
His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser Arg
325 330 335
Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser Asn
340 345 350
Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg Ser
355 360 365
Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly Leu Pro Arg Ala Asp
370 375 380
Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala Gly
385 390 395 400
Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser Gln
405 410 415
Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His Leu
420 425 430
Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn Ile
435 440 445
Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser Asn
450 455 460
Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln Ser
465 470 475 480
Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser Tyr
485 490 495
Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr Lys
500 505 510
Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Asn Leu
515 520 525
Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr Phe
530 535 540
Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro Thr
545 550 555 560
Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn Asn
565 570 575
Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His Ser
580 585 590
Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser His
595 600 605
Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu Gly
610 615 620
Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser Met
625 630 635 640
Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser Leu
645 650 655
Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu Leu
660 665 670
Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala Arg
675 680 685
Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His Thr
690 695 700
Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp Asp
705 710 715 720
Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val Pro
725 730 735
Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp Asn
740 745 750
Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro Ser
755 760 765
Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe Asp
770 775 780
Pro Trp Lys Ser Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys Glu
785 790 795 800
Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys Lys
805 810 815
Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu Gln
820 825 830
Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu Trp
835 840 845
Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu Lys
850 855 860
Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro Ala
865 870 875 880
Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys Asn
885 890 895
Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly Gly
900 905 910
Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala Leu
915 920 925
Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val Thr
930 935 940
Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala Lys
945 950 955 960
Ser Gly Pro Asn Gly His Pro Tyr Asn Arg Thr Asn Arg Ser Arg Met
965 970 975
Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly Gly Ser
980 985 990
Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp Gly Asp Tyr
995 1000 1005
Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly
1010 1015 1020
Ala Pro His His His His His His
1025 1030
<210> 82
<211> 1064
<212> PRT
<213> 人工序列
<220>
<223> pOptiVec中的MBip_Tκ28p_107_3xFlagHis_人-opt
<400> 82
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala Gly Asp Ala Ala
20 25 30
Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg
35 40 45
Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro
50 55 60
Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly
65 70 75 80
Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His
85 90 95
Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu
100 105 110
Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys
115 120 125
Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys
130 135 140
Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu
145 150 155 160
Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile
165 170 175
Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val
180 185 190
His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val
195 200 205
Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn
210 215 220
Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro
225 230 235 240
Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser
245 250 255
Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro
260 265 270
Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly
275 280 285
Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe
290 295 300
His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg
305 310 315 320
Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn
325 330 335
Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu
340 345 350
Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser
355 360 365
Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser
370 375 380
Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg
385 390 395 400
Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly Leu Pro Arg Ala
405 410 415
Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala
420 425 430
Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser
435 440 445
Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His
450 455 460
Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn
465 470 475 480
Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser
485 490 495
Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln
500 505 510
Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser
515 520 525
Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr
530 535 540
Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Asn
545 550 555 560
Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr
565 570 575
Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro
580 585 590
Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn
595 600 605
Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His
610 615 620
Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser
625 630 635 640
His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu
645 650 655
Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser
660 665 670
Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser
675 680 685
Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu
690 695 700
Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala
705 710 715 720
Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His
725 730 735
Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp
740 745 750
Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val
755 760 765
Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp
770 775 780
Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro
785 790 795 800
Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe
805 810 815
Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys
820 825 830
Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys
835 840 845
Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu
850 855 860
Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
865 870 875 880
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
885 890 895
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro
900 905 910
Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys
915 920 925
Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly
930 935 940
Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala
945 950 955 960
Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val
965 970 975
Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala
980 985 990
Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg Thr Asn Arg Ser Arg
995 1000 1005
Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly
1010 1015 1020
Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp
1025 1030 1035
Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
1040 1045 1050
Lys Asp Gly Ala Pro His His His His His His
1055 1060
<210> 83
<211> 1268
<212> PRT
<213> 人工序列
<220>
<223> -GST-P-TATκ28-CDKL5_107-P-FH_pVL1393 (昆虫)
<400> 83
Met Ser Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro
1 5 10 15
Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu
20 25 30
Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu
35 40 45
Gly Leu Glu Phe Pro Asn Leu Pro Tyr Tyr Ile Asp Gly Asp Val Lys
50 55 60
Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn
65 70 75 80
Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu
85 90 95
Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser
100 105 110
Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu
115 120 125
Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn
130 135 140
Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp
145 150 155 160
Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu
165 170 175
Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr
180 185 190
Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala
195 200 205
Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Gly Gly Gly Gly Ser
210 215 220
Leu Glu Val Leu Phe Gln Gly Pro Asp Ala Ala Gln Pro Ala Arg Arg
225 230 235 240
Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln
245 250 255
Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro Asn Ile Gly Asn Val
260 265 270
Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly Glu Gly Ala Tyr Gly
275 280 285
Val Val Leu Lys Cys Arg His Lys Glu Thr His Glu Ile Val Ala Ile
290 295 300
Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu Val Lys Glu Thr Thr
305 310 315 320
Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys Gln Glu Asn Ile Val
325 330 335
Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe
340 345 350
Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu Glu Glu Met Pro Asn
355 360 365
Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys
370 375 380
Ala Ile His Trp Cys His Lys Asn Asp Ile Val His Arg Asp Ile Lys
385 390 395 400
Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val Leu Lys Leu Cys Asp
405 410 415
Phe Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr
420 425 430
Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly
435 440 445
Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser Val Gly Cys Ile Leu
450 455 460
Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile
465 470 475 480
Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly Pro Leu Pro Ser Glu
485 490 495
Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe His Gly Leu Arg Phe
500 505 510
Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile
515 520 525
Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn Leu Leu Lys Leu Asp
530 535 540
Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu Asn His Pro Thr Phe
545 550 555 560
Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg
565 570 575
Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala
580 585 590
Gly Lys Ser Thr Ala Leu Gln Ser His His Arg Ser Asn Ser Lys Asp
595 600 605
Ile Gln Asn Leu Ser Val Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro
610 615 620
Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser
625 630 635 640
Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr
645 650 655
Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His Leu Leu Ser Pro Lys
660 665 670
Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro
675 680 685
Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln
690 695 700
Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln Ser Lys Ala Gly Thr
705 710 715 720
Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser Tyr Ile Asp Thr Ile
725 730 735
Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr Lys Ala Lys Ser His
740 745 750
Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Asn Leu Ser Glu Ala Arg
755 760 765
Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys
770 775 780
Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro Thr Arg His Ser Asp
785 790 795 800
Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly
805 810 815
Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His Ser Lys Thr Met Glu
820 825 830
Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser His Ser His Ser Leu
835 840 845
Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro
850 855 860
Phe Ser Ser Gln Gln Arg Pro His Arg His Ser Met Tyr Val Thr Arg
865 870 875 880
Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln
885 890 895
Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro
900 905 910
Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala Arg Ser Ser Val Lys
915 920 925
Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His Thr Arg Gln Lys Ser
930 935 940
Glu Gly Gly Val Tyr His Asp Pro His Ser Asp Asp Gly Thr Ala Pro
945 950 955 960
Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val Pro Arg Arg Val Gly
965 970 975
Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp Asn Ser Phe His Glu
980 985 990
Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro Ser Glu Ser Ser Ser
995 1000 1005
Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe Asp Pro Trp Lys
1010 1015 1020
Ser Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys Glu Lys Glu
1025 1030 1035
Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys Lys Ser
1040 1045 1050
Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu Gln
1055 1060 1065
Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
1070 1075 1080
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro
1085 1090 1095
Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn
1100 1105 1110
His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln
1115 1120 1125
Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser
1130 1135 1140
Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro
1145 1150 1155
Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly
1160 1165 1170
Trp His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser
1175 1180 1185
Tyr Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro
1190 1195 1200
Tyr Asn Arg Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu
1205 1210 1215
Lys Glu Thr Ala Leu Gly Gly Gly Gly Ser Leu Glu Val Leu Phe
1220 1225 1230
Gln Gly Pro Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His
1235 1240 1245
Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His
1250 1255 1260
His His His His His
1265
<210> 84
<211> 1252
<212> PRT
<213> 人工序列
<220>
<223> -GST-P-TATκ11-CDKL5_107-P-FH_pVL1393 (昆虫)
<400> 84
Met Ser Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro
1 5 10 15
Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu
20 25 30
Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu
35 40 45
Gly Leu Glu Phe Pro Asn Leu Pro Tyr Tyr Ile Asp Gly Asp Val Lys
50 55 60
Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn
65 70 75 80
Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu
85 90 95
Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser
100 105 110
Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu
115 120 125
Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn
130 135 140
Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp
145 150 155 160
Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu
165 170 175
Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr
180 185 190
Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala
195 200 205
Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Gly Gly Gly Gly Ser
210 215 220
Leu Glu Val Leu Phe Gln Gly Pro Tyr Ala Arg Lys Ala Ala Arg Gln
225 230 235 240
Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro Asn Ile Gly Asn Val
245 250 255
Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly Glu Gly Ala Tyr Gly
260 265 270
Val Val Leu Lys Cys Arg His Lys Glu Thr His Glu Ile Val Ala Ile
275 280 285
Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu Val Lys Glu Thr Thr
290 295 300
Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys Gln Glu Asn Ile Val
305 310 315 320
Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe
325 330 335
Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu Glu Glu Met Pro Asn
340 345 350
Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys
355 360 365
Ala Ile His Trp Cys His Lys Asn Asp Ile Val His Arg Asp Ile Lys
370 375 380
Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val Leu Lys Leu Cys Asp
385 390 395 400
Phe Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr
405 410 415
Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly
420 425 430
Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser Val Gly Cys Ile Leu
435 440 445
Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile
450 455 460
Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly Pro Leu Pro Ser Glu
465 470 475 480
Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe His Gly Leu Arg Phe
485 490 495
Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile
500 505 510
Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn Leu Leu Lys Leu Asp
515 520 525
Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu Asn His Pro Thr Phe
530 535 540
Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg
545 550 555 560
Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala
565 570 575
Gly Lys Ser Thr Ala Leu Gln Ser His His Arg Ser Asn Ser Lys Asp
580 585 590
Ile Gln Asn Leu Ser Val Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro
595 600 605
Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser
610 615 620
Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr
625 630 635 640
Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His Leu Leu Ser Pro Lys
645 650 655
Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro
660 665 670
Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln
675 680 685
Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln Ser Lys Ala Gly Thr
690 695 700
Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser Tyr Ile Asp Thr Ile
705 710 715 720
Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr Lys Ala Lys Ser His
725 730 735
Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Asn Leu Ser Glu Ala Arg
740 745 750
Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys
755 760 765
Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro Thr Arg His Ser Asp
770 775 780
Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly
785 790 795 800
Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His Ser Lys Thr Met Glu
805 810 815
Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser His Ser His Ser Leu
820 825 830
Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro
835 840 845
Phe Ser Ser Gln Gln Arg Pro His Arg His Ser Met Tyr Val Thr Arg
850 855 860
Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln
865 870 875 880
Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro
885 890 895
Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala Arg Ser Ser Val Lys
900 905 910
Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His Thr Arg Gln Lys Ser
915 920 925
Glu Gly Gly Val Tyr His Asp Pro His Ser Asp Asp Gly Thr Ala Pro
930 935 940
Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val Pro Arg Arg Val Gly
945 950 955 960
Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp Asn Ser Phe His Glu
965 970 975
Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro Ser Glu Ser Ser Ser
980 985 990
Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser
995 1000 1005
Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys Glu Lys Glu Lys
1010 1015 1020
Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys Lys Ser Gln
1025 1030 1035
Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu Gln Lys
1040 1045 1050
Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu Trp
1055 1060 1065
Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
1070 1075 1080
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His
1085 1090 1095
Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln
1100 1105 1110
Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln
1115 1120 1125
Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys
1130 1135 1140
Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp
1145 1150 1155
His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr
1160 1165 1170
Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr
1175 1180 1185
Asn Arg Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys
1190 1195 1200
Glu Thr Ala Leu Gly Gly Gly Gly Ser Leu Glu Val Leu Phe Gln
1205 1210 1215
Gly Pro Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp
1220 1225 1230
Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His His
1235 1240 1245
His His His His
1250
<210> 85
<211> 1268
<212> PRT
<213> 人工序列
<220>
<223> -GST-P-TAT28-CDKL5_107-P-FH_pVL1393 (昆虫)
<400> 85
Met Ser Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro
1 5 10 15
Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu
20 25 30
Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu
35 40 45
Gly Leu Glu Phe Pro Asn Leu Pro Tyr Tyr Ile Asp Gly Asp Val Lys
50 55 60
Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn
65 70 75 80
Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu
85 90 95
Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser
100 105 110
Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu
115 120 125
Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn
130 135 140
Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp
145 150 155 160
Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu
165 170 175
Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr
180 185 190
Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala
195 200 205
Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Gly Gly Gly Gly Ser
210 215 220
Leu Glu Val Leu Phe Gln Gly Pro Asp Ala Ala Gln Pro Ala Arg Arg
225 230 235 240
Ala Arg Arg Thr Lys Leu Ala Ala Tyr Gly Arg Lys Lys Arg Arg Gln
245 250 255
Arg Arg Arg Gly Gly Gly Gly Ser Lys Ile Pro Asn Ile Gly Asn Val
260 265 270
Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly Glu Gly Ala Tyr Gly
275 280 285
Val Val Leu Lys Cys Arg His Lys Glu Thr His Glu Ile Val Ala Ile
290 295 300
Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu Val Lys Glu Thr Thr
305 310 315 320
Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys Gln Glu Asn Ile Val
325 330 335
Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe
340 345 350
Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu Glu Glu Met Pro Asn
355 360 365
Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys
370 375 380
Ala Ile His Trp Cys His Lys Asn Asp Ile Val His Arg Asp Ile Lys
385 390 395 400
Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val Leu Lys Leu Cys Asp
405 410 415
Phe Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr
420 425 430
Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly
435 440 445
Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser Val Gly Cys Ile Leu
450 455 460
Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile
465 470 475 480
Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly Pro Leu Pro Ser Glu
485 490 495
Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe His Gly Leu Arg Phe
500 505 510
Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile
515 520 525
Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn Leu Leu Lys Leu Asp
530 535 540
Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu Asn His Pro Thr Phe
545 550 555 560
Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg
565 570 575
Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala
580 585 590
Gly Lys Ser Thr Ala Leu Gln Ser His His Arg Ser Asn Ser Lys Asp
595 600 605
Ile Gln Asn Leu Ser Val Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro
610 615 620
Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser
625 630 635 640
Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr
645 650 655
Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His Leu Leu Ser Pro Lys
660 665 670
Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro
675 680 685
Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln
690 695 700
Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln Ser Lys Ala Gly Thr
705 710 715 720
Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser Tyr Ile Asp Thr Ile
725 730 735
Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr Lys Ala Lys Ser His
740 745 750
Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Asn Leu Ser Glu Ala Arg
755 760 765
Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys
770 775 780
Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro Thr Arg His Ser Asp
785 790 795 800
Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly
805 810 815
Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His Ser Lys Thr Met Glu
820 825 830
Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser His Ser His Ser Leu
835 840 845
Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro
850 855 860
Phe Ser Ser Gln Gln Arg Pro His Arg His Ser Met Tyr Val Thr Arg
865 870 875 880
Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln
885 890 895
Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro
900 905 910
Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala Arg Ser Ser Val Lys
915 920 925
Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His Thr Arg Gln Lys Ser
930 935 940
Glu Gly Gly Val Tyr His Asp Pro His Ser Asp Asp Gly Thr Ala Pro
945 950 955 960
Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val Pro Arg Arg Val Gly
965 970 975
Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp Asn Ser Phe His Glu
980 985 990
Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro Ser Glu Ser Ser Ser
995 1000 1005
Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe Asp Pro Trp Lys
1010 1015 1020
Ser Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys Glu Lys Glu
1025 1030 1035
Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys Lys Ser
1040 1045 1050
Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu Gln
1055 1060 1065
Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
1070 1075 1080
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro
1085 1090 1095
Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn
1100 1105 1110
His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln
1115 1120 1125
Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser
1130 1135 1140
Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro
1145 1150 1155
Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly
1160 1165 1170
Trp His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser
1175 1180 1185
Tyr Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro
1190 1195 1200
Tyr Asn Arg Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu
1205 1210 1215
Lys Glu Thr Ala Leu Gly Gly Gly Gly Ser Leu Glu Val Leu Phe
1220 1225 1230
Gln Gly Pro Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His
1235 1240 1245
Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His
1250 1255 1260
His His His His His
1265
<210> 86
<211> 1252
<212> PRT
<213> 人工序列
<220>
<223> -GST-P-TAT11-CDKL5_107-P-FH_pVL1393 (昆虫)
<400> 86
Met Ser Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro
1 5 10 15
Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu
20 25 30
Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu
35 40 45
Gly Leu Glu Phe Pro Asn Leu Pro Tyr Tyr Ile Asp Gly Asp Val Lys
50 55 60
Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn
65 70 75 80
Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu
85 90 95
Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser
100 105 110
Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu
115 120 125
Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn
130 135 140
Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp
145 150 155 160
Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu
165 170 175
Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr
180 185 190
Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala
195 200 205
Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Gly Gly Gly Gly Ser
210 215 220
Leu Glu Val Leu Phe Gln Gly Pro Tyr Gly Arg Lys Lys Arg Arg Gln
225 230 235 240
Arg Arg Arg Gly Gly Gly Gly Ser Lys Ile Pro Asn Ile Gly Asn Val
245 250 255
Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly Glu Gly Ala Tyr Gly
260 265 270
Val Val Leu Lys Cys Arg His Lys Glu Thr His Glu Ile Val Ala Ile
275 280 285
Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu Val Lys Glu Thr Thr
290 295 300
Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys Gln Glu Asn Ile Val
305 310 315 320
Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe
325 330 335
Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu Glu Glu Met Pro Asn
340 345 350
Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys
355 360 365
Ala Ile His Trp Cys His Lys Asn Asp Ile Val His Arg Asp Ile Lys
370 375 380
Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val Leu Lys Leu Cys Asp
385 390 395 400
Phe Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr
405 410 415
Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly
420 425 430
Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser Val Gly Cys Ile Leu
435 440 445
Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile
450 455 460
Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly Pro Leu Pro Ser Glu
465 470 475 480
Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe His Gly Leu Arg Phe
485 490 495
Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile
500 505 510
Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn Leu Leu Lys Leu Asp
515 520 525
Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu Asn His Pro Thr Phe
530 535 540
Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg
545 550 555 560
Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala
565 570 575
Gly Lys Ser Thr Ala Leu Gln Ser His His Arg Ser Asn Ser Lys Asp
580 585 590
Ile Gln Asn Leu Ser Val Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro
595 600 605
Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser
610 615 620
Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr
625 630 635 640
Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His Leu Leu Ser Pro Lys
645 650 655
Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro
660 665 670
Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln
675 680 685
Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln Ser Lys Ala Gly Thr
690 695 700
Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser Tyr Ile Asp Thr Ile
705 710 715 720
Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr Lys Ala Lys Ser His
725 730 735
Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Asn Leu Ser Glu Ala Arg
740 745 750
Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys
755 760 765
Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro Thr Arg His Ser Asp
770 775 780
Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly
785 790 795 800
Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His Ser Lys Thr Met Glu
805 810 815
Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser His Ser His Ser Leu
820 825 830
Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro
835 840 845
Phe Ser Ser Gln Gln Arg Pro His Arg His Ser Met Tyr Val Thr Arg
850 855 860
Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln
865 870 875 880
Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro
885 890 895
Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala Arg Ser Ser Val Lys
900 905 910
Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His Thr Arg Gln Lys Ser
915 920 925
Glu Gly Gly Val Tyr His Asp Pro His Ser Asp Asp Gly Thr Ala Pro
930 935 940
Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val Pro Arg Arg Val Gly
945 950 955 960
Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp Asn Ser Phe His Glu
965 970 975
Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro Ser Glu Ser Ser Ser
980 985 990
Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser
995 1000 1005
Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys Glu Lys Glu Lys
1010 1015 1020
Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys Lys Ser Gln
1025 1030 1035
Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu Gln Lys
1040 1045 1050
Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu Trp
1055 1060 1065
Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
1070 1075 1080
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His
1085 1090 1095
Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln
1100 1105 1110
Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln
1115 1120 1125
Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys
1130 1135 1140
Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp
1145 1150 1155
His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr
1160 1165 1170
Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr
1175 1180 1185
Asn Arg Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys
1190 1195 1200
Glu Thr Ala Leu Gly Gly Gly Gly Ser Leu Glu Val Leu Phe Gln
1205 1210 1215
Gly Pro Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp
1220 1225 1230
Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His His
1235 1240 1245
His His His His
1250
<210> 87
<211> 1257
<212> PRT
<213> 人工序列
<220>
<223> -GST-P-ANTP-CDKL5_107-P-FH_pVL1393 (昆虫)
<400> 87
Met Ser Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro
1 5 10 15
Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu
20 25 30
Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu
35 40 45
Gly Leu Glu Phe Pro Asn Leu Pro Tyr Tyr Ile Asp Gly Asp Val Lys
50 55 60
Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn
65 70 75 80
Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu
85 90 95
Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser
100 105 110
Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu
115 120 125
Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn
130 135 140
Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp
145 150 155 160
Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu
165 170 175
Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr
180 185 190
Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala
195 200 205
Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Gly Gly Gly Gly Ser
210 215 220
Leu Glu Val Leu Phe Gln Gly Pro Arg Gln Ile Lys Ile Trp Phe Gln
225 230 235 240
Asn Arg Arg Met Lys Trp Lys Lys Gly Gly Gly Gly Ser Lys Ile Pro
245 250 255
Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly
260 265 270
Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His
275 280 285
Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu
290 295 300
Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys
305 310 315 320
Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys
325 330 335
Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu
340 345 350
Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile
355 360 365
Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val
370 375 380
His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val
385 390 395 400
Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn
405 410 415
Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro
420 425 430
Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser
435 440 445
Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro
450 455 460
Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly
465 470 475 480
Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe
485 490 495
His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg
500 505 510
Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn
515 520 525
Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu
530 535 540
Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser
545 550 555 560
Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser
565 570 575
Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg
580 585 590
Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly Leu Pro Arg Ala
595 600 605
Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala
610 615 620
Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser
625 630 635 640
Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His
645 650 655
Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn
660 665 670
Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser
675 680 685
Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln
690 695 700
Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser
705 710 715 720
Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr
725 730 735
Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Asn
740 745 750
Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr
755 760 765
Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro
770 775 780
Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn
785 790 795 800
Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His
805 810 815
Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser
820 825 830
His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu
835 840 845
Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser
850 855 860
Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser
865 870 875 880
Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu
885 890 895
Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala
900 905 910
Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His
915 920 925
Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp
930 935 940
Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val
945 950 955 960
Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp
965 970 975
Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro
980 985 990
Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe
995 1000 1005
Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His Ser Glu Gln Leu
1010 1015 1020
Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys
1025 1030 1035
Lys Lys Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu
1040 1045 1050
Leu Thr Leu Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser
1055 1060 1065
Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr
1070 1075 1080
Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser
1085 1090 1095
Ser Ala Ser Asn His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro
1100 1105 1110
Leu Thr Ala Gln Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile
1115 1120 1125
His Pro Leu Ser Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln
1130 1135 1140
Glu Pro Ala Pro Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln
1145 1150 1155
Met Asp Pro Gly Trp His Val Ser Ser Val Thr Arg Ser Ala Thr
1160 1165 1170
Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro
1175 1180 1185
Asn Gly His Pro Tyr Asn Arg Thr Asn Arg Ser Arg Met Pro Asn
1190 1195 1200
Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly Gly Ser Leu
1205 1210 1215
Glu Val Leu Phe Gln Gly Pro Asp Tyr Lys Asp His Asp Gly Asp
1220 1225 1230
Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp
1235 1240 1245
Gly Ala Pro His His His His His His
1250 1255
<210> 88
<211> 1262
<212> PRT
<213> 人工序列
<220>
<223> -GST-P-TRANSP-CDKL5_107-P-FH_pVL1393 (昆虫)
<400> 88
Met Ser Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro
1 5 10 15
Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu
20 25 30
Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu
35 40 45
Gly Leu Glu Phe Pro Asn Leu Pro Tyr Tyr Ile Asp Gly Asp Val Lys
50 55 60
Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn
65 70 75 80
Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu
85 90 95
Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser
100 105 110
Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu
115 120 125
Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn
130 135 140
Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp
145 150 155 160
Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu
165 170 175
Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr
180 185 190
Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala
195 200 205
Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Gly Gly Gly Gly Ser
210 215 220
Leu Glu Val Leu Phe Gln Gly Pro Ala Gly Tyr Leu Leu Gly Lys Ile
225 230 235 240
Asn Leu Lys Ala Leu Ala Ala Leu Ala Lys Lys Ile Leu Gly Gly Gly
245 250 255
Gly Ser Lys Ile Pro Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile
260 265 270
Leu Gly Val Val Gly Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg
275 280 285
His Lys Glu Thr His Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser
290 295 300
Glu Glu Asn Glu Glu Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met
305 310 315 320
Leu Arg Thr Leu Lys Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe
325 330 335
Arg Arg Arg Gly Lys Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn
340 345 350
Met Leu Glu Leu Leu Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys
355 360 365
Val Lys Ser Tyr Ile Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His
370 375 380
Lys Asn Asp Ile Val His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile
385 390 395 400
Ser His Asn Asp Val Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn
405 410 415
Leu Ser Glu Gly Asn Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg
420 425 430
Trp Tyr Arg Ser Pro Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser
435 440 445
Val Asp Met Trp Ser Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly
450 455 460
Gln Pro Leu Phe Pro Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile
465 470 475 480
Gln Lys Val Leu Gly Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr
485 490 495
Ser Asn Pro Arg Phe His Gly Leu Arg Phe Pro Ala Val Asn His Pro
500 505 510
Gln Ser Leu Glu Arg Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu
515 520 525
Asp Leu Met Lys Asn Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu
530 535 540
Thr Glu Gln Cys Leu Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu
545 550 555 560
Asp Arg Ser Pro Ser Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu
565 570 575
Ser Ser Thr Leu Ser Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu
580 585 590
Gln Ser His His Arg Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val
595 600 605
Gly Leu Pro Arg Ala Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu
610 615 620
Asn Gly Asn Leu Ala Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr
625 630 635 640
Tyr Gln Ala Ser Ser Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn
645 650 655
Asn Asn Ile Pro His Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr
660 665 670
Glu Phe Asp Phe Asn Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr
675 680 685
Lys Tyr Leu Lys Ser Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe
690 695 700
Met Glu Ser Ser Gln Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys
705 710 715 720
Gln Ser Arg His Ser Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser
725 730 735
Pro Ser Tyr Arg Thr Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser
740 745 750
Lys Ser Val Ser Asn Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro
755 760 765
Ser Thr Ser Arg Tyr Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro
770 775 780
Thr Ser Pro Thr Pro Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser
785 790 795 800
Pro Ser Gly Arg Asn Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg
805 810 815
Thr Thr Thr Arg His Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu
820 825 830
His Met Asp Ser Ser His Ser His Ser Leu Ser Ala Pro His Glu Ser
835 840 845
Phe Ser Tyr Gly Leu Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg
850 855 860
Pro His Arg His Ser Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys
865 870 875 880
Gly Leu Asp Gly Ser Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala
885 890 895
Asn Ser Leu Gln Leu Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro
900 905 910
Glu Met Thr Val Ala Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly
915 920 925
Thr Ser Ser Phe His Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His
930 935 940
Asp Pro His Ser Asp Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu
945 950 955 960
Tyr Asn Asp Pro Val Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro
965 970 975
Ser Pro Arg Pro Asp Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg
980 985 990
Val Ser Ser Leu Pro Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys
995 1000 1005
Arg Gln Pro Ala Phe Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser
1010 1015 1020
His Ser Glu Gln Leu Lys Glu Lys Glu Lys Gln Gly Phe Phe Arg
1025 1030 1035
Ser Met Lys Lys Lys Lys Lys Lys Ser Gln Thr Val Pro Asn Ser
1040 1045 1050
Asp Ser Pro Asp Leu Leu Thr Leu Gln Lys Ser Ile His Ser Ala
1055 1060 1065
Ser Thr Pro Ser Ser Arg Pro Lys Glu Trp Arg Pro Glu Lys Ile
1070 1075 1080
Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu Lys Ser Leu Arg Lys
1085 1090 1095
Leu Leu His Leu Ser Ser Ala Ser Asn His Pro Ala Ser Ser Asp
1100 1105 1110
Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys Asn Ser Phe
1115 1120 1125
Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly Gly Ser
1130 1135 1140
Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala Leu
1145 1150 1155
Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val
1160 1165 1170
Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly
1175 1180 1185
Ala Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg Thr Asn Arg
1190 1195 1200
Ser Arg Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly
1205 1210 1215
Gly Gly Gly Ser Leu Glu Val Leu Phe Gln Gly Pro Asp Tyr Lys
1220 1225 1230
Asp His Asp Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp
1235 1240 1245
Asp Asp Asp Lys Asp Gly Ala Pro His His His His His His
1250 1255 1260
<210> 89
<211> 1253
<212> PRT
<213> 人工序列
<220>
<223> -GST-P-P97P-CDKL5_107-P-FH_pVL1393 (昆虫)
<400> 89
Met Ser Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro
1 5 10 15
Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu
20 25 30
Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu
35 40 45
Gly Leu Glu Phe Pro Asn Leu Pro Tyr Tyr Ile Asp Gly Asp Val Lys
50 55 60
Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn
65 70 75 80
Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu
85 90 95
Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser
100 105 110
Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu
115 120 125
Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn
130 135 140
Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp
145 150 155 160
Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu
165 170 175
Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr
180 185 190
Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala
195 200 205
Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Gly Gly Gly Gly Ser
210 215 220
Leu Glu Val Leu Phe Gln Gly Pro Asp Ser Ser His Ala Phe Thr Leu
225 230 235 240
Asp Glu Leu Arg Gly Gly Gly Gly Ser Lys Ile Pro Asn Ile Gly Asn
245 250 255
Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly Glu Gly Ala Tyr
260 265 270
Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His Glu Ile Val Ala
275 280 285
Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu Val Lys Glu Thr
290 295 300
Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys Gln Glu Asn Ile
305 310 315 320
Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys Leu Tyr Leu Val
325 330 335
Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu Glu Glu Met Pro
340 345 350
Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile Tyr Gln Leu Ile
355 360 365
Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val His Arg Asp Ile
370 375 380
Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val Leu Lys Leu Cys
385 390 395 400
Asp Phe Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn Asn Ala Asn Tyr
405 410 415
Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro Glu Leu Leu Leu
420 425 430
Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser Val Gly Cys Ile
435 440 445
Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro Gly Glu Ser Glu
450 455 460
Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly Pro Leu Pro Ser
465 470 475 480
Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe His Gly Leu Arg
485 490 495
Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg Arg Tyr Leu Gly
500 505 510
Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn Leu Leu Lys Leu
515 520 525
Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu Asn His Pro Thr
530 535 540
Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser Arg Ser Ala Lys
545 550 555 560
Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser Asn Arg Asn Gln
565 570 575
Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg Ser Asn Ser Lys
580 585 590
Asp Ile Gln Asn Leu Ser Val Gly Leu Pro Arg Ala Asp Glu Gly Leu
595 600 605
Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala Gly Ala Ser Leu
610 615 620
Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser Gln Pro Gly Ser
625 630 635 640
Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His Leu Leu Ser Pro
645 650 655
Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn Ile Asp Pro Lys
660 665 670
Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser Asn Ser Arg Ser
675 680 685
Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln Ser Lys Ala Gly
690 695 700
Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser Tyr Ile Asp Thr
705 710 715 720
Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr Lys Ala Lys Ser
725 730 735
His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Asn Leu Ser Glu Ala
740 745 750
Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr Phe Pro Ser Ser
755 760 765
Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro Thr Arg His Ser
770 775 780
Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn Asn Arg Asn Glu
785 790 795 800
Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His Ser Lys Thr Met
805 810 815
Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser His Ser His Ser
820 825 830
Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu Gly Tyr Thr Ser
835 840 845
Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser Met Tyr Val Thr
850 855 860
Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser Leu Ser Ile Gly
865 870 875 880
Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu Leu Ser Pro Gln
885 890 895
Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala Arg Ser Ser Val
900 905 910
Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His Thr Arg Gln Lys
915 920 925
Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp Asp Gly Thr Ala
930 935 940
Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val Pro Arg Arg Val
945 950 955 960
Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp Asn Ser Phe His
965 970 975
Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro Ser Glu Ser Ser
980 985 990
Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe Asp Pro Trp Lys
995 1000 1005
Ser Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys Glu Lys Glu
1010 1015 1020
Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys Lys Ser
1025 1030 1035
Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu Gln
1040 1045 1050
Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
1055 1060 1065
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro
1070 1075 1080
Leu Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn
1085 1090 1095
His Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln
1100 1105 1110
Gln Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser
1115 1120 1125
Gln Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro
1130 1135 1140
Lys Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly
1145 1150 1155
Trp His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser
1160 1165 1170
Tyr Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro
1175 1180 1185
Tyr Asn Arg Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu
1190 1195 1200
Lys Glu Thr Ala Leu Gly Gly Gly Gly Ser Leu Glu Val Leu Phe
1205 1210 1215
Gln Gly Pro Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His
1220 1225 1230
Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His
1235 1240 1245
His His His His His
1250
<210> 90
<211> 516
<212> PRT
<213> 人工序列
<220>
<223> -GST-P-eGFP-P-FH_pVL1393 (昆虫)
<400> 90
Met Ser Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro
1 5 10 15
Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu
20 25 30
Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu
35 40 45
Gly Leu Glu Phe Pro Asn Leu Pro Tyr Tyr Ile Asp Gly Asp Val Lys
50 55 60
Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn
65 70 75 80
Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu
85 90 95
Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser
100 105 110
Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu
115 120 125
Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn
130 135 140
Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp
145 150 155 160
Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu
165 170 175
Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr
180 185 190
Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala
195 200 205
Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Gly Gly Gly Gly Ser
210 215 220
Leu Glu Val Leu Phe Gln Gly Pro Met Val Ser Lys Gly Glu Glu Leu
225 230 235 240
Phe Thr Gly Val Val Pro Ile Leu Val Glu Leu Asp Gly Asp Val Asn
245 250 255
Gly His Lys Phe Ser Val Ser Gly Glu Gly Glu Gly Asp Ala Thr Tyr
260 265 270
Gly Lys Leu Thr Leu Lys Phe Ile Cys Thr Thr Gly Lys Leu Pro Val
275 280 285
Pro Trp Pro Thr Leu Val Thr Thr Leu Thr Tyr Gly Val Gln Cys Phe
290 295 300
Ser Arg Tyr Pro Asp His Met Lys Gln His Asp Phe Phe Lys Ser Ala
305 310 315 320
Met Pro Glu Gly Tyr Val Gln Glu Arg Thr Ile Phe Phe Lys Asp Asp
325 330 335
Gly Asn Tyr Lys Thr Arg Ala Glu Val Lys Phe Glu Gly Asp Thr Leu
340 345 350
Val Asn Arg Ile Glu Leu Lys Gly Ile Asp Phe Lys Glu Asp Gly Asn
355 360 365
Ile Leu Gly His Lys Leu Glu Tyr Asn Tyr Asn Ser His Asn Val Tyr
370 375 380
Ile Met Ala Asp Lys Gln Lys Asn Gly Ile Lys Val Asn Phe Lys Ile
385 390 395 400
Arg His Asn Ile Glu Asp Gly Ser Val Gln Leu Ala Asp His Tyr Gln
405 410 415
Gln Asn Thr Pro Ile Gly Asp Gly Pro Val Leu Leu Pro Asp Asn His
420 425 430
Tyr Leu Ser Thr Gln Ser Ala Leu Ser Lys Asp Pro Asn Glu Lys Arg
435 440 445
Asp His Met Val Leu Leu Glu Phe Val Thr Ala Ala Gly Ile Thr Leu
450 455 460
Gly Met Asp Glu Leu Tyr Lys Gly Gly Gly Gly Ser Leu Glu Val Leu
465 470 475 480
Phe Gln Gly Pro Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His
485 490 495
Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His His
500 505 510
His His His His
515
<210> 91
<211> 548
<212> PRT
<213> 人工序列
<220>
<223> -GST-P-TATκ28-eGFP-P-FH_pVL1393 (昆虫)
<400> 91
Met Ser Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro
1 5 10 15
Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu
20 25 30
Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu
35 40 45
Gly Leu Glu Phe Pro Asn Leu Pro Tyr Tyr Ile Asp Gly Asp Val Lys
50 55 60
Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn
65 70 75 80
Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu
85 90 95
Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser
100 105 110
Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu
115 120 125
Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn
130 135 140
Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp
145 150 155 160
Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu
165 170 175
Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr
180 185 190
Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala
195 200 205
Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Gly Gly Gly Gly Ser
210 215 220
Leu Glu Val Leu Phe Gln Gly Pro Asp Ala Ala Gln Pro Ala Arg Arg
225 230 235 240
Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg Lys Ala Ala Arg Gln
245 250 255
Ala Arg Ala Gly Gly Gly Gly Ser Met Val Ser Lys Gly Glu Glu Leu
260 265 270
Phe Thr Gly Val Val Pro Ile Leu Val Glu Leu Asp Gly Asp Val Asn
275 280 285
Gly His Lys Phe Ser Val Ser Gly Glu Gly Glu Gly Asp Ala Thr Tyr
290 295 300
Gly Lys Leu Thr Leu Lys Phe Ile Cys Thr Thr Gly Lys Leu Pro Val
305 310 315 320
Pro Trp Pro Thr Leu Val Thr Thr Leu Thr Tyr Gly Val Gln Cys Phe
325 330 335
Ser Arg Tyr Pro Asp His Met Lys Gln His Asp Phe Phe Lys Ser Ala
340 345 350
Met Pro Glu Gly Tyr Val Gln Glu Arg Thr Ile Phe Phe Lys Asp Asp
355 360 365
Gly Asn Tyr Lys Thr Arg Ala Glu Val Lys Phe Glu Gly Asp Thr Leu
370 375 380
Val Asn Arg Ile Glu Leu Lys Gly Ile Asp Phe Lys Glu Asp Gly Asn
385 390 395 400
Ile Leu Gly His Lys Leu Glu Tyr Asn Tyr Asn Ser His Asn Val Tyr
405 410 415
Ile Met Ala Asp Lys Gln Lys Asn Gly Ile Lys Val Asn Phe Lys Ile
420 425 430
Arg His Asn Ile Glu Asp Gly Ser Val Gln Leu Ala Asp His Tyr Gln
435 440 445
Gln Asn Thr Pro Ile Gly Asp Gly Pro Val Leu Leu Pro Asp Asn His
450 455 460
Tyr Leu Ser Thr Gln Ser Ala Leu Ser Lys Asp Pro Asn Glu Lys Arg
465 470 475 480
Asp His Met Val Leu Leu Glu Phe Val Thr Ala Ala Gly Ile Thr Leu
485 490 495
Gly Met Asp Glu Leu Tyr Lys Gly Gly Gly Gly Ser Leu Glu Val Leu
500 505 510
Phe Gln Gly Pro Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His
515 520 525
Asp Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His His
530 535 540
His His His His
545
<210> 92
<211> 1237
<212> PRT
<213> 人工序列
<220>
<223> -GST-P-CDKL5_107-P-FH_pVL1393 (昆虫)
<400> 92
Met Ser Pro Ile Leu Gly Tyr Trp Lys Ile Lys Gly Leu Val Gln Pro
1 5 10 15
Thr Arg Leu Leu Leu Glu Tyr Leu Glu Glu Lys Tyr Glu Glu His Leu
20 25 30
Tyr Glu Arg Asp Glu Gly Asp Lys Trp Arg Asn Lys Lys Phe Glu Leu
35 40 45
Gly Leu Glu Phe Pro Asn Leu Pro Tyr Tyr Ile Asp Gly Asp Val Lys
50 55 60
Leu Thr Gln Ser Met Ala Ile Ile Arg Tyr Ile Ala Asp Lys His Asn
65 70 75 80
Met Leu Gly Gly Cys Pro Lys Glu Arg Ala Glu Ile Ser Met Leu Glu
85 90 95
Gly Ala Val Leu Asp Ile Arg Tyr Gly Val Ser Arg Ile Ala Tyr Ser
100 105 110
Lys Asp Phe Glu Thr Leu Lys Val Asp Phe Leu Ser Lys Leu Pro Glu
115 120 125
Met Leu Lys Met Phe Glu Asp Arg Leu Cys His Lys Thr Tyr Leu Asn
130 135 140
Gly Asp His Val Thr His Pro Asp Phe Met Leu Tyr Asp Ala Leu Asp
145 150 155 160
Val Val Leu Tyr Met Asp Pro Met Cys Leu Asp Ala Phe Pro Lys Leu
165 170 175
Val Cys Phe Lys Lys Arg Ile Glu Ala Ile Pro Gln Ile Asp Lys Tyr
180 185 190
Leu Lys Ser Ser Lys Tyr Ile Ala Trp Pro Leu Gln Gly Trp Gln Ala
195 200 205
Thr Phe Gly Gly Gly Asp His Pro Pro Lys Ser Gly Gly Gly Gly Ser
210 215 220
Leu Glu Val Leu Phe Gln Gly Pro Gly Lys Ile Pro Asn Ile Gly Asn
225 230 235 240
Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly Glu Gly Ala Tyr
245 250 255
Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His Glu Ile Val Ala
260 265 270
Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu Val Lys Glu Thr
275 280 285
Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys Gln Glu Asn Ile
290 295 300
Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys Leu Tyr Leu Val
305 310 315 320
Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu Glu Glu Met Pro
325 330 335
Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile Tyr Gln Leu Ile
340 345 350
Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val His Arg Asp Ile
355 360 365
Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val Leu Lys Leu Cys
370 375 380
Asp Phe Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn Asn Ala Asn Tyr
385 390 395 400
Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro Glu Leu Leu Leu
405 410 415
Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser Val Gly Cys Ile
420 425 430
Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro Gly Glu Ser Glu
435 440 445
Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly Pro Leu Pro Ser
450 455 460
Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe His Gly Leu Arg
465 470 475 480
Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg Arg Tyr Leu Gly
485 490 495
Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn Leu Leu Lys Leu
500 505 510
Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu Asn His Pro Thr
515 520 525
Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser Arg Ser Ala Lys
530 535 540
Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser Asn Arg Asn Gln
545 550 555 560
Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg Ser Asn Ser Lys
565 570 575
Asp Ile Gln Asn Leu Ser Val Gly Leu Pro Arg Ala Asp Glu Gly Leu
580 585 590
Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala Gly Ala Ser Leu
595 600 605
Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser Gln Pro Gly Ser
610 615 620
Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His Leu Leu Ser Pro
625 630 635 640
Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn Ile Asp Pro Lys
645 650 655
Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser Asn Ser Arg Ser
660 665 670
Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln Ser Lys Ala Gly
675 680 685
Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser Tyr Ile Asp Thr
690 695 700
Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr Lys Ala Lys Ser
705 710 715 720
His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Asn Leu Ser Glu Ala
725 730 735
Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr Phe Pro Ser Ser
740 745 750
Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro Thr Arg His Ser
755 760 765
Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn Asn Arg Asn Glu
770 775 780
Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His Ser Lys Thr Met
785 790 795 800
Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser His Ser His Ser
805 810 815
Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu Gly Tyr Thr Ser
820 825 830
Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser Met Tyr Val Thr
835 840 845
Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser Leu Ser Ile Gly
850 855 860
Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu Leu Ser Pro Gln
865 870 875 880
Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala Arg Ser Ser Val
885 890 895
Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His Thr Arg Gln Lys
900 905 910
Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp Asp Gly Thr Ala
915 920 925
Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val Pro Arg Arg Val
930 935 940
Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp Asn Ser Phe His
945 950 955 960
Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro Ser Glu Ser Ser
965 970 975
Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe Asp Pro Trp Lys
980 985 990
Ser Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys Glu Lys Glu Lys
995 1000 1005
Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys Lys Ser Gln
1010 1015 1020
Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu Gln Lys
1025 1030 1035
Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu Trp
1040 1045 1050
Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
1055 1060 1065
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His
1070 1075 1080
Pro Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln
1085 1090 1095
Thr Lys Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln
1100 1105 1110
Ala Ser Gly Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys
1115 1120 1125
Gly Arg Pro Ala Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp
1130 1135 1140
His Val Ser Ser Val Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr
1145 1150 1155
Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro Asn Gly His Pro Tyr
1160 1165 1170
Asn Arg Thr Asn Arg Ser Arg Met Pro Asn Leu Asn Asp Leu Lys
1175 1180 1185
Glu Thr Ala Leu Gly Gly Gly Gly Ser Leu Glu Val Leu Phe Gln
1190 1195 1200
Gly Pro Asp Tyr Lys Asp His Asp Gly Asp Tyr Lys Asp His Asp
1205 1210 1215
Ile Asp Tyr Lys Asp Asp Asp Asp Lys Asp Gly Ala Pro His His
1220 1225 1230
His His His His
1235
<210> 93
<211> 1064
<212> PRT
<213> 人工序列
<220>
<223> MBip-TATκ28-CDKL5_107-FH_cho[1-7NQ]
<400> 93
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala Gly Asp Ala Ala
20 25 30
Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg
35 40 45
Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro
50 55 60
Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly
65 70 75 80
Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His
85 90 95
Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu
100 105 110
Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys
115 120 125
Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys
130 135 140
Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu
145 150 155 160
Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile
165 170 175
Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val
180 185 190
His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val
195 200 205
Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu Ser Glu Gly Asn
210 215 220
Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro
225 230 235 240
Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser
245 250 255
Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro
260 265 270
Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly
275 280 285
Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe
290 295 300
His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg
305 310 315 320
Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn
325 330 335
Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu
340 345 350
Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser
355 360 365
Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser
370 375 380
Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg
385 390 395 400
Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly Leu Pro Arg Ala
405 410 415
Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala
420 425 430
Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser
435 440 445
Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His
450 455 460
Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn
465 470 475 480
Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser
485 490 495
Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln
500 505 510
Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser
515 520 525
Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr
530 535 540
Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Gln
545 550 555 560
Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr
565 570 575
Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro
580 585 590
Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn
595 600 605
Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His
610 615 620
Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser
625 630 635 640
His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu
645 650 655
Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser
660 665 670
Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser
675 680 685
Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu
690 695 700
Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala
705 710 715 720
Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His
725 730 735
Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp
740 745 750
Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val
755 760 765
Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp
770 775 780
Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro
785 790 795 800
Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe
805 810 815
Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser Glu Gln Leu Lys
820 825 830
Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys
835 840 845
Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu
850 855 860
Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
865 870 875 880
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
885 890 895
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro
900 905 910
Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys
915 920 925
Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly
930 935 940
Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala
945 950 955 960
Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val
965 970 975
Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala
980 985 990
Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr Gln Arg Ser Arg
995 1000 1005
Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly
1010 1015 1020
Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp
1025 1030 1035
Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
1040 1045 1050
Lys Asp Gly Ala Pro His His His His His His
1055 1060
<210> 94
<211> 1064
<212> PRT
<213> 人工序列
<220>
<223> MBip-TATκ28-CDKL5_107-FH_cho[2-7NQ]
<400> 94
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala Gly Asp Ala Ala
20 25 30
Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg
35 40 45
Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro
50 55 60
Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly
65 70 75 80
Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His
85 90 95
Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu
100 105 110
Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys
115 120 125
Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys
130 135 140
Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu
145 150 155 160
Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile
165 170 175
Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val
180 185 190
His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val
195 200 205
Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn
210 215 220
Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro
225 230 235 240
Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser
245 250 255
Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro
260 265 270
Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly
275 280 285
Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe
290 295 300
His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg
305 310 315 320
Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn
325 330 335
Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu
340 345 350
Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser
355 360 365
Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser
370 375 380
Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg
385 390 395 400
Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly Leu Pro Arg Ala
405 410 415
Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala
420 425 430
Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser
435 440 445
Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His
450 455 460
Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn
465 470 475 480
Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser
485 490 495
Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln
500 505 510
Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser
515 520 525
Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr
530 535 540
Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Gln
545 550 555 560
Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr
565 570 575
Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro
580 585 590
Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn
595 600 605
Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His
610 615 620
Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser
625 630 635 640
His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu
645 650 655
Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser
660 665 670
Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser
675 680 685
Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu
690 695 700
Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala
705 710 715 720
Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His
725 730 735
Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp
740 745 750
Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val
755 760 765
Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp
770 775 780
Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro
785 790 795 800
Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe
805 810 815
Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser Glu Gln Leu Lys
820 825 830
Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys
835 840 845
Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu
850 855 860
Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
865 870 875 880
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
885 890 895
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro
900 905 910
Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys
915 920 925
Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly
930 935 940
Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala
945 950 955 960
Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val
965 970 975
Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala
980 985 990
Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr Gln Arg Ser Arg
995 1000 1005
Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly
1010 1015 1020
Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp
1025 1030 1035
Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
1040 1045 1050
Lys Asp Gly Ala Pro His His His His His His
1055 1060
<210> 95
<211> 1064
<212> PRT
<213> 人工序列
<220>
<223> MBip-TATκ28-CDKL5_107-FH_cho[1,3-7NQ]
<400> 95
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala Gly Asp Ala Ala
20 25 30
Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg
35 40 45
Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro
50 55 60
Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly
65 70 75 80
Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His
85 90 95
Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu
100 105 110
Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys
115 120 125
Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys
130 135 140
Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu
145 150 155 160
Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile
165 170 175
Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val
180 185 190
His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val
195 200 205
Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu Ser Glu Gly Asn
210 215 220
Asn Ala Asn Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro
225 230 235 240
Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser
245 250 255
Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro
260 265 270
Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly
275 280 285
Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe
290 295 300
His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg
305 310 315 320
Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn
325 330 335
Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu
340 345 350
Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser
355 360 365
Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser
370 375 380
Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg
385 390 395 400
Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly Leu Pro Arg Ala
405 410 415
Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala
420 425 430
Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser
435 440 445
Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His
450 455 460
Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn
465 470 475 480
Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser
485 490 495
Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln
500 505 510
Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser
515 520 525
Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr
530 535 540
Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Gln
545 550 555 560
Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr
565 570 575
Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro
580 585 590
Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn
595 600 605
Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His
610 615 620
Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser
625 630 635 640
His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu
645 650 655
Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser
660 665 670
Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser
675 680 685
Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu
690 695 700
Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala
705 710 715 720
Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His
725 730 735
Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp
740 745 750
Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val
755 760 765
Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp
770 775 780
Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro
785 790 795 800
Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe
805 810 815
Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser Glu Gln Leu Lys
820 825 830
Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys
835 840 845
Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu
850 855 860
Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
865 870 875 880
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
885 890 895
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro
900 905 910
Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys
915 920 925
Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly
930 935 940
Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala
945 950 955 960
Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val
965 970 975
Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala
980 985 990
Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr Gln Arg Ser Arg
995 1000 1005
Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly
1010 1015 1020
Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp
1025 1030 1035
Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
1040 1045 1050
Lys Asp Gly Ala Pro His His His His His His
1055 1060
<210> 96
<211> 1064
<212> PRT
<213> 人工序列
<220>
<223> MBip-TATκ28-CDKL5_107-FH_cho[1-2,4-7NQ]
<400> 96
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala Gly Asp Ala Ala
20 25 30
Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg
35 40 45
Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro
50 55 60
Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly
65 70 75 80
Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His
85 90 95
Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu
100 105 110
Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys
115 120 125
Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys
130 135 140
Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu
145 150 155 160
Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile
165 170 175
Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val
180 185 190
His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val
195 200 205
Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu Ser Glu Gly Asn
210 215 220
Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro
225 230 235 240
Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser
245 250 255
Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro
260 265 270
Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly
275 280 285
Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe
290 295 300
His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg
305 310 315 320
Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn
325 330 335
Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu
340 345 350
Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser
355 360 365
Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser
370 375 380
Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg
385 390 395 400
Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly Leu Pro Arg Ala
405 410 415
Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala
420 425 430
Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser
435 440 445
Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His
450 455 460
Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn
465 470 475 480
Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser
485 490 495
Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln
500 505 510
Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser
515 520 525
Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr
530 535 540
Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Gln
545 550 555 560
Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr
565 570 575
Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro
580 585 590
Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn
595 600 605
Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His
610 615 620
Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser
625 630 635 640
His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu
645 650 655
Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser
660 665 670
Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser
675 680 685
Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu
690 695 700
Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala
705 710 715 720
Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His
725 730 735
Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp
740 745 750
Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val
755 760 765
Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp
770 775 780
Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro
785 790 795 800
Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe
805 810 815
Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser Glu Gln Leu Lys
820 825 830
Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys
835 840 845
Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu
850 855 860
Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
865 870 875 880
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
885 890 895
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro
900 905 910
Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys
915 920 925
Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly
930 935 940
Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala
945 950 955 960
Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val
965 970 975
Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala
980 985 990
Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr Gln Arg Ser Arg
995 1000 1005
Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly
1010 1015 1020
Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp
1025 1030 1035
Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
1040 1045 1050
Lys Asp Gly Ala Pro His His His His His His
1055 1060
<210> 97
<211> 1064
<212> PRT
<213> 人工序列
<220>
<223> MBip-TATκ28-CDKL5_107-FH_cho[1-3,5-7NQ]
<400> 97
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala Gly Asp Ala Ala
20 25 30
Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg
35 40 45
Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro
50 55 60
Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly
65 70 75 80
Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His
85 90 95
Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu
100 105 110
Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys
115 120 125
Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys
130 135 140
Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu
145 150 155 160
Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile
165 170 175
Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val
180 185 190
His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val
195 200 205
Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu Ser Glu Gly Asn
210 215 220
Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro
225 230 235 240
Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser
245 250 255
Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro
260 265 270
Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly
275 280 285
Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe
290 295 300
His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg
305 310 315 320
Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn
325 330 335
Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu
340 345 350
Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser
355 360 365
Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser
370 375 380
Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg
385 390 395 400
Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly Leu Pro Arg Ala
405 410 415
Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala
420 425 430
Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser
435 440 445
Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His
450 455 460
Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn
465 470 475 480
Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser
485 490 495
Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln
500 505 510
Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser
515 520 525
Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr
530 535 540
Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Asn
545 550 555 560
Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr
565 570 575
Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro
580 585 590
Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn
595 600 605
Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His
610 615 620
Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser
625 630 635 640
His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu
645 650 655
Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser
660 665 670
Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser
675 680 685
Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu
690 695 700
Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala
705 710 715 720
Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His
725 730 735
Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp
740 745 750
Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val
755 760 765
Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp
770 775 780
Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro
785 790 795 800
Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe
805 810 815
Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser Glu Gln Leu Lys
820 825 830
Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys
835 840 845
Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu
850 855 860
Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
865 870 875 880
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
885 890 895
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro
900 905 910
Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys
915 920 925
Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly
930 935 940
Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala
945 950 955 960
Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val
965 970 975
Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala
980 985 990
Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr Gln Arg Ser Arg
995 1000 1005
Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly
1010 1015 1020
Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp
1025 1030 1035
Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
1040 1045 1050
Lys Asp Gly Ala Pro His His His His His His
1055 1060
<210> 98
<211> 1064
<212> PRT
<213> 人工序列
<220>
<223> MBip-TATκ28-CDKL5_107-FH_cho[1-4,6-7NQ]
<400> 98
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala Gly Asp Ala Ala
20 25 30
Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg
35 40 45
Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro
50 55 60
Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly
65 70 75 80
Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His
85 90 95
Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu
100 105 110
Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys
115 120 125
Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys
130 135 140
Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu
145 150 155 160
Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile
165 170 175
Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val
180 185 190
His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val
195 200 205
Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu Ser Glu Gly Asn
210 215 220
Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro
225 230 235 240
Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser
245 250 255
Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro
260 265 270
Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly
275 280 285
Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe
290 295 300
His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg
305 310 315 320
Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn
325 330 335
Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu
340 345 350
Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser
355 360 365
Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser
370 375 380
Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg
385 390 395 400
Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly Leu Pro Arg Ala
405 410 415
Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala
420 425 430
Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser
435 440 445
Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His
450 455 460
Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn
465 470 475 480
Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser
485 490 495
Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln
500 505 510
Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser
515 520 525
Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr
530 535 540
Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Gln
545 550 555 560
Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr
565 570 575
Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro
580 585 590
Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn
595 600 605
Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His
610 615 620
Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser
625 630 635 640
His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu
645 650 655
Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser
660 665 670
Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser
675 680 685
Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu
690 695 700
Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala
705 710 715 720
Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His
725 730 735
Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp
740 745 750
Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val
755 760 765
Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp
770 775 780
Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro
785 790 795 800
Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe
805 810 815
Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys
820 825 830
Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys
835 840 845
Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu
850 855 860
Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
865 870 875 880
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
885 890 895
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro
900 905 910
Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys
915 920 925
Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly
930 935 940
Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala
945 950 955 960
Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val
965 970 975
Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala
980 985 990
Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr Gln Arg Ser Arg
995 1000 1005
Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly
1010 1015 1020
Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp
1025 1030 1035
Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
1040 1045 1050
Lys Asp Gly Ala Pro His His His His His His
1055 1060
<210> 99
<211> 1064
<212> PRT
<213> 人工序列
<220>
<223> MBip-TATκ28-CDKL5_107-FH_cho[1-5,7NQ]
<400> 99
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala Gly Asp Ala Ala
20 25 30
Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg
35 40 45
Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro
50 55 60
Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly
65 70 75 80
Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His
85 90 95
Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu
100 105 110
Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys
115 120 125
Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys
130 135 140
Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu
145 150 155 160
Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile
165 170 175
Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val
180 185 190
His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val
195 200 205
Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu Ser Glu Gly Asn
210 215 220
Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro
225 230 235 240
Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser
245 250 255
Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro
260 265 270
Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly
275 280 285
Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe
290 295 300
His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg
305 310 315 320
Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn
325 330 335
Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu
340 345 350
Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser
355 360 365
Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser
370 375 380
Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg
385 390 395 400
Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly Leu Pro Arg Ala
405 410 415
Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala
420 425 430
Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser
435 440 445
Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His
450 455 460
Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn
465 470 475 480
Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser
485 490 495
Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln
500 505 510
Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser
515 520 525
Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr
530 535 540
Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Gln
545 550 555 560
Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr
565 570 575
Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro
580 585 590
Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn
595 600 605
Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His
610 615 620
Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser
625 630 635 640
His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu
645 650 655
Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser
660 665 670
Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser
675 680 685
Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu
690 695 700
Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala
705 710 715 720
Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His
725 730 735
Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp
740 745 750
Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val
755 760 765
Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp
770 775 780
Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro
785 790 795 800
Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe
805 810 815
Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser Glu Gln Leu Lys
820 825 830
Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys
835 840 845
Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu
850 855 860
Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
865 870 875 880
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
885 890 895
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro
900 905 910
Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys
915 920 925
Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly
930 935 940
Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala
945 950 955 960
Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val
965 970 975
Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala
980 985 990
Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg Thr Gln Arg Ser Arg
995 1000 1005
Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly
1010 1015 1020
Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp
1025 1030 1035
Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
1040 1045 1050
Lys Asp Gly Ala Pro His His His His His His
1055 1060
<210> 100
<211> 1064
<212> PRT
<213> 人工序列
<220>
<223> MBip-TATκ28-CDKL5_107-FH_cho[1-6NQ]
<400> 100
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala Gly Asp Ala Ala
20 25 30
Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg
35 40 45
Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro
50 55 60
Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly
65 70 75 80
Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His
85 90 95
Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu
100 105 110
Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys
115 120 125
Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys
130 135 140
Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu
145 150 155 160
Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile
165 170 175
Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val
180 185 190
His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val
195 200 205
Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu Ser Glu Gly Asn
210 215 220
Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro
225 230 235 240
Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser
245 250 255
Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro
260 265 270
Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly
275 280 285
Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe
290 295 300
His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg
305 310 315 320
Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn
325 330 335
Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu
340 345 350
Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser
355 360 365
Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser
370 375 380
Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg
385 390 395 400
Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly Leu Pro Arg Ala
405 410 415
Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala
420 425 430
Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser
435 440 445
Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His
450 455 460
Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn
465 470 475 480
Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser
485 490 495
Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln
500 505 510
Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser
515 520 525
Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr
530 535 540
Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Gln
545 550 555 560
Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr
565 570 575
Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro
580 585 590
Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn
595 600 605
Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His
610 615 620
Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser
625 630 635 640
His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu
645 650 655
Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser
660 665 670
Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser
675 680 685
Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu
690 695 700
Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala
705 710 715 720
Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His
725 730 735
Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp
740 745 750
Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val
755 760 765
Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp
770 775 780
Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro
785 790 795 800
Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe
805 810 815
Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser Glu Gln Leu Lys
820 825 830
Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys
835 840 845
Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu
850 855 860
Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
865 870 875 880
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
885 890 895
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro
900 905 910
Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys
915 920 925
Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly
930 935 940
Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala
945 950 955 960
Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val
965 970 975
Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala
980 985 990
Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr Asn Arg Ser Arg
995 1000 1005
Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly
1010 1015 1020
Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp
1025 1030 1035
Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
1040 1045 1050
Lys Asp Gly Ala Pro His His His His His His
1055 1060
<210> 101
<211> 1064
<212> PRT
<213> 人工序列
<220>
<223> MBip-TATκ28-CDKL5_107-FH_cho[2NQ]
<400> 101
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala Gly Asp Ala Ala
20 25 30
Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg
35 40 45
Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro
50 55 60
Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly
65 70 75 80
Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His
85 90 95
Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu
100 105 110
Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys
115 120 125
Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys
130 135 140
Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu
145 150 155 160
Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile
165 170 175
Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val
180 185 190
His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val
195 200 205
Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn
210 215 220
Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro
225 230 235 240
Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser
245 250 255
Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro
260 265 270
Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly
275 280 285
Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe
290 295 300
His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg
305 310 315 320
Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn
325 330 335
Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu
340 345 350
Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser
355 360 365
Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser
370 375 380
Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg
385 390 395 400
Ser Asn Ser Lys Asp Ile Gln Asn Leu Ser Val Gly Leu Pro Arg Ala
405 410 415
Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala
420 425 430
Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser
435 440 445
Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His
450 455 460
Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn
465 470 475 480
Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser
485 490 495
Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln
500 505 510
Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser
515 520 525
Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr
530 535 540
Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Asn
545 550 555 560
Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr
565 570 575
Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro
580 585 590
Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn
595 600 605
Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His
610 615 620
Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser
625 630 635 640
His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu
645 650 655
Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser
660 665 670
Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser
675 680 685
Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu
690 695 700
Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala
705 710 715 720
Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His
725 730 735
Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp
740 745 750
Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val
755 760 765
Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp
770 775 780
Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro
785 790 795 800
Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe
805 810 815
Asp Pro Trp Lys Ser Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys
820 825 830
Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys
835 840 845
Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu
850 855 860
Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
865 870 875 880
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
885 890 895
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro
900 905 910
Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys
915 920 925
Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly
930 935 940
Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala
945 950 955 960
Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val
965 970 975
Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala
980 985 990
Lys Ser Gly Pro Asn Gly His Pro Tyr Asn Arg Thr Asn Arg Ser Arg
995 1000 1005
Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly
1010 1015 1020
Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp
1025 1030 1035
Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
1040 1045 1050
Lys Asp Gly Ala Pro His His His His His His
1055 1060
<210> 102
<211> 1064
<212> PRT
<213> 人工序列
<220>
<223> MBip-TATκ28-CDKL5_107-FH_cho[1-10NQ]
<400> 102
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala Gly Asp Ala Ala
20 25 30
Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg
35 40 45
Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro
50 55 60
Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly
65 70 75 80
Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His
85 90 95
Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu
100 105 110
Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys
115 120 125
Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys
130 135 140
Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu
145 150 155 160
Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile
165 170 175
Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val
180 185 190
His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val
195 200 205
Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu Ser Glu Gly Asn
210 215 220
Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro
225 230 235 240
Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser
245 250 255
Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro
260 265 270
Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly
275 280 285
Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe
290 295 300
His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg
305 310 315 320
Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn
325 330 335
Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu
340 345 350
Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser
355 360 365
Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser
370 375 380
Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg
385 390 395 400
Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly Leu Pro Arg Ala
405 410 415
Asp Glu Gly Leu Pro Ala Gln Glu Ser Phe Leu Asn Gly Asn Leu Ala
420 425 430
Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser
435 440 445
Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His
450 455 460
Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn
465 470 475 480
Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser
485 490 495
Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln
500 505 510
Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser
515 520 525
Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr
530 535 540
Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Gln
545 550 555 560
Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr
565 570 575
Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro
580 585 590
Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn
595 600 605
Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His
610 615 620
Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser
625 630 635 640
His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu
645 650 655
Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser
660 665 670
Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser
675 680 685
Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu
690 695 700
Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala
705 710 715 720
Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His
725 730 735
Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp
740 745 750
Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val
755 760 765
Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp
770 775 780
Asn Ser Phe His Glu Asn Gln Val Ser Thr Arg Val Ser Ser Leu Pro
785 790 795 800
Ser Glu Ser Ser Ser Gly Thr Gln His Ser Lys Arg Gln Pro Ala Phe
805 810 815
Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser Glu Gln Leu Lys
820 825 830
Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys
835 840 845
Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu
850 855 860
Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
865 870 875 880
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
885 890 895
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro
900 905 910
Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys
915 920 925
Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly
930 935 940
Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala
945 950 955 960
Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val
965 970 975
Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala
980 985 990
Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr Gln Arg Ser Arg
995 1000 1005
Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly
1010 1015 1020
Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp
1025 1030 1035
Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
1040 1045 1050
Lys Asp Gly Ala Pro His His His His His His
1055 1060
<210> 103
<211> 1064
<212> PRT
<213> 人工序列
<220>
<223> MBip-TATκ28-CDKL5_107-FH_cho[1-7,9-10NQ]
<400> 103
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala Gly Asp Ala Ala
20 25 30
Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg
35 40 45
Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro
50 55 60
Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly
65 70 75 80
Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His
85 90 95
Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu
100 105 110
Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys
115 120 125
Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys
130 135 140
Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu
145 150 155 160
Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile
165 170 175
Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val
180 185 190
His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val
195 200 205
Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu Ser Glu Gly Asn
210 215 220
Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro
225 230 235 240
Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser
245 250 255
Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro
260 265 270
Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly
275 280 285
Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe
290 295 300
His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg
305 310 315 320
Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn
325 330 335
Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu
340 345 350
Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser
355 360 365
Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser
370 375 380
Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg
385 390 395 400
Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly Leu Pro Arg Ala
405 410 415
Asp Glu Gly Leu Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala
420 425 430
Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser
435 440 445
Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His
450 455 460
Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn
465 470 475 480
Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser
485 490 495
Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln
500 505 510
Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser
515 520 525
Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr
530 535 540
Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Gln
545 550 555 560
Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr
565 570 575
Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro
580 585 590
Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn
595 600 605
Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His
610 615 620
Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser
625 630 635 640
His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu
645 650 655
Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser
660 665 670
Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser
675 680 685
Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu
690 695 700
Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala
705 710 715 720
Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His
725 730 735
Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp
740 745 750
Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val
755 760 765
Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp
770 775 780
Asn Ser Phe His Glu Asn Gln Val Ser Thr Arg Val Ser Ser Leu Pro
785 790 795 800
Ser Glu Ser Ser Ser Gly Thr Gln His Ser Lys Arg Gln Pro Ala Phe
805 810 815
Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser Glu Gln Leu Lys
820 825 830
Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys
835 840 845
Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu
850 855 860
Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
865 870 875 880
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
885 890 895
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro
900 905 910
Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys
915 920 925
Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly
930 935 940
Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala
945 950 955 960
Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val
965 970 975
Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala
980 985 990
Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr Gln Arg Ser Arg
995 1000 1005
Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly
1010 1015 1020
Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp
1025 1030 1035
Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
1040 1045 1050
Lys Asp Gly Ala Pro His His His His His His
1055 1060
<210> 104
<211> 1064
<212> PRT
<213> 人工序列
<220>
<223> MBip-TATκ28-CDKL5_107-FH_cho[1-8,10NQ]
<400> 104
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala Gly Asp Ala Ala
20 25 30
Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg
35 40 45
Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro
50 55 60
Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly
65 70 75 80
Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His
85 90 95
Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu
100 105 110
Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys
115 120 125
Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys
130 135 140
Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu
145 150 155 160
Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile
165 170 175
Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val
180 185 190
His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val
195 200 205
Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu Ser Glu Gly Asn
210 215 220
Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro
225 230 235 240
Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser
245 250 255
Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro
260 265 270
Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly
275 280 285
Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe
290 295 300
His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg
305 310 315 320
Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn
325 330 335
Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu
340 345 350
Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser
355 360 365
Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser
370 375 380
Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg
385 390 395 400
Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly Leu Pro Arg Ala
405 410 415
Asp Glu Gly Leu Pro Ala Gln Glu Ser Phe Leu Asn Gly Asn Leu Ala
420 425 430
Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser
435 440 445
Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His
450 455 460
Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn
465 470 475 480
Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser
485 490 495
Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln
500 505 510
Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser
515 520 525
Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr
530 535 540
Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Gln
545 550 555 560
Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr
565 570 575
Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro
580 585 590
Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn
595 600 605
Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His
610 615 620
Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser
625 630 635 640
His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu
645 650 655
Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser
660 665 670
Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser
675 680 685
Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu
690 695 700
Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala
705 710 715 720
Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His
725 730 735
Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp
740 745 750
Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val
755 760 765
Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp
770 775 780
Asn Ser Phe His Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro
785 790 795 800
Ser Glu Ser Ser Ser Gly Thr Gln His Ser Lys Arg Gln Pro Ala Phe
805 810 815
Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser Glu Gln Leu Lys
820 825 830
Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys
835 840 845
Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu
850 855 860
Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
865 870 875 880
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
885 890 895
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro
900 905 910
Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys
915 920 925
Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly
930 935 940
Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala
945 950 955 960
Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val
965 970 975
Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala
980 985 990
Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr Gln Arg Ser Arg
995 1000 1005
Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly
1010 1015 1020
Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp
1025 1030 1035
Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
1040 1045 1050
Lys Asp Gly Ala Pro His His His His His His
1055 1060
<210> 105
<211> 1064
<212> PRT
<213> 人工序列
<220>
<223> MBip-TATκ28-CDKL5_107-FH_cho[1-9NQ]
<400> 105
Met Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu Val
1 5 10 15
Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala Gly Asp Ala Ala
20 25 30
Gln Pro Ala Arg Arg Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg
35 40 45
Lys Ala Ala Arg Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro
50 55 60
Asn Ile Gly Asn Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly
65 70 75 80
Glu Gly Ala Tyr Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His
85 90 95
Glu Ile Val Ala Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu
100 105 110
Val Lys Glu Thr Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys
115 120 125
Gln Glu Asn Ile Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys
130 135 140
Leu Tyr Leu Val Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu
145 150 155 160
Glu Glu Met Pro Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile
165 170 175
Tyr Gln Leu Ile Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val
180 185 190
His Arg Asp Ile Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val
195 200 205
Leu Lys Leu Cys Asp Phe Gly Phe Ala Arg Gln Leu Ser Glu Gly Asn
210 215 220
Asn Ala Gln Tyr Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro
225 230 235 240
Glu Leu Leu Leu Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser
245 250 255
Val Gly Cys Ile Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro
260 265 270
Gly Glu Ser Glu Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly
275 280 285
Pro Leu Pro Ser Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe
290 295 300
His Gly Leu Arg Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg
305 310 315 320
Arg Tyr Leu Gly Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn
325 330 335
Leu Leu Lys Leu Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu
340 345 350
Asn His Pro Thr Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser
355 360 365
Arg Ser Ala Lys Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser
370 375 380
Asn Arg Asn Gln Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg
385 390 395 400
Ser Asn Ser Lys Asp Ile Gln Gln Leu Ser Val Gly Leu Pro Arg Ala
405 410 415
Asp Glu Gly Leu Pro Ala Gln Glu Ser Phe Leu Asn Gly Asn Leu Ala
420 425 430
Gly Ala Ser Leu Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser
435 440 445
Gln Pro Gly Ser Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His
450 455 460
Leu Leu Ser Pro Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn
465 470 475 480
Ile Asp Pro Lys Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser
485 490 495
Asn Ser Arg Ser Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln
500 505 510
Ser Lys Ala Gly Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser
515 520 525
Tyr Ile Asp Thr Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr
530 535 540
Lys Ala Lys Ser His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Gln
545 550 555 560
Leu Ser Glu Ala Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr
565 570 575
Phe Pro Ser Ser Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro
580 585 590
Thr Arg His Ser Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn
595 600 605
Asn Arg Asn Glu Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His
610 615 620
Ser Lys Thr Met Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser
625 630 635 640
His Ser His Ser Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu
645 650 655
Gly Tyr Thr Ser Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser
660 665 670
Met Tyr Val Thr Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser
675 680 685
Leu Ser Ile Gly Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu
690 695 700
Leu Ser Pro Gln Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala
705 710 715 720
Arg Ser Ser Val Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His
725 730 735
Thr Arg Gln Lys Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp
740 745 750
Asp Gly Thr Ala Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val
755 760 765
Pro Arg Arg Val Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp
770 775 780
Asn Ser Phe His Glu Asn Gln Val Ser Thr Arg Val Ser Ser Leu Pro
785 790 795 800
Ser Glu Ser Ser Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe
805 810 815
Asp Pro Trp Lys Ser Pro Glu Gln Ile Ser His Ser Glu Gln Leu Lys
820 825 830
Glu Lys Glu Lys Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys
835 840 845
Lys Ser Gln Thr Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu
850 855 860
Gln Lys Ser Ile His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu
865 870 875 880
Trp Arg Pro Glu Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu
885 890 895
Lys Ser Leu Arg Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro
900 905 910
Ala Ser Ser Asp Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys
915 920 925
Asn Ser Phe Ser Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly
930 935 940
Gly Ser Ser Asn Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala
945 950 955 960
Leu Gln Leu Pro Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val
965 970 975
Thr Arg Ser Ala Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala
980 985 990
Lys Ser Gly Pro Asn Gly His Pro Tyr Gln Arg Thr Gln Arg Ser Arg
995 1000 1005
Met Pro Asn Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Gly Gly
1010 1015 1020
Gly Ser Glu Asn Leu Tyr Phe Gln Gly Asp Tyr Lys Asp His Asp
1025 1030 1035
Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
1040 1045 1050
Lys Asp Gly Ala Pro His His His His His His
1055 1060
<210> 106
<211> 6886
<212> DNA
<213> 人工序列
<220>
<223> AAVC-CBh-hCDKL5-107
<400> 106
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc tgcggcctaa ggcaattgtt aatagtaatc aattacgggg 180
tcattagttc atagcccata tatggagttc cgcgttacat aacttacggt aaatggcccg 240
cctggctgac cgcccaacga cccccgccca ttgacgtcaa taatgacgta tgttcccata 300
gtaacgccaa tagggacttt ccattgacgt caatgggtgg agtatttacg gtaaactgcc 360
cacttggcag tacatcaagt gtatcatatg ccaagtacgc cccctattga cgtcaatgac 420
ggtaaatggc ccgcctggca ttatgcccag tacatgacct tacgggactt tcctacttgg 480
cagtacatct ccacgttctg cttcactctc cccatctccc ccccctcccc acccccaatt 540
ttgtatttat ttatttttta attattttgt gcagcgatgg gggcgggggg ggggggggcg 600
cgcgccaggc ggggcggggc ggggcgaggg gcggggcggg gcgaggcgga gaggtgcggc 660
ggcagccaat cagagcggcg cgctccgaaa gtttcctttt atggcgaggc ggcggcggcg 720
gcggccctat aaaaagcgaa gcgcgcggcg gggagtcgct gcgttgcctt cgccccgtgc 780
cccgctccgc gccgcctcgc gccgcccgcc ccggctctga ctgaccgcgt tactcccaca 840
ggtgagcggg cgggacggcc cttctcctcc gggctgtaat tagcaagagg taagggttta 900
agggatggtt ggttggtggg gtattaatgt ttaattacct gttttacagg cctgaaatca 960
cttggtttta ggttgggcta gccaaagctt gccgccacca tgaaaatccc taacattggt 1020
aacgtgatga acaagtttga aatcctcggg gtcgtcggag aaggtgccta cggggtcgtg 1080
ctgaagtgca gacacaagga gacacacgag atcgtggcca tcaagaagtt caaggatagc 1140
gaggagaacg aggaggtgaa ggagacaacc ctgagagagc tgaagatgct gcggacactg 1200
aagcaggaga acatcgtgga gctgaaggag gctttcagga gacggggaaa gctgtacctg 1260
gtgtttgagt acgtggagaa gaacatgctg gagctgctgg aggagatgcc taacggcgtg 1320
ccccctgaga aggtgaagtc ctacatctac cagctgatca aggccatcca ctggtgccac 1380
aagaacgaca tcgtgcacag agatatcaag ccagagaacc tgctgatctc ccacaacgac 1440
gtgctgaagc tgtgcgattt cggctttgcc cggaacctga gcgagggaaa caacgccaac 1500
tacacagagt acgtggctac cagatggtac cggagcccag agctgctgct gggagctcca 1560
tacggaaaga gcgtggacat gtggtccgtg ggctgcatcc tgggagagct gtctgacggc 1620
cagcctctgt tcccaggaga gagcgagatc gatcagctgt ttaccatcca gaaggtgctg 1680
ggccctctgc caagcgagca gatgaagctg ttctactcca accctagatt ccacggactg 1740
cggtttcccg ccgtgaacca ccctcagagc ctggagcgca ggtacctggg catcctgaac 1800
tccgtgctgc tggatctgat gaagaacctg ctgaagctgg accccgccga tagatacctg 1860
accgagcagt gtctgaacca ccctacattt cagacccagc gcctgctgga caggagccct 1920
tccagatctg ctaagcggaa gccataccac gtggagagct ccaccctgtc caacagaaac 1980
caggccggca agtctacagc tctgcagagc caccaccgga gcaactccaa ggacatccag 2040
aacctgtctg tgggcctgcc tagggctgat gagggactgc cagctaacga gagcttcctg 2100
aacggcaacc tggccggagc ttctctgagc ccactgcaca caaagaccta ccaggcctct 2160
agccagcccg gctccacatc taaggacctg accaacaaca acatcccaca cctgctgtct 2220
cccaaggagg ctaagagcaa gaccgagttc gactttaaca tcgatcccaa gcctagcgag 2280
ggcccaggaa caaagtacct gaagagcaac tcccgctctc agcagaacag gcactccttc 2340
atggagtcct ctcagtctaa ggccggcacc ctgcagccca acgagaagca gagcaggcac 2400
tcctacatcg ataccatccc ccagagctcc agaagccctt cctaccggac aaaggccaag 2460
agccacggcg ctctgtctga cagcaagtcc gtgtctaacc tgtccgaggc tagggctcag 2520
atcgctgagc caagcacctc caggtacttt ccttctagct gtctggacct gaactctcct 2580
acaagcccaa cacccacccg ccactccgat acaaggaccc tgctgtctcc aagcggcagg 2640
aacaacagga acgagggaac cctggattct agacggacca caacccgcca cagcaagaca 2700
atggaggagc tgaagctgcc agagcacatg gactcctctc actcccactc tctgagcgcc 2760
ccccacgagt ccttctctta cggcctggga tacacctccc ccttcagctc ccagcagagg 2820
ccccacaggc actctatgta cgtgacacgc gacaaggtga gggccaaggg cctggatgga 2880
agcctgtcca tcggacaggg aatggctgct agggctaact ccctgcagct gctgtctcct 2940
cagccaggag agcagctgcc accagagatg accgtggctc gctctagcgt gaaggagaca 3000
agcagggagg gcacctcctc tttccacaca cgccagaagt ccgagggcgg agtgtaccac 3060
gacccccact ctgacgatgg aacagctcct aaggagaaca ggcacctgta caacgatccc 3120
gtgcctcgca gggtgggctc cttctacaga gtgccatctc cccggcctga caacagcttt 3180
cacgagaaca acgtgtccac ccgcgtgagc tccctgcctt ctgagtctag ctccggaaca 3240
aaccactcta agaggcagcc cgcctttgac ccttggaaga gcccagagaa catctctcac 3300
agcgagcagc tgaaggagaa ggagaagcag ggcttctttc gcagcatgaa gaagaagaag 3360
aagaagagcc agaccgtgcc taactccgac tctccagatc tgctgaccct gcagaagtcc 3420
atccacagcg cctccacacc atctagccgc cctaaggagt ggaggcctga gaagatcagc 3480
gatctgcaga cacagagcca gccactgaag tccctgagga agctgctgca cctgtcctct 3540
gccagcaacc accccgctag ctccgaccca agattccagc ccctgacagc ccagcagacc 3600
aagaactctt ttagcgagat ccggatccac cctctgtccc aggcttctgg cggatctagc 3660
aacatcagac aggagccagc tccaaagggc cggcccgctc tgcagctgcc tggccagatg 3720
gacccaggat ggcacgtgtc ctctgtgaca agatccgcca ccgagggacc atcctactct 3780
gagcagctgg gcgctaagtc tggccctaac ggacacccat acaataggac taatagaagc 3840
agaatgccaa acctcaatga cctcaaggaa acagcactct gataagcggc cgcaactcga 3900
gactctagac gactgtgcct tctagttgcc agccatctgt tgtttgcccc tcccccgtgc 3960
cttccttgac cctggaaggt gccactccca ctgtcctttc ctaataaaat gaggaaattg 4020
catcgcattg tctgagtagg tgtcattcta ttctgggggg tggggtgggg caggacagca 4080
agggggagga ttgggaagac aatagcaggc atgctgggga tgcggtgggc tctatggccg 4140
cgggccgcag gaacccctag tgatggagtt ggccactccc tctctgcgcg ctcgctcgct 4200
cactgaggcc gggcgaccaa aggtcgcccg acgcccgggc tttgcccggg cggcctcagt 4260
gagcgagcga gcgcgcagct gcctgcaggg gcgcctgatg cggtattttc tccttacgca 4320
tctgtgcggt atttcacacc gcatacgtca aagcaaccat agtacgcgcc ctgtagcggc 4380
gcattaagcg cggcgggtgt ggtggttacg cgcagcgtga ccgctacact tgccagcgcc 4440
ctagcgcccg ctcctttcgc tttcttccct tcctttctcg ccacgttcgc cggctttccc 4500
cgtcaagctc taaatcgggg gctcccttta gggttccgat ttagtgcttt acggcacctc 4560
gaccccaaaa aacttgattt gggtgatggt tcacgtagtg ggccatcgcc ctgatagacg 4620
gtttttcgcc ctttgacgtt ggagtccacg ttctttaata gtggactctt gttccaaact 4680
ggaacaacac tcaaccctat ctcgggctat tcttttgatt tataagggat tttgccgatt 4740
tcggcctatt ggttaaaaaa tgagctgatt taacaaaaat ttaacgcgaa ttttaacaaa 4800
atattaacgt ttacaatttt atggtgcact ctcagtacaa tctgctctga tgccgcatag 4860
ttaagccagc cccgacaccc gccaacaccc gctgacgcgc cctgacgggc ttgtctgctc 4920
ccggcatccg cttacagaca agctgtgacc gtctccggga gctgcatgtg tcagaggttt 4980
tcaccgtcat caccgaaacg cgcgagacga aagggcctcg tgatacgcct atttttatag 5040
gttaatgtca tgataataat ggtttcttag acgtcaggtg gcacttttcg gggaaatgtg 5100
cgcggaaccc ctatttgttt atttttctaa atacattcaa atatgtatcc gctcatgaga 5160
caataaccct gataaatgct tcaataatat tgaaaaagga agagtatgag tattcaacat 5220
ttccgtgtcg cccttattcc cttttttgcg gcattttgcc ttcctgtttt tgctcaccca 5280
gaaacgctgg tgaaagtaaa agatgctgaa gatcagttgg gtgcacgagt gggttacatc 5340
gaactggatc tcaacagcgg taagatcctt gagagttttc gccccgaaga acgttttcca 5400
atgatgagca cttttaaagt tctgctatgt ggcgcggtat tatcccgtat tgacgccggg 5460
caagagcaac tcggtcgccg catacactat tctcagaatg acttggttga gtactcacca 5520
gtcacagaaa agcatcttac ggatggcatg acagtaagag aattatgcag tgctgccata 5580
accatgagtg ataacactgc ggccaactta cttctgacaa cgatcggagg accgaaggag 5640
ctaaccgctt ttttgcacaa catgggggat catgtaactc gccttgatcg ttgggaaccg 5700
gagctgaatg aagccatacc aaacgacgag cgtgacacca cgatgcctgt agcaatggca 5760
acaacgttgc gcaaactatt aactggcgaa ctacttactc tagcttcccg gcaacaatta 5820
atagactgga tggaggcgga taaagttgca ggaccacttc tgcgctcggc ccttccggct 5880
ggctggttta ttgctgataa atctggagcc ggtgagcgtg ggtctcgcgg tatcattgca 5940
gcactggggc cagatggtaa gccctcccgt atcgtagtta tctacacgac ggggagtcag 6000
gcaactatgg atgaacgaaa tagacagatc gctgagatag gtgcctcact gattaagcat 6060
tggtaactgt cagaccaagt ttactcatat atactttaga ttgatttaaa acttcatttt 6120
taatttaaaa ggatctaggt gaagatcctt tttgataatc tcatgaccaa aatcccttaa 6180
cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 6240
gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 6300
gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 6360
agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 6420
aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 6480
agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 6540
cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 6600
accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 6660
aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 6720
ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 6780
cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 6840
gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgt 6886
<210> 107
<211> 6886
<212> DNA
<213> 人工序列
<220>
<223> AAVC-CBh-hCDKL5-107(失活激酶)
<400> 107
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc tgcggcctaa ggcaattgtt aatagtaatc aattacgggg 180
tcattagttc atagcccata tatggagttc cgcgttacat aacttacggt aaatggcccg 240
cctggctgac cgcccaacga cccccgccca ttgacgtcaa taatgacgta tgttcccata 300
gtaacgccaa tagggacttt ccattgacgt caatgggtgg agtatttacg gtaaactgcc 360
cacttggcag tacatcaagt gtatcatatg ccaagtacgc cccctattga cgtcaatgac 420
ggtaaatggc ccgcctggca ttatgcccag tacatgacct tacgggactt tcctacttgg 480
cagtacatct ccacgttctg cttcactctc cccatctccc ccccctcccc acccccaatt 540
ttgtatttat ttatttttta attattttgt gcagcgatgg gggcgggggg ggggggggcg 600
cgcgccaggc ggggcggggc ggggcgaggg gcggggcggg gcgaggcgga gaggtgcggc 660
ggcagccaat cagagcggcg cgctccgaaa gtttcctttt atggcgaggc ggcggcggcg 720
gcggccctat aaaaagcgaa gcgcgcggcg gggagtcgct gcgttgcctt cgccccgtgc 780
cccgctccgc gccgcctcgc gccgcccgcc ccggctctga ctgaccgcgt tactcccaca 840
ggtgagcggg cgggacggcc cttctcctcc gggctgtaat tagcaagagg taagggttta 900
agggatggtt ggttggtggg gtattaatgt ttaattacct gttttacagg cctgaaatca 960
cttggtttta ggttgggcta gccaaagctt gccgccacca tgaaaatccc taatatcgga 1020
aatgtgatga ataagtttga aatcctcggg gtcgtcggag aaggtgccta cggggtcgtc 1080
ctgaaatgca gacacaagga gacacacgag atcgtggcca tcaggagatt caaggatagc 1140
gaggagaacg aggaggtgaa ggagacaacc ctgcgcgagc tgaagatgct gaggacactg 1200
aagcaggaga acatcgtgga gctgaaggag gctttccggc gcaggggaaa gctgtacctg 1260
gtgtttgagt acgtggagaa gaacatgctg gagctgctgg aggagatgcc taacggcgtg 1320
ccccctgaga aggtgaagtc ctacatctac cagctgatca aggccatcca ctggtgccac 1380
aagaacgaca tcgtgcaccg cgatatcaag ccagagaacc tgctgatctc ccacaacgac 1440
gtgctgaagc tgtgcgattt cggctttgcc aggaacctga gcgagggaaa caacgccaac 1500
tacacagagt acgtggctac ccgctggtac aggagcccag agctgctgct gggagctcca 1560
tacggaaaga gcgtggacat gtggtccgtg ggctgcatcc tgggagagct gtctgacggc 1620
cagcctctgt tcccaggaga gagcgagatc gatcagctgt ttaccatcca gaaggtgctg 1680
ggccctctgc caagcgagca gatgaagctg ttctactcca accctcgctt ccacggactg 1740
aggtttcccg ccgtgaacca ccctcagagc ctggagagac ggtacctggg catcctgaac 1800
tccgtgctgc tggatctgat gaagaacctg ctgaagctgg accccgccga tcgctacctg 1860
accgagcagt gtctgaacca ccctacattt cagacccaga gactgctgga ccggagccct 1920
tcccgctctg ctaagaggaa gccataccac gtggagagct ccaccctgtc caaccgcaac 1980
caggccggca agtctacagc tctgcagagc caccacagga gcaactccaa ggacatccag 2040
aacctgtctg tgggcctgcc tagggctgat gagggactgc cagctaacga gagcttcctg 2100
aacggcaacc tggccggagc ttctctgagc ccactgcaca caaagaccta ccaggcctct 2160
agccagcccg gctccacatc taaggacctg accaacaaca acatcccaca cctgctgtct 2220
cccaaggagg ctaagagcaa gaccgagttc gactttaaca tcgatcccaa gcctagcgag 2280
ggcccaggaa caaagtacct gaagagcaac tccagatctc agcagaaccg gcactccttc 2340
atggagtcct ctcagtctaa ggccggcacc ctgcagccca acgagaagca gagcaggcac 2400
tcctacatcg ataccatccc ccagagctcc cgcagccctt cctacaggac aaaggccaag 2460
agccacggcg ctctgtctga cagcaagtcc gtgtctaacc tgtccgaggc cagagctcag 2520
atcgctgagc ccagcacctc ccggtacttt ccttctagct gtctggacct gaactctcct 2580
acaagcccaa cacccaccag acactccgat acacggaccc tgctgtctcc aagcggcaga 2640
aacaaccgga acgagggaac cctggattct cgcaggacca caaccagaca cagcaagaca 2700
atggaggagc tgaagctgcc agagcacatg gactcctctc actcccactc tctgagcgcc 2760
ccccacgagt ccttctctta cggcctggga tacacctccc ccttcagctc ccagcagcgc 2820
ccccacaggc actctatgta cgtgacaaga gacaaggtgc gggccaaggg cctggatgga 2880
agcctgtcca tcggccaggg aatggccgct agggctaact ccctgcagct gctgtctcct 2940
cagccaggag agcagctgcc acccgagatg accgtggcca gatctagcgt gaaggagaca 3000
agccgggagg gcacctcctc tttccacaca agacagaagt ccgagggcgg agtgtaccac 3060
gacccccact ctgacgatgg aacagctcct aaggagaacc ggcacctgta caacgatccc 3120
gtgcctagac gggtgggctc cttctaccgc gtgccatctc ccaggcctga caacagcttt 3180
cacgagaaca acgtgtccac cagagtgagc tccctgcctt ctgagtctag ctccggaaca 3240
aaccactcta agcggcagcc cgcctttgac ccttggaaga gcccagagaa catctctcac 3300
agcgagcagc tgaaggagaa ggagaagcag ggcttcttta gaagcatgaa gaagaagaag 3360
aagaagagcc agaccgtgcc taactccgac tctccagatc tgctgaccct gcagaagtcc 3420
atccacagcg cctccacacc ctctagcaga cctaaggagt ggcggcctga gaagatcagc 3480
gatctgcaga cacagagcca gccactgaag tccctgcgga agctgctgca cctgtcctct 3540
gccagcaacc acccagctag ctccgaccca aggttccagc cactgacagc tcagcagacc 3600
aagaactctt ttagcgagat caggatccac cctctgtccc aggcttctgg cggatctagc 3660
aacatcaggc aggagccagc tccaaagggc aggcccgctc tgcagctgcc tggacagatg 3720
gacccaggat ggcacgtgtc ctctgtgaca agatccgcca ccgagggacc atcctactct 3780
gagcagctgg gcgctaagtc tggccctaac ggacacccat acaacagaac aaacagaagc 3840
agaatgccca acctcaatga cctcaaagaa acagcactct gataagcggc cgcaactcga 3900
gactctagac gactgtgcct tctagttgcc agccatctgt tgtttgcccc tcccccgtgc 3960
cttccttgac cctggaaggt gccactccca ctgtcctttc ctaataaaat gaggaaattg 4020
catcgcattg tctgagtagg tgtcattcta ttctgggggg tggggtgggg caggacagca 4080
agggggagga ttgggaagac aatagcaggc atgctgggga tgcggtgggc tctatggccg 4140
cgggccgcag gaacccctag tgatggagtt ggccactccc tctctgcgcg ctcgctcgct 4200
cactgaggcc gggcgaccaa aggtcgcccg acgcccgggc tttgcccggg cggcctcagt 4260
gagcgagcga gcgcgcagct gcctgcaggg gcgcctgatg cggtattttc tccttacgca 4320
tctgtgcggt atttcacacc gcatacgtca aagcaaccat agtacgcgcc ctgtagcggc 4380
gcattaagcg cggcgggtgt ggtggttacg cgcagcgtga ccgctacact tgccagcgcc 4440
ctagcgcccg ctcctttcgc tttcttccct tcctttctcg ccacgttcgc cggctttccc 4500
cgtcaagctc taaatcgggg gctcccttta gggttccgat ttagtgcttt acggcacctc 4560
gaccccaaaa aacttgattt gggtgatggt tcacgtagtg ggccatcgcc ctgatagacg 4620
gtttttcgcc ctttgacgtt ggagtccacg ttctttaata gtggactctt gttccaaact 4680
ggaacaacac tcaaccctat ctcgggctat tcttttgatt tataagggat tttgccgatt 4740
tcggcctatt ggttaaaaaa tgagctgatt taacaaaaat ttaacgcgaa ttttaacaaa 4800
atattaacgt ttacaatttt atggtgcact ctcagtacaa tctgctctga tgccgcatag 4860
ttaagccagc cccgacaccc gccaacaccc gctgacgcgc cctgacgggc ttgtctgctc 4920
ccggcatccg cttacagaca agctgtgacc gtctccggga gctgcatgtg tcagaggttt 4980
tcaccgtcat caccgaaacg cgcgagacga aagggcctcg tgatacgcct atttttatag 5040
gttaatgtca tgataataat ggtttcttag acgtcaggtg gcacttttcg gggaaatgtg 5100
cgcggaaccc ctatttgttt atttttctaa atacattcaa atatgtatcc gctcatgaga 5160
caataaccct gataaatgct tcaataatat tgaaaaagga agagtatgag tattcaacat 5220
ttccgtgtcg cccttattcc cttttttgcg gcattttgcc ttcctgtttt tgctcaccca 5280
gaaacgctgg tgaaagtaaa agatgctgaa gatcagttgg gtgcacgagt gggttacatc 5340
gaactggatc tcaacagcgg taagatcctt gagagttttc gccccgaaga acgttttcca 5400
atgatgagca cttttaaagt tctgctatgt ggcgcggtat tatcccgtat tgacgccggg 5460
caagagcaac tcggtcgccg catacactat tctcagaatg acttggttga gtactcacca 5520
gtcacagaaa agcatcttac ggatggcatg acagtaagag aattatgcag tgctgccata 5580
accatgagtg ataacactgc ggccaactta cttctgacaa cgatcggagg accgaaggag 5640
ctaaccgctt ttttgcacaa catgggggat catgtaactc gccttgatcg ttgggaaccg 5700
gagctgaatg aagccatacc aaacgacgag cgtgacacca cgatgcctgt agcaatggca 5760
acaacgttgc gcaaactatt aactggcgaa ctacttactc tagcttcccg gcaacaatta 5820
atagactgga tggaggcgga taaagttgca ggaccacttc tgcgctcggc ccttccggct 5880
ggctggttta ttgctgataa atctggagcc ggtgagcgtg ggtctcgcgg tatcattgca 5940
gcactggggc cagatggtaa gccctcccgt atcgtagtta tctacacgac ggggagtcag 6000
gcaactatgg atgaacgaaa tagacagatc gctgagatag gtgcctcact gattaagcat 6060
tggtaactgt cagaccaagt ttactcatat atactttaga ttgatttaaa acttcatttt 6120
taatttaaaa ggatctaggt gaagatcctt tttgataatc tcatgaccaa aatcccttaa 6180
cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 6240
gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 6300
gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 6360
agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 6420
aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 6480
agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 6540
cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 6600
accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 6660
aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 6720
ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 6780
cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 6840
gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgt 6886
<210> 108
<211> 4723
<212> DNA
<213> 人工序列
<220>
<223> AAVC-CBh-eGFP
<400> 108
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc tgcggcctaa ggcaattgtt aatagtaatc aattacgggg 180
tcattagttc atagcccata tatggagttc cgcgttacat aacttacggt aaatggcccg 240
cctggctgac cgcccaacga cccccgccca ttgacgtcaa taatgacgta tgttcccata 300
gtaacgccaa tagggacttt ccattgacgt caatgggtgg agtatttacg gtaaactgcc 360
cacttggcag tacatcaagt gtatcatatg ccaagtacgc cccctattga cgtcaatgac 420
ggtaaatggc ccgcctggca ttatgcccag tacatgacct tacgggactt tcctacttgg 480
cagtacatct ccacgttctg cttcactctc cccatctccc ccccctcccc acccccaatt 540
ttgtatttat ttatttttta attattttgt gcagcgatgg gggcgggggg ggggggggcg 600
cgcgccaggc ggggcggggc ggggcgaggg gcggggcggg gcgaggcgga gaggtgcggc 660
ggcagccaat cagagcggcg cgctccgaaa gtttcctttt atggcgaggc ggcggcggcg 720
gcggccctat aaaaagcgaa gcgcgcggcg gggagtcgct gcgttgcctt cgccccgtgc 780
cccgctccgc gccgcctcgc gccgcccgcc ccggctctga ctgaccgcgt tactcccaca 840
ggtgagcggg cgggacggcc cttctcctcc gggctgtaat tagcaagagg taagggttta 900
agggatggtt ggttggtggg gtattaatgt ttaattacct gttttacagg cctgaaatca 960
cttggtttta ggttgggcta gccaaagctt gccgccacca tggtgtcaaa gggggaggaa 1020
ctgtttactg gagtcgtgcc tattctggtc gaactggatg gggatgtcaa cggtcataag 1080
tttagcgtgt ccggagaggg agagggcgac gctacctacg gaaagctgac actgaagttc 1140
atctgcacca caggcaagct gcccgtgcct tggccaaccc tggtgaccac actgacatac 1200
ggcgtgcagt gttttagccg gtacccagac cacatgaagc agcacgattt ctttaagtcc 1260
gccatgcccg agggatacgt gcaggagagg accatcttct ttaaggacga tggcaactac 1320
aagaccagag ctgaggtgaa gttcgaggga gacacactgg tgaaccggat cgagctgaag 1380
ggcatcgact ttaaggagga tggaaacatc ctgggccaca agctggagta caactacaac 1440
tctcacaacg tgtacatcat ggccgataag cagaagaacg gaatcaaggt gaacttcaag 1500
atccgccaca acatcgagga cggcagcgtg cagctggctg atcactacca gcagaacacc 1560
cctatcggag acggacccgt gctgctgcct gataaccact acctgagcac acagtccgct 1620
ctgtctaagg acccaaacga gaagagggat cacatggtcc tcctggaatt tgtcactgct 1680
gctgggatta ctctggggat ggatgaactc tataagtgat aagcggccgc aactcgagac 1740
tctagacgac tgtgccttct agttgccagc catctgttgt ttgcccctcc cccgtgcctt 1800
ccttgaccct ggaaggtgcc actcccactg tcctttccta ataaaatgag gaaattgcat 1860
cgcattgtct gagtaggtgt cattctattc tggggggtgg ggtggggcag gacagcaagg 1920
gggaggattg ggaagacaat agcaggcatg ctggggatgc ggtgggctct atggccgcgg 1980
gccgcaggaa cccctagtga tggagttggc cactccctct ctgcgcgctc gctcgctcac 2040
tgaggccggg cgaccaaagg tcgcccgacg cccgggcttt gcccgggcgg cctcagtgag 2100
cgagcgagcg cgcagctgcc tgcaggggcg cctgatgcgg tattttctcc ttacgcatct 2160
gtgcggtatt tcacaccgca tacgtcaaag caaccatagt acgcgccctg tagcggcgca 2220
ttaagcgcgg cgggtgtggt ggttacgcgc agcgtgaccg ctacacttgc cagcgcccta 2280
gcgcccgctc ctttcgcttt cttcccttcc tttctcgcca cgttcgccgg ctttccccgt 2340
caagctctaa atcgggggct ccctttaggg ttccgattta gtgctttacg gcacctcgac 2400
cccaaaaaac ttgatttggg tgatggttca cgtagtgggc catcgccctg atagacggtt 2460
tttcgccctt tgacgttgga gtccacgttc tttaatagtg gactcttgtt ccaaactgga 2520
acaacactca accctatctc gggctattct tttgatttat aagggatttt gccgatttcg 2580
gcctattggt taaaaaatga gctgatttaa caaaaattta acgcgaattt taacaaaata 2640
ttaacgttta caattttatg gtgcactctc agtacaatct gctctgatgc cgcatagtta 2700
agccagcccc gacacccgcc aacacccgct gacgcgccct gacgggcttg tctgctcccg 2760
gcatccgctt acagacaagc tgtgaccgtc tccgggagct gcatgtgtca gaggttttca 2820
ccgtcatcac cgaaacgcgc gagacgaaag ggcctcgtga tacgcctatt tttataggtt 2880
aatgtcatga taataatggt ttcttagacg tcaggtggca cttttcgggg aaatgtgcgc 2940
ggaaccccta tttgtttatt tttctaaata cattcaaata tgtatccgct catgagacaa 3000
taaccctgat aaatgcttca ataatattga aaaaggaaga gtatgagtat tcaacatttc 3060
cgtgtcgccc ttattccctt ttttgcggca ttttgccttc ctgtttttgc tcacccagaa 3120
acgctggtga aagtaaaaga tgctgaagat cagttgggtg cacgagtggg ttacatcgaa 3180
ctggatctca acagcggtaa gatccttgag agttttcgcc ccgaagaacg ttttccaatg 3240
atgagcactt ttaaagttct gctatgtggc gcggtattat cccgtattga cgccgggcaa 3300
gagcaactcg gtcgccgcat acactattct cagaatgact tggttgagta ctcaccagtc 3360
acagaaaagc atcttacgga tggcatgaca gtaagagaat tatgcagtgc tgccataacc 3420
atgagtgata acactgcggc caacttactt ctgacaacga tcggaggacc gaaggagcta 3480
accgcttttt tgcacaacat gggggatcat gtaactcgcc ttgatcgttg ggaaccggag 3540
ctgaatgaag ccataccaaa cgacgagcgt gacaccacga tgcctgtagc aatggcaaca 3600
acgttgcgca aactattaac tggcgaacta cttactctag cttcccggca acaattaata 3660
gactggatgg aggcggataa agttgcagga ccacttctgc gctcggccct tccggctggc 3720
tggtttattg ctgataaatc tggagccggt gagcgtgggt ctcgcggtat cattgcagca 3780
ctggggccag atggtaagcc ctcccgtatc gtagttatct acacgacggg gagtcaggca 3840
actatggatg aacgaaatag acagatcgct gagataggtg cctcactgat taagcattgg 3900
taactgtcag accaagttta ctcatatata ctttagattg atttaaaact tcatttttaa 3960
tttaaaagga tctaggtgaa gatccttttt gataatctca tgaccaaaat cccttaacgt 4020
gagttttcgt tccactgagc gtcagacccc gtagaaaaga tcaaaggatc ttcttgagat 4080
cctttttttc tgcgcgtaat ctgctgcttg caaacaaaaa aaccaccgct accagcggtg 4140
gtttgtttgc cggatcaaga gctaccaact ctttttccga aggtaactgg cttcagcaga 4200
gcgcagatac caaatactgt ccttctagtg tagccgtagt taggccacca cttcaagaac 4260
tctgtagcac cgcctacata cctcgctctg ctaatcctgt taccagtggc tgctgccagt 4320
ggcgataagt cgtgtcttac cgggttggac tcaagacgat agttaccgga taaggcgcag 4380
cggtcgggct gaacgggggg ttcgtgcaca cagcccagct tggagcgaac gacctacacc 4440
gaactgagat acctacagcg tgagctatga gaaagcgcca cgcttcccga agggagaaag 4500
gcggacaggt atccggtaag cggcagggtc ggaacaggag agcgcacgag ggagcttcca 4560
gggggaaacg cctggtatct ttatagtcct gtcgggtttc gccacctctg acttgagcgt 4620
cgatttttgt gatgctcgtc aggggggcgg agcctatgga aaaacgccag caacgcggcc 4680
tttttacggt tcctggcctt ttgctggcct tttgctcaca tgt 4723
<210> 109
<211> 4783
<212> DNA
<213> 人工序列
<220>
<223> AAVC-CBh-NLS-eGFP
<400> 109
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc tgcggcctaa ggcaattgtt aatagtaatc aattacgggg 180
tcattagttc atagcccata tatggagttc cgcgttacat aacttacggt aaatggcccg 240
cctggctgac cgcccaacga cccccgccca ttgacgtcaa taatgacgta tgttcccata 300
gtaacgccaa tagggacttt ccattgacgt caatgggtgg agtatttacg gtaaactgcc 360
cacttggcag tacatcaagt gtatcatatg ccaagtacgc cccctattga cgtcaatgac 420
ggtaaatggc ccgcctggca ttatgcccag tacatgacct tacgggactt tcctacttgg 480
cagtacatct ccacgttctg cttcactctc cccatctccc ccccctcccc acccccaatt 540
ttgtatttat ttatttttta attattttgt gcagcgatgg gggcgggggg ggggggggcg 600
cgcgccaggc ggggcggggc ggggcgaggg gcggggcggg gcgaggcgga gaggtgcggc 660
ggcagccaat cagagcggcg cgctccgaaa gtttcctttt atggcgaggc ggcggcggcg 720
gcggccctat aaaaagcgaa gcgcgcggcg gggagtcgct gcgttgcctt cgccccgtgc 780
cccgctccgc gccgcctcgc gccgcccgcc ccggctctga ctgaccgcgt tactcccaca 840
ggtgagcggg cgggacggcc cttctcctcc gggctgtaat tagcaagagg taagggttta 900
agggatggtt ggttggtggg gtattaatgt ttaattacct gttttacagg cctgaaatca 960
cttggtttta ggttgggcta gccaaagctt gccgccacca tggccccaaa aaagaaaaga 1020
aaagtgaggt atcctgcatt cctgtacaaa gtcgctacta tggtgtcaaa aggtgaagag 1080
ctgttcaccg gagtggtgcc catcctggtg gagctggacg gagatgtgaa cggccacaag 1140
ttcagcgtgt ccggagaggg agagggcgac gccacctacg gaaagctgac actgaagttt 1200
atctgcacca caggcaagct gcccgtgcct tggccaaccc tggtgaccac actgacatac 1260
ggcgtgcagt gtttctctcg gtacccagac cacatgaagc agcacgattt ctttaagagc 1320
gccatgcccg agggatacgt gcaggagagg acaatcttct ttaaggacga tggcaactac 1380
aagaccagag ctgaggtgaa gttcgaggga gacacactgg tgaaccggat cgagctgaag 1440
ggcatcgact ttaaggagga tggaaacatc ctgggccaca agctggagta caactacaac 1500
tcccacaacg tgtacatcat ggccgataag cagaagaacg gaatcaaggt gaactttaag 1560
atccgccaca acatcgagga cggctctgtg cagctggctg atcactacca gcagaacacc 1620
cctatcggag acggacccgt gctgctgcct gataaccact acctgtctac acagagcgcc 1680
ctgtccaagg acccaaacga gaagagggat cacatggtgc tcctggaatt tgtcactgct 1740
gccggtatta ctctcgggat ggatgaactg tataaatgat aagcggccgc aactcgagac 1800
tctagacgac tgtgccttct agttgccagc catctgttgt ttgcccctcc cccgtgcctt 1860
ccttgaccct ggaaggtgcc actcccactg tcctttccta ataaaatgag gaaattgcat 1920
cgcattgtct gagtaggtgt cattctattc tggggggtgg ggtggggcag gacagcaagg 1980
gggaggattg ggaagacaat agcaggcatg ctggggatgc ggtgggctct atggccgcgg 2040
gccgcaggaa cccctagtga tggagttggc cactccctct ctgcgcgctc gctcgctcac 2100
tgaggccggg cgaccaaagg tcgcccgacg cccgggcttt gcccgggcgg cctcagtgag 2160
cgagcgagcg cgcagctgcc tgcaggggcg cctgatgcgg tattttctcc ttacgcatct 2220
gtgcggtatt tcacaccgca tacgtcaaag caaccatagt acgcgccctg tagcggcgca 2280
ttaagcgcgg cgggtgtggt ggttacgcgc agcgtgaccg ctacacttgc cagcgcccta 2340
gcgcccgctc ctttcgcttt cttcccttcc tttctcgcca cgttcgccgg ctttccccgt 2400
caagctctaa atcgggggct ccctttaggg ttccgattta gtgctttacg gcacctcgac 2460
cccaaaaaac ttgatttggg tgatggttca cgtagtgggc catcgccctg atagacggtt 2520
tttcgccctt tgacgttgga gtccacgttc tttaatagtg gactcttgtt ccaaactgga 2580
acaacactca accctatctc gggctattct tttgatttat aagggatttt gccgatttcg 2640
gcctattggt taaaaaatga gctgatttaa caaaaattta acgcgaattt taacaaaata 2700
ttaacgttta caattttatg gtgcactctc agtacaatct gctctgatgc cgcatagtta 2760
agccagcccc gacacccgcc aacacccgct gacgcgccct gacgggcttg tctgctcccg 2820
gcatccgctt acagacaagc tgtgaccgtc tccgggagct gcatgtgtca gaggttttca 2880
ccgtcatcac cgaaacgcgc gagacgaaag ggcctcgtga tacgcctatt tttataggtt 2940
aatgtcatga taataatggt ttcttagacg tcaggtggca cttttcgggg aaatgtgcgc 3000
ggaaccccta tttgtttatt tttctaaata cattcaaata tgtatccgct catgagacaa 3060
taaccctgat aaatgcttca ataatattga aaaaggaaga gtatgagtat tcaacatttc 3120
cgtgtcgccc ttattccctt ttttgcggca ttttgccttc ctgtttttgc tcacccagaa 3180
acgctggtga aagtaaaaga tgctgaagat cagttgggtg cacgagtggg ttacatcgaa 3240
ctggatctca acagcggtaa gatccttgag agttttcgcc ccgaagaacg ttttccaatg 3300
atgagcactt ttaaagttct gctatgtggc gcggtattat cccgtattga cgccgggcaa 3360
gagcaactcg gtcgccgcat acactattct cagaatgact tggttgagta ctcaccagtc 3420
acagaaaagc atcttacgga tggcatgaca gtaagagaat tatgcagtgc tgccataacc 3480
atgagtgata acactgcggc caacttactt ctgacaacga tcggaggacc gaaggagcta 3540
accgcttttt tgcacaacat gggggatcat gtaactcgcc ttgatcgttg ggaaccggag 3600
ctgaatgaag ccataccaaa cgacgagcgt gacaccacga tgcctgtagc aatggcaaca 3660
acgttgcgca aactattaac tggcgaacta cttactctag cttcccggca acaattaata 3720
gactggatgg aggcggataa agttgcagga ccacttctgc gctcggccct tccggctggc 3780
tggtttattg ctgataaatc tggagccggt gagcgtgggt ctcgcggtat cattgcagca 3840
ctggggccag atggtaagcc ctcccgtatc gtagttatct acacgacggg gagtcaggca 3900
actatggatg aacgaaatag acagatcgct gagataggtg cctcactgat taagcattgg 3960
taactgtcag accaagttta ctcatatata ctttagattg atttaaaact tcatttttaa 4020
tttaaaagga tctaggtgaa gatccttttt gataatctca tgaccaaaat cccttaacgt 4080
gagttttcgt tccactgagc gtcagacccc gtagaaaaga tcaaaggatc ttcttgagat 4140
cctttttttc tgcgcgtaat ctgctgcttg caaacaaaaa aaccaccgct accagcggtg 4200
gtttgtttgc cggatcaaga gctaccaact ctttttccga aggtaactgg cttcagcaga 4260
gcgcagatac caaatactgt ccttctagtg tagccgtagt taggccacca cttcaagaac 4320
tctgtagcac cgcctacata cctcgctctg ctaatcctgt taccagtggc tgctgccagt 4380
ggcgataagt cgtgtcttac cgggttggac tcaagacgat agttaccgga taaggcgcag 4440
cggtcgggct gaacgggggg ttcgtgcaca cagcccagct tggagcgaac gacctacacc 4500
gaactgagat acctacagcg tgagctatga gaaagcgcca cgcttcccga agggagaaag 4560
gcggacaggt atccggtaag cggcagggtc ggaacaggag agcgcacgag ggagcttcca 4620
gggggaaacg cctggtatct ttatagtcct gtcgggtttc gccacctctg acttgagcgt 4680
cgatttttgt gatgctcgtc aggggggcgg agcctatgga aaaacgccag caacgcggcc 4740
tttttacggt tcctggcctt ttgctggcct tttgctcaca tgt 4783
<210> 110
<211> 7066
<212> DNA
<213> 人工序列
<220>
<223> AAVC-CBh-mBPIP-TATκ28-hCDKL5-107
<400> 110
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc tgcggcctaa ggcaattgtt aatagtaatc aattacgggg 180
tcattagttc atagcccata tatggagttc cgcgttacat aacttacggt aaatggcccg 240
cctggctgac cgcccaacga cccccgccca ttgacgtcaa taatgacgta tgttcccata 300
gtaacgccaa tagggacttt ccattgacgt caatgggtgg agtatttacg gtaaactgcc 360
cacttggcag tacatcaagt gtatcatatg ccaagtacgc cccctattga cgtcaatgac 420
ggtaaatggc ccgcctggca ttatgcccag tacatgacct tacgggactt tcctacttgg 480
cagtacatct ccacgttctg cttcactctc cccatctccc ccccctcccc acccccaatt 540
ttgtatttat ttatttttta attattttgt gcagcgatgg gggcgggggg ggggggggcg 600
cgcgccaggc ggggcggggc ggggcgaggg gcggggcggg gcgaggcgga gaggtgcggc 660
ggcagccaat cagagcggcg cgctccgaaa gtttcctttt atggcgaggc ggcggcggcg 720
gcggccctat aaaaagcgaa gcgcgcggcg gggagtcgct gcgttgcctt cgccccgtgc 780
cccgctccgc gccgcctcgc gccgcccgcc ccggctctga ctgaccgcgt tactcccaca 840
ggtgagcggg cgggacggcc cttctcctcc gggctgtaat tagcaagagg taagggttta 900
agggatggtt ggttggtggg gtattaatgt ttaattacct gttttacagg cctgaaatca 960
cttggtttta ggttgggcta gccaaagctt gccgccacca tgaaactctc cctggtcgct 1020
gctatgctgc tcctcctgtc cctcgtcgct gctatgctcc tgctgctgtc tgccgctcgg 1080
gctggtgatg ctgctcagcc agctaggaga gctaggagga ccaagctggc tgcttacgct 1140
agaaaggctg ctagacaggc tagggctgga ggaggcggat ccaagatccc caacatcggc 1200
aacgtgatga acaagttcga gatcctggga gtggtgggag agggagctta cggagtggtg 1260
ctgaagtgcc ggcacaagga gacacacgag atcgtggcta tcaagaagtt taaggacagc 1320
gaggagaacg aggaggtgaa ggagacaacc ctgcgcgagc tgaagatgct gaggacactg 1380
aagcaggaga acatcgtgga gctgaaggag gccttcagga gacggggaaa gctgtacctg 1440
gtgtttgagt acgtggagaa gaacatgctg gagctgctgg aggagatgcc aaacggagtg 1500
ccacctgaga aggtgaagtc ctacatctac cagctgatca aggctatcca ctggtgccac 1560
aagaacgaca tcgtgcaccg cgatatcaag cctgagaacc tgctgatctc ccacaacgac 1620
gtgctgaagc tgtgcgattt cggctttgcc aggaacctga gcgagggaaa caacgccaac 1680
tacacagagt acgtggctac ccgctggtac aggagcccag agctgctgct gggagctcca 1740
tacggaaaga gcgtggacat gtggtccgtg ggctgcatcc tgggagagct gtctgacggc 1800
cagcctctgt tcccaggaga gagcgagatc gatcagctgt ttaccatcca gaaggtgctg 1860
ggccctctgc caagcgagca gatgaagctg ttctactcca accctcgctt ccacggactg 1920
aggtttcccg ccgtgaacca ccctcagagc ctggagcgca ggtacctggg catcctgaac 1980
tccgtgctgc tggatctgat gaagaacctg ctgaagctgg accccgccga tagatacctg 2040
accgagcagt gtctgaacca ccctacattt cagacccaga gactgctgga ccggagccct 2100
tcccgctctg ctaagaggaa gccataccac gtggagagct ccaccctgtc caaccgcaac 2160
caggccggca agtctacagc tctgcagagc caccacagga gcaactccaa ggacatccag 2220
aacctgtctg tgggcctgcc tagggctgat gagggactgc cagctaacga gagcttcctg 2280
aacggcaacc tggccggagc ttctctgagc ccactgcaca caaagaccta ccaggcctct 2340
agccagcccg gctccacatc taaggacctg accaacaaca acatcccaca cctgctgtct 2400
cccaaggagg ctaagagcaa gaccgagttc gactttaaca tcgatcccaa gcctagcgag 2460
ggccctggaa caaagtacct gaagagcaac tccagatctc agcagaaccg gcactccttc 2520
atggagtcct ctcagtctaa ggccggcacc ctgcagccaa acgagaagca gagccggcac 2580
tcctacatcg ataccatccc ccagagctcc cgcagccctt cctacaggac aaaggccaag 2640
agccacggcg ctctgtctga cagcaagtcc gtgtctaacc tgtccgaggc cagagctcag 2700
atcgctgagc caagcacctc caggtacttt ccttctagct gtctggacct gaactctcct 2760
acaagcccaa cacccaccag acacagcgat acacggaccc tgctgtctcc aagcggcaga 2820
aacaaccgga acgagggaac cctggattct agacggacca caaccaggca cagcaagaca 2880
atggaggagc tgaagctgcc agagcacatg gactcctctc actcccactc tctgagcgcc 2940
ccccacgagt ccttctctta cggcctggga tacacctccc ccttcagctc ccagcagcgc 3000
ccccacaggc actctatgta cgtgacaaga gacaaggtgc gggccaaggg cctggatgga 3060
agcctgtcca tcggccaggg aatggccgct agagctaact ccctgcagct gctgtctcct 3120
cagccaggag agcagctgcc acccgagatg accgtggcca gatctagcgt gaaggagaca 3180
agccgggagg gcacctcctc tttccacaca agacagaagt ccgagggcgg agtgtaccac 3240
gacccccact ctgacgatgg aacagctcct aaggagaacc ggcacctgta caacgatccc 3300
gtgcctcgca gggtgggctc cttctaccgc gtgccatctc ccaggcctga caacagcttt 3360
cacgagaaca acgtgtccac cagagtgagc tccctgccat ctgagtctag ctccggaaca 3420
aaccactcta agcggcagcc cgccttcgat ccttggaaga gcccagagaa catctctcac 3480
agcgagcagc tgaaggagaa ggagaagcag ggcttctttc gcagcatgaa gaagaagaag 3540
aagaagagcc agaccgtgcc taactccgac tctccagatc tgctgaccct gcagaagtcc 3600
atccacagcg cctccacacc ctctagcaga cctaaggagt ggcggcctga gaagatcagc 3660
gatctgcaga cacagagcca gccactgaag tccctgagga agctgctgca cctgtcctct 3720
gccagcaacc acccagctag ctccgaccca aggttccagc cactgacagc tcagcagacc 3780
aagaactctt ttagcgagat caggatccac cctctgtccc aggcttctgg cggatctagc 3840
aacatcaggc aggagccagc tccaaagggc aggcccgctc tgcagctgcc tggacagatg 3900
gacccaggat ggcacgtgtc ctctgtgaca aggtccgcca ccgagggacc atcctactct 3960
gagcagctgg gcgctaagtc tggccctaac ggacacccat acaaccgaac aaatagaagt 4020
aggatgccaa acctcaatga cctcaaggaa actgccctgt gataagcggc cgcaactcga 4080
gactctagac gactgtgcct tctagttgcc agccatctgt tgtttgcccc tcccccgtgc 4140
cttccttgac cctggaaggt gccactccca ctgtcctttc ctaataaaat gaggaaattg 4200
catcgcattg tctgagtagg tgtcattcta ttctgggggg tggggtgggg caggacagca 4260
agggggagga ttgggaagac aatagcaggc atgctgggga tgcggtgggc tctatggccg 4320
cgggccgcag gaacccctag tgatggagtt ggccactccc tctctgcgcg ctcgctcgct 4380
cactgaggcc gggcgaccaa aggtcgcccg acgcccgggc tttgcccggg cggcctcagt 4440
gagcgagcga gcgcgcagct gcctgcaggg gcgcctgatg cggtattttc tccttacgca 4500
tctgtgcggt atttcacacc gcatacgtca aagcaaccat agtacgcgcc ctgtagcggc 4560
gcattaagcg cggcgggtgt ggtggttacg cgcagcgtga ccgctacact tgccagcgcc 4620
ctagcgcccg ctcctttcgc tttcttccct tcctttctcg ccacgttcgc cggctttccc 4680
cgtcaagctc taaatcgggg gctcccttta gggttccgat ttagtgcttt acggcacctc 4740
gaccccaaaa aacttgattt gggtgatggt tcacgtagtg ggccatcgcc ctgatagacg 4800
gtttttcgcc ctttgacgtt ggagtccacg ttctttaata gtggactctt gttccaaact 4860
ggaacaacac tcaaccctat ctcgggctat tcttttgatt tataagggat tttgccgatt 4920
tcggcctatt ggttaaaaaa tgagctgatt taacaaaaat ttaacgcgaa ttttaacaaa 4980
atattaacgt ttacaatttt atggtgcact ctcagtacaa tctgctctga tgccgcatag 5040
ttaagccagc cccgacaccc gccaacaccc gctgacgcgc cctgacgggc ttgtctgctc 5100
ccggcatccg cttacagaca agctgtgacc gtctccggga gctgcatgtg tcagaggttt 5160
tcaccgtcat caccgaaacg cgcgagacga aagggcctcg tgatacgcct atttttatag 5220
gttaatgtca tgataataat ggtttcttag acgtcaggtg gcacttttcg gggaaatgtg 5280
cgcggaaccc ctatttgttt atttttctaa atacattcaa atatgtatcc gctcatgaga 5340
caataaccct gataaatgct tcaataatat tgaaaaagga agagtatgag tattcaacat 5400
ttccgtgtcg cccttattcc cttttttgcg gcattttgcc ttcctgtttt tgctcaccca 5460
gaaacgctgg tgaaagtaaa agatgctgaa gatcagttgg gtgcacgagt gggttacatc 5520
gaactggatc tcaacagcgg taagatcctt gagagttttc gccccgaaga acgttttcca 5580
atgatgagca cttttaaagt tctgctatgt ggcgcggtat tatcccgtat tgacgccggg 5640
caagagcaac tcggtcgccg catacactat tctcagaatg acttggttga gtactcacca 5700
gtcacagaaa agcatcttac ggatggcatg acagtaagag aattatgcag tgctgccata 5760
accatgagtg ataacactgc ggccaactta cttctgacaa cgatcggagg accgaaggag 5820
ctaaccgctt ttttgcacaa catgggggat catgtaactc gccttgatcg ttgggaaccg 5880
gagctgaatg aagccatacc aaacgacgag cgtgacacca cgatgcctgt agcaatggca 5940
acaacgttgc gcaaactatt aactggcgaa ctacttactc tagcttcccg gcaacaatta 6000
atagactgga tggaggcgga taaagttgca ggaccacttc tgcgctcggc ccttccggct 6060
ggctggttta ttgctgataa atctggagcc ggtgagcgtg ggtctcgcgg tatcattgca 6120
gcactggggc cagatggtaa gccctcccgt atcgtagtta tctacacgac ggggagtcag 6180
gcaactatgg atgaacgaaa tagacagatc gctgagatag gtgcctcact gattaagcat 6240
tggtaactgt cagaccaagt ttactcatat atactttaga ttgatttaaa acttcatttt 6300
taatttaaaa ggatctaggt gaagatcctt tttgataatc tcatgaccaa aatcccttaa 6360
cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 6420
gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 6480
gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 6540
agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 6600
aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 6660
agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 6720
cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 6780
accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 6840
aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 6900
ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 6960
cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 7020
gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgt 7066
<210> 111
<211> 7066
<212> DNA
<213> 人工序列
<220>
<223> AAVC-CBh-mBPIP-TATκ28-hCDKL5-107 (失活激酶)
<400> 111
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc tgcggcctaa ggcaattgtt aatagtaatc aattacgggg 180
tcattagttc atagcccata tatggagttc cgcgttacat aacttacggt aaatggcccg 240
cctggctgac cgcccaacga cccccgccca ttgacgtcaa taatgacgta tgttcccata 300
gtaacgccaa tagggacttt ccattgacgt caatgggtgg agtatttacg gtaaactgcc 360
cacttggcag tacatcaagt gtatcatatg ccaagtacgc cccctattga cgtcaatgac 420
ggtaaatggc ccgcctggca ttatgcccag tacatgacct tacgggactt tcctacttgg 480
cagtacatct ccacgttctg cttcactctc cccatctccc ccccctcccc acccccaatt 540
ttgtatttat ttatttttta attattttgt gcagcgatgg gggcgggggg ggggggggcg 600
cgcgccaggc ggggcggggc ggggcgaggg gcggggcggg gcgaggcgga gaggtgcggc 660
ggcagccaat cagagcggcg cgctccgaaa gtttcctttt atggcgaggc ggcggcggcg 720
gcggccctat aaaaagcgaa gcgcgcggcg gggagtcgct gcgttgcctt cgccccgtgc 780
cccgctccgc gccgcctcgc gccgcccgcc ccggctctga ctgaccgcgt tactcccaca 840
ggtgagcggg cgggacggcc cttctcctcc gggctgtaat tagcaagagg taagggttta 900
agggatggtt ggttggtggg gtattaatgt ttaattacct gttttacagg cctgaaatca 960
cttggtttta ggttgggcta gccaaagctt gccgccacca tgaaactctc cctcgtcgcc 1020
gctatgctcc tgctcctctc cctcgtcgct gccatgctcc tgctgctcag tgccgctcgg 1080
gccggagatg ctgctcagcc agctaggaga gctaggagga ccaagctggc tgcttacgct 1140
aggaaggctg ctaggcaggc tagggctggc ggaggcggat ccaagatccc caacatcggc 1200
aacgtgatga acaagttcga gatcctggga gtggtgggag agggagctta cggagtggtg 1260
ctgaagtgca ggcacaagga gacacacgag atcgtggcta tcaggaggtt caaggacagc 1320
gaggagaacg aggaggtgaa ggagacaacc ctgagagagc tgaagatgct gcggacactg 1380
aagcaggaga acatcgtgga gctgaaggag gccttccggc gcaggggaaa gctgtacctg 1440
gtgtttgagt acgtggagaa gaacatgctg gagctgctgg aggagatgcc aaacggagtg 1500
ccacctgaga aggtgaagtc ctacatctac cagctgatca aggctatcca ctggtgccac 1560
aagaacgaca tcgtgcacag agatatcaag cctgagaacc tgctgatctc ccacaacgac 1620
gtgctgaagc tgtgcgattt cggctttgcc cggaacctga gcgagggaaa caacgccaac 1680
tacacagagt acgtggctac cagatggtac cggagcccag agctgctgct gggagctcca 1740
tacggaaaga gcgtggacat gtggtccgtg ggctgcatcc tgggagagct gtctgacggc 1800
cagcctctgt tcccaggaga gagcgagatc gatcagctgt ttaccatcca gaaggtgctg 1860
ggccctctgc caagcgagca gatgaagctg ttctactcca accctagatt ccacggactg 1920
cggtttcccg ccgtgaacca ccctcagagc ctggagagac ggtacctggg catcctgaac 1980
tccgtgctgc tggatctgat gaagaacctg ctgaagctgg accccgccga tcgctacctg 2040
accgagcagt gtctgaacca ccctacattt cagacccagc gcctgctgga caggagccct 2100
tccagatctg ctaagcggaa gccataccac gtggagagct ccaccctgtc caacagaaac 2160
caggccggca agtctacagc tctgcagagc caccaccgga gcaactccaa ggacatccag 2220
aacctgtctg tgggcctgcc tagagccgat gagggactgc cagctaacga gagcttcctg 2280
aacggcaacc tggccggagc ttctctgagc ccactgcaca caaagaccta ccaggcctct 2340
agccagcccg gctccacatc taaggacctg accaacaaca acatcccaca cctgctgtct 2400
cccaaggagg ctaagagcaa gaccgagttc gactttaaca tcgatcccaa gcctagcgag 2460
ggccctggaa caaagtacct gaagagcaac tcccgctctc agcagaacag gcactccttc 2520
atggagtcct ctcagtctaa ggccggcacc ctgcagccaa acgagaagca gagcagacac 2580
tcctacatcg ataccatccc ccagagctcc agaagccctt cctaccggac aaaggccaag 2640
agccacggcg ctctgtctga cagcaagtcc gtgtctaacc tgtccgaggc tagggctcag 2700
atcgctgagc ccagcacctc caggtacttt ccttctagct gtctggacct gaactctcct 2760
acaagcccaa cacccacccg ccacagcgat acaaggaccc tgctgtctcc aagcggcagg 2820
aacaacagga acgagggaac cctggattct cgcaggacca caacccggca cagcaagaca 2880
atggaggagc tgaagctgcc agagcacatg gactcctctc actcccactc tctgagcgcc 2940
ccccacgagt ccttctctta cggcctggga tacacctccc ccttcagctc ccagcagagg 3000
ccccacaggc actctatgta cgtgacacgc gacaaggtga gggccaaggg cctggatgga 3060
agcctgtcca tcggccaggg aatggccgct agggctaact ccctgcagct gctgtctcct 3120
cagccaggag agcagctgcc accagagatg accgtggctc gctctagcgt gaaggagaca 3180
agcagggagg gcacctcctc tttccacaca cgccagaagt ccgagggcgg agtgtaccac 3240
gacccccact ctgacgatgg aacagctcct aaggagaaca ggcacctgta caacgatccc 3300
gtgcctagac gggtgggctc cttctacaga gtgccatctc cccggcctga caacagcttt 3360
cacgagaaca acgtgtccac ccgcgtgagc tccctgccat ctgagtctag ctccggaaca 3420
aaccactcta agaggcagcc cgccttcgat ccttggaaga gcccagagaa catctctcac 3480
agcgagcagc tgaaggagaa ggagaagcag ggcttcttta gaagcatgaa gaagaagaag 3540
aagaagagcc agaccgtgcc taactccgac tctccagatc tgctgaccct gcagaagtcc 3600
atccacagcg cctccacacc atctagccgc cctaaggagt ggaggcctga gaagatcagc 3660
gatctgcaga cacagagcca gccactgaag tccctgcgga agctgctgca cctgtcctct 3720
gccagcaacc accccgctag ctccgaccca agattccagc ccctgacagc ccagcagacc 3780
aagaactctt ttagcgagat ccggatccac cctctgtccc aggcttctgg cggatctagc 3840
aacatcagac aggagccagc tccaaagggc cggcccgctc tgcagctgcc tggccagatg 3900
gacccaggat ggcacgtgtc ctctgtgaca aggtccgcca ccgagggacc atcctactct 3960
gagcagctgg gcgctaagtc tggccctaac ggacacccat acaataggac taatcgcagc 4020
agaatgccca acctgaacga cctcaaggaa acagcactct gataagcggc cgcaactcga 4080
gactctagac gactgtgcct tctagttgcc agccatctgt tgtttgcccc tcccccgtgc 4140
cttccttgac cctggaaggt gccactccca ctgtcctttc ctaataaaat gaggaaattg 4200
catcgcattg tctgagtagg tgtcattcta ttctgggggg tggggtgggg caggacagca 4260
agggggagga ttgggaagac aatagcaggc atgctgggga tgcggtgggc tctatggccg 4320
cgggccgcag gaacccctag tgatggagtt ggccactccc tctctgcgcg ctcgctcgct 4380
cactgaggcc gggcgaccaa aggtcgcccg acgcccgggc tttgcccggg cggcctcagt 4440
gagcgagcga gcgcgcagct gcctgcaggg gcgcctgatg cggtattttc tccttacgca 4500
tctgtgcggt atttcacacc gcatacgtca aagcaaccat agtacgcgcc ctgtagcggc 4560
gcattaagcg cggcgggtgt ggtggttacg cgcagcgtga ccgctacact tgccagcgcc 4620
ctagcgcccg ctcctttcgc tttcttccct tcctttctcg ccacgttcgc cggctttccc 4680
cgtcaagctc taaatcgggg gctcccttta gggttccgat ttagtgcttt acggcacctc 4740
gaccccaaaa aacttgattt gggtgatggt tcacgtagtg ggccatcgcc ctgatagacg 4800
gtttttcgcc ctttgacgtt ggagtccacg ttctttaata gtggactctt gttccaaact 4860
ggaacaacac tcaaccctat ctcgggctat tcttttgatt tataagggat tttgccgatt 4920
tcggcctatt ggttaaaaaa tgagctgatt taacaaaaat ttaacgcgaa ttttaacaaa 4980
atattaacgt ttacaatttt atggtgcact ctcagtacaa tctgctctga tgccgcatag 5040
ttaagccagc cccgacaccc gccaacaccc gctgacgcgc cctgacgggc ttgtctgctc 5100
ccggcatccg cttacagaca agctgtgacc gtctccggga gctgcatgtg tcagaggttt 5160
tcaccgtcat caccgaaacg cgcgagacga aagggcctcg tgatacgcct atttttatag 5220
gttaatgtca tgataataat ggtttcttag acgtcaggtg gcacttttcg gggaaatgtg 5280
cgcggaaccc ctatttgttt atttttctaa atacattcaa atatgtatcc gctcatgaga 5340
caataaccct gataaatgct tcaataatat tgaaaaagga agagtatgag tattcaacat 5400
ttccgtgtcg cccttattcc cttttttgcg gcattttgcc ttcctgtttt tgctcaccca 5460
gaaacgctgg tgaaagtaaa agatgctgaa gatcagttgg gtgcacgagt gggttacatc 5520
gaactggatc tcaacagcgg taagatcctt gagagttttc gccccgaaga acgttttcca 5580
atgatgagca cttttaaagt tctgctatgt ggcgcggtat tatcccgtat tgacgccggg 5640
caagagcaac tcggtcgccg catacactat tctcagaatg acttggttga gtactcacca 5700
gtcacagaaa agcatcttac ggatggcatg acagtaagag aattatgcag tgctgccata 5760
accatgagtg ataacactgc ggccaactta cttctgacaa cgatcggagg accgaaggag 5820
ctaaccgctt ttttgcacaa catgggggat catgtaactc gccttgatcg ttgggaaccg 5880
gagctgaatg aagccatacc aaacgacgag cgtgacacca cgatgcctgt agcaatggca 5940
acaacgttgc gcaaactatt aactggcgaa ctacttactc tagcttcccg gcaacaatta 6000
atagactgga tggaggcgga taaagttgca ggaccacttc tgcgctcggc ccttccggct 6060
ggctggttta ttgctgataa atctggagcc ggtgagcgtg ggtctcgcgg tatcattgca 6120
gcactggggc cagatggtaa gccctcccgt atcgtagtta tctacacgac ggggagtcag 6180
gcaactatgg atgaacgaaa tagacagatc gctgagatag gtgcctcact gattaagcat 6240
tggtaactgt cagaccaagt ttactcatat atactttaga ttgatttaaa acttcatttt 6300
taatttaaaa ggatctaggt gaagatcctt tttgataatc tcatgaccaa aatcccttaa 6360
cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 6420
gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 6480
gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 6540
agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 6600
aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 6660
agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 6720
cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 6780
accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 6840
aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 6900
ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 6960
cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 7020
gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgt 7066
<210> 112
<211> 4906
<212> DNA
<213> 人工序列
<220>
<223> AAVC-CBh-mBPIP-TATκ28-eGFP
<400> 112
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc tgcggcctaa ggcaattgtt aatagtaatc aattacgggg 180
tcattagttc atagcccata tatggagttc cgcgttacat aacttacggt aaatggcccg 240
cctggctgac cgcccaacga cccccgccca ttgacgtcaa taatgacgta tgttcccata 300
gtaacgccaa tagggacttt ccattgacgt caatgggtgg agtatttacg gtaaactgcc 360
cacttggcag tacatcaagt gtatcatatg ccaagtacgc cccctattga cgtcaatgac 420
ggtaaatggc ccgcctggca ttatgcccag tacatgacct tacgggactt tcctacttgg 480
cagtacatct ccacgttctg cttcactctc cccatctccc ccccctcccc acccccaatt 540
ttgtatttat ttatttttta attattttgt gcagcgatgg gggcgggggg ggggggggcg 600
cgcgccaggc ggggcggggc ggggcgaggg gcggggcggg gcgaggcgga gaggtgcggc 660
ggcagccaat cagagcggcg cgctccgaaa gtttcctttt atggcgaggc ggcggcggcg 720
gcggccctat aaaaagcgaa gcgcgcggcg gggagtcgct gcgttgcctt cgccccgtgc 780
cccgctccgc gccgcctcgc gccgcccgcc ccggctctga ctgaccgcgt tactcccaca 840
ggtgagcggg cgggacggcc cttctcctcc gggctgtaat tagcaagagg taagggttta 900
agggatggtt ggttggtggg gtattaatgt ttaattacct gttttacagg cctgaaatca 960
cttggtttta ggttgggcta gccaaagctt gccgccacca tgaaactgtc cctggtcgcc 1020
gccatgctgc tcctcctgtc actggtcgcc gctatgctgc tcctcctctc cgctgctcgg 1080
gctggggacg ctgctcagcc agctaggaga gctaggagga ccaagctggc tgcttacgct 1140
aggaaggctg ctaggcaggc tagagctgga ggaggcggat ctatggtgag caagggagag 1200
gagctgttca caggcgtggt gcccatcctg gtggagctgg acggagatgt gaacggccac 1260
aagtttagcg tgtccggaga gggagagggc gacgctacct acggaaagct gacactgaag 1320
ttcatctgca ccacaggcaa gctgcccgtg ccttggccaa ccctggtgac cacactgaca 1380
tacggcgtgc agtgtttttc caggtaccca gaccacatga agcagcacga tttctttaag 1440
tctgccatgc ccgagggata cgtgcaggag cggaccatct tctttaagga cgatggcaac 1500
tacaagaccc gcgctgaggt gaagttcgag ggagacacac tggtgaacag gatcgagctg 1560
aagggcatcg actttaagga ggatggaaac atcctgggcc acaagctgga gtacaactac 1620
aacagccaca acgtgtacat catggccgat aagcagaaga acggaatcaa ggtgaacttc 1680
aagatcagac acaacatcga ggacggctcc gtgcagctgg ctgatcacta ccagcagaac 1740
acccctatcg gagacggacc cgtgctgctg cctgataacc actacctgtc cacacagtct 1800
gccctgagca aggacccaaa cgagaagcgg gatcacatgg tgctgctgga atttgtgact 1860
gctgctggta ttacactggg tatggatgaa ctctataaat gataagcggc cgcaactcga 1920
gactctagac gactgtgcct tctagttgcc agccatctgt tgtttgcccc tcccccgtgc 1980
cttccttgac cctggaaggt gccactccca ctgtcctttc ctaataaaat gaggaaattg 2040
catcgcattg tctgagtagg tgtcattcta ttctgggggg tggggtgggg caggacagca 2100
agggggagga ttgggaagac aatagcaggc atgctgggga tgcggtgggc tctatggccg 2160
cgggccgcag gaacccctag tgatggagtt ggccactccc tctctgcgcg ctcgctcgct 2220
cactgaggcc gggcgaccaa aggtcgcccg acgcccgggc tttgcccggg cggcctcagt 2280
gagcgagcga gcgcgcagct gcctgcaggg gcgcctgatg cggtattttc tccttacgca 2340
tctgtgcggt atttcacacc gcatacgtca aagcaaccat agtacgcgcc ctgtagcggc 2400
gcattaagcg cggcgggtgt ggtggttacg cgcagcgtga ccgctacact tgccagcgcc 2460
ctagcgcccg ctcctttcgc tttcttccct tcctttctcg ccacgttcgc cggctttccc 2520
cgtcaagctc taaatcgggg gctcccttta gggttccgat ttagtgcttt acggcacctc 2580
gaccccaaaa aacttgattt gggtgatggt tcacgtagtg ggccatcgcc ctgatagacg 2640
gtttttcgcc ctttgacgtt ggagtccacg ttctttaata gtggactctt gttccaaact 2700
ggaacaacac tcaaccctat ctcgggctat tcttttgatt tataagggat tttgccgatt 2760
tcggcctatt ggttaaaaaa tgagctgatt taacaaaaat ttaacgcgaa ttttaacaaa 2820
atattaacgt ttacaatttt atggtgcact ctcagtacaa tctgctctga tgccgcatag 2880
ttaagccagc cccgacaccc gccaacaccc gctgacgcgc cctgacgggc ttgtctgctc 2940
ccggcatccg cttacagaca agctgtgacc gtctccggga gctgcatgtg tcagaggttt 3000
tcaccgtcat caccgaaacg cgcgagacga aagggcctcg tgatacgcct atttttatag 3060
gttaatgtca tgataataat ggtttcttag acgtcaggtg gcacttttcg gggaaatgtg 3120
cgcggaaccc ctatttgttt atttttctaa atacattcaa atatgtatcc gctcatgaga 3180
caataaccct gataaatgct tcaataatat tgaaaaagga agagtatgag tattcaacat 3240
ttccgtgtcg cccttattcc cttttttgcg gcattttgcc ttcctgtttt tgctcaccca 3300
gaaacgctgg tgaaagtaaa agatgctgaa gatcagttgg gtgcacgagt gggttacatc 3360
gaactggatc tcaacagcgg taagatcctt gagagttttc gccccgaaga acgttttcca 3420
atgatgagca cttttaaagt tctgctatgt ggcgcggtat tatcccgtat tgacgccggg 3480
caagagcaac tcggtcgccg catacactat tctcagaatg acttggttga gtactcacca 3540
gtcacagaaa agcatcttac ggatggcatg acagtaagag aattatgcag tgctgccata 3600
accatgagtg ataacactgc ggccaactta cttctgacaa cgatcggagg accgaaggag 3660
ctaaccgctt ttttgcacaa catgggggat catgtaactc gccttgatcg ttgggaaccg 3720
gagctgaatg aagccatacc aaacgacgag cgtgacacca cgatgcctgt agcaatggca 3780
acaacgttgc gcaaactatt aactggcgaa ctacttactc tagcttcccg gcaacaatta 3840
atagactgga tggaggcgga taaagttgca ggaccacttc tgcgctcggc ccttccggct 3900
ggctggttta ttgctgataa atctggagcc ggtgagcgtg ggtctcgcgg tatcattgca 3960
gcactggggc cagatggtaa gccctcccgt atcgtagtta tctacacgac ggggagtcag 4020
gcaactatgg atgaacgaaa tagacagatc gctgagatag gtgcctcact gattaagcat 4080
tggtaactgt cagaccaagt ttactcatat atactttaga ttgatttaaa acttcatttt 4140
taatttaaaa ggatctaggt gaagatcctt tttgataatc tcatgaccaa aatcccttaa 4200
cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 4260
gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 4320
gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 4380
agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 4440
aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 4500
agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 4560
cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 4620
accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 4680
aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 4740
ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 4800
cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 4860
gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgt 4906
<210> 113
<211> 4966
<212> DNA
<213> 人工序列
<220>
<223> AAVC-CBh- mBPIP-TATκ28-NLS-eGFP
<400> 113
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc tgcggcctaa ggcaattgtt aatagtaatc aattacgggg 180
tcattagttc atagcccata tatggagttc cgcgttacat aacttacggt aaatggcccg 240
cctggctgac cgcccaacga cccccgccca ttgacgtcaa taatgacgta tgttcccata 300
gtaacgccaa tagggacttt ccattgacgt caatgggtgg agtatttacg gtaaactgcc 360
cacttggcag tacatcaagt gtatcatatg ccaagtacgc cccctattga cgtcaatgac 420
ggtaaatggc ccgcctggca ttatgcccag tacatgacct tacgggactt tcctacttgg 480
cagtacatct ccacgttctg cttcactctc cccatctccc ccccctcccc acccccaatt 540
ttgtatttat ttatttttta attattttgt gcagcgatgg gggcgggggg ggggggggcg 600
cgcgccaggc ggggcggggc ggggcgaggg gcggggcggg gcgaggcgga gaggtgcggc 660
ggcagccaat cagagcggcg cgctccgaaa gtttcctttt atggcgaggc ggcggcggcg 720
gcggccctat aaaaagcgaa gcgcgcggcg gggagtcgct gcgttgcctt cgccccgtgc 780
cccgctccgc gccgcctcgc gccgcccgcc ccggctctga ctgaccgcgt tactcccaca 840
ggtgagcggg cgggacggcc cttctcctcc gggctgtaat tagcaagagg taagggttta 900
agggatggtt ggttggtggg gtattaatgt ttaattacct gttttacagg cctgaaatca 960
cttggtttta ggttgggcta gccaaagctt gccgccacca tgaaactcag tctggtcgcc 1020
gctatgctcc tgctcctctc cctggtcgcc gctatgctcc tgctcctgtc tgctgcccgc 1080
gctggggacg ctgctcagcc agctaggaga gctaggagga ccaagctggc tgcttacgct 1140
agaaaggctg ctaggcaggc tagagctgga ggaggaggat ccatggctcc caagaagaag 1200
aggaaggtgc gctaccccgc cttcctgtac aaggtggcta ccatggtgtc taagggagag 1260
gagctgttta caggcgtggt gcccatcctg gtggagctgg acggagatgt gaacggccac 1320
aagttcagcg tgtccggaga gggagagggc gacgccacct acggaaagct gacactgaag 1380
tttatctgca ccacaggcaa gctgcccgtg ccttggccaa ccctggtgac cacactgaca 1440
tacggcgtgc agtgtttctc tcggtaccct gaccacatga agcagcacga tttctttaag 1500
agcgccatgc cagagggata cgtgcaggag aggacaatct tctttaagga cgatggcaac 1560
tacaagacca gagctgaggt gaagttcgag ggagacacac tggtgaaccg gatcgagctg 1620
aagggcatcg actttaagga ggatggaaac atcctgggcc acaagctgga gtacaactac 1680
aacagccaca acgtgtacat catggccgat aagcagaaga acggaatcaa ggtgaacttt 1740
aagatccgcc acaacatcga ggacggctcc gtgcagctgg ctgatcacta ccagcagaac 1800
accccaatcg gagacggacc cgtgctgctg cctgataacc actacctgtc tacacagagc 1860
gccctgtcca aggaccctaa cgagaagagg gatcacatgg tcctcctgga atttgtgact 1920
gctgctggga ttactctcgg tatggatgaa ctgtataaat gataagcggc cgcaactcga 1980
gactctagac gactgtgcct tctagttgcc agccatctgt tgtttgcccc tcccccgtgc 2040
cttccttgac cctggaaggt gccactccca ctgtcctttc ctaataaaat gaggaaattg 2100
catcgcattg tctgagtagg tgtcattcta ttctgggggg tggggtgggg caggacagca 2160
agggggagga ttgggaagac aatagcaggc atgctgggga tgcggtgggc tctatggccg 2220
cgggccgcag gaacccctag tgatggagtt ggccactccc tctctgcgcg ctcgctcgct 2280
cactgaggcc gggcgaccaa aggtcgcccg acgcccgggc tttgcccggg cggcctcagt 2340
gagcgagcga gcgcgcagct gcctgcaggg gcgcctgatg cggtattttc tccttacgca 2400
tctgtgcggt atttcacacc gcatacgtca aagcaaccat agtacgcgcc ctgtagcggc 2460
gcattaagcg cggcgggtgt ggtggttacg cgcagcgtga ccgctacact tgccagcgcc 2520
ctagcgcccg ctcctttcgc tttcttccct tcctttctcg ccacgttcgc cggctttccc 2580
cgtcaagctc taaatcgggg gctcccttta gggttccgat ttagtgcttt acggcacctc 2640
gaccccaaaa aacttgattt gggtgatggt tcacgtagtg ggccatcgcc ctgatagacg 2700
gtttttcgcc ctttgacgtt ggagtccacg ttctttaata gtggactctt gttccaaact 2760
ggaacaacac tcaaccctat ctcgggctat tcttttgatt tataagggat tttgccgatt 2820
tcggcctatt ggttaaaaaa tgagctgatt taacaaaaat ttaacgcgaa ttttaacaaa 2880
atattaacgt ttacaatttt atggtgcact ctcagtacaa tctgctctga tgccgcatag 2940
ttaagccagc cccgacaccc gccaacaccc gctgacgcgc cctgacgggc ttgtctgctc 3000
ccggcatccg cttacagaca agctgtgacc gtctccggga gctgcatgtg tcagaggttt 3060
tcaccgtcat caccgaaacg cgcgagacga aagggcctcg tgatacgcct atttttatag 3120
gttaatgtca tgataataat ggtttcttag acgtcaggtg gcacttttcg gggaaatgtg 3180
cgcggaaccc ctatttgttt atttttctaa atacattcaa atatgtatcc gctcatgaga 3240
caataaccct gataaatgct tcaataatat tgaaaaagga agagtatgag tattcaacat 3300
ttccgtgtcg cccttattcc cttttttgcg gcattttgcc ttcctgtttt tgctcaccca 3360
gaaacgctgg tgaaagtaaa agatgctgaa gatcagttgg gtgcacgagt gggttacatc 3420
gaactggatc tcaacagcgg taagatcctt gagagttttc gccccgaaga acgttttcca 3480
atgatgagca cttttaaagt tctgctatgt ggcgcggtat tatcccgtat tgacgccggg 3540
caagagcaac tcggtcgccg catacactat tctcagaatg acttggttga gtactcacca 3600
gtcacagaaa agcatcttac ggatggcatg acagtaagag aattatgcag tgctgccata 3660
accatgagtg ataacactgc ggccaactta cttctgacaa cgatcggagg accgaaggag 3720
ctaaccgctt ttttgcacaa catgggggat catgtaactc gccttgatcg ttgggaaccg 3780
gagctgaatg aagccatacc aaacgacgag cgtgacacca cgatgcctgt agcaatggca 3840
acaacgttgc gcaaactatt aactggcgaa ctacttactc tagcttcccg gcaacaatta 3900
atagactgga tggaggcgga taaagttgca ggaccacttc tgcgctcggc ccttccggct 3960
ggctggttta ttgctgataa atctggagcc ggtgagcgtg ggtctcgcgg tatcattgca 4020
gcactggggc cagatggtaa gccctcccgt atcgtagtta tctacacgac ggggagtcag 4080
gcaactatgg atgaacgaaa tagacagatc gctgagatag gtgcctcact gattaagcat 4140
tggtaactgt cagaccaagt ttactcatat atactttaga ttgatttaaa acttcatttt 4200
taatttaaaa ggatctaggt gaagatcctt tttgataatc tcatgaccaa aatcccttaa 4260
cgtgagtttt cgttccactg agcgtcagac cccgtagaaa agatcaaagg atcttcttga 4320
gatccttttt ttctgcgcgt aatctgctgc ttgcaaacaa aaaaaccacc gctaccagcg 4380
gtggtttgtt tgccggatca agagctacca actctttttc cgaaggtaac tggcttcagc 4440
agagcgcaga taccaaatac tgtccttcta gtgtagccgt agttaggcca ccacttcaag 4500
aactctgtag caccgcctac atacctcgct ctgctaatcc tgttaccagt ggctgctgcc 4560
agtggcgata agtcgtgtct taccgggttg gactcaagac gatagttacc ggataaggcg 4620
cagcggtcgg gctgaacggg gggttcgtgc acacagccca gcttggagcg aacgacctac 4680
accgaactga gatacctaca gcgtgagcta tgagaaagcg ccacgcttcc cgaagggaga 4740
aaggcggaca ggtatccggt aagcggcagg gtcggaacag gagagcgcac gagggagctt 4800
ccagggggaa acgcctggta tctttatagt cctgtcgggt ttcgccacct ctgacttgag 4860
cgtcgatttt tgtgatgctc gtcagggggg cggagcctat ggaaaaacgc cagcaacgcg 4920
gcctttttac ggttcctggc cttttgctgg ccttttgctc acatgt 4966
<210> 114
<211> 6640
<212> DNA
<213> 人工序列
<220>
<223> AAVC-Syn-hCDKL5-107
<400> 114
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc tgcggcctaa ggcaattgac tacaaaccga gtatctgcag 180
agggccctgc gtatgagtgc aagtgggttt taggaccagg atgaggcggg gtgggggtgc 240
ctacctgacg accgaccccg acccactgga caagcaccca acccccattc cccaaattgc 300
gcatccccta tcagagaggg ggaggggaaa caggatgcgg cgaggcgcgt gcgcactgcc 360
agcttcagca ccgcggacag tgccttcgcc cccgcctggc ggcgcgcgcc accgccgcct 420
cagcactgaa ggcgcgctga cgtcactcgc cggtcccccg caaactcccc ttcccggcca 480
ccttggtcgc gtccgcgccg ccgccggccc agccggaccg caccacgcga ggcgcgagat 540
aggggggcac gggcgcgacc atctgcgctg cggcgccggc gactcagcgc tgcctcagtc 600
tgcggtgggc agcggaggag tcgtgtcgtg cctgagagcg cagctgtgct cctgggcacc 660
gcgcagtccg cccccgcggc tcctggccag accaccccta ggaccccctg ccccaagtcg 720
cagccttcga gctagccaaa gcttgccgcc accatgaaaa tccctaacat tggtaacgtg 780
atgaacaagt ttgaaatcct cggggtcgtc ggagaaggtg cctacggggt cgtgctgaag 840
tgcagacaca aggagacaca cgagatcgtg gccatcaaga agttcaagga tagcgaggag 900
aacgaggagg tgaaggagac aaccctgaga gagctgaaga tgctgcggac actgaagcag 960
gagaacatcg tggagctgaa ggaggctttc aggagacggg gaaagctgta cctggtgttt 1020
gagtacgtgg agaagaacat gctggagctg ctggaggaga tgcctaacgg cgtgccccct 1080
gagaaggtga agtcctacat ctaccagctg atcaaggcca tccactggtg ccacaagaac 1140
gacatcgtgc acagagatat caagccagag aacctgctga tctcccacaa cgacgtgctg 1200
aagctgtgcg atttcggctt tgcccggaac ctgagcgagg gaaacaacgc caactacaca 1260
gagtacgtgg ctaccagatg gtaccggagc ccagagctgc tgctgggagc tccatacgga 1320
aagagcgtgg acatgtggtc cgtgggctgc atcctgggag agctgtctga cggccagcct 1380
ctgttcccag gagagagcga gatcgatcag ctgtttacca tccagaaggt gctgggccct 1440
ctgccaagcg agcagatgaa gctgttctac tccaacccta gattccacgg actgcggttt 1500
cccgccgtga accaccctca gagcctggag cgcaggtacc tgggcatcct gaactccgtg 1560
ctgctggatc tgatgaagaa cctgctgaag ctggaccccg ccgatagata cctgaccgag 1620
cagtgtctga accaccctac atttcagacc cagcgcctgc tggacaggag cccttccaga 1680
tctgctaagc ggaagccata ccacgtggag agctccaccc tgtccaacag aaaccaggcc 1740
ggcaagtcta cagctctgca gagccaccac cggagcaact ccaaggacat ccagaacctg 1800
tctgtgggcc tgcctagggc tgatgaggga ctgccagcta acgagagctt cctgaacggc 1860
aacctggccg gagcttctct gagcccactg cacacaaaga cctaccaggc ctctagccag 1920
cccggctcca catctaagga cctgaccaac aacaacatcc cacacctgct gtctcccaag 1980
gaggctaaga gcaagaccga gttcgacttt aacatcgatc ccaagcctag cgagggccca 2040
ggaacaaagt acctgaagag caactcccgc tctcagcaga acaggcactc cttcatggag 2100
tcctctcagt ctaaggccgg caccctgcag cccaacgaga agcagagcag gcactcctac 2160
atcgatacca tcccccagag ctccagaagc ccttcctacc ggacaaaggc caagagccac 2220
ggcgctctgt ctgacagcaa gtccgtgtct aacctgtccg aggctagggc tcagatcgct 2280
gagccaagca cctccaggta ctttccttct agctgtctgg acctgaactc tcctacaagc 2340
ccaacaccca cccgccactc cgatacaagg accctgctgt ctccaagcgg caggaacaac 2400
aggaacgagg gaaccctgga ttctagacgg accacaaccc gccacagcaa gacaatggag 2460
gagctgaagc tgccagagca catggactcc tctcactccc actctctgag cgccccccac 2520
gagtccttct cttacggcct gggatacacc tcccccttca gctcccagca gaggccccac 2580
aggcactcta tgtacgtgac acgcgacaag gtgagggcca agggcctgga tggaagcctg 2640
tccatcggac agggaatggc tgctagggct aactccctgc agctgctgtc tcctcagcca 2700
ggagagcagc tgccaccaga gatgaccgtg gctcgctcta gcgtgaagga gacaagcagg 2760
gagggcacct cctctttcca cacacgccag aagtccgagg gcggagtgta ccacgacccc 2820
cactctgacg atggaacagc tcctaaggag aacaggcacc tgtacaacga tcccgtgcct 2880
cgcagggtgg gctccttcta cagagtgcca tctccccggc ctgacaacag ctttcacgag 2940
aacaacgtgt ccacccgcgt gagctccctg ccttctgagt ctagctccgg aacaaaccac 3000
tctaagaggc agcccgcctt tgacccttgg aagagcccag agaacatctc tcacagcgag 3060
cagctgaagg agaaggagaa gcagggcttc tttcgcagca tgaagaagaa gaagaagaag 3120
agccagaccg tgcctaactc cgactctcca gatctgctga ccctgcagaa gtccatccac 3180
agcgcctcca caccatctag ccgccctaag gagtggaggc ctgagaagat cagcgatctg 3240
cagacacaga gccagccact gaagtccctg aggaagctgc tgcacctgtc ctctgccagc 3300
aaccaccccg ctagctccga cccaagattc cagcccctga cagcccagca gaccaagaac 3360
tcttttagcg agatccggat ccaccctctg tcccaggctt ctggcggatc tagcaacatc 3420
agacaggagc cagctccaaa gggccggccc gctctgcagc tgcctggcca gatggaccca 3480
ggatggcacg tgtcctctgt gacaagatcc gccaccgagg gaccatccta ctctgagcag 3540
ctgggcgcta agtctggccc taacggacac ccatacaata ggactaatag aagcagaatg 3600
ccaaacctca atgacctcaa ggaaacagca ctctgataag cggccgcaac tcgagactct 3660
agacgactgt gccttctagt tgccagccat ctgttgtttg cccctccccc gtgccttcct 3720
tgaccctgga aggtgccact cccactgtcc tttcctaata aaatgaggaa attgcatcgc 3780
attgtctgag taggtgtcat tctattctgg ggggtggggt ggggcaggac agcaaggggg 3840
aggattggga agacaatagc aggcatgctg gggatgcggt gggctctatg gccgcgggcc 3900
gcaggaaccc ctagtgatgg agttggccac tccctctctg cgcgctcgct cgctcactga 3960
ggccgggcga ccaaaggtcg cccgacgccc gggctttgcc cgggcggcct cagtgagcga 4020
gcgagcgcgc agctgcctgc aggggcgcct gatgcggtat tttctcctta cgcatctgtg 4080
cggtatttca caccgcatac gtcaaagcaa ccatagtacg cgccctgtag cggcgcatta 4140
agcgcggcgg gtgtggtggt tacgcgcagc gtgaccgcta cacttgccag cgccctagcg 4200
cccgctcctt tcgctttctt cccttccttt ctcgccacgt tcgccggctt tccccgtcaa 4260
gctctaaatc gggggctccc tttagggttc cgatttagtg ctttacggca cctcgacccc 4320
aaaaaacttg atttgggtga tggttcacgt agtgggccat cgccctgata gacggttttt 4380
cgccctttga cgttggagtc cacgttcttt aatagtggac tcttgttcca aactggaaca 4440
acactcaacc ctatctcggg ctattctttt gatttataag ggattttgcc gatttcggcc 4500
tattggttaa aaaatgagct gatttaacaa aaatttaacg cgaattttaa caaaatatta 4560
acgtttacaa ttttatggtg cactctcagt acaatctgct ctgatgccgc atagttaagc 4620
cagccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct gctcccggca 4680
tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag gttttcaccg 4740
tcatcaccga aacgcgcgag acgaaagggc ctcgtgatac gcctattttt ataggttaat 4800
gtcatgataa taatggtttc ttagacgtca ggtggcactt ttcggggaaa tgtgcgcgga 4860
acccctattt gtttattttt ctaaatacat tcaaatatgt atccgctcat gagacaataa 4920
ccctgataaa tgcttcaata atattgaaaa aggaagagta tgagtattca acatttccgt 4980
gtcgccctta ttcccttttt tgcggcattt tgccttcctg tttttgctca cccagaaacg 5040
ctggtgaaag taaaagatgc tgaagatcag ttgggtgcac gagtgggtta catcgaactg 5100
gatctcaaca gcggtaagat ccttgagagt tttcgccccg aagaacgttt tccaatgatg 5160
agcactttta aagttctgct atgtggcgcg gtattatccc gtattgacgc cgggcaagag 5220
caactcggtc gccgcataca ctattctcag aatgacttgg ttgagtactc accagtcaca 5280
gaaaagcatc ttacggatgg catgacagta agagaattat gcagtgctgc cataaccatg 5340
agtgataaca ctgcggccaa cttacttctg acaacgatcg gaggaccgaa ggagctaacc 5400
gcttttttgc acaacatggg ggatcatgta actcgccttg atcgttggga accggagctg 5460
aatgaagcca taccaaacga cgagcgtgac accacgatgc ctgtagcaat ggcaacaacg 5520
ttgcgcaaac tattaactgg cgaactactt actctagctt cccggcaaca attaatagac 5580
tggatggagg cggataaagt tgcaggacca cttctgcgct cggcccttcc ggctggctgg 5640
tttattgctg ataaatctgg agccggtgag cgtgggtctc gcggtatcat tgcagcactg 5700
gggccagatg gtaagccctc ccgtatcgta gttatctaca cgacggggag tcaggcaact 5760
atggatgaac gaaatagaca gatcgctgag ataggtgcct cactgattaa gcattggtaa 5820
ctgtcagacc aagtttactc atatatactt tagattgatt taaaacttca tttttaattt 5880
aaaaggatct aggtgaagat cctttttgat aatctcatga ccaaaatccc ttaacgtgag 5940
ttttcgttcc actgagcgtc agaccccgta gaaaagatca aaggatcttc ttgagatcct 6000
ttttttctgc gcgtaatctg ctgcttgcaa acaaaaaaac caccgctacc agcggtggtt 6060
tgtttgccgg atcaagagct accaactctt tttccgaagg taactggctt cagcagagcg 6120
cagataccaa atactgtcct tctagtgtag ccgtagttag gccaccactt caagaactct 6180
gtagcaccgc ctacatacct cgctctgcta atcctgttac cagtggctgc tgccagtggc 6240
gataagtcgt gtcttaccgg gttggactca agacgatagt taccggataa ggcgcagcgg 6300
tcgggctgaa cggggggttc gtgcacacag cccagcttgg agcgaacgac ctacaccgaa 6360
ctgagatacc tacagcgtga gctatgagaa agcgccacgc ttcccgaagg gagaaaggcg 6420
gacaggtatc cggtaagcgg cagggtcgga acaggagagc gcacgaggga gcttccaggg 6480
ggaaacgcct ggtatcttta tagtcctgtc gggtttcgcc acctctgact tgagcgtcga 6540
tttttgtgat gctcgtcagg ggggcggagc ctatggaaaa acgccagcaa cgcggccttt 6600
ttacggttcc tggccttttg ctggcctttt gctcacatgt 6640
<210> 115
<211> 6640
<212> DNA
<213> 人工序列
<220>
<223> AAVC-Syn-hCDKL5-107(失活激酶)
<400> 115
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc tgcggcctaa ggcaattgac tacaaaccga gtatctgcag 180
agggccctgc gtatgagtgc aagtgggttt taggaccagg atgaggcggg gtgggggtgc 240
ctacctgacg accgaccccg acccactgga caagcaccca acccccattc cccaaattgc 300
gcatccccta tcagagaggg ggaggggaaa caggatgcgg cgaggcgcgt gcgcactgcc 360
agcttcagca ccgcggacag tgccttcgcc cccgcctggc ggcgcgcgcc accgccgcct 420
cagcactgaa ggcgcgctga cgtcactcgc cggtcccccg caaactcccc ttcccggcca 480
ccttggtcgc gtccgcgccg ccgccggccc agccggaccg caccacgcga ggcgcgagat 540
aggggggcac gggcgcgacc atctgcgctg cggcgccggc gactcagcgc tgcctcagtc 600
tgcggtgggc agcggaggag tcgtgtcgtg cctgagagcg cagctgtgct cctgggcacc 660
gcgcagtccg cccccgcggc tcctggccag accaccccta ggaccccctg ccccaagtcg 720
cagccttcga gctagccaaa gcttgccgcc accatgaaaa tccctaatat cggaaatgtg 780
atgaataagt ttgaaatcct cggggtcgtc ggagaaggtg cctacggggt cgtcctgaaa 840
tgcagacaca aggagacaca cgagatcgtg gccatcagga gattcaagga tagcgaggag 900
aacgaggagg tgaaggagac aaccctgcgc gagctgaaga tgctgaggac actgaagcag 960
gagaacatcg tggagctgaa ggaggctttc cggcgcaggg gaaagctgta cctggtgttt 1020
gagtacgtgg agaagaacat gctggagctg ctggaggaga tgcctaacgg cgtgccccct 1080
gagaaggtga agtcctacat ctaccagctg atcaaggcca tccactggtg ccacaagaac 1140
gacatcgtgc accgcgatat caagccagag aacctgctga tctcccacaa cgacgtgctg 1200
aagctgtgcg atttcggctt tgccaggaac ctgagcgagg gaaacaacgc caactacaca 1260
gagtacgtgg ctacccgctg gtacaggagc ccagagctgc tgctgggagc tccatacgga 1320
aagagcgtgg acatgtggtc cgtgggctgc atcctgggag agctgtctga cggccagcct 1380
ctgttcccag gagagagcga gatcgatcag ctgtttacca tccagaaggt gctgggccct 1440
ctgccaagcg agcagatgaa gctgttctac tccaaccctc gcttccacgg actgaggttt 1500
cccgccgtga accaccctca gagcctggag agacggtacc tgggcatcct gaactccgtg 1560
ctgctggatc tgatgaagaa cctgctgaag ctggaccccg ccgatcgcta cctgaccgag 1620
cagtgtctga accaccctac atttcagacc cagagactgc tggaccggag cccttcccgc 1680
tctgctaaga ggaagccata ccacgtggag agctccaccc tgtccaaccg caaccaggcc 1740
ggcaagtcta cagctctgca gagccaccac aggagcaact ccaaggacat ccagaacctg 1800
tctgtgggcc tgcctagggc tgatgaggga ctgccagcta acgagagctt cctgaacggc 1860
aacctggccg gagcttctct gagcccactg cacacaaaga cctaccaggc ctctagccag 1920
cccggctcca catctaagga cctgaccaac aacaacatcc cacacctgct gtctcccaag 1980
gaggctaaga gcaagaccga gttcgacttt aacatcgatc ccaagcctag cgagggccca 2040
ggaacaaagt acctgaagag caactccaga tctcagcaga accggcactc cttcatggag 2100
tcctctcagt ctaaggccgg caccctgcag cccaacgaga agcagagcag gcactcctac 2160
atcgatacca tcccccagag ctcccgcagc ccttcctaca ggacaaaggc caagagccac 2220
ggcgctctgt ctgacagcaa gtccgtgtct aacctgtccg aggccagagc tcagatcgct 2280
gagcccagca cctcccggta ctttccttct agctgtctgg acctgaactc tcctacaagc 2340
ccaacaccca ccagacactc cgatacacgg accctgctgt ctccaagcgg cagaaacaac 2400
cggaacgagg gaaccctgga ttctcgcagg accacaacca gacacagcaa gacaatggag 2460
gagctgaagc tgccagagca catggactcc tctcactccc actctctgag cgccccccac 2520
gagtccttct cttacggcct gggatacacc tcccccttca gctcccagca gcgcccccac 2580
aggcactcta tgtacgtgac aagagacaag gtgcgggcca agggcctgga tggaagcctg 2640
tccatcggcc agggaatggc cgctagggct aactccctgc agctgctgtc tcctcagcca 2700
ggagagcagc tgccacccga gatgaccgtg gccagatcta gcgtgaagga gacaagccgg 2760
gagggcacct cctctttcca cacaagacag aagtccgagg gcggagtgta ccacgacccc 2820
cactctgacg atggaacagc tcctaaggag aaccggcacc tgtacaacga tcccgtgcct 2880
agacgggtgg gctccttcta ccgcgtgcca tctcccaggc ctgacaacag ctttcacgag 2940
aacaacgtgt ccaccagagt gagctccctg ccttctgagt ctagctccgg aacaaaccac 3000
tctaagcggc agcccgcctt tgacccttgg aagagcccag agaacatctc tcacagcgag 3060
cagctgaagg agaaggagaa gcagggcttc tttagaagca tgaagaagaa gaagaagaag 3120
agccagaccg tgcctaactc cgactctcca gatctgctga ccctgcagaa gtccatccac 3180
agcgcctcca caccctctag cagacctaag gagtggcggc ctgagaagat cagcgatctg 3240
cagacacaga gccagccact gaagtccctg cggaagctgc tgcacctgtc ctctgccagc 3300
aaccacccag ctagctccga cccaaggttc cagccactga cagctcagca gaccaagaac 3360
tcttttagcg agatcaggat ccaccctctg tcccaggctt ctggcggatc tagcaacatc 3420
aggcaggagc cagctccaaa gggcaggccc gctctgcagc tgcctggaca gatggaccca 3480
ggatggcacg tgtcctctgt gacaagatcc gccaccgagg gaccatccta ctctgagcag 3540
ctgggcgcta agtctggccc taacggacac ccatacaaca gaacaaacag aagcagaatg 3600
cccaacctca atgacctcaa agaaacagca ctctgataag cggccgcaac tcgagactct 3660
agacgactgt gccttctagt tgccagccat ctgttgtttg cccctccccc gtgccttcct 3720
tgaccctgga aggtgccact cccactgtcc tttcctaata aaatgaggaa attgcatcgc 3780
attgtctgag taggtgtcat tctattctgg ggggtggggt ggggcaggac agcaaggggg 3840
aggattggga agacaatagc aggcatgctg gggatgcggt gggctctatg gccgcgggcc 3900
gcaggaaccc ctagtgatgg agttggccac tccctctctg cgcgctcgct cgctcactga 3960
ggccgggcga ccaaaggtcg cccgacgccc gggctttgcc cgggcggcct cagtgagcga 4020
gcgagcgcgc agctgcctgc aggggcgcct gatgcggtat tttctcctta cgcatctgtg 4080
cggtatttca caccgcatac gtcaaagcaa ccatagtacg cgccctgtag cggcgcatta 4140
agcgcggcgg gtgtggtggt tacgcgcagc gtgaccgcta cacttgccag cgccctagcg 4200
cccgctcctt tcgctttctt cccttccttt ctcgccacgt tcgccggctt tccccgtcaa 4260
gctctaaatc gggggctccc tttagggttc cgatttagtg ctttacggca cctcgacccc 4320
aaaaaacttg atttgggtga tggttcacgt agtgggccat cgccctgata gacggttttt 4380
cgccctttga cgttggagtc cacgttcttt aatagtggac tcttgttcca aactggaaca 4440
acactcaacc ctatctcggg ctattctttt gatttataag ggattttgcc gatttcggcc 4500
tattggttaa aaaatgagct gatttaacaa aaatttaacg cgaattttaa caaaatatta 4560
acgtttacaa ttttatggtg cactctcagt acaatctgct ctgatgccgc atagttaagc 4620
cagccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct gctcccggca 4680
tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag gttttcaccg 4740
tcatcaccga aacgcgcgag acgaaagggc ctcgtgatac gcctattttt ataggttaat 4800
gtcatgataa taatggtttc ttagacgtca ggtggcactt ttcggggaaa tgtgcgcgga 4860
acccctattt gtttattttt ctaaatacat tcaaatatgt atccgctcat gagacaataa 4920
ccctgataaa tgcttcaata atattgaaaa aggaagagta tgagtattca acatttccgt 4980
gtcgccctta ttcccttttt tgcggcattt tgccttcctg tttttgctca cccagaaacg 5040
ctggtgaaag taaaagatgc tgaagatcag ttgggtgcac gagtgggtta catcgaactg 5100
gatctcaaca gcggtaagat ccttgagagt tttcgccccg aagaacgttt tccaatgatg 5160
agcactttta aagttctgct atgtggcgcg gtattatccc gtattgacgc cgggcaagag 5220
caactcggtc gccgcataca ctattctcag aatgacttgg ttgagtactc accagtcaca 5280
gaaaagcatc ttacggatgg catgacagta agagaattat gcagtgctgc cataaccatg 5340
agtgataaca ctgcggccaa cttacttctg acaacgatcg gaggaccgaa ggagctaacc 5400
gcttttttgc acaacatggg ggatcatgta actcgccttg atcgttggga accggagctg 5460
aatgaagcca taccaaacga cgagcgtgac accacgatgc ctgtagcaat ggcaacaacg 5520
ttgcgcaaac tattaactgg cgaactactt actctagctt cccggcaaca attaatagac 5580
tggatggagg cggataaagt tgcaggacca cttctgcgct cggcccttcc ggctggctgg 5640
tttattgctg ataaatctgg agccggtgag cgtgggtctc gcggtatcat tgcagcactg 5700
gggccagatg gtaagccctc ccgtatcgta gttatctaca cgacggggag tcaggcaact 5760
atggatgaac gaaatagaca gatcgctgag ataggtgcct cactgattaa gcattggtaa 5820
ctgtcagacc aagtttactc atatatactt tagattgatt taaaacttca tttttaattt 5880
aaaaggatct aggtgaagat cctttttgat aatctcatga ccaaaatccc ttaacgtgag 5940
ttttcgttcc actgagcgtc agaccccgta gaaaagatca aaggatcttc ttgagatcct 6000
ttttttctgc gcgtaatctg ctgcttgcaa acaaaaaaac caccgctacc agcggtggtt 6060
tgtttgccgg atcaagagct accaactctt tttccgaagg taactggctt cagcagagcg 6120
cagataccaa atactgtcct tctagtgtag ccgtagttag gccaccactt caagaactct 6180
gtagcaccgc ctacatacct cgctctgcta atcctgttac cagtggctgc tgccagtggc 6240
gataagtcgt gtcttaccgg gttggactca agacgatagt taccggataa ggcgcagcgg 6300
tcgggctgaa cggggggttc gtgcacacag cccagcttgg agcgaacgac ctacaccgaa 6360
ctgagatacc tacagcgtga gctatgagaa agcgccacgc ttcccgaagg gagaaaggcg 6420
gacaggtatc cggtaagcgg cagggtcgga acaggagagc gcacgaggga gcttccaggg 6480
ggaaacgcct ggtatcttta tagtcctgtc gggtttcgcc acctctgact tgagcgtcga 6540
tttttgtgat gctcgtcagg ggggcggagc ctatggaaaa acgccagcaa cgcggccttt 6600
ttacggttcc tggccttttg ctggcctttt gctcacatgt 6640
<210> 116
<211> 4477
<212> DNA
<213> 人工序列
<220>
<223> AAVC-Syn-eGFP
<400> 116
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc tgcggcctaa ggcaattgac tacaaaccga gtatctgcag 180
agggccctgc gtatgagtgc aagtgggttt taggaccagg atgaggcggg gtgggggtgc 240
ctacctgacg accgaccccg acccactgga caagcaccca acccccattc cccaaattgc 300
gcatccccta tcagagaggg ggaggggaaa caggatgcgg cgaggcgcgt gcgcactgcc 360
agcttcagca ccgcggacag tgccttcgcc cccgcctggc ggcgcgcgcc accgccgcct 420
cagcactgaa ggcgcgctga cgtcactcgc cggtcccccg caaactcccc ttcccggcca 480
ccttggtcgc gtccgcgccg ccgccggccc agccggaccg caccacgcga ggcgcgagat 540
aggggggcac gggcgcgacc atctgcgctg cggcgccggc gactcagcgc tgcctcagtc 600
tgcggtgggc agcggaggag tcgtgtcgtg cctgagagcg cagctgtgct cctgggcacc 660
gcgcagtccg cccccgcggc tcctggccag accaccccta ggaccccctg ccccaagtcg 720
cagccttcga gctagccaaa gcttgccgcc accatggtgt caaaggggga ggaactgttt 780
actggagtcg tgcctattct ggtcgaactg gatggggatg tcaacggtca taagtttagc 840
gtgtccggag agggagaggg cgacgctacc tacggaaagc tgacactgaa gttcatctgc 900
accacaggca agctgcccgt gccttggcca accctggtga ccacactgac atacggcgtg 960
cagtgtttta gccggtaccc agaccacatg aagcagcacg atttctttaa gtccgccatg 1020
cccgagggat acgtgcagga gaggaccatc ttctttaagg acgatggcaa ctacaagacc 1080
agagctgagg tgaagttcga gggagacaca ctggtgaacc ggatcgagct gaagggcatc 1140
gactttaagg aggatggaaa catcctgggc cacaagctgg agtacaacta caactctcac 1200
aacgtgtaca tcatggccga taagcagaag aacggaatca aggtgaactt caagatccgc 1260
cacaacatcg aggacggcag cgtgcagctg gctgatcact accagcagaa cacccctatc 1320
ggagacggac ccgtgctgct gcctgataac cactacctga gcacacagtc cgctctgtct 1380
aaggacccaa acgagaagag ggatcacatg gtcctcctgg aatttgtcac tgctgctggg 1440
attactctgg ggatggatga actctataag tgataagcgg ccgcaactcg agactctaga 1500
cgactgtgcc ttctagttgc cagccatctg ttgtttgccc ctcccccgtg ccttccttga 1560
ccctggaagg tgccactccc actgtccttt cctaataaaa tgaggaaatt gcatcgcatt 1620
gtctgagtag gtgtcattct attctggggg gtggggtggg gcaggacagc aagggggagg 1680
attgggaaga caatagcagg catgctgggg atgcggtggg ctctatggcc gcgggccgca 1740
ggaaccccta gtgatggagt tggccactcc ctctctgcgc gctcgctcgc tcactgaggc 1800
cgggcgacca aaggtcgccc gacgcccggg ctttgcccgg gcggcctcag tgagcgagcg 1860
agcgcgcagc tgcctgcagg ggcgcctgat gcggtatttt ctccttacgc atctgtgcgg 1920
tatttcacac cgcatacgtc aaagcaacca tagtacgcgc cctgtagcgg cgcattaagc 1980
gcggcgggtg tggtggttac gcgcagcgtg accgctacac ttgccagcgc cctagcgccc 2040
gctcctttcg ctttcttccc ttcctttctc gccacgttcg ccggctttcc ccgtcaagct 2100
ctaaatcggg ggctcccttt agggttccga tttagtgctt tacggcacct cgaccccaaa 2160
aaacttgatt tgggtgatgg ttcacgtagt gggccatcgc cctgatagac ggtttttcgc 2220
cctttgacgt tggagtccac gttctttaat agtggactct tgttccaaac tggaacaaca 2280
ctcaacccta tctcgggcta ttcttttgat ttataaggga ttttgccgat ttcggcctat 2340
tggttaaaaa atgagctgat ttaacaaaaa tttaacgcga attttaacaa aatattaacg 2400
tttacaattt tatggtgcac tctcagtaca atctgctctg atgccgcata gttaagccag 2460
ccccgacacc cgccaacacc cgctgacgcg ccctgacggg cttgtctgct cccggcatcc 2520
gcttacagac aagctgtgac cgtctccggg agctgcatgt gtcagaggtt ttcaccgtca 2580
tcaccgaaac gcgcgagacg aaagggcctc gtgatacgcc tatttttata ggttaatgtc 2640
atgataataa tggtttctta gacgtcaggt ggcacttttc ggggaaatgt gcgcggaacc 2700
cctatttgtt tatttttcta aatacattca aatatgtatc cgctcatgag acaataaccc 2760
tgataaatgc ttcaataata ttgaaaaagg aagagtatga gtattcaaca tttccgtgtc 2820
gcccttattc ccttttttgc ggcattttgc cttcctgttt ttgctcaccc agaaacgctg 2880
gtgaaagtaa aagatgctga agatcagttg ggtgcacgag tgggttacat cgaactggat 2940
ctcaacagcg gtaagatcct tgagagtttt cgccccgaag aacgttttcc aatgatgagc 3000
acttttaaag ttctgctatg tggcgcggta ttatcccgta ttgacgccgg gcaagagcaa 3060
ctcggtcgcc gcatacacta ttctcagaat gacttggttg agtactcacc agtcacagaa 3120
aagcatctta cggatggcat gacagtaaga gaattatgca gtgctgccat aaccatgagt 3180
gataacactg cggccaactt acttctgaca acgatcggag gaccgaagga gctaaccgct 3240
tttttgcaca acatggggga tcatgtaact cgccttgatc gttgggaacc ggagctgaat 3300
gaagccatac caaacgacga gcgtgacacc acgatgcctg tagcaatggc aacaacgttg 3360
cgcaaactat taactggcga actacttact ctagcttccc ggcaacaatt aatagactgg 3420
atggaggcgg ataaagttgc aggaccactt ctgcgctcgg cccttccggc tggctggttt 3480
attgctgata aatctggagc cggtgagcgt gggtctcgcg gtatcattgc agcactgggg 3540
ccagatggta agccctcccg tatcgtagtt atctacacga cggggagtca ggcaactatg 3600
gatgaacgaa atagacagat cgctgagata ggtgcctcac tgattaagca ttggtaactg 3660
tcagaccaag tttactcata tatactttag attgatttaa aacttcattt ttaatttaaa 3720
aggatctagg tgaagatcct ttttgataat ctcatgacca aaatccctta acgtgagttt 3780
tcgttccact gagcgtcaga ccccgtagaa aagatcaaag gatcttcttg agatcctttt 3840
tttctgcgcg taatctgctg cttgcaaaca aaaaaaccac cgctaccagc ggtggtttgt 3900
ttgccggatc aagagctacc aactcttttt ccgaaggtaa ctggcttcag cagagcgcag 3960
ataccaaata ctgtccttct agtgtagccg tagttaggcc accacttcaa gaactctgta 4020
gcaccgccta catacctcgc tctgctaatc ctgttaccag tggctgctgc cagtggcgat 4080
aagtcgtgtc ttaccgggtt ggactcaaga cgatagttac cggataaggc gcagcggtcg 4140
ggctgaacgg ggggttcgtg cacacagccc agcttggagc gaacgaccta caccgaactg 4200
agatacctac agcgtgagct atgagaaagc gccacgcttc ccgaagggag aaaggcggac 4260
aggtatccgg taagcggcag ggtcggaaca ggagagcgca cgagggagct tccaggggga 4320
aacgcctggt atctttatag tcctgtcggg tttcgccacc tctgacttga gcgtcgattt 4380
ttgtgatgct cgtcaggggg gcggagccta tggaaaaacg ccagcaacgc ggccttttta 4440
cggttcctgg ccttttgctg gccttttgct cacatgt 4477
<210> 117
<211> 4537
<212> DNA
<213> 人工序列
<220>
<223> AAVC-Syn-NLS-eGFP
<400> 117
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc tgcggcctaa ggcaattgac tacaaaccga gtatctgcag 180
agggccctgc gtatgagtgc aagtgggttt taggaccagg atgaggcggg gtgggggtgc 240
ctacctgacg accgaccccg acccactgga caagcaccca acccccattc cccaaattgc 300
gcatccccta tcagagaggg ggaggggaaa caggatgcgg cgaggcgcgt gcgcactgcc 360
agcttcagca ccgcggacag tgccttcgcc cccgcctggc ggcgcgcgcc accgccgcct 420
cagcactgaa ggcgcgctga cgtcactcgc cggtcccccg caaactcccc ttcccggcca 480
ccttggtcgc gtccgcgccg ccgccggccc agccggaccg caccacgcga ggcgcgagat 540
aggggggcac gggcgcgacc atctgcgctg cggcgccggc gactcagcgc tgcctcagtc 600
tgcggtgggc agcggaggag tcgtgtcgtg cctgagagcg cagctgtgct cctgggcacc 660
gcgcagtccg cccccgcggc tcctggccag accaccccta ggaccccctg ccccaagtcg 720
cagccttcga gctagccaaa gcttgccgcc accatggccc caaaaaagaa aagaaaagtg 780
aggtatcctg cattcctgta caaagtcgct actatggtgt caaaaggtga agagctgttc 840
accggagtgg tgcccatcct ggtggagctg gacggagatg tgaacggcca caagttcagc 900
gtgtccggag agggagaggg cgacgccacc tacggaaagc tgacactgaa gtttatctgc 960
accacaggca agctgcccgt gccttggcca accctggtga ccacactgac atacggcgtg 1020
cagtgtttct ctcggtaccc agaccacatg aagcagcacg atttctttaa gagcgccatg 1080
cccgagggat acgtgcagga gaggacaatc ttctttaagg acgatggcaa ctacaagacc 1140
agagctgagg tgaagttcga gggagacaca ctggtgaacc ggatcgagct gaagggcatc 1200
gactttaagg aggatggaaa catcctgggc cacaagctgg agtacaacta caactcccac 1260
aacgtgtaca tcatggccga taagcagaag aacggaatca aggtgaactt taagatccgc 1320
cacaacatcg aggacggctc tgtgcagctg gctgatcact accagcagaa cacccctatc 1380
ggagacggac ccgtgctgct gcctgataac cactacctgt ctacacagag cgccctgtcc 1440
aaggacccaa acgagaagag ggatcacatg gtgctcctgg aatttgtcac tgctgccggt 1500
attactctcg ggatggatga actgtataaa tgataagcgg ccgcaactcg agactctaga 1560
cgactgtgcc ttctagttgc cagccatctg ttgtttgccc ctcccccgtg ccttccttga 1620
ccctggaagg tgccactccc actgtccttt cctaataaaa tgaggaaatt gcatcgcatt 1680
gtctgagtag gtgtcattct attctggggg gtggggtggg gcaggacagc aagggggagg 1740
attgggaaga caatagcagg catgctgggg atgcggtggg ctctatggcc gcgggccgca 1800
ggaaccccta gtgatggagt tggccactcc ctctctgcgc gctcgctcgc tcactgaggc 1860
cgggcgacca aaggtcgccc gacgcccggg ctttgcccgg gcggcctcag tgagcgagcg 1920
agcgcgcagc tgcctgcagg ggcgcctgat gcggtatttt ctccttacgc atctgtgcgg 1980
tatttcacac cgcatacgtc aaagcaacca tagtacgcgc cctgtagcgg cgcattaagc 2040
gcggcgggtg tggtggttac gcgcagcgtg accgctacac ttgccagcgc cctagcgccc 2100
gctcctttcg ctttcttccc ttcctttctc gccacgttcg ccggctttcc ccgtcaagct 2160
ctaaatcggg ggctcccttt agggttccga tttagtgctt tacggcacct cgaccccaaa 2220
aaacttgatt tgggtgatgg ttcacgtagt gggccatcgc cctgatagac ggtttttcgc 2280
cctttgacgt tggagtccac gttctttaat agtggactct tgttccaaac tggaacaaca 2340
ctcaacccta tctcgggcta ttcttttgat ttataaggga ttttgccgat ttcggcctat 2400
tggttaaaaa atgagctgat ttaacaaaaa tttaacgcga attttaacaa aatattaacg 2460
tttacaattt tatggtgcac tctcagtaca atctgctctg atgccgcata gttaagccag 2520
ccccgacacc cgccaacacc cgctgacgcg ccctgacggg cttgtctgct cccggcatcc 2580
gcttacagac aagctgtgac cgtctccggg agctgcatgt gtcagaggtt ttcaccgtca 2640
tcaccgaaac gcgcgagacg aaagggcctc gtgatacgcc tatttttata ggttaatgtc 2700
atgataataa tggtttctta gacgtcaggt ggcacttttc ggggaaatgt gcgcggaacc 2760
cctatttgtt tatttttcta aatacattca aatatgtatc cgctcatgag acaataaccc 2820
tgataaatgc ttcaataata ttgaaaaagg aagagtatga gtattcaaca tttccgtgtc 2880
gcccttattc ccttttttgc ggcattttgc cttcctgttt ttgctcaccc agaaacgctg 2940
gtgaaagtaa aagatgctga agatcagttg ggtgcacgag tgggttacat cgaactggat 3000
ctcaacagcg gtaagatcct tgagagtttt cgccccgaag aacgttttcc aatgatgagc 3060
acttttaaag ttctgctatg tggcgcggta ttatcccgta ttgacgccgg gcaagagcaa 3120
ctcggtcgcc gcatacacta ttctcagaat gacttggttg agtactcacc agtcacagaa 3180
aagcatctta cggatggcat gacagtaaga gaattatgca gtgctgccat aaccatgagt 3240
gataacactg cggccaactt acttctgaca acgatcggag gaccgaagga gctaaccgct 3300
tttttgcaca acatggggga tcatgtaact cgccttgatc gttgggaacc ggagctgaat 3360
gaagccatac caaacgacga gcgtgacacc acgatgcctg tagcaatggc aacaacgttg 3420
cgcaaactat taactggcga actacttact ctagcttccc ggcaacaatt aatagactgg 3480
atggaggcgg ataaagttgc aggaccactt ctgcgctcgg cccttccggc tggctggttt 3540
attgctgata aatctggagc cggtgagcgt gggtctcgcg gtatcattgc agcactgggg 3600
ccagatggta agccctcccg tatcgtagtt atctacacga cggggagtca ggcaactatg 3660
gatgaacgaa atagacagat cgctgagata ggtgcctcac tgattaagca ttggtaactg 3720
tcagaccaag tttactcata tatactttag attgatttaa aacttcattt ttaatttaaa 3780
aggatctagg tgaagatcct ttttgataat ctcatgacca aaatccctta acgtgagttt 3840
tcgttccact gagcgtcaga ccccgtagaa aagatcaaag gatcttcttg agatcctttt 3900
tttctgcgcg taatctgctg cttgcaaaca aaaaaaccac cgctaccagc ggtggtttgt 3960
ttgccggatc aagagctacc aactcttttt ccgaaggtaa ctggcttcag cagagcgcag 4020
ataccaaata ctgtccttct agtgtagccg tagttaggcc accacttcaa gaactctgta 4080
gcaccgccta catacctcgc tctgctaatc ctgttaccag tggctgctgc cagtggcgat 4140
aagtcgtgtc ttaccgggtt ggactcaaga cgatagttac cggataaggc gcagcggtcg 4200
ggctgaacgg ggggttcgtg cacacagccc agcttggagc gaacgaccta caccgaactg 4260
agatacctac agcgtgagct atgagaaagc gccacgcttc ccgaagggag aaaggcggac 4320
aggtatccgg taagcggcag ggtcggaaca ggagagcgca cgagggagct tccaggggga 4380
aacgcctggt atctttatag tcctgtcggg tttcgccacc tctgacttga gcgtcgattt 4440
ttgtgatgct cgtcaggggg gcggagccta tggaaaaacg ccagcaacgc ggccttttta 4500
cggttcctgg ccttttgctg gccttttgct cacatgt 4537
<210> 118
<211> 6820
<212> DNA
<213> 人工序列
<220>
<223> AAVC-Syn-mBPIP-TATκ28-hCDKL5-107
<400> 118
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc tgcggcctaa ggcaattgac tacaaaccga gtatctgcag 180
agggccctgc gtatgagtgc aagtgggttt taggaccagg atgaggcggg gtgggggtgc 240
ctacctgacg accgaccccg acccactgga caagcaccca acccccattc cccaaattgc 300
gcatccccta tcagagaggg ggaggggaaa caggatgcgg cgaggcgcgt gcgcactgcc 360
agcttcagca ccgcggacag tgccttcgcc cccgcctggc ggcgcgcgcc accgccgcct 420
cagcactgaa ggcgcgctga cgtcactcgc cggtcccccg caaactcccc ttcccggcca 480
ccttggtcgc gtccgcgccg ccgccggccc agccggaccg caccacgcga ggcgcgagat 540
aggggggcac gggcgcgacc atctgcgctg cggcgccggc gactcagcgc tgcctcagtc 600
tgcggtgggc agcggaggag tcgtgtcgtg cctgagagcg cagctgtgct cctgggcacc 660
gcgcagtccg cccccgcggc tcctggccag accaccccta ggaccccctg ccccaagtcg 720
cagccttcga gctagccaaa gcttgccgcc accatgaaac tctccctggt cgctgctatg 780
ctgctcctcc tgtccctcgt cgctgctatg ctcctgctgc tgtctgccgc tcgggctggt 840
gatgctgctc agccagctag gagagctagg aggaccaagc tggctgctta cgctagaaag 900
gctgctagac aggctagggc tggaggaggc ggatccaaga tccccaacat cggcaacgtg 960
atgaacaagt tcgagatcct gggagtggtg ggagagggag cttacggagt ggtgctgaag 1020
tgccggcaca aggagacaca cgagatcgtg gctatcaaga agtttaagga cagcgaggag 1080
aacgaggagg tgaaggagac aaccctgcgc gagctgaaga tgctgaggac actgaagcag 1140
gagaacatcg tggagctgaa ggaggccttc aggagacggg gaaagctgta cctggtgttt 1200
gagtacgtgg agaagaacat gctggagctg ctggaggaga tgccaaacgg agtgccacct 1260
gagaaggtga agtcctacat ctaccagctg atcaaggcta tccactggtg ccacaagaac 1320
gacatcgtgc accgcgatat caagcctgag aacctgctga tctcccacaa cgacgtgctg 1380
aagctgtgcg atttcggctt tgccaggaac ctgagcgagg gaaacaacgc caactacaca 1440
gagtacgtgg ctacccgctg gtacaggagc ccagagctgc tgctgggagc tccatacgga 1500
aagagcgtgg acatgtggtc cgtgggctgc atcctgggag agctgtctga cggccagcct 1560
ctgttcccag gagagagcga gatcgatcag ctgtttacca tccagaaggt gctgggccct 1620
ctgccaagcg agcagatgaa gctgttctac tccaaccctc gcttccacgg actgaggttt 1680
cccgccgtga accaccctca gagcctggag cgcaggtacc tgggcatcct gaactccgtg 1740
ctgctggatc tgatgaagaa cctgctgaag ctggaccccg ccgatagata cctgaccgag 1800
cagtgtctga accaccctac atttcagacc cagagactgc tggaccggag cccttcccgc 1860
tctgctaaga ggaagccata ccacgtggag agctccaccc tgtccaaccg caaccaggcc 1920
ggcaagtcta cagctctgca gagccaccac aggagcaact ccaaggacat ccagaacctg 1980
tctgtgggcc tgcctagggc tgatgaggga ctgccagcta acgagagctt cctgaacggc 2040
aacctggccg gagcttctct gagcccactg cacacaaaga cctaccaggc ctctagccag 2100
cccggctcca catctaagga cctgaccaac aacaacatcc cacacctgct gtctcccaag 2160
gaggctaaga gcaagaccga gttcgacttt aacatcgatc ccaagcctag cgagggccct 2220
ggaacaaagt acctgaagag caactccaga tctcagcaga accggcactc cttcatggag 2280
tcctctcagt ctaaggccgg caccctgcag ccaaacgaga agcagagccg gcactcctac 2340
atcgatacca tcccccagag ctcccgcagc ccttcctaca ggacaaaggc caagagccac 2400
ggcgctctgt ctgacagcaa gtccgtgtct aacctgtccg aggccagagc tcagatcgct 2460
gagccaagca cctccaggta ctttccttct agctgtctgg acctgaactc tcctacaagc 2520
ccaacaccca ccagacacag cgatacacgg accctgctgt ctccaagcgg cagaaacaac 2580
cggaacgagg gaaccctgga ttctagacgg accacaacca ggcacagcaa gacaatggag 2640
gagctgaagc tgccagagca catggactcc tctcactccc actctctgag cgccccccac 2700
gagtccttct cttacggcct gggatacacc tcccccttca gctcccagca gcgcccccac 2760
aggcactcta tgtacgtgac aagagacaag gtgcgggcca agggcctgga tggaagcctg 2820
tccatcggcc agggaatggc cgctagagct aactccctgc agctgctgtc tcctcagcca 2880
ggagagcagc tgccacccga gatgaccgtg gccagatcta gcgtgaagga gacaagccgg 2940
gagggcacct cctctttcca cacaagacag aagtccgagg gcggagtgta ccacgacccc 3000
cactctgacg atggaacagc tcctaaggag aaccggcacc tgtacaacga tcccgtgcct 3060
cgcagggtgg gctccttcta ccgcgtgcca tctcccaggc ctgacaacag ctttcacgag 3120
aacaacgtgt ccaccagagt gagctccctg ccatctgagt ctagctccgg aacaaaccac 3180
tctaagcggc agcccgcctt cgatccttgg aagagcccag agaacatctc tcacagcgag 3240
cagctgaagg agaaggagaa gcagggcttc tttcgcagca tgaagaagaa gaagaagaag 3300
agccagaccg tgcctaactc cgactctcca gatctgctga ccctgcagaa gtccatccac 3360
agcgcctcca caccctctag cagacctaag gagtggcggc ctgagaagat cagcgatctg 3420
cagacacaga gccagccact gaagtccctg aggaagctgc tgcacctgtc ctctgccagc 3480
aaccacccag ctagctccga cccaaggttc cagccactga cagctcagca gaccaagaac 3540
tcttttagcg agatcaggat ccaccctctg tcccaggctt ctggcggatc tagcaacatc 3600
aggcaggagc cagctccaaa gggcaggccc gctctgcagc tgcctggaca gatggaccca 3660
ggatggcacg tgtcctctgt gacaaggtcc gccaccgagg gaccatccta ctctgagcag 3720
ctgggcgcta agtctggccc taacggacac ccatacaacc gaacaaatag aagtaggatg 3780
ccaaacctca atgacctcaa ggaaactgcc ctgtgataag cggccgcaac tcgagactct 3840
agacgactgt gccttctagt tgccagccat ctgttgtttg cccctccccc gtgccttcct 3900
tgaccctgga aggtgccact cccactgtcc tttcctaata aaatgaggaa attgcatcgc 3960
attgtctgag taggtgtcat tctattctgg ggggtggggt ggggcaggac agcaaggggg 4020
aggattggga agacaatagc aggcatgctg gggatgcggt gggctctatg gccgcgggcc 4080
gcaggaaccc ctagtgatgg agttggccac tccctctctg cgcgctcgct cgctcactga 4140
ggccgggcga ccaaaggtcg cccgacgccc gggctttgcc cgggcggcct cagtgagcga 4200
gcgagcgcgc agctgcctgc aggggcgcct gatgcggtat tttctcctta cgcatctgtg 4260
cggtatttca caccgcatac gtcaaagcaa ccatagtacg cgccctgtag cggcgcatta 4320
agcgcggcgg gtgtggtggt tacgcgcagc gtgaccgcta cacttgccag cgccctagcg 4380
cccgctcctt tcgctttctt cccttccttt ctcgccacgt tcgccggctt tccccgtcaa 4440
gctctaaatc gggggctccc tttagggttc cgatttagtg ctttacggca cctcgacccc 4500
aaaaaacttg atttgggtga tggttcacgt agtgggccat cgccctgata gacggttttt 4560
cgccctttga cgttggagtc cacgttcttt aatagtggac tcttgttcca aactggaaca 4620
acactcaacc ctatctcggg ctattctttt gatttataag ggattttgcc gatttcggcc 4680
tattggttaa aaaatgagct gatttaacaa aaatttaacg cgaattttaa caaaatatta 4740
acgtttacaa ttttatggtg cactctcagt acaatctgct ctgatgccgc atagttaagc 4800
cagccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct gctcccggca 4860
tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag gttttcaccg 4920
tcatcaccga aacgcgcgag acgaaagggc ctcgtgatac gcctattttt ataggttaat 4980
gtcatgataa taatggtttc ttagacgtca ggtggcactt ttcggggaaa tgtgcgcgga 5040
acccctattt gtttattttt ctaaatacat tcaaatatgt atccgctcat gagacaataa 5100
ccctgataaa tgcttcaata atattgaaaa aggaagagta tgagtattca acatttccgt 5160
gtcgccctta ttcccttttt tgcggcattt tgccttcctg tttttgctca cccagaaacg 5220
ctggtgaaag taaaagatgc tgaagatcag ttgggtgcac gagtgggtta catcgaactg 5280
gatctcaaca gcggtaagat ccttgagagt tttcgccccg aagaacgttt tccaatgatg 5340
agcactttta aagttctgct atgtggcgcg gtattatccc gtattgacgc cgggcaagag 5400
caactcggtc gccgcataca ctattctcag aatgacttgg ttgagtactc accagtcaca 5460
gaaaagcatc ttacggatgg catgacagta agagaattat gcagtgctgc cataaccatg 5520
agtgataaca ctgcggccaa cttacttctg acaacgatcg gaggaccgaa ggagctaacc 5580
gcttttttgc acaacatggg ggatcatgta actcgccttg atcgttggga accggagctg 5640
aatgaagcca taccaaacga cgagcgtgac accacgatgc ctgtagcaat ggcaacaacg 5700
ttgcgcaaac tattaactgg cgaactactt actctagctt cccggcaaca attaatagac 5760
tggatggagg cggataaagt tgcaggacca cttctgcgct cggcccttcc ggctggctgg 5820
tttattgctg ataaatctgg agccggtgag cgtgggtctc gcggtatcat tgcagcactg 5880
gggccagatg gtaagccctc ccgtatcgta gttatctaca cgacggggag tcaggcaact 5940
atggatgaac gaaatagaca gatcgctgag ataggtgcct cactgattaa gcattggtaa 6000
ctgtcagacc aagtttactc atatatactt tagattgatt taaaacttca tttttaattt 6060
aaaaggatct aggtgaagat cctttttgat aatctcatga ccaaaatccc ttaacgtgag 6120
ttttcgttcc actgagcgtc agaccccgta gaaaagatca aaggatcttc ttgagatcct 6180
ttttttctgc gcgtaatctg ctgcttgcaa acaaaaaaac caccgctacc agcggtggtt 6240
tgtttgccgg atcaagagct accaactctt tttccgaagg taactggctt cagcagagcg 6300
cagataccaa atactgtcct tctagtgtag ccgtagttag gccaccactt caagaactct 6360
gtagcaccgc ctacatacct cgctctgcta atcctgttac cagtggctgc tgccagtggc 6420
gataagtcgt gtcttaccgg gttggactca agacgatagt taccggataa ggcgcagcgg 6480
tcgggctgaa cggggggttc gtgcacacag cccagcttgg agcgaacgac ctacaccgaa 6540
ctgagatacc tacagcgtga gctatgagaa agcgccacgc ttcccgaagg gagaaaggcg 6600
gacaggtatc cggtaagcgg cagggtcgga acaggagagc gcacgaggga gcttccaggg 6660
ggaaacgcct ggtatcttta tagtcctgtc gggtttcgcc acctctgact tgagcgtcga 6720
tttttgtgat gctcgtcagg ggggcggagc ctatggaaaa acgccagcaa cgcggccttt 6780
ttacggttcc tggccttttg ctggcctttt gctcacatgt 6820
<210> 119
<211> 6820
<212> DNA
<213> 人工序列
<220>
<223> AAVC-Syn-mBPIP-TATκ28-hCDKL5-107 (失活激酶)
<400> 119
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc tgcggcctaa ggcaattgac tacaaaccga gtatctgcag 180
agggccctgc gtatgagtgc aagtgggttt taggaccagg atgaggcggg gtgggggtgc 240
ctacctgacg accgaccccg acccactgga caagcaccca acccccattc cccaaattgc 300
gcatccccta tcagagaggg ggaggggaaa caggatgcgg cgaggcgcgt gcgcactgcc 360
agcttcagca ccgcggacag tgccttcgcc cccgcctggc ggcgcgcgcc accgccgcct 420
cagcactgaa ggcgcgctga cgtcactcgc cggtcccccg caaactcccc ttcccggcca 480
ccttggtcgc gtccgcgccg ccgccggccc agccggaccg caccacgcga ggcgcgagat 540
aggggggcac gggcgcgacc atctgcgctg cggcgccggc gactcagcgc tgcctcagtc 600
tgcggtgggc agcggaggag tcgtgtcgtg cctgagagcg cagctgtgct cctgggcacc 660
gcgcagtccg cccccgcggc tcctggccag accaccccta ggaccccctg ccccaagtcg 720
cagccttcga gctagccaaa gcttgccgcc accatgaaac tctccctcgt cgccgctatg 780
ctcctgctcc tctccctcgt cgctgccatg ctcctgctgc tcagtgccgc tcgggccgga 840
gatgctgctc agccagctag gagagctagg aggaccaagc tggctgctta cgctaggaag 900
gctgctaggc aggctagggc tggcggaggc ggatccaaga tccccaacat cggcaacgtg 960
atgaacaagt tcgagatcct gggagtggtg ggagagggag cttacggagt ggtgctgaag 1020
tgcaggcaca aggagacaca cgagatcgtg gctatcagga ggttcaagga cagcgaggag 1080
aacgaggagg tgaaggagac aaccctgaga gagctgaaga tgctgcggac actgaagcag 1140
gagaacatcg tggagctgaa ggaggccttc cggcgcaggg gaaagctgta cctggtgttt 1200
gagtacgtgg agaagaacat gctggagctg ctggaggaga tgccaaacgg agtgccacct 1260
gagaaggtga agtcctacat ctaccagctg atcaaggcta tccactggtg ccacaagaac 1320
gacatcgtgc acagagatat caagcctgag aacctgctga tctcccacaa cgacgtgctg 1380
aagctgtgcg atttcggctt tgcccggaac ctgagcgagg gaaacaacgc caactacaca 1440
gagtacgtgg ctaccagatg gtaccggagc ccagagctgc tgctgggagc tccatacgga 1500
aagagcgtgg acatgtggtc cgtgggctgc atcctgggag agctgtctga cggccagcct 1560
ctgttcccag gagagagcga gatcgatcag ctgtttacca tccagaaggt gctgggccct 1620
ctgccaagcg agcagatgaa gctgttctac tccaacccta gattccacgg actgcggttt 1680
cccgccgtga accaccctca gagcctggag agacggtacc tgggcatcct gaactccgtg 1740
ctgctggatc tgatgaagaa cctgctgaag ctggaccccg ccgatcgcta cctgaccgag 1800
cagtgtctga accaccctac atttcagacc cagcgcctgc tggacaggag cccttccaga 1860
tctgctaagc ggaagccata ccacgtggag agctccaccc tgtccaacag aaaccaggcc 1920
ggcaagtcta cagctctgca gagccaccac cggagcaact ccaaggacat ccagaacctg 1980
tctgtgggcc tgcctagagc cgatgaggga ctgccagcta acgagagctt cctgaacggc 2040
aacctggccg gagcttctct gagcccactg cacacaaaga cctaccaggc ctctagccag 2100
cccggctcca catctaagga cctgaccaac aacaacatcc cacacctgct gtctcccaag 2160
gaggctaaga gcaagaccga gttcgacttt aacatcgatc ccaagcctag cgagggccct 2220
ggaacaaagt acctgaagag caactcccgc tctcagcaga acaggcactc cttcatggag 2280
tcctctcagt ctaaggccgg caccctgcag ccaaacgaga agcagagcag acactcctac 2340
atcgatacca tcccccagag ctccagaagc ccttcctacc ggacaaaggc caagagccac 2400
ggcgctctgt ctgacagcaa gtccgtgtct aacctgtccg aggctagggc tcagatcgct 2460
gagcccagca cctccaggta ctttccttct agctgtctgg acctgaactc tcctacaagc 2520
ccaacaccca cccgccacag cgatacaagg accctgctgt ctccaagcgg caggaacaac 2580
aggaacgagg gaaccctgga ttctcgcagg accacaaccc ggcacagcaa gacaatggag 2640
gagctgaagc tgccagagca catggactcc tctcactccc actctctgag cgccccccac 2700
gagtccttct cttacggcct gggatacacc tcccccttca gctcccagca gaggccccac 2760
aggcactcta tgtacgtgac acgcgacaag gtgagggcca agggcctgga tggaagcctg 2820
tccatcggcc agggaatggc cgctagggct aactccctgc agctgctgtc tcctcagcca 2880
ggagagcagc tgccaccaga gatgaccgtg gctcgctcta gcgtgaagga gacaagcagg 2940
gagggcacct cctctttcca cacacgccag aagtccgagg gcggagtgta ccacgacccc 3000
cactctgacg atggaacagc tcctaaggag aacaggcacc tgtacaacga tcccgtgcct 3060
agacgggtgg gctccttcta cagagtgcca tctccccggc ctgacaacag ctttcacgag 3120
aacaacgtgt ccacccgcgt gagctccctg ccatctgagt ctagctccgg aacaaaccac 3180
tctaagaggc agcccgcctt cgatccttgg aagagcccag agaacatctc tcacagcgag 3240
cagctgaagg agaaggagaa gcagggcttc tttagaagca tgaagaagaa gaagaagaag 3300
agccagaccg tgcctaactc cgactctcca gatctgctga ccctgcagaa gtccatccac 3360
agcgcctcca caccatctag ccgccctaag gagtggaggc ctgagaagat cagcgatctg 3420
cagacacaga gccagccact gaagtccctg cggaagctgc tgcacctgtc ctctgccagc 3480
aaccaccccg ctagctccga cccaagattc cagcccctga cagcccagca gaccaagaac 3540
tcttttagcg agatccggat ccaccctctg tcccaggctt ctggcggatc tagcaacatc 3600
agacaggagc cagctccaaa gggccggccc gctctgcagc tgcctggcca gatggaccca 3660
ggatggcacg tgtcctctgt gacaaggtcc gccaccgagg gaccatccta ctctgagcag 3720
ctgggcgcta agtctggccc taacggacac ccatacaata ggactaatcg cagcagaatg 3780
cccaacctga acgacctcaa ggaaacagca ctctgataag cggccgcaac tcgagactct 3840
agacgactgt gccttctagt tgccagccat ctgttgtttg cccctccccc gtgccttcct 3900
tgaccctgga aggtgccact cccactgtcc tttcctaata aaatgaggaa attgcatcgc 3960
attgtctgag taggtgtcat tctattctgg ggggtggggt ggggcaggac agcaaggggg 4020
aggattggga agacaatagc aggcatgctg gggatgcggt gggctctatg gccgcgggcc 4080
gcaggaaccc ctagtgatgg agttggccac tccctctctg cgcgctcgct cgctcactga 4140
ggccgggcga ccaaaggtcg cccgacgccc gggctttgcc cgggcggcct cagtgagcga 4200
gcgagcgcgc agctgcctgc aggggcgcct gatgcggtat tttctcctta cgcatctgtg 4260
cggtatttca caccgcatac gtcaaagcaa ccatagtacg cgccctgtag cggcgcatta 4320
agcgcggcgg gtgtggtggt tacgcgcagc gtgaccgcta cacttgccag cgccctagcg 4380
cccgctcctt tcgctttctt cccttccttt ctcgccacgt tcgccggctt tccccgtcaa 4440
gctctaaatc gggggctccc tttagggttc cgatttagtg ctttacggca cctcgacccc 4500
aaaaaacttg atttgggtga tggttcacgt agtgggccat cgccctgata gacggttttt 4560
cgccctttga cgttggagtc cacgttcttt aatagtggac tcttgttcca aactggaaca 4620
acactcaacc ctatctcggg ctattctttt gatttataag ggattttgcc gatttcggcc 4680
tattggttaa aaaatgagct gatttaacaa aaatttaacg cgaattttaa caaaatatta 4740
acgtttacaa ttttatggtg cactctcagt acaatctgct ctgatgccgc atagttaagc 4800
cagccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct gctcccggca 4860
tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag gttttcaccg 4920
tcatcaccga aacgcgcgag acgaaagggc ctcgtgatac gcctattttt ataggttaat 4980
gtcatgataa taatggtttc ttagacgtca ggtggcactt ttcggggaaa tgtgcgcgga 5040
acccctattt gtttattttt ctaaatacat tcaaatatgt atccgctcat gagacaataa 5100
ccctgataaa tgcttcaata atattgaaaa aggaagagta tgagtattca acatttccgt 5160
gtcgccctta ttcccttttt tgcggcattt tgccttcctg tttttgctca cccagaaacg 5220
ctggtgaaag taaaagatgc tgaagatcag ttgggtgcac gagtgggtta catcgaactg 5280
gatctcaaca gcggtaagat ccttgagagt tttcgccccg aagaacgttt tccaatgatg 5340
agcactttta aagttctgct atgtggcgcg gtattatccc gtattgacgc cgggcaagag 5400
caactcggtc gccgcataca ctattctcag aatgacttgg ttgagtactc accagtcaca 5460
gaaaagcatc ttacggatgg catgacagta agagaattat gcagtgctgc cataaccatg 5520
agtgataaca ctgcggccaa cttacttctg acaacgatcg gaggaccgaa ggagctaacc 5580
gcttttttgc acaacatggg ggatcatgta actcgccttg atcgttggga accggagctg 5640
aatgaagcca taccaaacga cgagcgtgac accacgatgc ctgtagcaat ggcaacaacg 5700
ttgcgcaaac tattaactgg cgaactactt actctagctt cccggcaaca attaatagac 5760
tggatggagg cggataaagt tgcaggacca cttctgcgct cggcccttcc ggctggctgg 5820
tttattgctg ataaatctgg agccggtgag cgtgggtctc gcggtatcat tgcagcactg 5880
gggccagatg gtaagccctc ccgtatcgta gttatctaca cgacggggag tcaggcaact 5940
atggatgaac gaaatagaca gatcgctgag ataggtgcct cactgattaa gcattggtaa 6000
ctgtcagacc aagtttactc atatatactt tagattgatt taaaacttca tttttaattt 6060
aaaaggatct aggtgaagat cctttttgat aatctcatga ccaaaatccc ttaacgtgag 6120
ttttcgttcc actgagcgtc agaccccgta gaaaagatca aaggatcttc ttgagatcct 6180
ttttttctgc gcgtaatctg ctgcttgcaa acaaaaaaac caccgctacc agcggtggtt 6240
tgtttgccgg atcaagagct accaactctt tttccgaagg taactggctt cagcagagcg 6300
cagataccaa atactgtcct tctagtgtag ccgtagttag gccaccactt caagaactct 6360
gtagcaccgc ctacatacct cgctctgcta atcctgttac cagtggctgc tgccagtggc 6420
gataagtcgt gtcttaccgg gttggactca agacgatagt taccggataa ggcgcagcgg 6480
tcgggctgaa cggggggttc gtgcacacag cccagcttgg agcgaacgac ctacaccgaa 6540
ctgagatacc tacagcgtga gctatgagaa agcgccacgc ttcccgaagg gagaaaggcg 6600
gacaggtatc cggtaagcgg cagggtcgga acaggagagc gcacgaggga gcttccaggg 6660
ggaaacgcct ggtatcttta tagtcctgtc gggtttcgcc acctctgact tgagcgtcga 6720
tttttgtgat gctcgtcagg ggggcggagc ctatggaaaa acgccagcaa cgcggccttt 6780
ttacggttcc tggccttttg ctggcctttt gctcacatgt 6820
<210> 120
<211> 4660
<212> DNA
<213> 人工序列
<220>
<223> AAVC-Syn-mBPIP-TATκ28-eGFP
<400> 120
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc tgcggcctaa ggcaattgac tacaaaccga gtatctgcag 180
agggccctgc gtatgagtgc aagtgggttt taggaccagg atgaggcggg gtgggggtgc 240
ctacctgacg accgaccccg acccactgga caagcaccca acccccattc cccaaattgc 300
gcatccccta tcagagaggg ggaggggaaa caggatgcgg cgaggcgcgt gcgcactgcc 360
agcttcagca ccgcggacag tgccttcgcc cccgcctggc ggcgcgcgcc accgccgcct 420
cagcactgaa ggcgcgctga cgtcactcgc cggtcccccg caaactcccc ttcccggcca 480
ccttggtcgc gtccgcgccg ccgccggccc agccggaccg caccacgcga ggcgcgagat 540
aggggggcac gggcgcgacc atctgcgctg cggcgccggc gactcagcgc tgcctcagtc 600
tgcggtgggc agcggaggag tcgtgtcgtg cctgagagcg cagctgtgct cctgggcacc 660
gcgcagtccg cccccgcggc tcctggccag accaccccta ggaccccctg ccccaagtcg 720
cagccttcga gctagccaaa gcttgccgcc accatgaaac tgtccctggt cgccgccatg 780
ctgctcctcc tgtcactggt cgccgctatg ctgctcctcc tctccgctgc tcgggctggg 840
gacgctgctc agccagctag gagagctagg aggaccaagc tggctgctta cgctaggaag 900
gctgctaggc aggctagagc tggaggaggc ggatctatgg tgagcaaggg agaggagctg 960
ttcacaggcg tggtgcccat cctggtggag ctggacggag atgtgaacgg ccacaagttt 1020
agcgtgtccg gagagggaga gggcgacgct acctacggaa agctgacact gaagttcatc 1080
tgcaccacag gcaagctgcc cgtgccttgg ccaaccctgg tgaccacact gacatacggc 1140
gtgcagtgtt tttccaggta cccagaccac atgaagcagc acgatttctt taagtctgcc 1200
atgcccgagg gatacgtgca ggagcggacc atcttcttta aggacgatgg caactacaag 1260
acccgcgctg aggtgaagtt cgagggagac acactggtga acaggatcga gctgaagggc 1320
atcgacttta aggaggatgg aaacatcctg ggccacaagc tggagtacaa ctacaacagc 1380
cacaacgtgt acatcatggc cgataagcag aagaacggaa tcaaggtgaa cttcaagatc 1440
agacacaaca tcgaggacgg ctccgtgcag ctggctgatc actaccagca gaacacccct 1500
atcggagacg gacccgtgct gctgcctgat aaccactacc tgtccacaca gtctgccctg 1560
agcaaggacc caaacgagaa gcgggatcac atggtgctgc tggaatttgt gactgctgct 1620
ggtattacac tgggtatgga tgaactctat aaatgataag cggccgcaac tcgagactct 1680
agacgactgt gccttctagt tgccagccat ctgttgtttg cccctccccc gtgccttcct 1740
tgaccctgga aggtgccact cccactgtcc tttcctaata aaatgaggaa attgcatcgc 1800
attgtctgag taggtgtcat tctattctgg ggggtggggt ggggcaggac agcaaggggg 1860
aggattggga agacaatagc aggcatgctg gggatgcggt gggctctatg gccgcgggcc 1920
gcaggaaccc ctagtgatgg agttggccac tccctctctg cgcgctcgct cgctcactga 1980
ggccgggcga ccaaaggtcg cccgacgccc gggctttgcc cgggcggcct cagtgagcga 2040
gcgagcgcgc agctgcctgc aggggcgcct gatgcggtat tttctcctta cgcatctgtg 2100
cggtatttca caccgcatac gtcaaagcaa ccatagtacg cgccctgtag cggcgcatta 2160
agcgcggcgg gtgtggtggt tacgcgcagc gtgaccgcta cacttgccag cgccctagcg 2220
cccgctcctt tcgctttctt cccttccttt ctcgccacgt tcgccggctt tccccgtcaa 2280
gctctaaatc gggggctccc tttagggttc cgatttagtg ctttacggca cctcgacccc 2340
aaaaaacttg atttgggtga tggttcacgt agtgggccat cgccctgata gacggttttt 2400
cgccctttga cgttggagtc cacgttcttt aatagtggac tcttgttcca aactggaaca 2460
acactcaacc ctatctcggg ctattctttt gatttataag ggattttgcc gatttcggcc 2520
tattggttaa aaaatgagct gatttaacaa aaatttaacg cgaattttaa caaaatatta 2580
acgtttacaa ttttatggtg cactctcagt acaatctgct ctgatgccgc atagttaagc 2640
cagccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct gctcccggca 2700
tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag gttttcaccg 2760
tcatcaccga aacgcgcgag acgaaagggc ctcgtgatac gcctattttt ataggttaat 2820
gtcatgataa taatggtttc ttagacgtca ggtggcactt ttcggggaaa tgtgcgcgga 2880
acccctattt gtttattttt ctaaatacat tcaaatatgt atccgctcat gagacaataa 2940
ccctgataaa tgcttcaata atattgaaaa aggaagagta tgagtattca acatttccgt 3000
gtcgccctta ttcccttttt tgcggcattt tgccttcctg tttttgctca cccagaaacg 3060
ctggtgaaag taaaagatgc tgaagatcag ttgggtgcac gagtgggtta catcgaactg 3120
gatctcaaca gcggtaagat ccttgagagt tttcgccccg aagaacgttt tccaatgatg 3180
agcactttta aagttctgct atgtggcgcg gtattatccc gtattgacgc cgggcaagag 3240
caactcggtc gccgcataca ctattctcag aatgacttgg ttgagtactc accagtcaca 3300
gaaaagcatc ttacggatgg catgacagta agagaattat gcagtgctgc cataaccatg 3360
agtgataaca ctgcggccaa cttacttctg acaacgatcg gaggaccgaa ggagctaacc 3420
gcttttttgc acaacatggg ggatcatgta actcgccttg atcgttggga accggagctg 3480
aatgaagcca taccaaacga cgagcgtgac accacgatgc ctgtagcaat ggcaacaacg 3540
ttgcgcaaac tattaactgg cgaactactt actctagctt cccggcaaca attaatagac 3600
tggatggagg cggataaagt tgcaggacca cttctgcgct cggcccttcc ggctggctgg 3660
tttattgctg ataaatctgg agccggtgag cgtgggtctc gcggtatcat tgcagcactg 3720
gggccagatg gtaagccctc ccgtatcgta gttatctaca cgacggggag tcaggcaact 3780
atggatgaac gaaatagaca gatcgctgag ataggtgcct cactgattaa gcattggtaa 3840
ctgtcagacc aagtttactc atatatactt tagattgatt taaaacttca tttttaattt 3900
aaaaggatct aggtgaagat cctttttgat aatctcatga ccaaaatccc ttaacgtgag 3960
ttttcgttcc actgagcgtc agaccccgta gaaaagatca aaggatcttc ttgagatcct 4020
ttttttctgc gcgtaatctg ctgcttgcaa acaaaaaaac caccgctacc agcggtggtt 4080
tgtttgccgg atcaagagct accaactctt tttccgaagg taactggctt cagcagagcg 4140
cagataccaa atactgtcct tctagtgtag ccgtagttag gccaccactt caagaactct 4200
gtagcaccgc ctacatacct cgctctgcta atcctgttac cagtggctgc tgccagtggc 4260
gataagtcgt gtcttaccgg gttggactca agacgatagt taccggataa ggcgcagcgg 4320
tcgggctgaa cggggggttc gtgcacacag cccagcttgg agcgaacgac ctacaccgaa 4380
ctgagatacc tacagcgtga gctatgagaa agcgccacgc ttcccgaagg gagaaaggcg 4440
gacaggtatc cggtaagcgg cagggtcgga acaggagagc gcacgaggga gcttccaggg 4500
ggaaacgcct ggtatcttta tagtcctgtc gggtttcgcc acctctgact tgagcgtcga 4560
tttttgtgat gctcgtcagg ggggcggagc ctatggaaaa acgccagcaa cgcggccttt 4620
ttacggttcc tggccttttg ctggcctttt gctcacatgt 4660
<210> 121
<211> 4720
<212> DNA
<213> 人工序列
<220>
<223> AAVC-Syn- mBPIP-TATκ28-NLS-eGFP
<400> 121
cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60
gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120
actccatcac taggggttcc tgcggcctaa ggcaattgac tacaaaccga gtatctgcag 180
agggccctgc gtatgagtgc aagtgggttt taggaccagg atgaggcggg gtgggggtgc 240
ctacctgacg accgaccccg acccactgga caagcaccca acccccattc cccaaattgc 300
gcatccccta tcagagaggg ggaggggaaa caggatgcgg cgaggcgcgt gcgcactgcc 360
agcttcagca ccgcggacag tgccttcgcc cccgcctggc ggcgcgcgcc accgccgcct 420
cagcactgaa ggcgcgctga cgtcactcgc cggtcccccg caaactcccc ttcccggcca 480
ccttggtcgc gtccgcgccg ccgccggccc agccggaccg caccacgcga ggcgcgagat 540
aggggggcac gggcgcgacc atctgcgctg cggcgccggc gactcagcgc tgcctcagtc 600
tgcggtgggc agcggaggag tcgtgtcgtg cctgagagcg cagctgtgct cctgggcacc 660
gcgcagtccg cccccgcggc tcctggccag accaccccta ggaccccctg ccccaagtcg 720
cagccttcga gctagccaaa gcttgccgcc accatgaaac tcagtctggt cgccgctatg 780
ctcctgctcc tctccctggt cgccgctatg ctcctgctcc tgtctgctgc ccgcgctggg 840
gacgctgctc agccagctag gagagctagg aggaccaagc tggctgctta cgctagaaag 900
gctgctaggc aggctagagc tggaggagga ggatccatgg ctcccaagaa gaagaggaag 960
gtgcgctacc ccgccttcct gtacaaggtg gctaccatgg tgtctaaggg agaggagctg 1020
tttacaggcg tggtgcccat cctggtggag ctggacggag atgtgaacgg ccacaagttc 1080
agcgtgtccg gagagggaga gggcgacgcc acctacggaa agctgacact gaagtttatc 1140
tgcaccacag gcaagctgcc cgtgccttgg ccaaccctgg tgaccacact gacatacggc 1200
gtgcagtgtt tctctcggta ccctgaccac atgaagcagc acgatttctt taagagcgcc 1260
atgccagagg gatacgtgca ggagaggaca atcttcttta aggacgatgg caactacaag 1320
accagagctg aggtgaagtt cgagggagac acactggtga accggatcga gctgaagggc 1380
atcgacttta aggaggatgg aaacatcctg ggccacaagc tggagtacaa ctacaacagc 1440
cacaacgtgt acatcatggc cgataagcag aagaacggaa tcaaggtgaa ctttaagatc 1500
cgccacaaca tcgaggacgg ctccgtgcag ctggctgatc actaccagca gaacacccca 1560
atcggagacg gacccgtgct gctgcctgat aaccactacc tgtctacaca gagcgccctg 1620
tccaaggacc ctaacgagaa gagggatcac atggtcctcc tggaatttgt gactgctgct 1680
gggattactc tcggtatgga tgaactgtat aaatgataag cggccgcaac tcgagactct 1740
agacgactgt gccttctagt tgccagccat ctgttgtttg cccctccccc gtgccttcct 1800
tgaccctgga aggtgccact cccactgtcc tttcctaata aaatgaggaa attgcatcgc 1860
attgtctgag taggtgtcat tctattctgg ggggtggggt ggggcaggac agcaaggggg 1920
aggattggga agacaatagc aggcatgctg gggatgcggt gggctctatg gccgcgggcc 1980
gcaggaaccc ctagtgatgg agttggccac tccctctctg cgcgctcgct cgctcactga 2040
ggccgggcga ccaaaggtcg cccgacgccc gggctttgcc cgggcggcct cagtgagcga 2100
gcgagcgcgc agctgcctgc aggggcgcct gatgcggtat tttctcctta cgcatctgtg 2160
cggtatttca caccgcatac gtcaaagcaa ccatagtacg cgccctgtag cggcgcatta 2220
agcgcggcgg gtgtggtggt tacgcgcagc gtgaccgcta cacttgccag cgccctagcg 2280
cccgctcctt tcgctttctt cccttccttt ctcgccacgt tcgccggctt tccccgtcaa 2340
gctctaaatc gggggctccc tttagggttc cgatttagtg ctttacggca cctcgacccc 2400
aaaaaacttg atttgggtga tggttcacgt agtgggccat cgccctgata gacggttttt 2460
cgccctttga cgttggagtc cacgttcttt aatagtggac tcttgttcca aactggaaca 2520
acactcaacc ctatctcggg ctattctttt gatttataag ggattttgcc gatttcggcc 2580
tattggttaa aaaatgagct gatttaacaa aaatttaacg cgaattttaa caaaatatta 2640
acgtttacaa ttttatggtg cactctcagt acaatctgct ctgatgccgc atagttaagc 2700
cagccccgac acccgccaac acccgctgac gcgccctgac gggcttgtct gctcccggca 2760
tccgcttaca gacaagctgt gaccgtctcc gggagctgca tgtgtcagag gttttcaccg 2820
tcatcaccga aacgcgcgag acgaaagggc ctcgtgatac gcctattttt ataggttaat 2880
gtcatgataa taatggtttc ttagacgtca ggtggcactt ttcggggaaa tgtgcgcgga 2940
acccctattt gtttattttt ctaaatacat tcaaatatgt atccgctcat gagacaataa 3000
ccctgataaa tgcttcaata atattgaaaa aggaagagta tgagtattca acatttccgt 3060
gtcgccctta ttcccttttt tgcggcattt tgccttcctg tttttgctca cccagaaacg 3120
ctggtgaaag taaaagatgc tgaagatcag ttgggtgcac gagtgggtta catcgaactg 3180
gatctcaaca gcggtaagat ccttgagagt tttcgccccg aagaacgttt tccaatgatg 3240
agcactttta aagttctgct atgtggcgcg gtattatccc gtattgacgc cgggcaagag 3300
caactcggtc gccgcataca ctattctcag aatgacttgg ttgagtactc accagtcaca 3360
gaaaagcatc ttacggatgg catgacagta agagaattat gcagtgctgc cataaccatg 3420
agtgataaca ctgcggccaa cttacttctg acaacgatcg gaggaccgaa ggagctaacc 3480
gcttttttgc acaacatggg ggatcatgta actcgccttg atcgttggga accggagctg 3540
aatgaagcca taccaaacga cgagcgtgac accacgatgc ctgtagcaat ggcaacaacg 3600
ttgcgcaaac tattaactgg cgaactactt actctagctt cccggcaaca attaatagac 3660
tggatggagg cggataaagt tgcaggacca cttctgcgct cggcccttcc ggctggctgg 3720
tttattgctg ataaatctgg agccggtgag cgtgggtctc gcggtatcat tgcagcactg 3780
gggccagatg gtaagccctc ccgtatcgta gttatctaca cgacggggag tcaggcaact 3840
atggatgaac gaaatagaca gatcgctgag ataggtgcct cactgattaa gcattggtaa 3900
ctgtcagacc aagtttactc atatatactt tagattgatt taaaacttca tttttaattt 3960
aaaaggatct aggtgaagat cctttttgat aatctcatga ccaaaatccc ttaacgtgag 4020
ttttcgttcc actgagcgtc agaccccgta gaaaagatca aaggatcttc ttgagatcct 4080
ttttttctgc gcgtaatctg ctgcttgcaa acaaaaaaac caccgctacc agcggtggtt 4140
tgtttgccgg atcaagagct accaactctt tttccgaagg taactggctt cagcagagcg 4200
cagataccaa atactgtcct tctagtgtag ccgtagttag gccaccactt caagaactct 4260
gtagcaccgc ctacatacct cgctctgcta atcctgttac cagtggctgc tgccagtggc 4320
gataagtcgt gtcttaccgg gttggactca agacgatagt taccggataa ggcgcagcgg 4380
tcgggctgaa cggggggttc gtgcacacag cccagcttgg agcgaacgac ctacaccgaa 4440
ctgagatacc tacagcgtga gctatgagaa agcgccacgc ttcccgaagg gagaaaggcg 4500
gacaggtatc cggtaagcgg cagggtcgga acaggagagc gcacgaggga gcttccaggg 4560
ggaaacgcct ggtatcttta tagtcctgtc gggtttcgcc acctctgact tgagcgtcga 4620
tttttgtgat gctcgtcagg ggggcggagc ctatggaaaa acgccagcaa cgcggccttt 4680
ttacggttcc tggccttttg ctggcctttt gctcacatgt 4720
<210> 122
<211> 3063
<212> DNA
<213> 人工序列
<220>
<223> mBPIP-TATκ28-CDKL5-107的DNA序列 (人优化)
<400> 122
atgaagctgt ccctggtggc cgctatgctg ctgctgctgt ctctggtcgc tgccatgtta 60
ttactgctgt ctgccgctag ggccggggac gcagcacagc ccgcaagaag agcaagaaga 120
actaaactgg ccgcttacgc aaggaaggca gcaagacagg caagagcagg cggcggcggc 180
tccaagatcc ccaatatcgg caacgtgatg aataagttcg agatcctggg agtggtggga 240
gagggagcct acggcgtggt gctgaagtgc agacacaagg agacacacga gatcgtggcc 300
atcaagaagt ttaaggacag cgaggagaat gaggaggtga aggagacaac cctgcgcgag 360
ctgaagatgc tgcggacact gaagcaggag aacatcgtgg agctgaagga ggccttccgg 420
agaaggggca agctgtacct ggtgtttgag tatgtggaga agaacatgct ggagctgctg 480
gaggagatgc ctaatggcgt gccccctgag aaggtgaagt cctacatcta tcagctgatc 540
aaggccatcc actggtgcca caagaacgat atcgtgcacc gcgacatcaa gcccgagaac 600
ctgctgatct cccacaatga cgtgctgaag ctgtgcgact tcggctttgc ccggaacctg 660
agcgagggca acaatgccaa ttacacagag tatgtggcca cccgctggta cagaagcccc 720
gagctgctgc tgggcgcccc ctatggcaag agcgtggata tgtggtccgt gggctgcatc 780
ctgggcgagc tgtctgatgg ccagcctctg ttcccaggcg agagcgagat cgaccagctg 840
tttaccatcc agaaggtgct gggccctctg ccaagcgagc agatgaagct gttctactcc 900
aacccaaggt tccacggcct gaggtttcca gccgtgaatc accctcagag cctggagcgc 960
cggtatctgg gcatcctgaa ctccgtgctg ctggacctga tgaagaacct gctgaagctg 1020
gaccccgccg acagatacct gaccgagcag tgtctgaatc accctacatt tcagacccag 1080
agactgctgg ataggagccc ttcccgctct gccaagcgga agccatatca cgtggagagc 1140
agcaccctgt ccaatcgcaa ccaggccggc aagtctacag ccctgcagag ccaccaccgg 1200
agcaactcca aggatatcca gaatctgtcc gtgggcctgc ctagggccga cgagggcctg 1260
ccagcaaacg agagcttcct gaatggaaac ctggcaggag cctctctgag cccactgcac 1320
acaaagacct accaggcctc tagccagccc ggctccacat ctaaggacct gaccaacaat 1380
aacatcccac acctgctgtc tcccaaggag gccaagagca agaccgagtt cgacttcaac 1440
atcgacccaa agcctagcga gggacctggc acaaagtatc tgaagagcaa cagccggagc 1500
cagcagaata ggcactcctt catggagtcc tctcagtcta aggccggcac cctgcagcca 1560
aacgagaagc agagcaggca ctcctacatc gacaccatcc cacagagcag ccggagcccc 1620
tcctatcgga caaaggccaa gtctcacggc gccctgtctg atagcaagtc cgtgtctaat 1680
ctgagcgagg ccagagccca gatcgcagag cccagcacct ccaggtactt tccttctagc 1740
tgtctggatc tgaactctcc tacaagccca acacccacca gacacagcga cacaaggacc 1800
ctgctgtctc caagcggcag aaataacagg aacgagggca ccctggacag ccggcggacc 1860
acaaccaggc acagcaagac aatggaggag ctgaagctgc cagagcacat ggattcctct 1920
cactcccact ctctgagcgc cccccacgag tccttctctt acggcctggg ctatacctcc 1980
cccttcagca gccagcagcg cccccaccgg cactctatgt acgtgacaag agataaggtg 2040
agggcaaagg gcctggacgg cagcctgtcc atcggacagg gaatggcagc ccgggccaac 2100
tccctgcagc tgctgtctcc tcagccagga gagcagctgc caccagagat gaccgtggca 2160
cggagcagcg tgaaggagac aagcagggag ggcacctcct ctttccacac aagacagaag 2220
tccgagggcg gcgtgtatca cgatccccac tctgacgatg gcacagcccc taaggagaac 2280
aggcacctgt acaatgaccc cgtgcctagg agggtgggct ccttctatcg cgtgccatct 2340
ccccggcctg ataatagctt tcacgagaat aacgtgagca cccgggtgag cagcctgcca 2400
tctgagtcta gctccggcac aaaccactct aagaggcagc ccgcctttga cccttggaag 2460
agcccagaga atatctctca cagcgagcag ctgaaggaga aggagaagca gggcttcttt 2520
cgcagcatga agaagaagaa gaagaagagc cagaccgtgc ctaactccga ttctccagac 2580
ctgctgaccc tgcagaagtc catccacagc gcctccacac cctctagcag acctaaggag 2640
tggaggcctg agaagatcag cgacctgcag acccagagcc agccactgaa gtccctgcgg 2700
aagctgctgc acctgtcctc tgccagcaac cacccagcca gctccgatcc aaggttccag 2760
cccctgacag cccagcagac caagaacagc ttcagcgaga tcagaatcca ccctctgtcc 2820
caggcctctg gaggctctag caacatcagg caggagccag caccaaaggg ccggcccgcc 2880
ctgcagctgc ctggccagat ggacccaggc tggcacgtgt cctctgtgac aagatccgcc 2940
accgagggcc catcctactc tgagcagctg ggagcaaaga gcggacctaa tggacaccca 3000
tataacagga ccaatagatc caggatgccc aatctgaacg atctgaagga gacagccctg 3060
tga 3063
<210> 123
<211> 2877
<212> DNA
<213> 人工序列
<220>
<223> CDKL5-107的DNA序列 (人优化)
<400> 123
aagatcccca atatcggcaa cgtgatgaat aagttcgaga tcctgggagt ggtgggagag 60
ggagcctacg gcgtggtgct gaagtgcaga cacaaggaga cacacgagat cgtggccatc 120
aagaagttta aggacagcga ggagaatgag gaggtgaagg agacaaccct gcgcgagctg 180
aagatgctgc ggacactgaa gcaggagaac atcgtggagc tgaaggaggc cttccggaga 240
aggggcaagc tgtacctggt gtttgagtat gtggagaaga acatgctgga gctgctggag 300
gagatgccta atggcgtgcc ccctgagaag gtgaagtcct acatctatca gctgatcaag 360
gccatccact ggtgccacaa gaacgatatc gtgcaccgcg acatcaagcc cgagaacctg 420
ctgatctccc acaatgacgt gctgaagctg tgcgacttcg gctttgcccg gaacctgagc 480
gagggcaaca atgccaatta cacagagtat gtggccaccc gctggtacag aagccccgag 540
ctgctgctgg gcgcccccta tggcaagagc gtggatatgt ggtccgtggg ctgcatcctg 600
ggcgagctgt ctgatggcca gcctctgttc ccaggcgaga gcgagatcga ccagctgttt 660
accatccaga aggtgctggg ccctctgcca agcgagcaga tgaagctgtt ctactccaac 720
ccaaggttcc acggcctgag gtttccagcc gtgaatcacc ctcagagcct ggagcgccgg 780
tatctgggca tcctgaactc cgtgctgctg gacctgatga agaacctgct gaagctggac 840
cccgccgaca gatacctgac cgagcagtgt ctgaatcacc ctacatttca gacccagaga 900
ctgctggata ggagcccttc ccgctctgcc aagcggaagc catatcacgt ggagagcagc 960
accctgtcca atcgcaacca ggccggcaag tctacagccc tgcagagcca ccaccggagc 1020
aactccaagg atatccagaa tctgtccgtg ggcctgccta gggccgacga gggcctgcca 1080
gcaaacgaga gcttcctgaa tggaaacctg gcaggagcct ctctgagccc actgcacaca 1140
aagacctacc aggcctctag ccagcccggc tccacatcta aggacctgac caacaataac 1200
atcccacacc tgctgtctcc caaggaggcc aagagcaaga ccgagttcga cttcaacatc 1260
gacccaaagc ctagcgaggg acctggcaca aagtatctga agagcaacag ccggagccag 1320
cagaataggc actccttcat ggagtcctct cagtctaagg ccggcaccct gcagccaaac 1380
gagaagcaga gcaggcactc ctacatcgac accatcccac agagcagccg gagcccctcc 1440
tatcggacaa aggccaagtc tcacggcgcc ctgtctgata gcaagtccgt gtctaatctg 1500
agcgaggcca gagcccagat cgcagagccc agcacctcca ggtactttcc ttctagctgt 1560
ctggatctga actctcctac aagcccaaca cccaccagac acagcgacac aaggaccctg 1620
ctgtctccaa gcggcagaaa taacaggaac gagggcaccc tggacagccg gcggaccaca 1680
accaggcaca gcaagacaat ggaggagctg aagctgccag agcacatgga ttcctctcac 1740
tcccactctc tgagcgcccc ccacgagtcc ttctcttacg gcctgggcta tacctccccc 1800
ttcagcagcc agcagcgccc ccaccggcac tctatgtacg tgacaagaga taaggtgagg 1860
gcaaagggcc tggacggcag cctgtccatc ggacagggaa tggcagcccg ggccaactcc 1920
ctgcagctgc tgtctcctca gccaggagag cagctgccac cagagatgac cgtggcacgg 1980
agcagcgtga aggagacaag cagggagggc acctcctctt tccacacaag acagaagtcc 2040
gagggcggcg tgtatcacga tccccactct gacgatggca cagcccctaa ggagaacagg 2100
cacctgtaca atgaccccgt gcctaggagg gtgggctcct tctatcgcgt gccatctccc 2160
cggcctgata atagctttca cgagaataac gtgagcaccc gggtgagcag cctgccatct 2220
gagtctagct ccggcacaaa ccactctaag aggcagcccg cctttgaccc ttggaagagc 2280
ccagagaata tctctcacag cgagcagctg aaggagaagg agaagcaggg cttctttcgc 2340
agcatgaaga agaagaagaa gaagagccag accgtgccta actccgattc tccagacctg 2400
ctgaccctgc agaagtccat ccacagcgcc tccacaccct ctagcagacc taaggagtgg 2460
aggcctgaga agatcagcga cctgcagacc cagagccagc cactgaagtc cctgcggaag 2520
ctgctgcacc tgtcctctgc cagcaaccac ccagccagct ccgatccaag gttccagccc 2580
ctgacagccc agcagaccaa gaacagcttc agcgagatca gaatccaccc tctgtcccag 2640
gcctctggag gctctagcaa catcaggcag gagccagcac caaagggccg gcccgccctg 2700
cagctgcctg gccagatgga cccaggctgg cacgtgtcct ctgtgacaag atccgccacc 2760
gagggcccat cctactctga gcagctggga gcaaagagcg gacctaatgg acacccatat 2820
aacaggacca atagatccag gatgcccaat ctgaacgatc tgaaggagac agccctg 2877
<210> 124
<211> 3195
<212> DNA
<213> 人工序列
<220>
<223> MBIP-TATκ28-CDKL5_107-FH [1-7NQ]的DNA序列 (人
优化)
<400> 124
atgaagctgt ccctggtggc cgctatgctg ctgctgctgt ctctggtcgc tgccatgtta 60
ttactgctgt ctgccgctag ggccggggac gcagcacagc ccgcaagaag agcaagaaga 120
actaaactgg ccgcttacgc aaggaaggca gcaagacagg caagagcagg cggcggcggc 180
tccaagatcc ccaatatcgg caacgtgatg aataagttcg agatcctggg agtggtggga 240
gagggagcct acggcgtggt gctgaagtgc agacacaagg agacacacga gatcgtggcc 300
atcaagaagt ttaaggacag cgaggagaat gaggaggtga aggagacaac cctgcgcgag 360
ctgaagatgc tgcggacact gaagcaggag aacatcgtgg agctgaagga ggccttccgg 420
agaaggggca agctgtacct ggtgtttgag tatgtggaga agaacatgct ggagctgctg 480
gaggagatgc ctaatggcgt gccccctgag aaggtgaagt cctacatcta tcagctgatc 540
aaggccatcc actggtgcca caagaacgat atcgtgcacc gcgacatcaa gcccgagaac 600
ctgctgatct cccacaatga cgtgctgaag ctgtgcgact tcggctttgc ccggcagctg 660
agcgagggca acaatgccca gtacacagag tatgtggcca cccgctggta cagaagcccc 720
gagctgctgc tgggcgcccc ctatggcaag agcgtggata tgtggtccgt gggctgcatc 780
ctgggcgagc tgtctgatgg ccagcctctg ttcccaggcg agagcgagat cgaccagctg 840
tttaccatcc agaaggtgct gggccctctg ccaagcgagc agatgaagct gttctactcc 900
aacccaaggt tccacggcct gaggtttcca gccgtgaatc accctcagag cctggagcgc 960
cggtatctgg gcatcctgaa ctccgtgctg ctggacctga tgaagaacct gctgaagctg 1020
gaccccgccg acagatacct gaccgagcag tgtctgaatc accctacatt tcagacccag 1080
agactgctgg ataggagccc ttcccgctct gccaagcgga agccatatca cgtggagagc 1140
agcaccctgt ccaatcgcaa ccaggccggc aagtctacag ccctgcagag ccaccaccgg 1200
agcaactcca aggatatcca gcagctgtcc gtgggcctgc ctagggccga cgagggcctg 1260
ccagcaaacg agagcttcct gaatggaaac ctggcaggag cctctctgag cccactgcac 1320
acaaagacct accaggcctc tagccagccc ggctccacat ctaaggacct gaccaacaat 1380
aacatcccac acctgctgtc tcccaaggag gccaagagca agaccgagtt cgacttcaac 1440
atcgacccaa agcctagcga gggacctggc acaaagtatc tgaagagcaa cagccggagc 1500
cagcagaata ggcactcctt catggagtcc tctcagtcta aggccggcac cctgcagcca 1560
aacgagaagc agagcaggca ctcctacatc gacaccatcc cacagagcag ccggagcccc 1620
tcctatcgga caaaggccaa gtctcacggc gccctgtctg atagcaagtc cgtgtctcag 1680
ctgagcgagg ccagagccca gatcgcagag cccagcacct ccaggtactt tccttctagc 1740
tgtctggatc tgaactctcc tacaagccca acacccacca gacacagcga cacaaggacc 1800
ctgctgtctc caagcggcag aaataacagg aacgagggca ccctggacag ccggcggacc 1860
acaaccaggc acagcaagac aatggaggag ctgaagctgc cagagcacat ggattcctct 1920
cactcccact ctctgagcgc cccccacgag tccttctctt acggcctggg ctatacctcc 1980
cccttcagca gccagcagcg cccccaccgg cactctatgt acgtgacaag agataaggtg 2040
agggcaaagg gcctggacgg cagcctgtcc atcggacagg gaatggcagc ccgggccaac 2100
tccctgcagc tgctgtctcc tcagccagga gagcagctgc caccagagat gaccgtggca 2160
cggagcagcg tgaaggagac aagcagggag ggcacctcct ctttccacac aagacagaag 2220
tccgagggcg gcgtgtatca cgatccccac tctgacgatg gcacagcccc taaggagaac 2280
aggcacctgt acaatgaccc cgtgcctagg agggtgggct ccttctatcg cgtgccatct 2340
ccccggcctg ataatagctt tcacgagaat aacgtgagca cccgggtgag cagcctgcca 2400
tctgagtcta gctccggcac aaaccactct aagaggcagc ccgcctttga cccttggaag 2460
agcccagagc agatctctca cagcgagcag ctgaaggaga aggagaagca gggcttcttt 2520
cgcagcatga agaagaagaa gaagaagagc cagaccgtgc ctaactccga ttctccagac 2580
ctgctgaccc tgcagaagtc catccacagc gcctccacac cctctagcag acctaaggag 2640
tggaggcctg agaagatcag cgacctgcag acccagagcc agccactgaa gtccctgcgg 2700
aagctgctgc acctgtcctc tgccagcaac cacccagcca gctccgatcc aaggttccag 2760
cccctgacag cccagcagac caagaacagc ttcagcgaga tcagaatcca ccctctgtcc 2820
caggcctctg gaggctctag caacatcagg caggagccag caccaaaggg ccggcccgcc 2880
ctgcagctgc ctggccagat ggacccaggc tggcacgtgt cctctgtgac aagatccgcc 2940
accgagggcc catcctactc tgagcagctg ggagcaaaga gcggacctaa tggacaccca 3000
tatcagagga cccagagatc caggatgccc aatctgaacg atctgaagga gacagccctg 3060
ggaggaggag gcagcgagaa cctgtacttc cagggcgatt ataaggacca cgatggcgac 3120
tacaaggacc acgacattga ctacaaggac gacgacgata aagacggagc accccatcac 3180
caccaccatc attga 3195
<210> 125
<211> 2877
<212> DNA
<213> 人工序列
<220>
<223> CDKL5_107 [1-7NQ]的DNA序列 (人优化)
<400> 125
aagatcccca atatcggcaa cgtgatgaat aagttcgaga tcctgggagt ggtgggagag 60
ggagcctacg gcgtggtgct gaagtgcaga cacaaggaga cacacgagat cgtggccatc 120
aagaagttta aggacagcga ggagaatgag gaggtgaagg agacaaccct gcgcgagctg 180
aagatgctgc ggacactgaa gcaggagaac atcgtggagc tgaaggaggc cttccggaga 240
aggggcaagc tgtacctggt gtttgagtat gtggagaaga acatgctgga gctgctggag 300
gagatgccta atggcgtgcc ccctgagaag gtgaagtcct acatctatca gctgatcaag 360
gccatccact ggtgccacaa gaacgatatc gtgcaccgcg acatcaagcc cgagaacctg 420
ctgatctccc acaatgacgt gctgaagctg tgcgacttcg gctttgcccg gcagctgagc 480
gagggcaaca atgcccagta cacagagtat gtggccaccc gctggtacag aagccccgag 540
ctgctgctgg gcgcccccta tggcaagagc gtggatatgt ggtccgtggg ctgcatcctg 600
ggcgagctgt ctgatggcca gcctctgttc ccaggcgaga gcgagatcga ccagctgttt 660
accatccaga aggtgctggg ccctctgcca agcgagcaga tgaagctgtt ctactccaac 720
ccaaggttcc acggcctgag gtttccagcc gtgaatcacc ctcagagcct ggagcgccgg 780
tatctgggca tcctgaactc cgtgctgctg gacctgatga agaacctgct gaagctggac 840
cccgccgaca gatacctgac cgagcagtgt ctgaatcacc ctacatttca gacccagaga 900
ctgctggata ggagcccttc ccgctctgcc aagcggaagc catatcacgt ggagagcagc 960
accctgtcca atcgcaacca ggccggcaag tctacagccc tgcagagcca ccaccggagc 1020
aactccaagg atatccagca gctgtccgtg ggcctgccta gggccgacga gggcctgcca 1080
gcaaacgaga gcttcctgaa tggaaacctg gcaggagcct ctctgagccc actgcacaca 1140
aagacctacc aggcctctag ccagcccggc tccacatcta aggacctgac caacaataac 1200
atcccacacc tgctgtctcc caaggaggcc aagagcaaga ccgagttcga cttcaacatc 1260
gacccaaagc ctagcgaggg acctggcaca aagtatctga agagcaacag ccggagccag 1320
cagaataggc actccttcat ggagtcctct cagtctaagg ccggcaccct gcagccaaac 1380
gagaagcaga gcaggcactc ctacatcgac accatcccac agagcagccg gagcccctcc 1440
tatcggacaa aggccaagtc tcacggcgcc ctgtctgata gcaagtccgt gtctcagctg 1500
agcgaggcca gagcccagat cgcagagccc agcacctcca ggtactttcc ttctagctgt 1560
ctggatctga actctcctac aagcccaaca cccaccagac acagcgacac aaggaccctg 1620
ctgtctccaa gcggcagaaa taacaggaac gagggcaccc tggacagccg gcggaccaca 1680
accaggcaca gcaagacaat ggaggagctg aagctgccag agcacatgga ttcctctcac 1740
tcccactctc tgagcgcccc ccacgagtcc ttctcttacg gcctgggcta tacctccccc 1800
ttcagcagcc agcagcgccc ccaccggcac tctatgtacg tgacaagaga taaggtgagg 1860
gcaaagggcc tggacggcag cctgtccatc ggacagggaa tggcagcccg ggccaactcc 1920
ctgcagctgc tgtctcctca gccaggagag cagctgccac cagagatgac cgtggcacgg 1980
agcagcgtga aggagacaag cagggagggc acctcctctt tccacacaag acagaagtcc 2040
gagggcggcg tgtatcacga tccccactct gacgatggca cagcccctaa ggagaacagg 2100
cacctgtaca atgaccccgt gcctaggagg gtgggctcct tctatcgcgt gccatctccc 2160
cggcctgata atagctttca cgagaataac gtgagcaccc gggtgagcag cctgccatct 2220
gagtctagct ccggcacaaa ccactctaag aggcagcccg cctttgaccc ttggaagagc 2280
ccagagcaga tctctcacag cgagcagctg aaggagaagg agaagcaggg cttctttcgc 2340
agcatgaaga agaagaagaa gaagagccag accgtgccta actccgattc tccagacctg 2400
ctgaccctgc agaagtccat ccacagcgcc tccacaccct ctagcagacc taaggagtgg 2460
aggcctgaga agatcagcga cctgcagacc cagagccagc cactgaagtc cctgcggaag 2520
ctgctgcacc tgtcctctgc cagcaaccac ccagccagct ccgatccaag gttccagccc 2580
ctgacagccc agcagaccaa gaacagcttc agcgagatca gaatccaccc tctgtcccag 2640
gcctctggag gctctagcaa catcaggcag gagccagcac caaagggccg gcccgccctg 2700
cagctgcctg gccagatgga cccaggctgg cacgtgtcct ctgtgacaag atccgccacc 2760
gagggcccat cctactctga gcagctggga gcaaagagcg gacctaatgg acacccatat 2820
cagaggaccc agagatccag gatgcccaat ctgaacgatc tgaaggagac agccctg 2877
<210> 126
<211> 3195
<212> DNA
<213> 人工序列
<220>
<223> MBIP-TATκ28-CDKL5_107-FH [2-7NQ]的DNA序列 (人
优化)
<400> 126
atgaagctgt ccctggtggc cgctatgctg ctgctgctgt ctctggtcgc tgccatgtta 60
ttactgctgt ctgccgctag ggccggggac gcagcacagc ccgcaagaag agcaagaaga 120
actaaactgg ccgcttacgc aaggaaggca gcaagacagg caagagcagg cggcggcggc 180
tccaagatcc ccaatatcgg caacgtgatg aataagttcg agatcctggg agtggtggga 240
gagggagcct acggcgtggt gctgaagtgc agacacaagg agacacacga gatcgtggcc 300
atcaagaagt ttaaggacag cgaggagaat gaggaggtga aggagacaac cctgcgcgag 360
ctgaagatgc tgcggacact gaagcaggag aacatcgtgg agctgaagga ggccttccgg 420
agaaggggca agctgtacct ggtgtttgag tatgtggaga agaacatgct ggagctgctg 480
gaggagatgc ctaatggcgt gccccctgag aaggtgaagt cctacatcta tcagctgatc 540
aaggccatcc actggtgcca caagaacgat atcgtgcacc gcgacatcaa gcccgagaac 600
ctgctgatct cccacaatga cgtgctgaag ctgtgcgact tcggctttgc ccggaacctg 660
agcgagggca acaatgccca gtacacagag tatgtggcca cccgctggta cagaagcccc 720
gagctgctgc tgggcgcccc ctatggcaag agcgtggata tgtggtccgt gggctgcatc 780
ctgggcgagc tgtctgatgg ccagcctctg ttcccaggcg agagcgagat cgaccagctg 840
tttaccatcc agaaggtgct gggccctctg ccaagcgagc agatgaagct gttctactcc 900
aacccaaggt tccacggcct gaggtttcca gccgtgaatc accctcagag cctggagcgc 960
cggtatctgg gcatcctgaa ctccgtgctg ctggacctga tgaagaacct gctgaagctg 1020
gaccccgccg acagatacct gaccgagcag tgtctgaatc accctacatt tcagacccag 1080
agactgctgg ataggagccc ttcccgctct gccaagcgga agccatatca cgtggagagc 1140
agcaccctgt ccaatcgcaa ccaggccggc aagtctacag ccctgcagag ccaccaccgg 1200
agcaactcca aggatatcca gcagctgtcc gtgggcctgc ctagggccga cgagggcctg 1260
ccagcaaacg agagcttcct gaatggaaac ctggcaggag cctctctgag cccactgcac 1320
acaaagacct accaggcctc tagccagccc ggctccacat ctaaggacct gaccaacaat 1380
aacatcccac acctgctgtc tcccaaggag gccaagagca agaccgagtt cgacttcaac 1440
atcgacccaa agcctagcga gggacctggc acaaagtatc tgaagagcaa cagccggagc 1500
cagcagaata ggcactcctt catggagtcc tctcagtcta aggccggcac cctgcagcca 1560
aacgagaagc agagcaggca ctcctacatc gacaccatcc cacagagcag ccggagcccc 1620
tcctatcgga caaaggccaa gtctcacggc gccctgtctg atagcaagtc cgtgtctcag 1680
ctgagcgagg ccagagccca gatcgcagag cccagcacct ccaggtactt tccttctagc 1740
tgtctggatc tgaactctcc tacaagccca acacccacca gacacagcga cacaaggacc 1800
ctgctgtctc caagcggcag aaataacagg aacgagggca ccctggacag ccggcggacc 1860
acaaccaggc acagcaagac aatggaggag ctgaagctgc cagagcacat ggattcctct 1920
cactcccact ctctgagcgc cccccacgag tccttctctt acggcctggg ctatacctcc 1980
cccttcagca gccagcagcg cccccaccgg cactctatgt acgtgacaag agataaggtg 2040
agggcaaagg gcctggacgg cagcctgtcc atcggacagg gaatggcagc ccgggccaac 2100
tccctgcagc tgctgtctcc tcagccagga gagcagctgc caccagagat gaccgtggca 2160
cggagcagcg tgaaggagac aagcagggag ggcacctcct ctttccacac aagacagaag 2220
tccgagggcg gcgtgtatca cgatccccac tctgacgatg gcacagcccc taaggagaac 2280
aggcacctgt acaatgaccc cgtgcctagg agggtgggct ccttctatcg cgtgccatct 2340
ccccggcctg ataatagctt tcacgagaat aacgtgagca cccgggtgag cagcctgcca 2400
tctgagtcta gctccggcac aaaccactct aagaggcagc ccgcctttga cccttggaag 2460
agcccagagc agatctctca cagcgagcag ctgaaggaga aggagaagca gggcttcttt 2520
cgcagcatga agaagaagaa gaagaagagc cagaccgtgc ctaactccga ttctccagac 2580
ctgctgaccc tgcagaagtc catccacagc gcctccacac cctctagcag acctaaggag 2640
tggaggcctg agaagatcag cgacctgcag acccagagcc agccactgaa gtccctgcgg 2700
aagctgctgc acctgtcctc tgccagcaac cacccagcca gctccgatcc aaggttccag 2760
cccctgacag cccagcagac caagaacagc ttcagcgaga tcagaatcca ccctctgtcc 2820
caggcctctg gaggctctag caacatcagg caggagccag caccaaaggg ccggcccgcc 2880
ctgcagctgc ctggccagat ggacccaggc tggcacgtgt cctctgtgac aagatccgcc 2940
accgagggcc catcctactc tgagcagctg ggagcaaaga gcggacctaa tggacaccca 3000
tatcagagga cccagagatc caggatgccc aatctgaacg atctgaagga gacagccctg 3060
ggaggaggag gcagcgagaa cctgtacttc cagggcgatt ataaggacca cgatggcgac 3120
tacaaggacc acgacattga ctacaaggac gacgacgata aagacggagc accccatcac 3180
caccaccatc attga 3195
<210> 127
<211> 2877
<212> DNA
<213> 人工序列
<220>
<223> CDKL5_107 [2-7NQ]的DNA序列 (人优化)
<400> 127
aagatcccca atatcggcaa cgtgatgaat aagttcgaga tcctgggagt ggtgggagag 60
ggagcctacg gcgtggtgct gaagtgcaga cacaaggaga cacacgagat cgtggccatc 120
aagaagttta aggacagcga ggagaatgag gaggtgaagg agacaaccct gcgcgagctg 180
aagatgctgc ggacactgaa gcaggagaac atcgtggagc tgaaggaggc cttccggaga 240
aggggcaagc tgtacctggt gtttgagtat gtggagaaga acatgctgga gctgctggag 300
gagatgccta atggcgtgcc ccctgagaag gtgaagtcct acatctatca gctgatcaag 360
gccatccact ggtgccacaa gaacgatatc gtgcaccgcg acatcaagcc cgagaacctg 420
ctgatctccc acaatgacgt gctgaagctg tgcgacttcg gctttgcccg gaacctgagc 480
gagggcaaca atgcccagta cacagagtat gtggccaccc gctggtacag aagccccgag 540
ctgctgctgg gcgcccccta tggcaagagc gtggatatgt ggtccgtggg ctgcatcctg 600
ggcgagctgt ctgatggcca gcctctgttc ccaggcgaga gcgagatcga ccagctgttt 660
accatccaga aggtgctggg ccctctgcca agcgagcaga tgaagctgtt ctactccaac 720
ccaaggttcc acggcctgag gtttccagcc gtgaatcacc ctcagagcct ggagcgccgg 780
tatctgggca tcctgaactc cgtgctgctg gacctgatga agaacctgct gaagctggac 840
cccgccgaca gatacctgac cgagcagtgt ctgaatcacc ctacatttca gacccagaga 900
ctgctggata ggagcccttc ccgctctgcc aagcggaagc catatcacgt ggagagcagc 960
accctgtcca atcgcaacca ggccggcaag tctacagccc tgcagagcca ccaccggagc 1020
aactccaagg atatccagca gctgtccgtg ggcctgccta gggccgacga gggcctgcca 1080
gcaaacgaga gcttcctgaa tggaaacctg gcaggagcct ctctgagccc actgcacaca 1140
aagacctacc aggcctctag ccagcccggc tccacatcta aggacctgac caacaataac 1200
atcccacacc tgctgtctcc caaggaggcc aagagcaaga ccgagttcga cttcaacatc 1260
gacccaaagc ctagcgaggg acctggcaca aagtatctga agagcaacag ccggagccag 1320
cagaataggc actccttcat ggagtcctct cagtctaagg ccggcaccct gcagccaaac 1380
gagaagcaga gcaggcactc ctacatcgac accatcccac agagcagccg gagcccctcc 1440
tatcggacaa aggccaagtc tcacggcgcc ctgtctgata gcaagtccgt gtctcagctg 1500
agcgaggcca gagcccagat cgcagagccc agcacctcca ggtactttcc ttctagctgt 1560
ctggatctga actctcctac aagcccaaca cccaccagac acagcgacac aaggaccctg 1620
ctgtctccaa gcggcagaaa taacaggaac gagggcaccc tggacagccg gcggaccaca 1680
accaggcaca gcaagacaat ggaggagctg aagctgccag agcacatgga ttcctctcac 1740
tcccactctc tgagcgcccc ccacgagtcc ttctcttacg gcctgggcta tacctccccc 1800
ttcagcagcc agcagcgccc ccaccggcac tctatgtacg tgacaagaga taaggtgagg 1860
gcaaagggcc tggacggcag cctgtccatc ggacagggaa tggcagcccg ggccaactcc 1920
ctgcagctgc tgtctcctca gccaggagag cagctgccac cagagatgac cgtggcacgg 1980
agcagcgtga aggagacaag cagggagggc acctcctctt tccacacaag acagaagtcc 2040
gagggcggcg tgtatcacga tccccactct gacgatggca cagcccctaa ggagaacagg 2100
cacctgtaca atgaccccgt gcctaggagg gtgggctcct tctatcgcgt gccatctccc 2160
cggcctgata atagctttca cgagaataac gtgagcaccc gggtgagcag cctgccatct 2220
gagtctagct ccggcacaaa ccactctaag aggcagcccg cctttgaccc ttggaagagc 2280
ccagagcaga tctctcacag cgagcagctg aaggagaagg agaagcaggg cttctttcgc 2340
agcatgaaga agaagaagaa gaagagccag accgtgccta actccgattc tccagacctg 2400
ctgaccctgc agaagtccat ccacagcgcc tccacaccct ctagcagacc taaggagtgg 2460
aggcctgaga agatcagcga cctgcagacc cagagccagc cactgaagtc cctgcggaag 2520
ctgctgcacc tgtcctctgc cagcaaccac ccagccagct ccgatccaag gttccagccc 2580
ctgacagccc agcagaccaa gaacagcttc agcgagatca gaatccaccc tctgtcccag 2640
gcctctggag gctctagcaa catcaggcag gagccagcac caaagggccg gcccgccctg 2700
cagctgcctg gccagatgga cccaggctgg cacgtgtcct ctgtgacaag atccgccacc 2760
gagggcccat cctactctga gcagctggga gcaaagagcg gacctaatgg acacccatat 2820
cagaggaccc agagatccag gatgcccaat ctgaacgatc tgaaggagac agccctg 2877
<210> 128
<211> 3195
<212> DNA
<213> 人工序列
<220>
<223> MBIP-TATκ28-CDKL5_107-FH [1,3-7NQ]的DNA序列 (人
优化)
<400> 128
atgaagctgt ccctggtggc cgctatgctg ctgctgctgt ctctggtcgc tgccatgtta 60
ttactgctgt ctgccgctag ggccggggac gcagcacagc ccgcaagaag agcaagaaga 120
actaaactgg ccgcttacgc aaggaaggca gcaagacagg caagagcagg cggcggcggc 180
tccaagatcc ccaatatcgg caacgtgatg aataagttcg agatcctggg agtggtggga 240
gagggagcct acggcgtggt gctgaagtgc agacacaagg agacacacga gatcgtggcc 300
atcaagaagt ttaaggacag cgaggagaat gaggaggtga aggagacaac cctgcgcgag 360
ctgaagatgc tgcggacact gaagcaggag aacatcgtgg agctgaagga ggccttccgg 420
agaaggggca agctgtacct ggtgtttgag tatgtggaga agaacatgct ggagctgctg 480
gaggagatgc ctaatggcgt gccccctgag aaggtgaagt cctacatcta tcagctgatc 540
aaggccatcc actggtgcca caagaacgat atcgtgcacc gcgacatcaa gcccgagaac 600
ctgctgatct cccacaatga cgtgctgaag ctgtgcgact tcggctttgc ccggcagctg 660
agcgagggca acaatgccaa ttacacagag tatgtggcca cccgctggta cagaagcccc 720
gagctgctgc tgggcgcccc ctatggcaag agcgtggata tgtggtccgt gggctgcatc 780
ctgggcgagc tgtctgatgg ccagcctctg ttcccaggcg agagcgagat cgaccagctg 840
tttaccatcc agaaggtgct gggccctctg ccaagcgagc agatgaagct gttctactcc 900
aacccaaggt tccacggcct gaggtttcca gccgtgaatc accctcagag cctggagcgc 960
cggtatctgg gcatcctgaa ctccgtgctg ctggacctga tgaagaacct gctgaagctg 1020
gaccccgccg acagatacct gaccgagcag tgtctgaatc accctacatt tcagacccag 1080
agactgctgg ataggagccc ttcccgctct gccaagcgga agccatatca cgtggagagc 1140
agcaccctgt ccaatcgcaa ccaggccggc aagtctacag ccctgcagag ccaccaccgg 1200
agcaactcca aggatatcca gcagctgtcc gtgggcctgc ctagggccga cgagggcctg 1260
ccagcaaacg agagcttcct gaatggaaac ctggcaggag cctctctgag cccactgcac 1320
acaaagacct accaggcctc tagccagccc ggctccacat ctaaggacct gaccaacaat 1380
aacatcccac acctgctgtc tcccaaggag gccaagagca agaccgagtt cgacttcaac 1440
atcgacccaa agcctagcga gggacctggc acaaagtatc tgaagagcaa cagccggagc 1500
cagcagaata ggcactcctt catggagtcc tctcagtcta aggccggcac cctgcagcca 1560
aacgagaagc agagcaggca ctcctacatc gacaccatcc cacagagcag ccggagcccc 1620
tcctatcgga caaaggccaa gtctcacggc gccctgtctg atagcaagtc cgtgtctcag 1680
ctgagcgagg ccagagccca gatcgcagag cccagcacct ccaggtactt tccttctagc 1740
tgtctggatc tgaactctcc tacaagccca acacccacca gacacagcga cacaaggacc 1800
ctgctgtctc caagcggcag aaataacagg aacgagggca ccctggacag ccggcggacc 1860
acaaccaggc acagcaagac aatggaggag ctgaagctgc cagagcacat ggattcctct 1920
cactcccact ctctgagcgc cccccacgag tccttctctt acggcctggg ctatacctcc 1980
cccttcagca gccagcagcg cccccaccgg cactctatgt acgtgacaag agataaggtg 2040
agggcaaagg gcctggacgg cagcctgtcc atcggacagg gaatggcagc ccgggccaac 2100
tccctgcagc tgctgtctcc tcagccagga gagcagctgc caccagagat gaccgtggca 2160
cggagcagcg tgaaggagac aagcagggag ggcacctcct ctttccacac aagacagaag 2220
tccgagggcg gcgtgtatca cgatccccac tctgacgatg gcacagcccc taaggagaac 2280
aggcacctgt acaatgaccc cgtgcctagg agggtgggct ccttctatcg cgtgccatct 2340
ccccggcctg ataatagctt tcacgagaat aacgtgagca cccgggtgag cagcctgcca 2400
tctgagtcta gctccggcac aaaccactct aagaggcagc ccgcctttga cccttggaag 2460
agcccagagc agatctctca cagcgagcag ctgaaggaga aggagaagca gggcttcttt 2520
cgcagcatga agaagaagaa gaagaagagc cagaccgtgc ctaactccga ttctccagac 2580
ctgctgaccc tgcagaagtc catccacagc gcctccacac cctctagcag acctaaggag 2640
tggaggcctg agaagatcag cgacctgcag acccagagcc agccactgaa gtccctgcgg 2700
aagctgctgc acctgtcctc tgccagcaac cacccagcca gctccgatcc aaggttccag 2760
cccctgacag cccagcagac caagaacagc ttcagcgaga tcagaatcca ccctctgtcc 2820
caggcctctg gaggctctag caacatcagg caggagccag caccaaaggg ccggcccgcc 2880
ctgcagctgc ctggccagat ggacccaggc tggcacgtgt cctctgtgac aagatccgcc 2940
accgagggcc catcctactc tgagcagctg ggagcaaaga gcggacctaa tggacaccca 3000
tatcagagga cccagagatc caggatgccc aatctgaacg atctgaagga gacagccctg 3060
ggaggaggag gcagcgagaa cctgtacttc cagggcgatt ataaggacca cgatggcgac 3120
tacaaggacc acgacattga ctacaaggac gacgacgata aagacggagc accccatcac 3180
caccaccatc attga 3195
<210> 129
<211> 2877
<212> DNA
<213> 人工序列
<220>
<223> CDKL5_107 [1,3-7NQ]的DNA序列 (人优化)
<400> 129
aagatcccca atatcggcaa cgtgatgaat aagttcgaga tcctgggagt ggtgggagag 60
ggagcctacg gcgtggtgct gaagtgcaga cacaaggaga cacacgagat cgtggccatc 120
aagaagttta aggacagcga ggagaatgag gaggtgaagg agacaaccct gcgcgagctg 180
aagatgctgc ggacactgaa gcaggagaac atcgtggagc tgaaggaggc cttccggaga 240
aggggcaagc tgtacctggt gtttgagtat gtggagaaga acatgctgga gctgctggag 300
gagatgccta atggcgtgcc ccctgagaag gtgaagtcct acatctatca gctgatcaag 360
gccatccact ggtgccacaa gaacgatatc gtgcaccgcg acatcaagcc cgagaacctg 420
ctgatctccc acaatgacgt gctgaagctg tgcgacttcg gctttgcccg gcagctgagc 480
gagggcaaca atgccaatta cacagagtat gtggccaccc gctggtacag aagccccgag 540
ctgctgctgg gcgcccccta tggcaagagc gtggatatgt ggtccgtggg ctgcatcctg 600
ggcgagctgt ctgatggcca gcctctgttc ccaggcgaga gcgagatcga ccagctgttt 660
accatccaga aggtgctggg ccctctgcca agcgagcaga tgaagctgtt ctactccaac 720
ccaaggttcc acggcctgag gtttccagcc gtgaatcacc ctcagagcct ggagcgccgg 780
tatctgggca tcctgaactc cgtgctgctg gacctgatga agaacctgct gaagctggac 840
cccgccgaca gatacctgac cgagcagtgt ctgaatcacc ctacatttca gacccagaga 900
ctgctggata ggagcccttc ccgctctgcc aagcggaagc catatcacgt ggagagcagc 960
accctgtcca atcgcaacca ggccggcaag tctacagccc tgcagagcca ccaccggagc 1020
aactccaagg atatccagca gctgtccgtg ggcctgccta gggccgacga gggcctgcca 1080
gcaaacgaga gcttcctgaa tggaaacctg gcaggagcct ctctgagccc actgcacaca 1140
aagacctacc aggcctctag ccagcccggc tccacatcta aggacctgac caacaataac 1200
atcccacacc tgctgtctcc caaggaggcc aagagcaaga ccgagttcga cttcaacatc 1260
gacccaaagc ctagcgaggg acctggcaca aagtatctga agagcaacag ccggagccag 1320
cagaataggc actccttcat ggagtcctct cagtctaagg ccggcaccct gcagccaaac 1380
gagaagcaga gcaggcactc ctacatcgac accatcccac agagcagccg gagcccctcc 1440
tatcggacaa aggccaagtc tcacggcgcc ctgtctgata gcaagtccgt gtctcagctg 1500
agcgaggcca gagcccagat cgcagagccc agcacctcca ggtactttcc ttctagctgt 1560
ctggatctga actctcctac aagcccaaca cccaccagac acagcgacac aaggaccctg 1620
ctgtctccaa gcggcagaaa taacaggaac gagggcaccc tggacagccg gcggaccaca 1680
accaggcaca gcaagacaat ggaggagctg aagctgccag agcacatgga ttcctctcac 1740
tcccactctc tgagcgcccc ccacgagtcc ttctcttacg gcctgggcta tacctccccc 1800
ttcagcagcc agcagcgccc ccaccggcac tctatgtacg tgacaagaga taaggtgagg 1860
gcaaagggcc tggacggcag cctgtccatc ggacagggaa tggcagcccg ggccaactcc 1920
ctgcagctgc tgtctcctca gccaggagag cagctgccac cagagatgac cgtggcacgg 1980
agcagcgtga aggagacaag cagggagggc acctcctctt tccacacaag acagaagtcc 2040
gagggcggcg tgtatcacga tccccactct gacgatggca cagcccctaa ggagaacagg 2100
cacctgtaca atgaccccgt gcctaggagg gtgggctcct tctatcgcgt gccatctccc 2160
cggcctgata atagctttca cgagaataac gtgagcaccc gggtgagcag cctgccatct 2220
gagtctagct ccggcacaaa ccactctaag aggcagcccg cctttgaccc ttggaagagc 2280
ccagagcaga tctctcacag cgagcagctg aaggagaagg agaagcaggg cttctttcgc 2340
agcatgaaga agaagaagaa gaagagccag accgtgccta actccgattc tccagacctg 2400
ctgaccctgc agaagtccat ccacagcgcc tccacaccct ctagcagacc taaggagtgg 2460
aggcctgaga agatcagcga cctgcagacc cagagccagc cactgaagtc cctgcggaag 2520
ctgctgcacc tgtcctctgc cagcaaccac ccagccagct ccgatccaag gttccagccc 2580
ctgacagccc agcagaccaa gaacagcttc agcgagatca gaatccaccc tctgtcccag 2640
gcctctggag gctctagcaa catcaggcag gagccagcac caaagggccg gcccgccctg 2700
cagctgcctg gccagatgga cccaggctgg cacgtgtcct ctgtgacaag atccgccacc 2760
gagggcccat cctactctga gcagctggga gcaaagagcg gacctaatgg acacccatat 2820
cagaggaccc agagatccag gatgcccaat ctgaacgatc tgaaggagac agccctg 2877
<210> 130
<211> 3195
<212> DNA
<213> 人工序列
<220>
<223> MBIP-TATκ28-CDKL5_107-FH [1-2,4-7NQ]的DNA序列 (人
优化)
<400> 130
atgaagctgt ccctggtggc cgctatgctg ctgctgctgt ctctggtcgc tgccatgtta 60
ttactgctgt ctgccgctag ggccggggac gcagcacagc ccgcaagaag agcaagaaga 120
actaaactgg ccgcttacgc aaggaaggca gcaagacagg caagagcagg cggcggcggc 180
tccaagatcc ccaatatcgg caacgtgatg aataagttcg agatcctggg agtggtggga 240
gagggagcct acggcgtggt gctgaagtgc agacacaagg agacacacga gatcgtggcc 300
atcaagaagt ttaaggacag cgaggagaat gaggaggtga aggagacaac cctgcgcgag 360
ctgaagatgc tgcggacact gaagcaggag aacatcgtgg agctgaagga ggccttccgg 420
agaaggggca agctgtacct ggtgtttgag tatgtggaga agaacatgct ggagctgctg 480
gaggagatgc ctaatggcgt gccccctgag aaggtgaagt cctacatcta tcagctgatc 540
aaggccatcc actggtgcca caagaacgat atcgtgcacc gcgacatcaa gcccgagaac 600
ctgctgatct cccacaatga cgtgctgaag ctgtgcgact tcggctttgc ccggcagctg 660
agcgagggca acaatgccca gtacacagag tatgtggcca cccgctggta cagaagcccc 720
gagctgctgc tgggcgcccc ctatggcaag agcgtggata tgtggtccgt gggctgcatc 780
ctgggcgagc tgtctgatgg ccagcctctg ttcccaggcg agagcgagat cgaccagctg 840
tttaccatcc agaaggtgct gggccctctg ccaagcgagc agatgaagct gttctactcc 900
aacccaaggt tccacggcct gaggtttcca gccgtgaatc accctcagag cctggagcgc 960
cggtatctgg gcatcctgaa ctccgtgctg ctggacctga tgaagaacct gctgaagctg 1020
gaccccgccg acagatacct gaccgagcag tgtctgaatc accctacatt tcagacccag 1080
agactgctgg ataggagccc ttcccgctct gccaagcgga agccatatca cgtggagagc 1140
agcaccctgt ccaatcgcaa ccaggccggc aagtctacag ccctgcagag ccaccaccgg 1200
agcaactcca aggatatcca gaatctgtcc gtgggcctgc ctagggccga cgagggcctg 1260
ccagcaaacg agagcttcct gaatggaaac ctggcaggag cctctctgag cccactgcac 1320
acaaagacct accaggcctc tagccagccc ggctccacat ctaaggacct gaccaacaat 1380
aacatcccac acctgctgtc tcccaaggag gccaagagca agaccgagtt cgacttcaac 1440
atcgacccaa agcctagcga gggacctggc acaaagtatc tgaagagcaa cagccggagc 1500
cagcagaata ggcactcctt catggagtcc tctcagtcta aggccggcac cctgcagcca 1560
aacgagaagc agagcaggca ctcctacatc gacaccatcc cacagagcag ccggagcccc 1620
tcctatcgga caaaggccaa gtctcacggc gccctgtctg atagcaagtc cgtgtctcag 1680
ctgagcgagg ccagagccca gatcgcagag cccagcacct ccaggtactt tccttctagc 1740
tgtctggatc tgaactctcc tacaagccca acacccacca gacacagcga cacaaggacc 1800
ctgctgtctc caagcggcag aaataacagg aacgagggca ccctggacag ccggcggacc 1860
acaaccaggc acagcaagac aatggaggag ctgaagctgc cagagcacat ggattcctct 1920
cactcccact ctctgagcgc cccccacgag tccttctctt acggcctggg ctatacctcc 1980
cccttcagca gccagcagcg cccccaccgg cactctatgt acgtgacaag agataaggtg 2040
agggcaaagg gcctggacgg cagcctgtcc atcggacagg gaatggcagc ccgggccaac 2100
tccctgcagc tgctgtctcc tcagccagga gagcagctgc caccagagat gaccgtggca 2160
cggagcagcg tgaaggagac aagcagggag ggcacctcct ctttccacac aagacagaag 2220
tccgagggcg gcgtgtatca cgatccccac tctgacgatg gcacagcccc taaggagaac 2280
aggcacctgt acaatgaccc cgtgcctagg agggtgggct ccttctatcg cgtgccatct 2340
ccccggcctg ataatagctt tcacgagaat aacgtgagca cccgggtgag cagcctgcca 2400
tctgagtcta gctccggcac aaaccactct aagaggcagc ccgcctttga cccttggaag 2460
agcccagagc agatctctca cagcgagcag ctgaaggaga aggagaagca gggcttcttt 2520
cgcagcatga agaagaagaa gaagaagagc cagaccgtgc ctaactccga ttctccagac 2580
ctgctgaccc tgcagaagtc catccacagc gcctccacac cctctagcag acctaaggag 2640
tggaggcctg agaagatcag cgacctgcag acccagagcc agccactgaa gtccctgcgg 2700
aagctgctgc acctgtcctc tgccagcaac cacccagcca gctccgatcc aaggttccag 2760
cccctgacag cccagcagac caagaacagc ttcagcgaga tcagaatcca ccctctgtcc 2820
caggcctctg gaggctctag caacatcagg caggagccag caccaaaggg ccggcccgcc 2880
ctgcagctgc ctggccagat ggacccaggc tggcacgtgt cctctgtgac aagatccgcc 2940
accgagggcc catcctactc tgagcagctg ggagcaaaga gcggacctaa tggacaccca 3000
tatcagagga cccagagatc caggatgccc aatctgaacg atctgaagga gacagccctg 3060
ggaggaggag gcagcgagaa cctgtacttc cagggcgatt ataaggacca cgatggcgac 3120
tacaaggacc acgacattga ctacaaggac gacgacgata aagacggagc accccatcac 3180
caccaccatc attga 3195
<210> 131
<211> 2877
<212> DNA
<213> 人工序列
<220>
<223> CDKL5_107 [1-2,4-7NQ]的DNA序列 (人优化)
<400> 131
aagatcccca atatcggcaa cgtgatgaat aagttcgaga tcctgggagt ggtgggagag 60
ggagcctacg gcgtggtgct gaagtgcaga cacaaggaga cacacgagat cgtggccatc 120
aagaagttta aggacagcga ggagaatgag gaggtgaagg agacaaccct gcgcgagctg 180
aagatgctgc ggacactgaa gcaggagaac atcgtggagc tgaaggaggc cttccggaga 240
aggggcaagc tgtacctggt gtttgagtat gtggagaaga acatgctgga gctgctggag 300
gagatgccta atggcgtgcc ccctgagaag gtgaagtcct acatctatca gctgatcaag 360
gccatccact ggtgccacaa gaacgatatc gtgcaccgcg acatcaagcc cgagaacctg 420
ctgatctccc acaatgacgt gctgaagctg tgcgacttcg gctttgcccg gcagctgagc 480
gagggcaaca atgcccagta cacagagtat gtggccaccc gctggtacag aagccccgag 540
ctgctgctgg gcgcccccta tggcaagagc gtggatatgt ggtccgtggg ctgcatcctg 600
ggcgagctgt ctgatggcca gcctctgttc ccaggcgaga gcgagatcga ccagctgttt 660
accatccaga aggtgctggg ccctctgcca agcgagcaga tgaagctgtt ctactccaac 720
ccaaggttcc acggcctgag gtttccagcc gtgaatcacc ctcagagcct ggagcgccgg 780
tatctgggca tcctgaactc cgtgctgctg gacctgatga agaacctgct gaagctggac 840
cccgccgaca gatacctgac cgagcagtgt ctgaatcacc ctacatttca gacccagaga 900
ctgctggata ggagcccttc ccgctctgcc aagcggaagc catatcacgt ggagagcagc 960
accctgtcca atcgcaacca ggccggcaag tctacagccc tgcagagcca ccaccggagc 1020
aactccaagg atatccagaa tctgtccgtg ggcctgccta gggccgacga gggcctgcca 1080
gcaaacgaga gcttcctgaa tggaaacctg gcaggagcct ctctgagccc actgcacaca 1140
aagacctacc aggcctctag ccagcccggc tccacatcta aggacctgac caacaataac 1200
atcccacacc tgctgtctcc caaggaggcc aagagcaaga ccgagttcga cttcaacatc 1260
gacccaaagc ctagcgaggg acctggcaca aagtatctga agagcaacag ccggagccag 1320
cagaataggc actccttcat ggagtcctct cagtctaagg ccggcaccct gcagccaaac 1380
gagaagcaga gcaggcactc ctacatcgac accatcccac agagcagccg gagcccctcc 1440
tatcggacaa aggccaagtc tcacggcgcc ctgtctgata gcaagtccgt gtctcagctg 1500
agcgaggcca gagcccagat cgcagagccc agcacctcca ggtactttcc ttctagctgt 1560
ctggatctga actctcctac aagcccaaca cccaccagac acagcgacac aaggaccctg 1620
ctgtctccaa gcggcagaaa taacaggaac gagggcaccc tggacagccg gcggaccaca 1680
accaggcaca gcaagacaat ggaggagctg aagctgccag agcacatgga ttcctctcac 1740
tcccactctc tgagcgcccc ccacgagtcc ttctcttacg gcctgggcta tacctccccc 1800
ttcagcagcc agcagcgccc ccaccggcac tctatgtacg tgacaagaga taaggtgagg 1860
gcaaagggcc tggacggcag cctgtccatc ggacagggaa tggcagcccg ggccaactcc 1920
ctgcagctgc tgtctcctca gccaggagag cagctgccac cagagatgac cgtggcacgg 1980
agcagcgtga aggagacaag cagggagggc acctcctctt tccacacaag acagaagtcc 2040
gagggcggcg tgtatcacga tccccactct gacgatggca cagcccctaa ggagaacagg 2100
cacctgtaca atgaccccgt gcctaggagg gtgggctcct tctatcgcgt gccatctccc 2160
cggcctgata atagctttca cgagaataac gtgagcaccc gggtgagcag cctgccatct 2220
gagtctagct ccggcacaaa ccactctaag aggcagcccg cctttgaccc ttggaagagc 2280
ccagagcaga tctctcacag cgagcagctg aaggagaagg agaagcaggg cttctttcgc 2340
agcatgaaga agaagaagaa gaagagccag accgtgccta actccgattc tccagacctg 2400
ctgaccctgc agaagtccat ccacagcgcc tccacaccct ctagcagacc taaggagtgg 2460
aggcctgaga agatcagcga cctgcagacc cagagccagc cactgaagtc cctgcggaag 2520
ctgctgcacc tgtcctctgc cagcaaccac ccagccagct ccgatccaag gttccagccc 2580
ctgacagccc agcagaccaa gaacagcttc agcgagatca gaatccaccc tctgtcccag 2640
gcctctggag gctctagcaa catcaggcag gagccagcac caaagggccg gcccgccctg 2700
cagctgcctg gccagatgga cccaggctgg cacgtgtcct ctgtgacaag atccgccacc 2760
gagggcccat cctactctga gcagctggga gcaaagagcg gacctaatgg acacccatat 2820
cagaggaccc agagatccag gatgcccaat ctgaacgatc tgaaggagac agccctg 2877
<210> 132
<211> 3195
<212> DNA
<213> 人工序列
<220>
<223> MBIP-TATκ28-CDKL5_107-FH [1-3,5-7NQ]的DNA序列 (人
优化)
<400> 132
atgaagctgt ccctggtggc cgctatgctg ctgctgctgt ctctggtcgc tgccatgtta 60
ttactgctgt ctgccgctag ggccggggac gcagcacagc ccgcaagaag agcaagaaga 120
actaaactgg ccgcttacgc aaggaaggca gcaagacagg caagagcagg cggcggcggc 180
tccaagatcc ccaatatcgg caacgtgatg aataagttcg agatcctggg agtggtggga 240
gagggagcct acggcgtggt gctgaagtgc agacacaagg agacacacga gatcgtggcc 300
atcaagaagt ttaaggacag cgaggagaat gaggaggtga aggagacaac cctgcgcgag 360
ctgaagatgc tgcggacact gaagcaggag aacatcgtgg agctgaagga ggccttccgg 420
agaaggggca agctgtacct ggtgtttgag tatgtggaga agaacatgct ggagctgctg 480
gaggagatgc ctaatggcgt gccccctgag aaggtgaagt cctacatcta tcagctgatc 540
aaggccatcc actggtgcca caagaacgat atcgtgcacc gcgacatcaa gcccgagaac 600
ctgctgatct cccacaatga cgtgctgaag ctgtgcgact tcggctttgc ccggcagctg 660
agcgagggca acaatgccca gtacacagag tatgtggcca cccgctggta cagaagcccc 720
gagctgctgc tgggcgcccc ctatggcaag agcgtggata tgtggtccgt gggctgcatc 780
ctgggcgagc tgtctgatgg ccagcctctg ttcccaggcg agagcgagat cgaccagctg 840
tttaccatcc agaaggtgct gggccctctg ccaagcgagc agatgaagct gttctactcc 900
aacccaaggt tccacggcct gaggtttcca gccgtgaatc accctcagag cctggagcgc 960
cggtatctgg gcatcctgaa ctccgtgctg ctggacctga tgaagaacct gctgaagctg 1020
gaccccgccg acagatacct gaccgagcag tgtctgaatc accctacatt tcagacccag 1080
agactgctgg ataggagccc ttcccgctct gccaagcgga agccatatca cgtggagagc 1140
agcaccctgt ccaatcgcaa ccaggccggc aagtctacag ccctgcagag ccaccaccgg 1200
agcaactcca aggatatcca gcagctgtcc gtgggcctgc ctagggccga cgagggcctg 1260
ccagcaaacg agagcttcct gaatggaaac ctggcaggag cctctctgag cccactgcac 1320
acaaagacct accaggcctc tagccagccc ggctccacat ctaaggacct gaccaacaat 1380
aacatcccac acctgctgtc tcccaaggag gccaagagca agaccgagtt cgacttcaac 1440
atcgacccaa agcctagcga gggacctggc acaaagtatc tgaagagcaa cagccggagc 1500
cagcagaata ggcactcctt catggagtcc tctcagtcta aggccggcac cctgcagcca 1560
aacgagaagc agagcaggca ctcctacatc gacaccatcc cacagagcag ccggagcccc 1620
tcctatcgga caaaggccaa gtctcacggc gccctgtctg atagcaagtc cgtgtctaat 1680
ctgagcgagg ccagagccca gatcgcagag cccagcacct ccaggtactt tccttctagc 1740
tgtctggatc tgaactctcc tacaagccca acacccacca gacacagcga cacaaggacc 1800
ctgctgtctc caagcggcag aaataacagg aacgagggca ccctggacag ccggcggacc 1860
acaaccaggc acagcaagac aatggaggag ctgaagctgc cagagcacat ggattcctct 1920
cactcccact ctctgagcgc cccccacgag tccttctctt acggcctggg ctatacctcc 1980
cccttcagca gccagcagcg cccccaccgg cactctatgt acgtgacaag agataaggtg 2040
agggcaaagg gcctggacgg cagcctgtcc atcggacagg gaatggcagc ccgggccaac 2100
tccctgcagc tgctgtctcc tcagccagga gagcagctgc caccagagat gaccgtggca 2160
cggagcagcg tgaaggagac aagcagggag ggcacctcct ctttccacac aagacagaag 2220
tccgagggcg gcgtgtatca cgatccccac tctgacgatg gcacagcccc taaggagaac 2280
aggcacctgt acaatgaccc cgtgcctagg agggtgggct ccttctatcg cgtgccatct 2340
ccccggcctg ataatagctt tcacgagaat aacgtgagca cccgggtgag cagcctgcca 2400
tctgagtcta gctccggcac aaaccactct aagaggcagc ccgcctttga cccttggaag 2460
agcccagagc agatctctca cagcgagcag ctgaaggaga aggagaagca gggcttcttt 2520
cgcagcatga agaagaagaa gaagaagagc cagaccgtgc ctaactccga ttctccagac 2580
ctgctgaccc tgcagaagtc catccacagc gcctccacac cctctagcag acctaaggag 2640
tggaggcctg agaagatcag cgacctgcag acccagagcc agccactgaa gtccctgcgg 2700
aagctgctgc acctgtcctc tgccagcaac cacccagcca gctccgatcc aaggttccag 2760
cccctgacag cccagcagac caagaacagc ttcagcgaga tcagaatcca ccctctgtcc 2820
caggcctctg gaggctctag caacatcagg caggagccag caccaaaggg ccggcccgcc 2880
ctgcagctgc ctggccagat ggacccaggc tggcacgtgt cctctgtgac aagatccgcc 2940
accgagggcc catcctactc tgagcagctg ggagcaaaga gcggacctaa tggacaccca 3000
tatcagagga cccagagatc caggatgccc aatctgaacg atctgaagga gacagccctg 3060
ggaggaggag gcagcgagaa cctgtacttc cagggcgatt ataaggacca cgatggcgac 3120
tacaaggacc acgacattga ctacaaggac gacgacgata aagacggagc accccatcac 3180
caccaccatc attga 3195
<210> 133
<211> 2877
<212> DNA
<213> 人工序列
<220>
<223> CDKL5_107 [1-3,5-7NQ]的DNA序列 (人优化)
<400> 133
aagatcccca atatcggcaa cgtgatgaat aagttcgaga tcctgggagt ggtgggagag 60
ggagcctacg gcgtggtgct gaagtgcaga cacaaggaga cacacgagat cgtggccatc 120
aagaagttta aggacagcga ggagaatgag gaggtgaagg agacaaccct gcgcgagctg 180
aagatgctgc ggacactgaa gcaggagaac atcgtggagc tgaaggaggc cttccggaga 240
aggggcaagc tgtacctggt gtttgagtat gtggagaaga acatgctgga gctgctggag 300
gagatgccta atggcgtgcc ccctgagaag gtgaagtcct acatctatca gctgatcaag 360
gccatccact ggtgccacaa gaacgatatc gtgcaccgcg acatcaagcc cgagaacctg 420
ctgatctccc acaatgacgt gctgaagctg tgcgacttcg gctttgcccg gcagctgagc 480
gagggcaaca atgcccagta cacagagtat gtggccaccc gctggtacag aagccccgag 540
ctgctgctgg gcgcccccta tggcaagagc gtggatatgt ggtccgtggg ctgcatcctg 600
ggcgagctgt ctgatggcca gcctctgttc ccaggcgaga gcgagatcga ccagctgttt 660
accatccaga aggtgctggg ccctctgcca agcgagcaga tgaagctgtt ctactccaac 720
ccaaggttcc acggcctgag gtttccagcc gtgaatcacc ctcagagcct ggagcgccgg 780
tatctgggca tcctgaactc cgtgctgctg gacctgatga agaacctgct gaagctggac 840
cccgccgaca gatacctgac cgagcagtgt ctgaatcacc ctacatttca gacccagaga 900
ctgctggata ggagcccttc ccgctctgcc aagcggaagc catatcacgt ggagagcagc 960
accctgtcca atcgcaacca ggccggcaag tctacagccc tgcagagcca ccaccggagc 1020
aactccaagg atatccagca gctgtccgtg ggcctgccta gggccgacga gggcctgcca 1080
gcaaacgaga gcttcctgaa tggaaacctg gcaggagcct ctctgagccc actgcacaca 1140
aagacctacc aggcctctag ccagcccggc tccacatcta aggacctgac caacaataac 1200
atcccacacc tgctgtctcc caaggaggcc aagagcaaga ccgagttcga cttcaacatc 1260
gacccaaagc ctagcgaggg acctggcaca aagtatctga agagcaacag ccggagccag 1320
cagaataggc actccttcat ggagtcctct cagtctaagg ccggcaccct gcagccaaac 1380
gagaagcaga gcaggcactc ctacatcgac accatcccac agagcagccg gagcccctcc 1440
tatcggacaa aggccaagtc tcacggcgcc ctgtctgata gcaagtccgt gtctaatctg 1500
agcgaggcca gagcccagat cgcagagccc agcacctcca ggtactttcc ttctagctgt 1560
ctggatctga actctcctac aagcccaaca cccaccagac acagcgacac aaggaccctg 1620
ctgtctccaa gcggcagaaa taacaggaac gagggcaccc tggacagccg gcggaccaca 1680
accaggcaca gcaagacaat ggaggagctg aagctgccag agcacatgga ttcctctcac 1740
tcccactctc tgagcgcccc ccacgagtcc ttctcttacg gcctgggcta tacctccccc 1800
ttcagcagcc agcagcgccc ccaccggcac tctatgtacg tgacaagaga taaggtgagg 1860
gcaaagggcc tggacggcag cctgtccatc ggacagggaa tggcagcccg ggccaactcc 1920
ctgcagctgc tgtctcctca gccaggagag cagctgccac cagagatgac cgtggcacgg 1980
agcagcgtga aggagacaag cagggagggc acctcctctt tccacacaag acagaagtcc 2040
gagggcggcg tgtatcacga tccccactct gacgatggca cagcccctaa ggagaacagg 2100
cacctgtaca atgaccccgt gcctaggagg gtgggctcct tctatcgcgt gccatctccc 2160
cggcctgata atagctttca cgagaataac gtgagcaccc gggtgagcag cctgccatct 2220
gagtctagct ccggcacaaa ccactctaag aggcagcccg cctttgaccc ttggaagagc 2280
ccagagcaga tctctcacag cgagcagctg aaggagaagg agaagcaggg cttctttcgc 2340
agcatgaaga agaagaagaa gaagagccag accgtgccta actccgattc tccagacctg 2400
ctgaccctgc agaagtccat ccacagcgcc tccacaccct ctagcagacc taaggagtgg 2460
aggcctgaga agatcagcga cctgcagacc cagagccagc cactgaagtc cctgcggaag 2520
ctgctgcacc tgtcctctgc cagcaaccac ccagccagct ccgatccaag gttccagccc 2580
ctgacagccc agcagaccaa gaacagcttc agcgagatca gaatccaccc tctgtcccag 2640
gcctctggag gctctagcaa catcaggcag gagccagcac caaagggccg gcccgccctg 2700
cagctgcctg gccagatgga cccaggctgg cacgtgtcct ctgtgacaag atccgccacc 2760
gagggcccat cctactctga gcagctggga gcaaagagcg gacctaatgg acacccatat 2820
cagaggaccc agagatccag gatgcccaat ctgaacgatc tgaaggagac agccctg 2877
<210> 134
<211> 3195
<212> DNA
<213> 人工序列
<220>
<223> MBIP-TATκ28-CDKL5_107-FH [1-4,6-7NQ]的DNA序列 (人
优化)
<400> 134
atgaagctgt ccctggtggc cgctatgctg ctgctgctgt ctctggtcgc tgccatgtta 60
ttactgctgt ctgccgctag ggccggggac gcagcacagc ccgcaagaag agcaagaaga 120
actaaactgg ccgcttacgc aaggaaggca gcaagacagg caagagcagg cggcggcggc 180
tccaagatcc ccaatatcgg caacgtgatg aataagttcg agatcctggg agtggtggga 240
gagggagcct acggcgtggt gctgaagtgc agacacaagg agacacacga gatcgtggcc 300
atcaagaagt ttaaggacag cgaggagaat gaggaggtga aggagacaac cctgcgcgag 360
ctgaagatgc tgcggacact gaagcaggag aacatcgtgg agctgaagga ggccttccgg 420
agaaggggca agctgtacct ggtgtttgag tatgtggaga agaacatgct ggagctgctg 480
gaggagatgc ctaatggcgt gccccctgag aaggtgaagt cctacatcta tcagctgatc 540
aaggccatcc actggtgcca caagaacgat atcgtgcacc gcgacatcaa gcccgagaac 600
ctgctgatct cccacaatga cgtgctgaag ctgtgcgact tcggctttgc ccggcagctg 660
agcgagggca acaatgccca gtacacagag tatgtggcca cccgctggta cagaagcccc 720
gagctgctgc tgggcgcccc ctatggcaag agcgtggata tgtggtccgt gggctgcatc 780
ctgggcgagc tgtctgatgg ccagcctctg ttcccaggcg agagcgagat cgaccagctg 840
tttaccatcc agaaggtgct gggccctctg ccaagcgagc agatgaagct gttctactcc 900
aacccaaggt tccacggcct gaggtttcca gccgtgaatc accctcagag cctggagcgc 960
cggtatctgg gcatcctgaa ctccgtgctg ctggacctga tgaagaacct gctgaagctg 1020
gaccccgccg acagatacct gaccgagcag tgtctgaatc accctacatt tcagacccag 1080
agactgctgg ataggagccc ttcccgctct gccaagcgga agccatatca cgtggagagc 1140
agcaccctgt ccaatcgcaa ccaggccggc aagtctacag ccctgcagag ccaccaccgg 1200
agcaactcca aggatatcca gcagctgtcc gtgggcctgc ctagggccga cgagggcctg 1260
ccagcaaacg agagcttcct gaatggaaac ctggcaggag cctctctgag cccactgcac 1320
acaaagacct accaggcctc tagccagccc ggctccacat ctaaggacct gaccaacaat 1380
aacatcccac acctgctgtc tcccaaggag gccaagagca agaccgagtt cgacttcaac 1440
atcgacccaa agcctagcga gggacctggc acaaagtatc tgaagagcaa cagccggagc 1500
cagcagaata ggcactcctt catggagtcc tctcagtcta aggccggcac cctgcagcca 1560
aacgagaagc agagcaggca ctcctacatc gacaccatcc cacagagcag ccggagcccc 1620
tcctatcgga caaaggccaa gtctcacggc gccctgtctg atagcaagtc cgtgtctcag 1680
ctgagcgagg ccagagccca gatcgcagag cccagcacct ccaggtactt tccttctagc 1740
tgtctggatc tgaactctcc tacaagccca acacccacca gacacagcga cacaaggacc 1800
ctgctgtctc caagcggcag aaataacagg aacgagggca ccctggacag ccggcggacc 1860
acaaccaggc acagcaagac aatggaggag ctgaagctgc cagagcacat ggattcctct 1920
cactcccact ctctgagcgc cccccacgag tccttctctt acggcctggg ctatacctcc 1980
cccttcagca gccagcagcg cccccaccgg cactctatgt acgtgacaag agataaggtg 2040
agggcaaagg gcctggacgg cagcctgtcc atcggacagg gaatggcagc ccgggccaac 2100
tccctgcagc tgctgtctcc tcagccagga gagcagctgc caccagagat gaccgtggca 2160
cggagcagcg tgaaggagac aagcagggag ggcacctcct ctttccacac aagacagaag 2220
tccgagggcg gcgtgtatca cgatccccac tctgacgatg gcacagcccc taaggagaac 2280
aggcacctgt acaatgaccc cgtgcctagg agggtgggct ccttctatcg cgtgccatct 2340
ccccggcctg ataatagctt tcacgagaat aacgtgagca cccgggtgag cagcctgcca 2400
tctgagtcta gctccggcac aaaccactct aagaggcagc ccgcctttga cccttggaag 2460
agcccagaga atatctctca cagcgagcag ctgaaggaga aggagaagca gggcttcttt 2520
cgcagcatga agaagaagaa gaagaagagc cagaccgtgc ctaactccga ttctccagac 2580
ctgctgaccc tgcagaagtc catccacagc gcctccacac cctctagcag acctaaggag 2640
tggaggcctg agaagatcag cgacctgcag acccagagcc agccactgaa gtccctgcgg 2700
aagctgctgc acctgtcctc tgccagcaac cacccagcca gctccgatcc aaggttccag 2760
cccctgacag cccagcagac caagaacagc ttcagcgaga tcagaatcca ccctctgtcc 2820
caggcctctg gaggctctag caacatcagg caggagccag caccaaaggg ccggcccgcc 2880
ctgcagctgc ctggccagat ggacccaggc tggcacgtgt cctctgtgac aagatccgcc 2940
accgagggcc catcctactc tgagcagctg ggagcaaaga gcggacctaa tggacaccca 3000
tatcagagga cccagagatc caggatgccc aatctgaacg atctgaagga gacagccctg 3060
ggaggaggag gcagcgagaa cctgtacttc cagggcgatt ataaggacca cgatggcgac 3120
tacaaggacc acgacattga ctacaaggac gacgacgata aagacggagc accccatcac 3180
caccaccatc attga 3195
<210> 135
<211> 2877
<212> DNA
<213> 人工序列
<220>
<223> CDKL5_107 [1-4,6-7NQ]的DNA序列 (人优化)
<400> 135
aagatcccca atatcggcaa cgtgatgaat aagttcgaga tcctgggagt ggtgggagag 60
ggagcctacg gcgtggtgct gaagtgcaga cacaaggaga cacacgagat cgtggccatc 120
aagaagttta aggacagcga ggagaatgag gaggtgaagg agacaaccct gcgcgagctg 180
aagatgctgc ggacactgaa gcaggagaac atcgtggagc tgaaggaggc cttccggaga 240
aggggcaagc tgtacctggt gtttgagtat gtggagaaga acatgctgga gctgctggag 300
gagatgccta atggcgtgcc ccctgagaag gtgaagtcct acatctatca gctgatcaag 360
gccatccact ggtgccacaa gaacgatatc gtgcaccgcg acatcaagcc cgagaacctg 420
ctgatctccc acaatgacgt gctgaagctg tgcgacttcg gctttgcccg gcagctgagc 480
gagggcaaca atgcccagta cacagagtat gtggccaccc gctggtacag aagccccgag 540
ctgctgctgg gcgcccccta tggcaagagc gtggatatgt ggtccgtggg ctgcatcctg 600
ggcgagctgt ctgatggcca gcctctgttc ccaggcgaga gcgagatcga ccagctgttt 660
accatccaga aggtgctggg ccctctgcca agcgagcaga tgaagctgtt ctactccaac 720
ccaaggttcc acggcctgag gtttccagcc gtgaatcacc ctcagagcct ggagcgccgg 780
tatctgggca tcctgaactc cgtgctgctg gacctgatga agaacctgct gaagctggac 840
cccgccgaca gatacctgac cgagcagtgt ctgaatcacc ctacatttca gacccagaga 900
ctgctggata ggagcccttc ccgctctgcc aagcggaagc catatcacgt ggagagcagc 960
accctgtcca atcgcaacca ggccggcaag tctacagccc tgcagagcca ccaccggagc 1020
aactccaagg atatccagca gctgtccgtg ggcctgccta gggccgacga gggcctgcca 1080
gcaaacgaga gcttcctgaa tggaaacctg gcaggagcct ctctgagccc actgcacaca 1140
aagacctacc aggcctctag ccagcccggc tccacatcta aggacctgac caacaataac 1200
atcccacacc tgctgtctcc caaggaggcc aagagcaaga ccgagttcga cttcaacatc 1260
gacccaaagc ctagcgaggg acctggcaca aagtatctga agagcaacag ccggagccag 1320
cagaataggc actccttcat ggagtcctct cagtctaagg ccggcaccct gcagccaaac 1380
gagaagcaga gcaggcactc ctacatcgac accatcccac agagcagccg gagcccctcc 1440
tatcggacaa aggccaagtc tcacggcgcc ctgtctgata gcaagtccgt gtctcagctg 1500
agcgaggcca gagcccagat cgcagagccc agcacctcca ggtactttcc ttctagctgt 1560
ctggatctga actctcctac aagcccaaca cccaccagac acagcgacac aaggaccctg 1620
ctgtctccaa gcggcagaaa taacaggaac gagggcaccc tggacagccg gcggaccaca 1680
accaggcaca gcaagacaat ggaggagctg aagctgccag agcacatgga ttcctctcac 1740
tcccactctc tgagcgcccc ccacgagtcc ttctcttacg gcctgggcta tacctccccc 1800
ttcagcagcc agcagcgccc ccaccggcac tctatgtacg tgacaagaga taaggtgagg 1860
gcaaagggcc tggacggcag cctgtccatc ggacagggaa tggcagcccg ggccaactcc 1920
ctgcagctgc tgtctcctca gccaggagag cagctgccac cagagatgac cgtggcacgg 1980
agcagcgtga aggagacaag cagggagggc acctcctctt tccacacaag acagaagtcc 2040
gagggcggcg tgtatcacga tccccactct gacgatggca cagcccctaa ggagaacagg 2100
cacctgtaca atgaccccgt gcctaggagg gtgggctcct tctatcgcgt gccatctccc 2160
cggcctgata atagctttca cgagaataac gtgagcaccc gggtgagcag cctgccatct 2220
gagtctagct ccggcacaaa ccactctaag aggcagcccg cctttgaccc ttggaagagc 2280
ccagagaata tctctcacag cgagcagctg aaggagaagg agaagcaggg cttctttcgc 2340
agcatgaaga agaagaagaa gaagagccag accgtgccta actccgattc tccagacctg 2400
ctgaccctgc agaagtccat ccacagcgcc tccacaccct ctagcagacc taaggagtgg 2460
aggcctgaga agatcagcga cctgcagacc cagagccagc cactgaagtc cctgcggaag 2520
ctgctgcacc tgtcctctgc cagcaaccac ccagccagct ccgatccaag gttccagccc 2580
ctgacagccc agcagaccaa gaacagcttc agcgagatca gaatccaccc tctgtcccag 2640
gcctctggag gctctagcaa catcaggcag gagccagcac caaagggccg gcccgccctg 2700
cagctgcctg gccagatgga cccaggctgg cacgtgtcct ctgtgacaag atccgccacc 2760
gagggcccat cctactctga gcagctggga gcaaagagcg gacctaatgg acacccatat 2820
cagaggaccc agagatccag gatgcccaat ctgaacgatc tgaaggagac agccctg 2877
<210> 136
<211> 3195
<212> DNA
<213> 人工序列
<220>
<223> MBIP-TATκ28-CDKL5_107-FH [1-5,7NQ]的DNA序列 (人
优化)
<400> 136
atgaagctgt ccctggtggc cgctatgctg ctgctgctgt ctctggtcgc tgccatgtta 60
ttactgctgt ctgccgctag ggccggggac gcagcacagc ccgcaagaag agcaagaaga 120
actaaactgg ccgcttacgc aaggaaggca gcaagacagg caagagcagg cggcggcggc 180
tccaagatcc ccaatatcgg caacgtgatg aataagttcg agatcctggg agtggtggga 240
gagggagcct acggcgtggt gctgaagtgc agacacaagg agacacacga gatcgtggcc 300
atcaagaagt ttaaggacag cgaggagaat gaggaggtga aggagacaac cctgcgcgag 360
ctgaagatgc tgcggacact gaagcaggag aacatcgtgg agctgaagga ggccttccgg 420
agaaggggca agctgtacct ggtgtttgag tatgtggaga agaacatgct ggagctgctg 480
gaggagatgc ctaatggcgt gccccctgag aaggtgaagt cctacatcta tcagctgatc 540
aaggccatcc actggtgcca caagaacgat atcgtgcacc gcgacatcaa gcccgagaac 600
ctgctgatct cccacaatga cgtgctgaag ctgtgcgact tcggctttgc ccggcagctg 660
agcgagggca acaatgccca gtacacagag tatgtggcca cccgctggta cagaagcccc 720
gagctgctgc tgggcgcccc ctatggcaag agcgtggata tgtggtccgt gggctgcatc 780
ctgggcgagc tgtctgatgg ccagcctctg ttcccaggcg agagcgagat cgaccagctg 840
tttaccatcc agaaggtgct gggccctctg ccaagcgagc agatgaagct gttctactcc 900
aacccaaggt tccacggcct gaggtttcca gccgtgaatc accctcagag cctggagcgc 960
cggtatctgg gcatcctgaa ctccgtgctg ctggacctga tgaagaacct gctgaagctg 1020
gaccccgccg acagatacct gaccgagcag tgtctgaatc accctacatt tcagacccag 1080
agactgctgg ataggagccc ttcccgctct gccaagcgga agccatatca cgtggagagc 1140
agcaccctgt ccaatcgcaa ccaggccggc aagtctacag ccctgcagag ccaccaccgg 1200
agcaactcca aggatatcca gcagctgtcc gtgggcctgc ctagggccga cgagggcctg 1260
ccagcaaacg agagcttcct gaatggaaac ctggcaggag cctctctgag cccactgcac 1320
acaaagacct accaggcctc tagccagccc ggctccacat ctaaggacct gaccaacaat 1380
aacatcccac acctgctgtc tcccaaggag gccaagagca agaccgagtt cgacttcaac 1440
atcgacccaa agcctagcga gggacctggc acaaagtatc tgaagagcaa cagccggagc 1500
cagcagaata ggcactcctt catggagtcc tctcagtcta aggccggcac cctgcagcca 1560
aacgagaagc agagcaggca ctcctacatc gacaccatcc cacagagcag ccggagcccc 1620
tcctatcgga caaaggccaa gtctcacggc gccctgtctg atagcaagtc cgtgtctcag 1680
ctgagcgagg ccagagccca gatcgcagag cccagcacct ccaggtactt tccttctagc 1740
tgtctggatc tgaactctcc tacaagccca acacccacca gacacagcga cacaaggacc 1800
ctgctgtctc caagcggcag aaataacagg aacgagggca ccctggacag ccggcggacc 1860
acaaccaggc acagcaagac aatggaggag ctgaagctgc cagagcacat ggattcctct 1920
cactcccact ctctgagcgc cccccacgag tccttctctt acggcctggg ctatacctcc 1980
cccttcagca gccagcagcg cccccaccgg cactctatgt acgtgacaag agataaggtg 2040
agggcaaagg gcctggacgg cagcctgtcc atcggacagg gaatggcagc ccgggccaac 2100
tccctgcagc tgctgtctcc tcagccagga gagcagctgc caccagagat gaccgtggca 2160
cggagcagcg tgaaggagac aagcagggag ggcacctcct ctttccacac aagacagaag 2220
tccgagggcg gcgtgtatca cgatccccac tctgacgatg gcacagcccc taaggagaac 2280
aggcacctgt acaatgaccc cgtgcctagg agggtgggct ccttctatcg cgtgccatct 2340
ccccggcctg ataatagctt tcacgagaat aacgtgagca cccgggtgag cagcctgcca 2400
tctgagtcta gctccggcac aaaccactct aagaggcagc ccgcctttga cccttggaag 2460
agcccagagc agatctctca cagcgagcag ctgaaggaga aggagaagca gggcttcttt 2520
cgcagcatga agaagaagaa gaagaagagc cagaccgtgc ctaactccga ttctccagac 2580
ctgctgaccc tgcagaagtc catccacagc gcctccacac cctctagcag acctaaggag 2640
tggaggcctg agaagatcag cgacctgcag acccagagcc agccactgaa gtccctgcgg 2700
aagctgctgc acctgtcctc tgccagcaac cacccagcca gctccgatcc aaggttccag 2760
cccctgacag cccagcagac caagaacagc ttcagcgaga tcagaatcca ccctctgtcc 2820
caggcctctg gaggctctag caacatcagg caggagccag caccaaaggg ccggcccgcc 2880
ctgcagctgc ctggccagat ggacccaggc tggcacgtgt cctctgtgac aagatccgcc 2940
accgagggcc catcctactc tgagcagctg ggagcaaaga gcggacctaa tggacaccca 3000
tataacagga cccagagatc caggatgccc aatctgaacg atctgaagga gacagccctg 3060
ggaggaggag gcagcgagaa cctgtacttc cagggcgatt ataaggacca cgatggcgac 3120
tacaaggacc acgacattga ctacaaggac gacgacgata aagacggagc accccatcac 3180
caccaccatc attga 3195
<210> 137
<211> 2877
<212> DNA
<213> 人工序列
<220>
<223> CDKL5_107 [1-5,7NQ]的DNA序列 (人优化)
<400> 137
aagatcccca atatcggcaa cgtgatgaat aagttcgaga tcctgggagt ggtgggagag 60
ggagcctacg gcgtggtgct gaagtgcaga cacaaggaga cacacgagat cgtggccatc 120
aagaagttta aggacagcga ggagaatgag gaggtgaagg agacaaccct gcgcgagctg 180
aagatgctgc ggacactgaa gcaggagaac atcgtggagc tgaaggaggc cttccggaga 240
aggggcaagc tgtacctggt gtttgagtat gtggagaaga acatgctgga gctgctggag 300
gagatgccta atggcgtgcc ccctgagaag gtgaagtcct acatctatca gctgatcaag 360
gccatccact ggtgccacaa gaacgatatc gtgcaccgcg acatcaagcc cgagaacctg 420
ctgatctccc acaatgacgt gctgaagctg tgcgacttcg gctttgcccg gcagctgagc 480
gagggcaaca atgcccagta cacagagtat gtggccaccc gctggtacag aagccccgag 540
ctgctgctgg gcgcccccta tggcaagagc gtggatatgt ggtccgtggg ctgcatcctg 600
ggcgagctgt ctgatggcca gcctctgttc ccaggcgaga gcgagatcga ccagctgttt 660
accatccaga aggtgctggg ccctctgcca agcgagcaga tgaagctgtt ctactccaac 720
ccaaggttcc acggcctgag gtttccagcc gtgaatcacc ctcagagcct ggagcgccgg 780
tatctgggca tcctgaactc cgtgctgctg gacctgatga agaacctgct gaagctggac 840
cccgccgaca gatacctgac cgagcagtgt ctgaatcacc ctacatttca gacccagaga 900
ctgctggata ggagcccttc ccgctctgcc aagcggaagc catatcacgt ggagagcagc 960
accctgtcca atcgcaacca ggccggcaag tctacagccc tgcagagcca ccaccggagc 1020
aactccaagg atatccagca gctgtccgtg ggcctgccta gggccgacga gggcctgcca 1080
gcaaacgaga gcttcctgaa tggaaacctg gcaggagcct ctctgagccc actgcacaca 1140
aagacctacc aggcctctag ccagcccggc tccacatcta aggacctgac caacaataac 1200
atcccacacc tgctgtctcc caaggaggcc aagagcaaga ccgagttcga cttcaacatc 1260
gacccaaagc ctagcgaggg acctggcaca aagtatctga agagcaacag ccggagccag 1320
cagaataggc actccttcat ggagtcctct cagtctaagg ccggcaccct gcagccaaac 1380
gagaagcaga gcaggcactc ctacatcgac accatcccac agagcagccg gagcccctcc 1440
tatcggacaa aggccaagtc tcacggcgcc ctgtctgata gcaagtccgt gtctcagctg 1500
agcgaggcca gagcccagat cgcagagccc agcacctcca ggtactttcc ttctagctgt 1560
ctggatctga actctcctac aagcccaaca cccaccagac acagcgacac aaggaccctg 1620
ctgtctccaa gcggcagaaa taacaggaac gagggcaccc tggacagccg gcggaccaca 1680
accaggcaca gcaagacaat ggaggagctg aagctgccag agcacatgga ttcctctcac 1740
tcccactctc tgagcgcccc ccacgagtcc ttctcttacg gcctgggcta tacctccccc 1800
ttcagcagcc agcagcgccc ccaccggcac tctatgtacg tgacaagaga taaggtgagg 1860
gcaaagggcc tggacggcag cctgtccatc ggacagggaa tggcagcccg ggccaactcc 1920
ctgcagctgc tgtctcctca gccaggagag cagctgccac cagagatgac cgtggcacgg 1980
agcagcgtga aggagacaag cagggagggc acctcctctt tccacacaag acagaagtcc 2040
gagggcggcg tgtatcacga tccccactct gacgatggca cagcccctaa ggagaacagg 2100
cacctgtaca atgaccccgt gcctaggagg gtgggctcct tctatcgcgt gccatctccc 2160
cggcctgata atagctttca cgagaataac gtgagcaccc gggtgagcag cctgccatct 2220
gagtctagct ccggcacaaa ccactctaag aggcagcccg cctttgaccc ttggaagagc 2280
ccagagcaga tctctcacag cgagcagctg aaggagaagg agaagcaggg cttctttcgc 2340
agcatgaaga agaagaagaa gaagagccag accgtgccta actccgattc tccagacctg 2400
ctgaccctgc agaagtccat ccacagcgcc tccacaccct ctagcagacc taaggagtgg 2460
aggcctgaga agatcagcga cctgcagacc cagagccagc cactgaagtc cctgcggaag 2520
ctgctgcacc tgtcctctgc cagcaaccac ccagccagct ccgatccaag gttccagccc 2580
ctgacagccc agcagaccaa gaacagcttc agcgagatca gaatccaccc tctgtcccag 2640
gcctctggag gctctagcaa catcaggcag gagccagcac caaagggccg gcccgccctg 2700
cagctgcctg gccagatgga cccaggctgg cacgtgtcct ctgtgacaag atccgccacc 2760
gagggcccat cctactctga gcagctggga gcaaagagcg gacctaatgg acacccatat 2820
aacaggaccc agagatccag gatgcccaat ctgaacgatc tgaaggagac agccctg 2877
<210> 138
<211> 3195
<212> DNA
<213> 人工序列
<220>
<223> MBIP-TATκ28-CDKL5_107-FH [1-6NQ]的DNA序列 (人
优化)
<400> 138
atgaagctgt ccctggtggc cgctatgctg ctgctgctgt ctctggtcgc tgccatgtta 60
ttactgctgt ctgccgctag ggccggggac gcagcacagc ccgcaagaag agcaagaaga 120
actaaactgg ccgcttacgc aaggaaggca gcaagacagg caagagcagg cggcggcggc 180
tccaagatcc ccaatatcgg caacgtgatg aataagttcg agatcctggg agtggtggga 240
gagggagcct acggcgtggt gctgaagtgc agacacaagg agacacacga gatcgtggcc 300
atcaagaagt ttaaggacag cgaggagaat gaggaggtga aggagacaac cctgcgcgag 360
ctgaagatgc tgcggacact gaagcaggag aacatcgtgg agctgaagga ggccttccgg 420
agaaggggca agctgtacct ggtgtttgag tatgtggaga agaacatgct ggagctgctg 480
gaggagatgc ctaatggcgt gccccctgag aaggtgaagt cctacatcta tcagctgatc 540
aaggccatcc actggtgcca caagaacgat atcgtgcacc gcgacatcaa gcccgagaac 600
ctgctgatct cccacaatga cgtgctgaag ctgtgcgact tcggctttgc ccggcagctg 660
agcgagggca acaatgccca gtacacagag tatgtggcca cccgctggta cagaagcccc 720
gagctgctgc tgggcgcccc ctatggcaag agcgtggata tgtggtccgt gggctgcatc 780
ctgggcgagc tgtctgatgg ccagcctctg ttcccaggcg agagcgagat cgaccagctg 840
tttaccatcc agaaggtgct gggccctctg ccaagcgagc agatgaagct gttctactcc 900
aacccaaggt tccacggcct gaggtttcca gccgtgaatc accctcagag cctggagcgc 960
cggtatctgg gcatcctgaa ctccgtgctg ctggacctga tgaagaacct gctgaagctg 1020
gaccccgccg acagatacct gaccgagcag tgtctgaatc accctacatt tcagacccag 1080
agactgctgg ataggagccc ttcccgctct gccaagcgga agccatatca cgtggagagc 1140
agcaccctgt ccaatcgcaa ccaggccggc aagtctacag ccctgcagag ccaccaccgg 1200
agcaactcca aggatatcca gcagctgtcc gtgggcctgc ctagggccga cgagggcctg 1260
ccagcaaacg agagcttcct gaatggaaac ctggcaggag cctctctgag cccactgcac 1320
acaaagacct accaggcctc tagccagccc ggctccacat ctaaggacct gaccaacaat 1380
aacatcccac acctgctgtc tcccaaggag gccaagagca agaccgagtt cgacttcaac 1440
atcgacccaa agcctagcga gggacctggc acaaagtatc tgaagagcaa cagccggagc 1500
cagcagaata ggcactcctt catggagtcc tctcagtcta aggccggcac cctgcagcca 1560
aacgagaagc agagcaggca ctcctacatc gacaccatcc cacagagcag ccggagcccc 1620
tcctatcgga caaaggccaa gtctcacggc gccctgtctg atagcaagtc cgtgtctcag 1680
ctgagcgagg ccagagccca gatcgcagag cccagcacct ccaggtactt tccttctagc 1740
tgtctggatc tgaactctcc tacaagccca acacccacca gacacagcga cacaaggacc 1800
ctgctgtctc caagcggcag aaataacagg aacgagggca ccctggacag ccggcggacc 1860
acaaccaggc acagcaagac aatggaggag ctgaagctgc cagagcacat ggattcctct 1920
cactcccact ctctgagcgc cccccacgag tccttctctt acggcctggg ctatacctcc 1980
cccttcagca gccagcagcg cccccaccgg cactctatgt acgtgacaag agataaggtg 2040
agggcaaagg gcctggacgg cagcctgtcc atcggacagg gaatggcagc ccgggccaac 2100
tccctgcagc tgctgtctcc tcagccagga gagcagctgc caccagagat gaccgtggca 2160
cggagcagcg tgaaggagac aagcagggag ggcacctcct ctttccacac aagacagaag 2220
tccgagggcg gcgtgtatca cgatccccac tctgacgatg gcacagcccc taaggagaac 2280
aggcacctgt acaatgaccc cgtgcctagg agggtgggct ccttctatcg cgtgccatct 2340
ccccggcctg ataatagctt tcacgagaat aacgtgagca cccgggtgag cagcctgcca 2400
tctgagtcta gctccggcac aaaccactct aagaggcagc ccgcctttga cccttggaag 2460
agcccagagc agatctctca cagcgagcag ctgaaggaga aggagaagca gggcttcttt 2520
cgcagcatga agaagaagaa gaagaagagc cagaccgtgc ctaactccga ttctccagac 2580
ctgctgaccc tgcagaagtc catccacagc gcctccacac cctctagcag acctaaggag 2640
tggaggcctg agaagatcag cgacctgcag acccagagcc agccactgaa gtccctgcgg 2700
aagctgctgc acctgtcctc tgccagcaac cacccagcca gctccgatcc aaggttccag 2760
cccctgacag cccagcagac caagaacagc ttcagcgaga tcagaatcca ccctctgtcc 2820
caggcctctg gaggctctag caacatcagg caggagccag caccaaaggg ccggcccgcc 2880
ctgcagctgc ctggccagat ggacccaggc tggcacgtgt cctctgtgac aagatccgcc 2940
accgagggcc catcctactc tgagcagctg ggagcaaaga gcggacctaa tggacaccca 3000
tatcagagga ccaatagatc caggatgccc aatctgaacg atctgaagga gacagccctg 3060
ggaggaggag gcagcgagaa cctgtacttc cagggcgatt ataaggacca cgatggcgac 3120
tacaaggacc acgacattga ctacaaggac gacgacgata aagacggagc accccatcac 3180
caccaccatc attga 3195
<210> 139
<211> 2877
<212> DNA
<213> 人工序列
<220>
<223> CDKL5_107 [1-6NQ]的DNA序列 (人优化)
<400> 139
aagatcccca atatcggcaa cgtgatgaat aagttcgaga tcctgggagt ggtgggagag 60
ggagcctacg gcgtggtgct gaagtgcaga cacaaggaga cacacgagat cgtggccatc 120
aagaagttta aggacagcga ggagaatgag gaggtgaagg agacaaccct gcgcgagctg 180
aagatgctgc ggacactgaa gcaggagaac atcgtggagc tgaaggaggc cttccggaga 240
aggggcaagc tgtacctggt gtttgagtat gtggagaaga acatgctgga gctgctggag 300
gagatgccta atggcgtgcc ccctgagaag gtgaagtcct acatctatca gctgatcaag 360
gccatccact ggtgccacaa gaacgatatc gtgcaccgcg acatcaagcc cgagaacctg 420
ctgatctccc acaatgacgt gctgaagctg tgcgacttcg gctttgcccg gcagctgagc 480
gagggcaaca atgcccagta cacagagtat gtggccaccc gctggtacag aagccccgag 540
ctgctgctgg gcgcccccta tggcaagagc gtggatatgt ggtccgtggg ctgcatcctg 600
ggcgagctgt ctgatggcca gcctctgttc ccaggcgaga gcgagatcga ccagctgttt 660
accatccaga aggtgctggg ccctctgcca agcgagcaga tgaagctgtt ctactccaac 720
ccaaggttcc acggcctgag gtttccagcc gtgaatcacc ctcagagcct ggagcgccgg 780
tatctgggca tcctgaactc cgtgctgctg gacctgatga agaacctgct gaagctggac 840
cccgccgaca gatacctgac cgagcagtgt ctgaatcacc ctacatttca gacccagaga 900
ctgctggata ggagcccttc ccgctctgcc aagcggaagc catatcacgt ggagagcagc 960
accctgtcca atcgcaacca ggccggcaag tctacagccc tgcagagcca ccaccggagc 1020
aactccaagg atatccagca gctgtccgtg ggcctgccta gggccgacga gggcctgcca 1080
gcaaacgaga gcttcctgaa tggaaacctg gcaggagcct ctctgagccc actgcacaca 1140
aagacctacc aggcctctag ccagcccggc tccacatcta aggacctgac caacaataac 1200
atcccacacc tgctgtctcc caaggaggcc aagagcaaga ccgagttcga cttcaacatc 1260
gacccaaagc ctagcgaggg acctggcaca aagtatctga agagcaacag ccggagccag 1320
cagaataggc actccttcat ggagtcctct cagtctaagg ccggcaccct gcagccaaac 1380
gagaagcaga gcaggcactc ctacatcgac accatcccac agagcagccg gagcccctcc 1440
tatcggacaa aggccaagtc tcacggcgcc ctgtctgata gcaagtccgt gtctcagctg 1500
agcgaggcca gagcccagat cgcagagccc agcacctcca ggtactttcc ttctagctgt 1560
ctggatctga actctcctac aagcccaaca cccaccagac acagcgacac aaggaccctg 1620
ctgtctccaa gcggcagaaa taacaggaac gagggcaccc tggacagccg gcggaccaca 1680
accaggcaca gcaagacaat ggaggagctg aagctgccag agcacatgga ttcctctcac 1740
tcccactctc tgagcgcccc ccacgagtcc ttctcttacg gcctgggcta tacctccccc 1800
ttcagcagcc agcagcgccc ccaccggcac tctatgtacg tgacaagaga taaggtgagg 1860
gcaaagggcc tggacggcag cctgtccatc ggacagggaa tggcagcccg ggccaactcc 1920
ctgcagctgc tgtctcctca gccaggagag cagctgccac cagagatgac cgtggcacgg 1980
agcagcgtga aggagacaag cagggagggc acctcctctt tccacacaag acagaagtcc 2040
gagggcggcg tgtatcacga tccccactct gacgatggca cagcccctaa ggagaacagg 2100
cacctgtaca atgaccccgt gcctaggagg gtgggctcct tctatcgcgt gccatctccc 2160
cggcctgata atagctttca cgagaataac gtgagcaccc gggtgagcag cctgccatct 2220
gagtctagct ccggcacaaa ccactctaag aggcagcccg cctttgaccc ttggaagagc 2280
ccagagcaga tctctcacag cgagcagctg aaggagaagg agaagcaggg cttctttcgc 2340
agcatgaaga agaagaagaa gaagagccag accgtgccta actccgattc tccagacctg 2400
ctgaccctgc agaagtccat ccacagcgcc tccacaccct ctagcagacc taaggagtgg 2460
aggcctgaga agatcagcga cctgcagacc cagagccagc cactgaagtc cctgcggaag 2520
ctgctgcacc tgtcctctgc cagcaaccac ccagccagct ccgatccaag gttccagccc 2580
ctgacagccc agcagaccaa gaacagcttc agcgagatca gaatccaccc tctgtcccag 2640
gcctctggag gctctagcaa catcaggcag gagccagcac caaagggccg gcccgccctg 2700
cagctgcctg gccagatgga cccaggctgg cacgtgtcct ctgtgacaag atccgccacc 2760
gagggcccat cctactctga gcagctggga gcaaagagcg gacctaatgg acacccatat 2820
cagaggacca atagatccag gatgcccaat ctgaacgatc tgaaggagac agccctg 2877
<210> 140
<211> 3195
<212> DNA
<213> 人工序列
<220>
<223> MBIP-TATκ28-CDKL5_107-FH [2NQ]的DNA序列 (人
优化)
<400> 140
atgaagctgt ccctggtggc cgctatgctg ctgctgctgt ctctggtcgc tgccatgtta 60
ttactgctgt ctgccgctag ggccggggac gcagcacagc ccgcaagaag agcaagaaga 120
actaaactgg ccgcttacgc aaggaaggca gcaagacagg caagagcagg cggcggcggc 180
tccaagatcc ccaatatcgg caacgtgatg aataagttcg agatcctggg agtggtggga 240
gagggagcct acggcgtggt gctgaagtgc agacacaagg agacacacga gatcgtggcc 300
atcaagaagt ttaaggacag cgaggagaat gaggaggtga aggagacaac cctgcgcgag 360
ctgaagatgc tgcggacact gaagcaggag aacatcgtgg agctgaagga ggccttccgg 420
agaaggggca agctgtacct ggtgtttgag tatgtggaga agaacatgct ggagctgctg 480
gaggagatgc ctaatggcgt gccccctgag aaggtgaagt cctacatcta tcagctgatc 540
aaggccatcc actggtgcca caagaacgat atcgtgcacc gcgacatcaa gcccgagaac 600
ctgctgatct cccacaatga cgtgctgaag ctgtgcgact tcggctttgc ccggaacctg 660
agcgagggca acaatgccca ttacacagag tatgtggcca cccgctggta cagaagcccc 720
gagctgctgc tgggcgcccc ctatggcaag agcgtggata tgtggtccgt gggctgcatc 780
ctgggcgagc tgtctgatgg ccagcctctg ttcccaggcg agagcgagat cgaccagctg 840
tttaccatcc agaaggtgct gggccctctg ccaagcgagc agatgaagct gttctactcc 900
aacccaaggt tccacggcct gaggtttcca gccgtgaatc accctcagag cctggagcgc 960
cggtatctgg gcatcctgaa ctccgtgctg ctggacctga tgaagaacct gctgaagctg 1020
gaccccgccg acagatacct gaccgagcag tgtctgaatc accctacatt tcagacccag 1080
agactgctgg ataggagccc ttcccgctct gccaagcgga agccatatca cgtggagagc 1140
agcaccctgt ccaatcgcaa ccaggccggc aagtctacag ccctgcagag ccaccaccgg 1200
agcaactcca aggatatcca gaatctgtcc gtgggcctgc ctagggccga cgagggcctg 1260
ccagcaaacg agagcttcct gaatggaaac ctggcaggag cctctctgag cccactgcac 1320
acaaagacct accaggcctc tagccagccc ggctccacat ctaaggacct gaccaacaat 1380
aacatcccac acctgctgtc tcccaaggag gccaagagca agaccgagtt cgacttcaac 1440
atcgacccaa agcctagcga gggacctggc acaaagtatc tgaagagcaa cagccggagc 1500
cagcagaata ggcactcctt catggagtcc tctcagtcta aggccggcac cctgcagcca 1560
aacgagaagc agagcaggca ctcctacatc gacaccatcc cacagagcag ccggagcccc 1620
tcctatcgga caaaggccaa gtctcacggc gccctgtctg atagcaagtc cgtgtctaat 1680
ctgagcgagg ccagagccca gatcgcagag cccagcacct ccaggtactt tccttctagc 1740
tgtctggatc tgaactctcc tacaagccca acacccacca gacacagcga cacaaggacc 1800
ctgctgtctc caagcggcag aaataacagg aacgagggca ccctggacag ccggcggacc 1860
acaaccaggc acagcaagac aatggaggag ctgaagctgc cagagcacat ggattcctct 1920
cactcccact ctctgagcgc cccccacgag tccttctctt acggcctggg ctatacctcc 1980
cccttcagca gccagcagcg cccccaccgg cactctatgt acgtgacaag agataaggtg 2040
agggcaaagg gcctggacgg cagcctgtcc atcggacagg gaatggcagc ccgggccaac 2100
tccctgcagc tgctgtctcc tcagccagga gagcagctgc caccagagat gaccgtggca 2160
cggagcagcg tgaaggagac aagcagggag ggcacctcct ctttccacac aagacagaag 2220
tccgagggcg gcgtgtatca cgatccccac tctgacgatg gcacagcccc taaggagaac 2280
aggcacctgt acaatgaccc cgtgcctagg agggtgggct ccttctatcg cgtgccatct 2340
ccccggcctg ataatagctt tcacgagaat aacgtgagca cccgggtgag cagcctgcca 2400
tctgagtcta gctccggcac aaaccactct aagaggcagc ccgcctttga cccttggaag 2460
agcccagaga atatctctca cagcgagcag ctgaaggaga aggagaagca gggcttcttt 2520
cgcagcatga agaagaagaa gaagaagagc cagaccgtgc ctaactccga ttctccagac 2580
ctgctgaccc tgcagaagtc catccacagc gcctccacac cctctagcag acctaaggag 2640
tggaggcctg agaagatcag cgacctgcag acccagagcc agccactgaa gtccctgcgg 2700
aagctgctgc acctgtcctc tgccagcaac cacccagcca gctccgatcc aaggttccag 2760
cccctgacag cccagcagac caagaacagc ttcagcgaga tcagaatcca ccctctgtcc 2820
caggcctctg gaggctctag caacatcagg caggagccag caccaaaggg ccggcccgcc 2880
ctgcagctgc ctggccagat ggacccaggc tggcacgtgt cctctgtgac aagatccgcc 2940
accgagggcc catcctactc tgagcagctg ggagcaaaga gcggacctaa tggacaccca 3000
tataacagga ccaatagatc caggatgccc aatctgaacg atctgaagga gacagccctg 3060
ggaggaggag gcagcgagaa cctgtacttc cagggcgatt ataaggacca cgatggcgac 3120
tacaaggacc acgacattga ctacaaggac gacgacgata aagacggagc accccatcac 3180
caccaccatc attga 3195
<210> 141
<211> 2877
<212> DNA
<213> 人工序列
<220>
<223> CDKL5_107 [2NQ]的DNA序列 (人优化)
<400> 141
aagatcccca atatcggcaa cgtgatgaat aagttcgaga tcctgggagt ggtgggagag 60
ggagcctacg gcgtggtgct gaagtgcaga cacaaggaga cacacgagat cgtggccatc 120
aagaagttta aggacagcga ggagaatgag gaggtgaagg agacaaccct gcgcgagctg 180
aagatgctgc ggacactgaa gcaggagaac atcgtggagc tgaaggaggc cttccggaga 240
aggggcaagc tgtacctggt gtttgagtat gtggagaaga acatgctgga gctgctggag 300
gagatgccta atggcgtgcc ccctgagaag gtgaagtcct acatctatca gctgatcaag 360
gccatccact ggtgccacaa gaacgatatc gtgcaccgcg acatcaagcc cgagaacctg 420
ctgatctccc acaatgacgt gctgaagctg tgcgacttcg gctttgcccg gaacctgagc 480
gagggcaaca atgcccatta cacagagtat gtggccaccc gctggtacag aagccccgag 540
ctgctgctgg gcgcccccta tggcaagagc gtggatatgt ggtccgtggg ctgcatcctg 600
ggcgagctgt ctgatggcca gcctctgttc ccaggcgaga gcgagatcga ccagctgttt 660
accatccaga aggtgctggg ccctctgcca agcgagcaga tgaagctgtt ctactccaac 720
ccaaggttcc acggcctgag gtttccagcc gtgaatcacc ctcagagcct ggagcgccgg 780
tatctgggca tcctgaactc cgtgctgctg gacctgatga agaacctgct gaagctggac 840
cccgccgaca gatacctgac cgagcagtgt ctgaatcacc ctacatttca gacccagaga 900
ctgctggata ggagcccttc ccgctctgcc aagcggaagc catatcacgt ggagagcagc 960
accctgtcca atcgcaacca ggccggcaag tctacagccc tgcagagcca ccaccggagc 1020
aactccaagg atatccagaa tctgtccgtg ggcctgccta gggccgacga gggcctgcca 1080
gcaaacgaga gcttcctgaa tggaaacctg gcaggagcct ctctgagccc actgcacaca 1140
aagacctacc aggcctctag ccagcccggc tccacatcta aggacctgac caacaataac 1200
atcccacacc tgctgtctcc caaggaggcc aagagcaaga ccgagttcga cttcaacatc 1260
gacccaaagc ctagcgaggg acctggcaca aagtatctga agagcaacag ccggagccag 1320
cagaataggc actccttcat ggagtcctct cagtctaagg ccggcaccct gcagccaaac 1380
gagaagcaga gcaggcactc ctacatcgac accatcccac agagcagccg gagcccctcc 1440
tatcggacaa aggccaagtc tcacggcgcc ctgtctgata gcaagtccgt gtctaatctg 1500
agcgaggcca gagcccagat cgcagagccc agcacctcca ggtactttcc ttctagctgt 1560
ctggatctga actctcctac aagcccaaca cccaccagac acagcgacac aaggaccctg 1620
ctgtctccaa gcggcagaaa taacaggaac gagggcaccc tggacagccg gcggaccaca 1680
accaggcaca gcaagacaat ggaggagctg aagctgccag agcacatgga ttcctctcac 1740
tcccactctc tgagcgcccc ccacgagtcc ttctcttacg gcctgggcta tacctccccc 1800
ttcagcagcc agcagcgccc ccaccggcac tctatgtacg tgacaagaga taaggtgagg 1860
gcaaagggcc tggacggcag cctgtccatc ggacagggaa tggcagcccg ggccaactcc 1920
ctgcagctgc tgtctcctca gccaggagag cagctgccac cagagatgac cgtggcacgg 1980
agcagcgtga aggagacaag cagggagggc acctcctctt tccacacaag acagaagtcc 2040
gagggcggcg tgtatcacga tccccactct gacgatggca cagcccctaa ggagaacagg 2100
cacctgtaca atgaccccgt gcctaggagg gtgggctcct tctatcgcgt gccatctccc 2160
cggcctgata atagctttca cgagaataac gtgagcaccc gggtgagcag cctgccatct 2220
gagtctagct ccggcacaaa ccactctaag aggcagcccg cctttgaccc ttggaagagc 2280
ccagagaata tctctcacag cgagcagctg aaggagaagg agaagcaggg cttctttcgc 2340
agcatgaaga agaagaagaa gaagagccag accgtgccta actccgattc tccagacctg 2400
ctgaccctgc agaagtccat ccacagcgcc tccacaccct ctagcagacc taaggagtgg 2460
aggcctgaga agatcagcga cctgcagacc cagagccagc cactgaagtc cctgcggaag 2520
ctgctgcacc tgtcctctgc cagcaaccac ccagccagct ccgatccaag gttccagccc 2580
ctgacagccc agcagaccaa gaacagcttc agcgagatca gaatccaccc tctgtcccag 2640
gcctctggag gctctagcaa catcaggcag gagccagcac caaagggccg gcccgccctg 2700
cagctgcctg gccagatgga cccaggctgg cacgtgtcct ctgtgacaag atccgccacc 2760
gagggcccat cctactctga gcagctggga gcaaagagcg gacctaatgg acacccatat 2820
aacaggacca atagatccag gatgcccaat ctgaacgatc tgaaggagac agccctg 2877
<210> 142
<211> 3195
<212> DNA
<213> 人工序列
<220>
<223> MBIP-TATκ28-CDKL5_107-FH [1-10NQ]的DNA序列 (人
优化)
<400> 142
atgaagctgt ccctggtggc cgctatgctg ctgctgctgt ctctggtcgc tgccatgtta 60
ttactgctgt ctgccgctag ggccggggac gcagcacagc ccgcaagaag agcaagaaga 120
actaaactgg ccgcttacgc aaggaaggca gcaagacagg caagagcagg cggcggcggc 180
tccaagatcc ccaatatcgg caacgtgatg aataagttcg agatcctggg agtggtggga 240
gagggagcct acggcgtggt gctgaagtgc agacacaagg agacacacga gatcgtggcc 300
atcaagaagt ttaaggacag cgaggagaat gaggaggtga aggagacaac cctgcgcgag 360
ctgaagatgc tgcggacact gaagcaggag aacatcgtgg agctgaagga ggccttccgg 420
agaaggggca agctgtacct ggtgtttgag tatgtggaga agaacatgct ggagctgctg 480
gaggagatgc ctaatggcgt gccccctgag aaggtgaagt cctacatcta tcagctgatc 540
aaggccatcc actggtgcca caagaacgat atcgtgcacc gcgacatcaa gcccgagaac 600
ctgctgatct cccacaatga cgtgctgaag ctgtgcgact tcggctttgc ccggcagctg 660
agcgagggca acaatgccca gtacacagag tatgtggcca cccgctggta cagaagcccc 720
gagctgctgc tgggcgcccc ctatggcaag agcgtggata tgtggtccgt gggctgcatc 780
ctgggcgagc tgtctgatgg ccagcctctg ttcccaggcg agagcgagat cgaccagctg 840
tttaccatcc agaaggtgct gggccctctg ccaagcgagc agatgaagct gttctactcc 900
aacccaaggt tccacggcct gaggtttcca gccgtgaatc accctcagag cctggagcgc 960
cggtatctgg gcatcctgaa ctccgtgctg ctggacctga tgaagaacct gctgaagctg 1020
gaccccgccg acagatacct gaccgagcag tgtctgaatc accctacatt tcagacccag 1080
agactgctgg ataggagccc ttcccgctct gccaagcgga agccatatca cgtggagagc 1140
agcaccctgt ccaatcgcaa ccaggccggc aagtctacag ccctgcagag ccaccaccgg 1200
agcaactcca aggatatcca gcagctgtcc gtgggcctgc ctagggccga cgagggcctg 1260
ccagcacagg agagcttcct gaatggaaac ctggcaggag cctctctgag cccactgcac 1320
acaaagacct accaggcctc tagccagccc ggctccacat ctaaggacct gaccaacaat 1380
aacatcccac acctgctgtc tcccaaggag gccaagagca agaccgagtt cgacttcaac 1440
atcgacccaa agcctagcga gggacctggc acaaagtatc tgaagagcaa cagccggagc 1500
cagcagaata ggcactcctt catggagtcc tctcagtcta aggccggcac cctgcagcca 1560
aacgagaagc agagcaggca ctcctacatc gacaccatcc cacagagcag ccggagcccc 1620
tcctatcgga caaaggccaa gtctcacggc gccctgtctg atagcaagtc cgtgtctcag 1680
ctgagcgagg ccagagccca gatcgcagag cccagcacct ccaggtactt tccttctagc 1740
tgtctggatc tgaactctcc tacaagccca acacccacca gacacagcga cacaaggacc 1800
ctgctgtctc caagcggcag aaataacagg aacgagggca ccctggacag ccggcggacc 1860
acaaccaggc acagcaagac aatggaggag ctgaagctgc cagagcacat ggattcctct 1920
cactcccact ctctgagcgc cccccacgag tccttctctt acggcctggg ctatacctcc 1980
cccttcagca gccagcagcg cccccaccgg cactctatgt acgtgacaag agataaggtg 2040
agggcaaagg gcctggacgg cagcctgtcc atcggacagg gaatggcagc ccgggccaac 2100
tccctgcagc tgctgtctcc tcagccagga gagcagctgc caccagagat gaccgtggca 2160
cggagcagcg tgaaggagac aagcagggag ggcacctcct ctttccacac aagacagaag 2220
tccgagggcg gcgtgtatca cgatccccac tctgacgatg gcacagcccc taaggagaac 2280
aggcacctgt acaatgaccc cgtgcctagg agggtgggct ccttctatcg cgtgccatct 2340
ccccggcctg ataatagctt tcacgagaat caggtgagca cccgggtgag cagcctgcca 2400
tctgagtcta gctccggcac acagcactct aagaggcagc ccgcctttga cccttggaag 2460
agcccagagc agatctctca cagcgagcag ctgaaggaga aggagaagca gggcttcttt 2520
cgcagcatga agaagaagaa gaagaagagc cagaccgtgc ctaactccga ttctccagac 2580
ctgctgaccc tgcagaagtc catccacagc gcctccacac cctctagcag acctaaggag 2640
tggaggcctg agaagatcag cgacctgcag acccagagcc agccactgaa gtccctgcgg 2700
aagctgctgc acctgtcctc tgccagcaac cacccagcca gctccgatcc aaggttccag 2760
cccctgacag cccagcagac caagaacagc ttcagcgaga tcagaatcca ccctctgtcc 2820
caggcctctg gaggctctag caacatcagg caggagccag caccaaaggg ccggcccgcc 2880
ctgcagctgc ctggccagat ggacccaggc tggcacgtgt cctctgtgac aagatccgcc 2940
accgagggcc catcctactc tgagcagctg ggagcaaaga gcggacctaa tggacaccca 3000
tatcagagga cccagagatc caggatgccc aatctgaacg atctgaagga gacagccctg 3060
ggaggaggag gcagcgagaa cctgtacttc cagggcgatt ataaggacca cgatggcgac 3120
tacaaggacc acgacattga ctacaaggac gacgacgata aagacggagc accccatcac 3180
caccaccatc attga 3195
<210> 143
<211> 2877
<212> DNA
<213> 人工序列
<220>
<223> CDKL5_107 [1-10NQ]的DNA序列 (人优化)
<400> 143
aagatcccca atatcggcaa cgtgatgaat aagttcgaga tcctgggagt ggtgggagag 60
ggagcctacg gcgtggtgct gaagtgcaga cacaaggaga cacacgagat cgtggccatc 120
aagaagttta aggacagcga ggagaatgag gaggtgaagg agacaaccct gcgcgagctg 180
aagatgctgc ggacactgaa gcaggagaac atcgtggagc tgaaggaggc cttccggaga 240
aggggcaagc tgtacctggt gtttgagtat gtggagaaga acatgctgga gctgctggag 300
gagatgccta atggcgtgcc ccctgagaag gtgaagtcct acatctatca gctgatcaag 360
gccatccact ggtgccacaa gaacgatatc gtgcaccgcg acatcaagcc cgagaacctg 420
ctgatctccc acaatgacgt gctgaagctg tgcgacttcg gctttgcccg gcagctgagc 480
gagggcaaca atgcccagta cacagagtat gtggccaccc gctggtacag aagccccgag 540
ctgctgctgg gcgcccccta tggcaagagc gtggatatgt ggtccgtggg ctgcatcctg 600
ggcgagctgt ctgatggcca gcctctgttc ccaggcgaga gcgagatcga ccagctgttt 660
accatccaga aggtgctggg ccctctgcca agcgagcaga tgaagctgtt ctactccaac 720
ccaaggttcc acggcctgag gtttccagcc gtgaatcacc ctcagagcct ggagcgccgg 780
tatctgggca tcctgaactc cgtgctgctg gacctgatga agaacctgct gaagctggac 840
cccgccgaca gatacctgac cgagcagtgt ctgaatcacc ctacatttca gacccagaga 900
ctgctggata ggagcccttc ccgctctgcc aagcggaagc catatcacgt ggagagcagc 960
accctgtcca atcgcaacca ggccggcaag tctacagccc tgcagagcca ccaccggagc 1020
aactccaagg atatccagca gctgtccgtg ggcctgccta gggccgacga gggcctgcca 1080
gcacaggaga gcttcctgaa tggaaacctg gcaggagcct ctctgagccc actgcacaca 1140
aagacctacc aggcctctag ccagcccggc tccacatcta aggacctgac caacaataac 1200
atcccacacc tgctgtctcc caaggaggcc aagagcaaga ccgagttcga cttcaacatc 1260
gacccaaagc ctagcgaggg acctggcaca aagtatctga agagcaacag ccggagccag 1320
cagaataggc actccttcat ggagtcctct cagtctaagg ccggcaccct gcagccaaac 1380
gagaagcaga gcaggcactc ctacatcgac accatcccac agagcagccg gagcccctcc 1440
tatcggacaa aggccaagtc tcacggcgcc ctgtctgata gcaagtccgt gtctcagctg 1500
agcgaggcca gagcccagat cgcagagccc agcacctcca ggtactttcc ttctagctgt 1560
ctggatctga actctcctac aagcccaaca cccaccagac acagcgacac aaggaccctg 1620
ctgtctccaa gcggcagaaa taacaggaac gagggcaccc tggacagccg gcggaccaca 1680
accaggcaca gcaagacaat ggaggagctg aagctgccag agcacatgga ttcctctcac 1740
tcccactctc tgagcgcccc ccacgagtcc ttctcttacg gcctgggcta tacctccccc 1800
ttcagcagcc agcagcgccc ccaccggcac tctatgtacg tgacaagaga taaggtgagg 1860
gcaaagggcc tggacggcag cctgtccatc ggacagggaa tggcagcccg ggccaactcc 1920
ctgcagctgc tgtctcctca gccaggagag cagctgccac cagagatgac cgtggcacgg 1980
agcagcgtga aggagacaag cagggagggc acctcctctt tccacacaag acagaagtcc 2040
gagggcggcg tgtatcacga tccccactct gacgatggca cagcccctaa ggagaacagg 2100
cacctgtaca atgaccccgt gcctaggagg gtgggctcct tctatcgcgt gccatctccc 2160
cggcctgata atagctttca cgagaatcag gtgagcaccc gggtgagcag cctgccatct 2220
gagtctagct ccggcacaca gcactctaag aggcagcccg cctttgaccc ttggaagagc 2280
ccagagcaga tctctcacag cgagcagctg aaggagaagg agaagcaggg cttctttcgc 2340
agcatgaaga agaagaagaa gaagagccag accgtgccta actccgattc tccagacctg 2400
ctgaccctgc agaagtccat ccacagcgcc tccacaccct ctagcagacc taaggagtgg 2460
aggcctgaga agatcagcga cctgcagacc cagagccagc cactgaagtc cctgcggaag 2520
ctgctgcacc tgtcctctgc cagcaaccac ccagccagct ccgatccaag gttccagccc 2580
ctgacagccc agcagaccaa gaacagcttc agcgagatca gaatccaccc tctgtcccag 2640
gcctctggag gctctagcaa catcaggcag gagccagcac caaagggccg gcccgccctg 2700
cagctgcctg gccagatgga cccaggctgg cacgtgtcct ctgtgacaag atccgccacc 2760
gagggcccat cctactctga gcagctggga gcaaagagcg gacctaatgg acacccatat 2820
cagaggaccc agagatccag gatgcccaat ctgaacgatc tgaaggagac agccctg 2877
<210> 144
<211> 3195
<212> DNA
<213> 人工序列
<220>
<223> MBIP-TATκ28-CDKL5_107-FH [1-7,9-10NQ]的DNA序列 (人
优化)
<400> 144
atgaagctgt ccctggtggc cgctatgctg ctgctgctgt ctctggtcgc tgccatgtta 60
ttactgctgt ctgccgctag ggccggggac gcagcacagc ccgcaagaag agcaagaaga 120
actaaactgg ccgcttacgc aaggaaggca gcaagacagg caagagcagg cggcggcggc 180
tccaagatcc ccaatatcgg caacgtgatg aataagttcg agatcctggg agtggtggga 240
gagggagcct acggcgtggt gctgaagtgc agacacaagg agacacacga gatcgtggcc 300
atcaagaagt ttaaggacag cgaggagaat gaggaggtga aggagacaac cctgcgcgag 360
ctgaagatgc tgcggacact gaagcaggag aacatcgtgg agctgaagga ggccttccgg 420
agaaggggca agctgtacct ggtgtttgag tatgtggaga agaacatgct ggagctgctg 480
gaggagatgc ctaatggcgt gccccctgag aaggtgaagt cctacatcta tcagctgatc 540
aaggccatcc actggtgcca caagaacgat atcgtgcacc gcgacatcaa gcccgagaac 600
ctgctgatct cccacaatga cgtgctgaag ctgtgcgact tcggctttgc ccggcagctg 660
agcgagggca acaatgccca gtacacagag tatgtggcca cccgctggta cagaagcccc 720
gagctgctgc tgggcgcccc ctatggcaag agcgtggata tgtggtccgt gggctgcatc 780
ctgggcgagc tgtctgatgg ccagcctctg ttcccaggcg agagcgagat cgaccagctg 840
tttaccatcc agaaggtgct gggccctctg ccaagcgagc agatgaagct gttctactcc 900
aacccaaggt tccacggcct gaggtttcca gccgtgaatc accctcagag cctggagcgc 960
cggtatctgg gcatcctgaa ctccgtgctg ctggacctga tgaagaacct gctgaagctg 1020
gaccccgccg acagatacct gaccgagcag tgtctgaatc accctacatt tcagacccag 1080
agactgctgg ataggagccc ttcccgctct gccaagcgga agccatatca cgtggagagc 1140
agcaccctgt ccaatcgcaa ccaggccggc aagtctacag ccctgcagag ccaccaccgg 1200
agcaactcca aggatatcca gcagctgtcc gtgggcctgc ctagggccga cgagggcctg 1260
ccagcaaacg agagcttcct gaatggaaac ctggcaggag cctctctgag cccactgcac 1320
acaaagacct accaggcctc tagccagccc ggctccacat ctaaggacct gaccaacaat 1380
aacatcccac acctgctgtc tcccaaggag gccaagagca agaccgagtt cgacttcaac 1440
atcgacccaa agcctagcga gggacctggc acaaagtatc tgaagagcaa cagccggagc 1500
cagcagaata ggcactcctt catggagtcc tctcagtcta aggccggcac cctgcagcca 1560
aacgagaagc agagcaggca ctcctacatc gacaccatcc cacagagcag ccggagcccc 1620
tcctatcgga caaaggccaa gtctcacggc gccctgtctg atagcaagtc cgtgtctcag 1680
ctgagcgagg ccagagccca gatcgcagag cccagcacct ccaggtactt tccttctagc 1740
tgtctggatc tgaactctcc tacaagccca acacccacca gacacagcga cacaaggacc 1800
ctgctgtctc caagcggcag aaataacagg aacgagggca ccctggacag ccggcggacc 1860
acaaccaggc acagcaagac aatggaggag ctgaagctgc cagagcacat ggattcctct 1920
cactcccact ctctgagcgc cccccacgag tccttctctt acggcctggg ctatacctcc 1980
cccttcagca gccagcagcg cccccaccgg cactctatgt acgtgacaag agataaggtg 2040
agggcaaagg gcctggacgg cagcctgtcc atcggacagg gaatggcagc ccgggccaac 2100
tccctgcagc tgctgtctcc tcagccagga gagcagctgc caccagagat gaccgtggca 2160
cggagcagcg tgaaggagac aagcagggag ggcacctcct ctttccacac aagacagaag 2220
tccgagggcg gcgtgtatca cgatccccac tctgacgatg gcacagcccc taaggagaac 2280
aggcacctgt acaatgaccc cgtgcctagg agggtgggct ccttctatcg cgtgccatct 2340
ccccggcctg ataatagctt tcacgagaat caggtgagca cccgggtgag cagcctgcca 2400
tctgagtcta gctccggcac acagcactct aagaggcagc ccgcctttga cccttggaag 2460
agcccagagc agatctctca cagcgagcag ctgaaggaga aggagaagca gggcttcttt 2520
cgcagcatga agaagaagaa gaagaagagc cagaccgtgc ctaactccga ttctccagac 2580
ctgctgaccc tgcagaagtc catccacagc gcctccacac cctctagcag acctaaggag 2640
tggaggcctg agaagatcag cgacctgcag acccagagcc agccactgaa gtccctgcgg 2700
aagctgctgc acctgtcctc tgccagcaac cacccagcca gctccgatcc aaggttccag 2760
cccctgacag cccagcagac caagaacagc ttcagcgaga tcagaatcca ccctctgtcc 2820
caggcctctg gaggctctag caacatcagg caggagccag caccaaaggg ccggcccgcc 2880
ctgcagctgc ctggccagat ggacccaggc tggcacgtgt cctctgtgac aagatccgcc 2940
accgagggcc catcctactc tgagcagctg ggagcaaaga gcggacctaa tggacaccca 3000
tatcagagga cccagagatc caggatgccc aatctgaacg atctgaagga gacagccctg 3060
ggaggaggag gcagcgagaa cctgtacttc cagggcgatt ataaggacca cgatggcgac 3120
tacaaggacc acgacattga ctacaaggac gacgacgata aagacggagc accccatcac 3180
caccaccatc attga 3195
<210> 145
<211> 2877
<212> DNA
<213> 人工序列
<220>
<223> CDKL5_107 [1-7,9-10NQ]的DNA序列 (人优化)
<400> 145
aagatcccca atatcggcaa cgtgatgaat aagttcgaga tcctgggagt ggtgggagag 60
ggagcctacg gcgtggtgct gaagtgcaga cacaaggaga cacacgagat cgtggccatc 120
aagaagttta aggacagcga ggagaatgag gaggtgaagg agacaaccct gcgcgagctg 180
aagatgctgc ggacactgaa gcaggagaac atcgtggagc tgaaggaggc cttccggaga 240
aggggcaagc tgtacctggt gtttgagtat gtggagaaga acatgctgga gctgctggag 300
gagatgccta atggcgtgcc ccctgagaag gtgaagtcct acatctatca gctgatcaag 360
gccatccact ggtgccacaa gaacgatatc gtgcaccgcg acatcaagcc cgagaacctg 420
ctgatctccc acaatgacgt gctgaagctg tgcgacttcg gctttgcccg gcagctgagc 480
gagggcaaca atgcccagta cacagagtat gtggccaccc gctggtacag aagccccgag 540
ctgctgctgg gcgcccccta tggcaagagc gtggatatgt ggtccgtggg ctgcatcctg 600
ggcgagctgt ctgatggcca gcctctgttc ccaggcgaga gcgagatcga ccagctgttt 660
accatccaga aggtgctggg ccctctgcca agcgagcaga tgaagctgtt ctactccaac 720
ccaaggttcc acggcctgag gtttccagcc gtgaatcacc ctcagagcct ggagcgccgg 780
tatctgggca tcctgaactc cgtgctgctg gacctgatga agaacctgct gaagctggac 840
cccgccgaca gatacctgac cgagcagtgt ctgaatcacc ctacatttca gacccagaga 900
ctgctggata ggagcccttc ccgctctgcc aagcggaagc catatcacgt ggagagcagc 960
accctgtcca atcgcaacca ggccggcaag tctacagccc tgcagagcca ccaccggagc 1020
aactccaagg atatccagca gctgtccgtg ggcctgccta gggccgacga gggcctgcca 1080
gcaaacgaga gcttcctgaa tggaaacctg gcaggagcct ctctgagccc actgcacaca 1140
aagacctacc aggcctctag ccagcccggc tccacatcta aggacctgac caacaataac 1200
atcccacacc tgctgtctcc caaggaggcc aagagcaaga ccgagttcga cttcaacatc 1260
gacccaaagc ctagcgaggg acctggcaca aagtatctga agagcaacag ccggagccag 1320
cagaataggc actccttcat ggagtcctct cagtctaagg ccggcaccct gcagccaaac 1380
gagaagcaga gcaggcactc ctacatcgac accatcccac agagcagccg gagcccctcc 1440
tatcggacaa aggccaagtc tcacggcgcc ctgtctgata gcaagtccgt gtctcagctg 1500
agcgaggcca gagcccagat cgcagagccc agcacctcca ggtactttcc ttctagctgt 1560
ctggatctga actctcctac aagcccaaca cccaccagac acagcgacac aaggaccctg 1620
ctgtctccaa gcggcagaaa taacaggaac gagggcaccc tggacagccg gcggaccaca 1680
accaggcaca gcaagacaat ggaggagctg aagctgccag agcacatgga ttcctctcac 1740
tcccactctc tgagcgcccc ccacgagtcc ttctcttacg gcctgggcta tacctccccc 1800
ttcagcagcc agcagcgccc ccaccggcac tctatgtacg tgacaagaga taaggtgagg 1860
gcaaagggcc tggacggcag cctgtccatc ggacagggaa tggcagcccg ggccaactcc 1920
ctgcagctgc tgtctcctca gccaggagag cagctgccac cagagatgac cgtggcacgg 1980
agcagcgtga aggagacaag cagggagggc acctcctctt tccacacaag acagaagtcc 2040
gagggcggcg tgtatcacga tccccactct gacgatggca cagcccctaa ggagaacagg 2100
cacctgtaca atgaccccgt gcctaggagg gtgggctcct tctatcgcgt gccatctccc 2160
cggcctgata atagctttca cgagaatcag gtgagcaccc gggtgagcag cctgccatct 2220
gagtctagct ccggcacaca gcactctaag aggcagcccg cctttgaccc ttggaagagc 2280
ccagagcaga tctctcacag cgagcagctg aaggagaagg agaagcaggg cttctttcgc 2340
agcatgaaga agaagaagaa gaagagccag accgtgccta actccgattc tccagacctg 2400
ctgaccctgc agaagtccat ccacagcgcc tccacaccct ctagcagacc taaggagtgg 2460
aggcctgaga agatcagcga cctgcagacc cagagccagc cactgaagtc cctgcggaag 2520
ctgctgcacc tgtcctctgc cagcaaccac ccagccagct ccgatccaag gttccagccc 2580
ctgacagccc agcagaccaa gaacagcttc agcgagatca gaatccaccc tctgtcccag 2640
gcctctggag gctctagcaa catcaggcag gagccagcac caaagggccg gcccgccctg 2700
cagctgcctg gccagatgga cccaggctgg cacgtgtcct ctgtgacaag atccgccacc 2760
gagggcccat cctactctga gcagctggga gcaaagagcg gacctaatgg acacccatat 2820
cagaggaccc agagatccag gatgcccaat ctgaacgatc tgaaggagac agccctg 2877
<210> 146
<211> 3195
<212> DNA
<213> 人工序列
<220>
<223> MBIP-TATκ28-CDKL5_107-FH [1-8, 10NQ]的DNA序列 (人
优化)
<400> 146
atgaagctgt ccctggtggc cgctatgctg ctgctgctgt ctctggtcgc tgccatgtta 60
ttactgctgt ctgccgctag ggccggggac gcagcacagc ccgcaagaag agcaagaaga 120
actaaactgg ccgcttacgc aaggaaggca gcaagacagg caagagcagg cggcggcggc 180
tccaagatcc ccaatatcgg caacgtgatg aataagttcg agatcctggg agtggtggga 240
gagggagcct acggcgtggt gctgaagtgc agacacaagg agacacacga gatcgtggcc 300
atcaagaagt ttaaggacag cgaggagaat gaggaggtga aggagacaac cctgcgcgag 360
ctgaagatgc tgcggacact gaagcaggag aacatcgtgg agctgaagga ggccttccgg 420
agaaggggca agctgtacct ggtgtttgag tatgtggaga agaacatgct ggagctgctg 480
gaggagatgc ctaatggcgt gccccctgag aaggtgaagt cctacatcta tcagctgatc 540
aaggccatcc actggtgcca caagaacgat atcgtgcacc gcgacatcaa gcccgagaac 600
ctgctgatct cccacaatga cgtgctgaag ctgtgcgact tcggctttgc ccggcagctg 660
agcgagggca acaatgccca gtacacagag tatgtggcca cccgctggta cagaagcccc 720
gagctgctgc tgggcgcccc ctatggcaag agcgtggata tgtggtccgt gggctgcatc 780
ctgggcgagc tgtctgatgg ccagcctctg ttcccaggcg agagcgagat cgaccagctg 840
tttaccatcc agaaggtgct gggccctctg ccaagcgagc agatgaagct gttctactcc 900
aacccaaggt tccacggcct gaggtttcca gccgtgaatc accctcagag cctggagcgc 960
cggtatctgg gcatcctgaa ctccgtgctg ctggacctga tgaagaacct gctgaagctg 1020
gaccccgccg acagatacct gaccgagcag tgtctgaatc accctacatt tcagacccag 1080
agactgctgg ataggagccc ttcccgctct gccaagcgga agccatatca cgtggagagc 1140
agcaccctgt ccaatcgcaa ccaggccggc aagtctacag ccctgcagag ccaccaccgg 1200
agcaactcca aggatatcca gcagctgtcc gtgggcctgc ctagggccga cgagggcctg 1260
ccagcacagg agagcttcct gaatggaaac ctggcaggag cctctctgag cccactgcac 1320
acaaagacct accaggcctc tagccagccc ggctccacat ctaaggacct gaccaacaat 1380
aacatcccac acctgctgtc tcccaaggag gccaagagca agaccgagtt cgacttcaac 1440
atcgacccaa agcctagcga gggacctggc acaaagtatc tgaagagcaa cagccggagc 1500
cagcagaata ggcactcctt catggagtcc tctcagtcta aggccggcac cctgcagcca 1560
aacgagaagc agagcaggca ctcctacatc gacaccatcc cacagagcag ccggagcccc 1620
tcctatcgga caaaggccaa gtctcacggc gccctgtctg atagcaagtc cgtgtctcag 1680
ctgagcgagg ccagagccca gatcgcagag cccagcacct ccaggtactt tccttctagc 1740
tgtctggatc tgaactctcc tacaagccca acacccacca gacacagcga cacaaggacc 1800
ctgctgtctc caagcggcag aaataacagg aacgagggca ccctggacag ccggcggacc 1860
acaaccaggc acagcaagac aatggaggag ctgaagctgc cagagcacat ggattcctct 1920
cactcccact ctctgagcgc cccccacgag tccttctctt acggcctggg ctatacctcc 1980
cccttcagca gccagcagcg cccccaccgg cactctatgt acgtgacaag agataaggtg 2040
agggcaaagg gcctggacgg cagcctgtcc atcggacagg gaatggcagc ccgggccaac 2100
tccctgcagc tgctgtctcc tcagccagga gagcagctgc caccagagat gaccgtggca 2160
cggagcagcg tgaaggagac aagcagggag ggcacctcct ctttccacac aagacagaag 2220
tccgagggcg gcgtgtatca cgatccccac tctgacgatg gcacagcccc taaggagaac 2280
aggcacctgt acaatgaccc cgtgcctagg agggtgggct ccttctatcg cgtgccatct 2340
ccccggcctg ataatagctt tcacgagaat aacgtgagca cccgggtgag cagcctgcca 2400
tctgagtcta gctccggcac acagcactct aagaggcagc ccgcctttga cccttggaag 2460
agcccagagc agatctctca cagcgagcag ctgaaggaga aggagaagca gggcttcttt 2520
cgcagcatga agaagaagaa gaagaagagc cagaccgtgc ctaactccga ttctccagac 2580
ctgctgaccc tgcagaagtc catccacagc gcctccacac cctctagcag acctaaggag 2640
tggaggcctg agaagatcag cgacctgcag acccagagcc agccactgaa gtccctgcgg 2700
aagctgctgc acctgtcctc tgccagcaac cacccagcca gctccgatcc aaggttccag 2760
cccctgacag cccagcagac caagaacagc ttcagcgaga tcagaatcca ccctctgtcc 2820
caggcctctg gaggctctag caacatcagg caggagccag caccaaaggg ccggcccgcc 2880
ctgcagctgc ctggccagat ggacccaggc tggcacgtgt cctctgtgac aagatccgcc 2940
accgagggcc catcctactc tgagcagctg ggagcaaaga gcggacctaa tggacaccca 3000
tatcagagga cccagagatc caggatgccc aatctgaacg atctgaagga gacagccctg 3060
ggaggaggag gcagcgagaa cctgtacttc cagggcgatt ataaggacca cgatggcgac 3120
tacaaggacc acgacattga ctacaaggac gacgacgata aagacggagc accccatcac 3180
caccaccatc attga 3195
<210> 147
<211> 2877
<212> DNA
<213> 人工序列
<220>
<223> CDKL5_107 [1-8,10NQ]的DNA序列 (人优化)
<400> 147
aagatcccca atatcggcaa cgtgatgaat aagttcgaga tcctgggagt ggtgggagag 60
ggagcctacg gcgtggtgct gaagtgcaga cacaaggaga cacacgagat cgtggccatc 120
aagaagttta aggacagcga ggagaatgag gaggtgaagg agacaaccct gcgcgagctg 180
aagatgctgc ggacactgaa gcaggagaac atcgtggagc tgaaggaggc cttccggaga 240
aggggcaagc tgtacctggt gtttgagtat gtggagaaga acatgctgga gctgctggag 300
gagatgccta atggcgtgcc ccctgagaag gtgaagtcct acatctatca gctgatcaag 360
gccatccact ggtgccacaa gaacgatatc gtgcaccgcg acatcaagcc cgagaacctg 420
ctgatctccc acaatgacgt gctgaagctg tgcgacttcg gctttgcccg gcagctgagc 480
gagggcaaca atgcccagta cacagagtat gtggccaccc gctggtacag aagccccgag 540
ctgctgctgg gcgcccccta tggcaagagc gtggatatgt ggtccgtggg ctgcatcctg 600
ggcgagctgt ctgatggcca gcctctgttc ccaggcgaga gcgagatcga ccagctgttt 660
accatccaga aggtgctggg ccctctgcca agcgagcaga tgaagctgtt ctactccaac 720
ccaaggttcc acggcctgag gtttccagcc gtgaatcacc ctcagagcct ggagcgccgg 780
tatctgggca tcctgaactc cgtgctgctg gacctgatga agaacctgct gaagctggac 840
cccgccgaca gatacctgac cgagcagtgt ctgaatcacc ctacatttca gacccagaga 900
ctgctggata ggagcccttc ccgctctgcc aagcggaagc catatcacgt ggagagcagc 960
accctgtcca atcgcaacca ggccggcaag tctacagccc tgcagagcca ccaccggagc 1020
aactccaagg atatccagca gctgtccgtg ggcctgccta gggccgacga gggcctgcca 1080
gcacaggaga gcttcctgaa tggaaacctg gcaggagcct ctctgagccc actgcacaca 1140
aagacctacc aggcctctag ccagcccggc tccacatcta aggacctgac caacaataac 1200
atcccacacc tgctgtctcc caaggaggcc aagagcaaga ccgagttcga cttcaacatc 1260
gacccaaagc ctagcgaggg acctggcaca aagtatctga agagcaacag ccggagccag 1320
cagaataggc actccttcat ggagtcctct cagtctaagg ccggcaccct gcagccaaac 1380
gagaagcaga gcaggcactc ctacatcgac accatcccac agagcagccg gagcccctcc 1440
tatcggacaa aggccaagtc tcacggcgcc ctgtctgata gcaagtccgt gtctcagctg 1500
agcgaggcca gagcccagat cgcagagccc agcacctcca ggtactttcc ttctagctgt 1560
ctggatctga actctcctac aagcccaaca cccaccagac acagcgacac aaggaccctg 1620
ctgtctccaa gcggcagaaa taacaggaac gagggcaccc tggacagccg gcggaccaca 1680
accaggcaca gcaagacaat ggaggagctg aagctgccag agcacatgga ttcctctcac 1740
tcccactctc tgagcgcccc ccacgagtcc ttctcttacg gcctgggcta tacctccccc 1800
ttcagcagcc agcagcgccc ccaccggcac tctatgtacg tgacaagaga taaggtgagg 1860
gcaaagggcc tggacggcag cctgtccatc ggacagggaa tggcagcccg ggccaactcc 1920
ctgcagctgc tgtctcctca gccaggagag cagctgccac cagagatgac cgtggcacgg 1980
agcagcgtga aggagacaag cagggagggc acctcctctt tccacacaag acagaagtcc 2040
gagggcggcg tgtatcacga tccccactct gacgatggca cagcccctaa ggagaacagg 2100
cacctgtaca atgaccccgt gcctaggagg gtgggctcct tctatcgcgt gccatctccc 2160
cggcctgata atagctttca cgagaataac gtgagcaccc gggtgagcag cctgccatct 2220
gagtctagct ccggcacaca gcactctaag aggcagcccg cctttgaccc ttggaagagc 2280
ccagagcaga tctctcacag cgagcagctg aaggagaagg agaagcaggg cttctttcgc 2340
agcatgaaga agaagaagaa gaagagccag accgtgccta actccgattc tccagacctg 2400
ctgaccctgc agaagtccat ccacagcgcc tccacaccct ctagcagacc taaggagtgg 2460
aggcctgaga agatcagcga cctgcagacc cagagccagc cactgaagtc cctgcggaag 2520
ctgctgcacc tgtcctctgc cagcaaccac ccagccagct ccgatccaag gttccagccc 2580
ctgacagccc agcagaccaa gaacagcttc agcgagatca gaatccaccc tctgtcccag 2640
gcctctggag gctctagcaa catcaggcag gagccagcac caaagggccg gcccgccctg 2700
cagctgcctg gccagatgga cccaggctgg cacgtgtcct ctgtgacaag atccgccacc 2760
gagggcccat cctactctga gcagctggga gcaaagagcg gacctaatgg acacccatat 2820
cagaggaccc agagatccag gatgcccaat ctgaacgatc tgaaggagac agccctg 2877
<210> 148
<211> 3195
<212> DNA
<213> 人工序列
<220>
<223> MBIP-TATκ28-CDKL5_107-FH [1-9NQ]的DNA序列 (人
优化)
<400> 148
atgaagctgt ccctggtggc cgctatgctg ctgctgctgt ctctggtcgc tgccatgtta 60
ttactgctgt ctgccgctag ggccggggac gcagcacagc ccgcaagaag agcaagaaga 120
actaaactgg ccgcttacgc aaggaaggca gcaagacagg caagagcagg cggcggcggc 180
tccaagatcc ccaatatcgg caacgtgatg aataagttcg agatcctggg agtggtggga 240
gagggagcct acggcgtggt gctgaagtgc agacacaagg agacacacga gatcgtggcc 300
atcaagaagt ttaaggacag cgaggagaat gaggaggtga aggagacaac cctgcgcgag 360
ctgaagatgc tgcggacact gaagcaggag aacatcgtgg agctgaagga ggccttccgg 420
agaaggggca agctgtacct ggtgtttgag tatgtggaga agaacatgct ggagctgctg 480
gaggagatgc ctaatggcgt gccccctgag aaggtgaagt cctacatcta tcagctgatc 540
aaggccatcc actggtgcca caagaacgat atcgtgcacc gcgacatcaa gcccgagaac 600
ctgctgatct cccacaatga cgtgctgaag ctgtgcgact tcggctttgc ccggcagctg 660
agcgagggca acaatgccca gtacacagag tatgtggcca cccgctggta cagaagcccc 720
gagctgctgc tgggcgcccc ctatggcaag agcgtggata tgtggtccgt gggctgcatc 780
ctgggcgagc tgtctgatgg ccagcctctg ttcccaggcg agagcgagat cgaccagctg 840
tttaccatcc agaaggtgct gggccctctg ccaagcgagc agatgaagct gttctactcc 900
aacccaaggt tccacggcct gaggtttcca gccgtgaatc accctcagag cctggagcgc 960
cggtatctgg gcatcctgaa ctccgtgctg ctggacctga tgaagaacct gctgaagctg 1020
gaccccgccg acagatacct gaccgagcag tgtctgaatc accctacatt tcagacccag 1080
agactgctgg ataggagccc ttcccgctct gccaagcgga agccatatca cgtggagagc 1140
agcaccctgt ccaatcgcaa ccaggccggc aagtctacag ccctgcagag ccaccaccgg 1200
agcaactcca aggatatcca gcagctgtcc gtgggcctgc ctagggccga cgagggcctg 1260
ccagcacagg agagcttcct gaatggaaac ctggcaggag cctctctgag cccactgcac 1320
acaaagacct accaggcctc tagccagccc ggctccacat ctaaggacct gaccaacaat 1380
aacatcccac acctgctgtc tcccaaggag gccaagagca agaccgagtt cgacttcaac 1440
atcgacccaa agcctagcga gggacctggc acaaagtatc tgaagagcaa cagccggagc 1500
cagcagaata ggcactcctt catggagtcc tctcagtcta aggccggcac cctgcagcca 1560
aacgagaagc agagcaggca ctcctacatc gacaccatcc cacagagcag ccggagcccc 1620
tcctatcgga caaaggccaa gtctcacggc gccctgtctg atagcaagtc cgtgtctcag 1680
ctgagcgagg ccagagccca gatcgcagag cccagcacct ccaggtactt tccttctagc 1740
tgtctggatc tgaactctcc tacaagccca acacccacca gacacagcga cacaaggacc 1800
ctgctgtctc caagcggcag aaataacagg aacgagggca ccctggacag ccggcggacc 1860
acaaccaggc acagcaagac aatggaggag ctgaagctgc cagagcacat ggattcctct 1920
cactcccact ctctgagcgc cccccacgag tccttctctt acggcctggg ctatacctcc 1980
cccttcagca gccagcagcg cccccaccgg cactctatgt acgtgacaag agataaggtg 2040
agggcaaagg gcctggacgg cagcctgtcc atcggacagg gaatggcagc ccgggccaac 2100
tccctgcagc tgctgtctcc tcagccagga gagcagctgc caccagagat gaccgtggca 2160
cggagcagcg tgaaggagac aagcagggag ggcacctcct ctttccacac aagacagaag 2220
tccgagggcg gcgtgtatca cgatccccac tctgacgatg gcacagcccc taaggagaac 2280
aggcacctgt acaatgaccc cgtgcctagg agggtgggct ccttctatcg cgtgccatct 2340
ccccggcctg ataatagctt tcacgagaat caggtgagca cccgggtgag cagcctgcca 2400
tctgagtcta gctccggcac aaaccactct aagaggcagc ccgcctttga cccttggaag 2460
agcccagagc agatctctca cagcgagcag ctgaaggaga aggagaagca gggcttcttt 2520
cgcagcatga agaagaagaa gaagaagagc cagaccgtgc ctaactccga ttctccagac 2580
ctgctgaccc tgcagaagtc catccacagc gcctccacac cctctagcag acctaaggag 2640
tggaggcctg agaagatcag cgacctgcag acccagagcc agccactgaa gtccctgcgg 2700
aagctgctgc acctgtcctc tgccagcaac cacccagcca gctccgatcc aaggttccag 2760
cccctgacag cccagcagac caagaacagc ttcagcgaga tcagaatcca ccctctgtcc 2820
caggcctctg gaggctctag caacatcagg caggagccag caccaaaggg ccggcccgcc 2880
ctgcagctgc ctggccagat ggacccaggc tggcacgtgt cctctgtgac aagatccgcc 2940
accgagggcc catcctactc tgagcagctg ggagcaaaga gcggacctaa tggacaccca 3000
tatcagagga cccagagatc caggatgccc aatctgaacg atctgaagga gacagccctg 3060
ggaggaggag gcagcgagaa cctgtacttc cagggcgatt ataaggacca cgatggcgac 3120
tacaaggacc acgacattga ctacaaggac gacgacgata aagacggagc accccatcac 3180
caccaccatc attga 3195
<210> 149
<211> 2877
<212> DNA
<213> 人工序列
<220>
<223> CDKL5_107 [1-9NQ]的DNA序列 (人优化)
<400> 149
aagatcccca atatcggcaa cgtgatgaat aagttcgaga tcctgggagt ggtgggagag 60
ggagcctacg gcgtggtgct gaagtgcaga cacaaggaga cacacgagat cgtggccatc 120
aagaagttta aggacagcga ggagaatgag gaggtgaagg agacaaccct gcgcgagctg 180
aagatgctgc ggacactgaa gcaggagaac atcgtggagc tgaaggaggc cttccggaga 240
aggggcaagc tgtacctggt gtttgagtat gtggagaaga acatgctgga gctgctggag 300
gagatgccta atggcgtgcc ccctgagaag gtgaagtcct acatctatca gctgatcaag 360
gccatccact ggtgccacaa gaacgatatc gtgcaccgcg acatcaagcc cgagaacctg 420
ctgatctccc acaatgacgt gctgaagctg tgcgacttcg gctttgcccg gcagctgagc 480
gagggcaaca atgcccagta cacagagtat gtggccaccc gctggtacag aagccccgag 540
ctgctgctgg gcgcccccta tggcaagagc gtggatatgt ggtccgtggg ctgcatcctg 600
ggcgagctgt ctgatggcca gcctctgttc ccaggcgaga gcgagatcga ccagctgttt 660
accatccaga aggtgctggg ccctctgcca agcgagcaga tgaagctgtt ctactccaac 720
ccaaggttcc acggcctgag gtttccagcc gtgaatcacc ctcagagcct ggagcgccgg 780
tatctgggca tcctgaactc cgtgctgctg gacctgatga agaacctgct gaagctggac 840
cccgccgaca gatacctgac cgagcagtgt ctgaatcacc ctacatttca gacccagaga 900
ctgctggata ggagcccttc ccgctctgcc aagcggaagc catatcacgt ggagagcagc 960
accctgtcca atcgcaacca ggccggcaag tctacagccc tgcagagcca ccaccggagc 1020
aactccaagg atatccagca gctgtccgtg ggcctgccta gggccgacga gggcctgcca 1080
gcacaggaga gcttcctgaa tggaaacctg gcaggagcct ctctgagccc actgcacaca 1140
aagacctacc aggcctctag ccagcccggc tccacatcta aggacctgac caacaataac 1200
atcccacacc tgctgtctcc caaggaggcc aagagcaaga ccgagttcga cttcaacatc 1260
gacccaaagc ctagcgaggg acctggcaca aagtatctga agagcaacag ccggagccag 1320
cagaataggc actccttcat ggagtcctct cagtctaagg ccggcaccct gcagccaaac 1380
gagaagcaga gcaggcactc ctacatcgac accatcccac agagcagccg gagcccctcc 1440
tatcggacaa aggccaagtc tcacggcgcc ctgtctgata gcaagtccgt gtctcagctg 1500
agcgaggcca gagcccagat cgcagagccc agcacctcca ggtactttcc ttctagctgt 1560
ctggatctga actctcctac aagcccaaca cccaccagac acagcgacac aaggaccctg 1620
ctgtctccaa gcggcagaaa taacaggaac gagggcaccc tggacagccg gcggaccaca 1680
accaggcaca gcaagacaat ggaggagctg aagctgccag agcacatgga ttcctctcac 1740
tcccactctc tgagcgcccc ccacgagtcc ttctcttacg gcctgggcta tacctccccc 1800
ttcagcagcc agcagcgccc ccaccggcac tctatgtacg tgacaagaga taaggtgagg 1860
gcaaagggcc tggacggcag cctgtccatc ggacagggaa tggcagcccg ggccaactcc 1920
ctgcagctgc tgtctcctca gccaggagag cagctgccac cagagatgac cgtggcacgg 1980
agcagcgtga aggagacaag cagggagggc acctcctctt tccacacaag acagaagtcc 2040
gagggcggcg tgtatcacga tccccactct gacgatggca cagcccctaa ggagaacagg 2100
cacctgtaca atgaccccgt gcctaggagg gtgggctcct tctatcgcgt gccatctccc 2160
cggcctgata atagctttca cgagaatcag gtgagcaccc gggtgagcag cctgccatct 2220
gagtctagct ccggcacaaa ccactctaag aggcagcccg cctttgaccc ttggaagagc 2280
ccagagcaga tctctcacag cgagcagctg aaggagaagg agaagcaggg cttctttcgc 2340
agcatgaaga agaagaagaa gaagagccag accgtgccta actccgattc tccagacctg 2400
ctgaccctgc agaagtccat ccacagcgcc tccacaccct ctagcagacc taaggagtgg 2460
aggcctgaga agatcagcga cctgcagacc cagagccagc cactgaagtc cctgcggaag 2520
ctgctgcacc tgtcctctgc cagcaaccac ccagccagct ccgatccaag gttccagccc 2580
ctgacagccc agcagaccaa gaacagcttc agcgagatca gaatccaccc tctgtcccag 2640
gcctctggag gctctagcaa catcaggcag gagccagcac caaagggccg gcccgccctg 2700
cagctgcctg gccagatgga cccaggctgg cacgtgtcct ctgtgacaag atccgccacc 2760
gagggcccat cctactctga gcagctggga gcaaagagcg gacctaatgg acacccatat 2820
cagaggaccc agagatccag gatgcccaat ctgaacgatc tgaaggagac agccctg 2877
<210> 150
<211> 33
<212> DNA
<213> 人工序列
<220>
<223> TATκ11的DNA序列 (人优化)
<400> 150
tacgcccgga aggccgcccg gcaggccaga gcc 33
<210> 151
<211> 81
<212> DNA
<213> 人工序列
<220>
<223> TATκ28的DNA序列 (人优化)
<400> 151
gacgcagcac agcccgcaag aagagcaaga agaactaaac tggccgctta cgcaaggaag 60
gcagcaagac aggcaagagc a 81
<210> 152
<211> 48
<212> DNA
<213> 人工序列
<220>
<223> 穿膜肽CPP的DNA序列 (人优化)
<400> 152
cggcagatca agatttggtt ccagaaccgg agaatgaagt ggaagaag 48
<210> 153
<211> 63
<212> DNA
<213> 人工序列
<220>
<223> 转运肽CPP的DNA序列 (人优化)
<400> 153
gccggctacc tgctgggcaa gatcaacctg aaggccctgg ccgccctggc caagaagatc 60
ctg 63
<210> 154
<211> 36
<212> DNA
<213> 人工序列
<220>
<223> P97 CPP的DNA序列 (人优化)
<400> 154
gacagctccc acgccttcac cctggatgag ctgcgg 36
<210> 155
<211> 84
<212> DNA
<213> 人工序列
<220>
<223> mBIP的DNA序列 (人优化)
<400> 155
atgaagctgt ccctggtggc cgctatgctg ctgctgctgt ctctggtcgc tgccatgtta 60
ttactgctgt ctgccgctag ggcc 84
<210> 156
<211> 67
<212> PRT
<213> 人工序列
<220>
<223> IGF
<400> 156
Ala Tyr Arg Pro Ser Glu Thr Leu Cys Gly Gly Glu Leu Val Asp Thr
1 5 10 15
Leu Gln Phe Val Cys Gly Asp Arg Gly Phe Tyr Phe Ser Arg Pro Ala
20 25 30
Ser Arg Val Ser Arg Arg Ser Arg Gly Ile Val Glu Glu Cys Cys Phe
35 40 45
Arg Ser Cys Asp Leu Ala Leu Leu Glu Thr Tyr Cys Ala Thr Pro Ala
50 55 60
Lys Ser Glu
65
<210> 157
<211> 67
<212> PRT
<213> 人工序列
<220>
<223> IGF F26S
<400> 157
Ala Tyr Arg Pro Ser Glu Thr Leu Cys Gly Gly Glu Leu Val Asp Thr
1 5 10 15
Leu Gln Phe Val Cys Gly Asp Arg Gly Ser Tyr Phe Ser Arg Pro Ala
20 25 30
Ser Arg Val Ser Arg Arg Ser Arg Gly Ile Val Glu Glu Cys Cys Phe
35 40 45
Arg Ser Cys Asp Leu Ala Leu Leu Glu Thr Tyr Cys Ala Thr Pro Ala
50 55 60
Lys Ser Glu
65
<210> 158
<211> 67
<212> PRT
<213> 人工序列
<220>
<223> IGF Y27L
<400> 158
Ala Tyr Arg Pro Ser Glu Thr Leu Cys Gly Gly Glu Leu Val Asp Thr
1 5 10 15
Leu Gln Phe Val Cys Gly Asp Arg Gly Phe Leu Phe Ser Arg Pro Ala
20 25 30
Ser Arg Val Ser Arg Arg Ser Arg Gly Ile Val Glu Glu Cys Cys Phe
35 40 45
Arg Ser Cys Asp Leu Ala Leu Leu Glu Thr Tyr Cys Ala Thr Pro Ala
50 55 60
Lys Ser Glu
65
<210> 159
<211> 67
<212> PRT
<213> 人工序列
<220>
<223> IGF V43L
<400> 159
Ala Tyr Arg Pro Ser Glu Thr Leu Cys Gly Gly Glu Leu Val Asp Thr
1 5 10 15
Leu Gln Phe Val Cys Gly Asp Arg Gly Phe Tyr Phe Ser Arg Pro Ala
20 25 30
Ser Arg Val Ser Arg Arg Ser Arg Gly Ile Leu Glu Glu Cys Cys Phe
35 40 45
Arg Ser Cys Asp Leu Ala Leu Leu Glu Thr Tyr Cys Ala Thr Pro Ala
50 55 60
Lys Ser Glu
65
<210> 160
<211> 67
<212> PRT
<213> 人工序列
<220>
<223> IGF F48T
<400> 160
Ala Tyr Arg Pro Ser Glu Thr Leu Cys Gly Gly Glu Leu Val Asp Thr
1 5 10 15
Leu Gln Phe Val Cys Gly Asp Arg Gly Phe Tyr Phe Ser Arg Pro Ala
20 25 30
Ser Arg Val Ser Arg Arg Ser Arg Gly Ile Val Glu Glu Cys Cys Thr
35 40 45
Arg Ser Cys Asp Leu Ala Leu Leu Glu Thr Tyr Cys Ala Thr Pro Ala
50 55 60
Lys Ser Glu
65
<210> 161
<211> 67
<212> PRT
<213> 人工序列
<220>
<223> IGF R49S
<400> 161
Ala Tyr Arg Pro Ser Glu Thr Leu Cys Gly Gly Glu Leu Val Asp Thr
1 5 10 15
Leu Gln Phe Val Cys Gly Asp Arg Gly Phe Tyr Phe Ser Arg Pro Ala
20 25 30
Ser Arg Val Ser Arg Arg Ser Arg Gly Ile Val Glu Glu Cys Cys Phe
35 40 45
Ser Ser Cys Asp Leu Ala Leu Leu Glu Thr Tyr Cys Ala Thr Pro Ala
50 55 60
Lys Ser Glu
65
<210> 162
<211> 67
<212> PRT
<213> 人工序列
<220>
<223> IGF S50I
<400> 162
Ala Tyr Arg Pro Ser Glu Thr Leu Cys Gly Gly Glu Leu Val Asp Thr
1 5 10 15
Leu Gln Phe Val Cys Gly Asp Arg Gly Phe Tyr Phe Ser Arg Pro Ala
20 25 30
Ser Arg Val Ser Arg Arg Ser Arg Gly Ile Val Glu Glu Cys Cys Phe
35 40 45
Arg Ile Cys Asp Leu Ala Leu Leu Glu Thr Tyr Cys Ala Thr Pro Ala
50 55 60
Lys Ser Glu
65
<210> 163
<211> 67
<212> PRT
<213> 人工序列
<220>
<223> IGF A54R
<400> 163
Ala Tyr Arg Pro Ser Glu Thr Leu Cys Gly Gly Glu Leu Val Asp Thr
1 5 10 15
Leu Gln Phe Val Cys Gly Asp Arg Gly Phe Tyr Phe Ser Arg Pro Ala
20 25 30
Ser Arg Val Ser Arg Arg Ser Arg Gly Ile Val Glu Glu Cys Cys Phe
35 40 45
Arg Ser Cys Asp Leu Arg Leu Leu Glu Thr Tyr Cys Ala Thr Pro Ala
50 55 60
Lys Ser Glu
65
<210> 164
<211> 67
<212> PRT
<213> 人工序列
<220>
<223> IGF L55R
<400> 164
Ala Tyr Arg Pro Ser Glu Thr Leu Cys Gly Gly Glu Leu Val Asp Thr
1 5 10 15
Leu Gln Phe Val Cys Gly Asp Arg Gly Phe Tyr Phe Ser Arg Pro Ala
20 25 30
Ser Arg Val Ser Arg Arg Ser Arg Gly Ile Val Glu Glu Cys Cys Phe
35 40 45
Arg Ser Cys Asp Leu Ala Arg Leu Glu Thr Tyr Cys Ala Thr Pro Ala
50 55 60
Lys Ser Glu
65
<210> 165
<211> 67
<212> PRT
<213> 人工序列
<220>
<223> IGF F26S、Y27L、V43L、F48T、R49S、S50I、A54R、L55R
<400> 165
Ala Tyr Arg Pro Ser Glu Thr Leu Cys Gly Gly Glu Leu Val Asp Thr
1 5 10 15
Leu Gln Phe Val Cys Gly Asp Arg Gly Ser Leu Phe Ser Arg Pro Ala
20 25 30
Ser Arg Val Ser Arg Arg Ser Arg Gly Ile Leu Glu Glu Cys Cys Thr
35 40 45
Ser Ile Cys Asp Leu Arg Arg Leu Glu Thr Tyr Cys Ala Thr Pro Ala
50 55 60
Lys Ser Glu
65
<210> 166
<211> 61
<212> PRT
<213> 人工序列
<220>
<223> IGF Δl-7、Y27L、K65R
<400> 166
Thr Leu Cys Gly Gly Glu Leu Val Asp Thr Leu Gln Phe Val Cys Gly
1 5 10 15
Asp Arg Gly Phe Leu Phe Ser Arg Pro Ala Ser Arg Val Ser Arg Arg
20 25 30
Ser Arg Gly Ile Val Glu Glu Cys Cys Phe Arg Ser Cys Asp Leu Ala
35 40 45
Leu Leu Glu Thr Tyr Cys Ala Thr Pro Ala Arg Ser Glu
50 55 60
<210> 167
<211> 27
<212> PRT
<213> 人工序列
<220>
<223> TATκκ28 CPP
<400> 167
Asp Ala Ala Gln Pro Ala Arg Arg Ala Ala Arg Thr Lys Leu Ala Ala
1 5 10 15
Tyr Ala Arg Lys Ala Ala Arg Gln Ala Arg Ala
20 25
<210> 168
<211> 29
<212> PRT
<213> 人工序列
<220>
<223> mvBIP
<400> 168
Met Val Lys Leu Ser Leu Val Ala Ala Met Leu Leu Leu Leu Ser Leu
1 5 10 15
Val Ala Ala Met Leu Leu Leu Leu Ser Ala Ala Arg Ala
20 25
<210> 169
<211> 84
<212> DNA
<213> 人工序列
<220>
<223> mvBIP的示例性DNA序列
<400> 169
atgaagctgt ccctggtggc cgctatgctg ctgctgctgt ctctggtcgc tgccatgtta 60
ttactgctgt ctgccgctag ggcc 84
<210> 170
<211> 84
<212> DNA
<213> 人工序列
<220>
<223> TATκκ28的示例性DNA序列
<400> 170
tctgatgctg cccagcctgc tagaagggcc gccaggacaa aactggccgc ctatgccaga 60
aaagccgcca gacaggccag agcc 84
<210> 171
<211> 84
<212> DNA
<213> 人工序列
<220>
<223> TATκκ28的示例性DNA序列
<400> 171
agcgacgccg ctcaaccagc tcgacgcgcc gccagaacca agctggccgc ctacgcccgg 60
aaggccgcca gacaggccag agcc 84
<210> 172
<211> 84
<212> DNA
<213> 人工序列
<220>
<223> TATκκ28的示例性DNA序列
<400> 172
agcgacgccg cccagcccgc cagaagagcc gccagaacca agctggccgc ctacgccaga 60
aaggccgcca gacaggccag agcc 84
<210> 173
<211> 84
<212> DNA
<213> 人工序列
<220>
<223> TATκκ28的示例性DNA序列
<400> 173
tctgatgccg cccagcctgc cagacgggct gcacggacga agctggccgc ctacgccaga 60
aaggcggcca gacaggccag agcc 84
<210> 174
<211> 1091
<212> PRT
<213> 人工序列
<220>
<223> TwinStrep-3cV2-TATκ28-hCDKL5-Flag-His-HPC4 (氨基酸
序列)
<400> 174
Met Ser Ala Trp Ser His Pro Gln Phe Glu Lys Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Ser Gly Gly Ser Ala Trp Ser His Pro Gln Phe Glu Lys Gly
20 25 30
Ser Leu Glu Val Leu Phe Gln Gly Pro Asp Ala Ala Gln Pro Ala Arg
35 40 45
Arg Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg Lys Ala Ala Arg
50 55 60
Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro Asn Ile Gly Asn
65 70 75 80
Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly Glu Gly Ala Tyr
85 90 95
Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His Glu Ile Val Ala
100 105 110
Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu Val Lys Glu Thr
115 120 125
Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys Gln Glu Asn Ile
130 135 140
Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys Leu Tyr Leu Val
145 150 155 160
Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu Glu Glu Met Pro
165 170 175
Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile Tyr Gln Leu Ile
180 185 190
Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val His Arg Asp Ile
195 200 205
Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val Leu Lys Leu Cys
210 215 220
Asp Phe Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn Asn Ala Asn Tyr
225 230 235 240
Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro Glu Leu Leu Leu
245 250 255
Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser Val Gly Cys Ile
260 265 270
Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro Gly Glu Ser Glu
275 280 285
Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly Pro Leu Pro Ser
290 295 300
Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe His Gly Leu Arg
305 310 315 320
Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg Arg Tyr Leu Gly
325 330 335
Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn Leu Leu Lys Leu
340 345 350
Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu Asn His Pro Thr
355 360 365
Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser Arg Ser Ala Lys
370 375 380
Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser Asn Arg Asn Gln
385 390 395 400
Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg Ser Asn Ser Lys
405 410 415
Asp Ile Gln Asn Leu Ser Val Gly Leu Pro Arg Ala Asp Glu Gly Leu
420 425 430
Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala Gly Ala Ser Leu
435 440 445
Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser Gln Pro Gly Ser
450 455 460
Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His Leu Leu Ser Pro
465 470 475 480
Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn Ile Asp Pro Lys
485 490 495
Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser Asn Ser Arg Ser
500 505 510
Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln Ser Lys Ala Gly
515 520 525
Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser Tyr Ile Asp Thr
530 535 540
Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr Lys Ala Lys Ser
545 550 555 560
His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Asn Leu Ser Glu Ala
565 570 575
Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr Phe Pro Ser Ser
580 585 590
Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro Thr Arg His Ser
595 600 605
Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn Asn Arg Asn Glu
610 615 620
Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His Ser Lys Thr Met
625 630 635 640
Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser His Ser His Ser
645 650 655
Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu Gly Tyr Thr Ser
660 665 670
Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser Met Tyr Val Thr
675 680 685
Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser Leu Ser Ile Gly
690 695 700
Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu Leu Ser Pro Gln
705 710 715 720
Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala Arg Ser Ser Val
725 730 735
Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His Thr Arg Gln Lys
740 745 750
Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp Asp Gly Thr Ala
755 760 765
Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val Pro Arg Arg Val
770 775 780
Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp Asn Ser Phe His
785 790 795 800
Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro Ser Glu Ser Ser
805 810 815
Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe Asp Pro Trp Lys
820 825 830
Ser Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys Glu Lys Glu Lys
835 840 845
Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys Lys Ser Gln Thr
850 855 860
Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu Gln Lys Ser Ile
865 870 875 880
His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu Trp Arg Pro Glu
885 890 895
Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu Lys Ser Leu Arg
900 905 910
Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro Ala Ser Ser Asp
915 920 925
Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys Asn Ser Phe Ser
930 935 940
Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly Gly Ser Ser Asn
945 950 955 960
Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala Leu Gln Leu Pro
965 970 975
Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val Thr Arg Ser Ala
980 985 990
Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro
995 1000 1005
Asn Gly His Pro Tyr Asn Arg Thr Asn Arg Ser Arg Met Pro Asn
1010 1015 1020
Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Ala Gly Gly Gly Gly
1025 1030 1035
Ser Leu Glu Val Leu Phe Gln Gly Pro Asp Tyr Lys Asp His Asp
1040 1045 1050
Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
1055 1060 1065
Lys Asp Gly Ala Pro His His His His His His Glu Asp Gln Val
1070 1075 1080
Asp Pro Arg Leu Ile Asp Gly Lys
1085 1090
<210> 175
<211> 3276
<212> DNA
<213> 人工序列
<220>
<223> TwinStrep-3cV2-TATκ28-hCDKL5-Flag-His-HPC4 (DNA序列)
<400> 175
atgtcagcgt ggtcgcatcc tcaattcgaa aagggcggcg gttcgggtgg aggaagtggc 60
ggatcggcct ggtctcaccc gcaattcgaa aagggttccc tcgaggtcct ttttcaaggt 120
cccgacgctg ctcagcctgc tcgccgtgcc aggagaacca agctggctgc ctacgctcgt 180
aaggctgcta gacaagctag ggccggtggc ggaggtagca agatcccaaa catcggtaac 240
gtgatgaaca agttcgagat cctgggcgtg gtcggtgaag gcgcttacgg agtggtcctg 300
aagtgcaggc acaaggagac ccacgaaatc gtggccatca agaagttcaa ggactctgag 360
gaaaacgagg aagtcaaaga gaccactctg cgtgaactga agatgctgag gactctgaag 420
caggagaaca tcgtcgagct gaaggaagct ttccgccgta ggggaaagct gtacctggtg 480
ttcgagtacg tcgaaaagaa catgctggag ctgctggagg aaatgccaaa cggtgtgcct 540
cccgaaaagg tcaagagcta catctaccag ctgatcaagg ccatccactg gtgccacaag 600
aacgacatcg tgcaccgtga catcaagcct gagaacctgc tgatcagcca caacgacgtc 660
ctgaagctgt gcgacttcgg tttcgctagg aacctgtctg agggcaacaa cgctaactac 720
actgaatacg tggccacccg ttggtacagg tctccagagc tgctgctggg tgccccttac 780
ggcaagtctg tggacatgtg gtctgtcgga tgcatcctgg gtgaactgag cgacggacag 840
cccctgttcc caggagagtc tgaaatcgac cagctgttca ccatccagaa ggtcctgggc 900
cccctgccaa gcgagcagat gaagctgttc tactctaacc cccgtttcca cggactgagg 960
ttccctgctg tgaaccaccc ccagagcctg gaaagacgct acctgggtat cctgaactct 1020
gtcctgctgg acctgatgaa gaacctgctg aagctggacc ctgctgaccg ctacctgacc 1080
gagcagtgcc tgaaccaccc cactttccag acccagagac tgctggaccg cagcccctct 1140
cgttcagcca agaggaagcc ataccacgtg gaatccagca ccctgagcaa ccgtaaccag 1200
gctggcaagt ccactgccct gcagagccac cacaggtcca acagcaagga catccaaaac 1260
ctgtcagtgg gactgccaag ggctgacgag ggactgccag ccaacgaatc cttcctgaac 1320
ggcaacctgg ctggagcctc tctgtcacca ctgcacacta agacctacca ggcttcttca 1380
cagcctggtt ccactagcaa ggacctgacc aacaacaaca tcccacacct gctgtctcct 1440
aaggaagcta aatcaaagac cgagttcgac ttcaacatcg accctaagcc ctccgaggga 1500
cctggtacta agtacctgaa gtctaactca agatcccagc agaaccgcca ctcattcatg 1560
gagtccagcc agtccaaggc tggtaccctg cagcccaacg aaaagcagtc ccgccacagc 1620
tacatcgaca ccatccctca gtcttcacgt agcccctctt acaggactaa ggctaagagc 1680
cacggcgccc tgtcagactc caagagcgtg tctaacctgt ctgaggctag agcccagatc 1740
gccgaacctt caacctcccg ctacttcccc tccagctgcc tggacctgaa ctctcccact 1800
tcaccaactc ctaccagaca ctccgacact cgcaccctgc tgagcccatc tggtagaaac 1860
aaccgcaacg agggcaccct ggactcacgt aggaccacta cccgtcactc caagactatg 1920
gaggaactga agctgccaga gcacatggac tcttcacact cacactccct gagcgctcct 1980
cacgaatctt tctcatacgg cctgggatac accagcccat tctccagcca gcagcgtcct 2040
cacaggcact ctatgtacgt gactagagac aaggtccgcg ctaagggact ggacggttcc 2100
ctgtctatcg gtcagggaat ggctgctagg gccaactctc tgcagctgct gtcaccccag 2160
ccaggagagc agctgccacc tgaaatgacc gtggctagat cttcagtcaa ggagacttcc 2220
cgcgaaggca cctccagctt ccacactaga cagaagtcag agggcggagt gtaccacgac 2280
cctcactctg acgacggaac tgctcccaag gaaaaccgcc acctgtacaa cgaccctgtg 2340
cccagacgcg tcggatcctt ctaccgtgtc ccaagcccta ggcccgacaa ctctttccac 2400
gagaacaacg tgagcaccag agtctcttca ctgccctctg aatccagctc tggcactaac 2460
cactcaaagc gccagcctgc tttcgacccc tggaagtccc cagagaacat ctctcactca 2520
gaacagctga aggagaagga aaagcaggga ttcttccgct caatgaagaa gaagaagaag 2580
aagtcccaga ccgtgcccaa ctccgacagc ccagacctgc tgaccctgca gaagtcaatc 2640
cactctgcct caactccttc atccagaccc aaggagtggc gccccgaaaa gatctccgac 2700
ctgcagactc agtcccagcc actgaagagc ctgcgtaagc tgctgcacct gagctctgct 2760
tccaaccacc ctgcctcatc cgacccacgt ttccagcctc tgactgctca gcagaccaag 2820
aactccttca gcgagatcag gatccaccca ctgtcccagg ctagcggtgg cagctctaac 2880
atccgtcagg aaccagctcc taagggacgt ccagctctgc agctgcctgg tcagatggac 2940
ccaggctggc acgtgtcatc cgtcactaga tcagctaccg agggaccatc ttactcagaa 3000
cagctgggtg ccaagtcagg ccccaacgga cacccataca accgcaccaa ccgttccagg 3060
atgcctaacc tgaacgacct gaaggagact gctctggggg ccggaggtgg cggatccctg 3120
gaagtgctgt tccagggccc tgactacaag gaccacgacg gtgactacaa agatcacgac 3180
atcgactaca aggacgacga cgacaaggac ggtgccccac accaccacca ccaccacgaa 3240
gatcaggtgg atcctcgcct gatcgatggc aagtaa 3276
<210> 176
<211> 1109
<212> PRT
<213> 人工序列
<220>
<223> TwinStrep-3cV2-TATκ28-hCDKL5-Flag-His-TwinStrep (氨基酸
序列)
<400> 176
Met Ser Ala Trp Ser His Pro Gln Phe Glu Lys Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Ser Gly Gly Ser Ala Trp Ser His Pro Gln Phe Glu Lys Gly
20 25 30
Ser Leu Glu Val Leu Phe Gln Gly Pro Asp Ala Ala Gln Pro Ala Arg
35 40 45
Arg Ala Arg Arg Thr Lys Leu Ala Ala Tyr Ala Arg Lys Ala Ala Arg
50 55 60
Gln Ala Arg Ala Gly Gly Gly Gly Ser Lys Ile Pro Asn Ile Gly Asn
65 70 75 80
Val Met Asn Lys Phe Glu Ile Leu Gly Val Val Gly Glu Gly Ala Tyr
85 90 95
Gly Val Val Leu Lys Cys Arg His Lys Glu Thr His Glu Ile Val Ala
100 105 110
Ile Lys Lys Phe Lys Asp Ser Glu Glu Asn Glu Glu Val Lys Glu Thr
115 120 125
Thr Leu Arg Glu Leu Lys Met Leu Arg Thr Leu Lys Gln Glu Asn Ile
130 135 140
Val Glu Leu Lys Glu Ala Phe Arg Arg Arg Gly Lys Leu Tyr Leu Val
145 150 155 160
Phe Glu Tyr Val Glu Lys Asn Met Leu Glu Leu Leu Glu Glu Met Pro
165 170 175
Asn Gly Val Pro Pro Glu Lys Val Lys Ser Tyr Ile Tyr Gln Leu Ile
180 185 190
Lys Ala Ile His Trp Cys His Lys Asn Asp Ile Val His Arg Asp Ile
195 200 205
Lys Pro Glu Asn Leu Leu Ile Ser His Asn Asp Val Leu Lys Leu Cys
210 215 220
Asp Phe Gly Phe Ala Arg Asn Leu Ser Glu Gly Asn Asn Ala Asn Tyr
225 230 235 240
Thr Glu Tyr Val Ala Thr Arg Trp Tyr Arg Ser Pro Glu Leu Leu Leu
245 250 255
Gly Ala Pro Tyr Gly Lys Ser Val Asp Met Trp Ser Val Gly Cys Ile
260 265 270
Leu Gly Glu Leu Ser Asp Gly Gln Pro Leu Phe Pro Gly Glu Ser Glu
275 280 285
Ile Asp Gln Leu Phe Thr Ile Gln Lys Val Leu Gly Pro Leu Pro Ser
290 295 300
Glu Gln Met Lys Leu Phe Tyr Ser Asn Pro Arg Phe His Gly Leu Arg
305 310 315 320
Phe Pro Ala Val Asn His Pro Gln Ser Leu Glu Arg Arg Tyr Leu Gly
325 330 335
Ile Leu Asn Ser Val Leu Leu Asp Leu Met Lys Asn Leu Leu Lys Leu
340 345 350
Asp Pro Ala Asp Arg Tyr Leu Thr Glu Gln Cys Leu Asn His Pro Thr
355 360 365
Phe Gln Thr Gln Arg Leu Leu Asp Arg Ser Pro Ser Arg Ser Ala Lys
370 375 380
Arg Lys Pro Tyr His Val Glu Ser Ser Thr Leu Ser Asn Arg Asn Gln
385 390 395 400
Ala Gly Lys Ser Thr Ala Leu Gln Ser His His Arg Ser Asn Ser Lys
405 410 415
Asp Ile Gln Asn Leu Ser Val Gly Leu Pro Arg Ala Asp Glu Gly Leu
420 425 430
Pro Ala Asn Glu Ser Phe Leu Asn Gly Asn Leu Ala Gly Ala Ser Leu
435 440 445
Ser Pro Leu His Thr Lys Thr Tyr Gln Ala Ser Ser Gln Pro Gly Ser
450 455 460
Thr Ser Lys Asp Leu Thr Asn Asn Asn Ile Pro His Leu Leu Ser Pro
465 470 475 480
Lys Glu Ala Lys Ser Lys Thr Glu Phe Asp Phe Asn Ile Asp Pro Lys
485 490 495
Pro Ser Glu Gly Pro Gly Thr Lys Tyr Leu Lys Ser Asn Ser Arg Ser
500 505 510
Gln Gln Asn Arg His Ser Phe Met Glu Ser Ser Gln Ser Lys Ala Gly
515 520 525
Thr Leu Gln Pro Asn Glu Lys Gln Ser Arg His Ser Tyr Ile Asp Thr
530 535 540
Ile Pro Gln Ser Ser Arg Ser Pro Ser Tyr Arg Thr Lys Ala Lys Ser
545 550 555 560
His Gly Ala Leu Ser Asp Ser Lys Ser Val Ser Asn Leu Ser Glu Ala
565 570 575
Arg Ala Gln Ile Ala Glu Pro Ser Thr Ser Arg Tyr Phe Pro Ser Ser
580 585 590
Cys Leu Asp Leu Asn Ser Pro Thr Ser Pro Thr Pro Thr Arg His Ser
595 600 605
Asp Thr Arg Thr Leu Leu Ser Pro Ser Gly Arg Asn Asn Arg Asn Glu
610 615 620
Gly Thr Leu Asp Ser Arg Arg Thr Thr Thr Arg His Ser Lys Thr Met
625 630 635 640
Glu Glu Leu Lys Leu Pro Glu His Met Asp Ser Ser His Ser His Ser
645 650 655
Leu Ser Ala Pro His Glu Ser Phe Ser Tyr Gly Leu Gly Tyr Thr Ser
660 665 670
Pro Phe Ser Ser Gln Gln Arg Pro His Arg His Ser Met Tyr Val Thr
675 680 685
Arg Asp Lys Val Arg Ala Lys Gly Leu Asp Gly Ser Leu Ser Ile Gly
690 695 700
Gln Gly Met Ala Ala Arg Ala Asn Ser Leu Gln Leu Leu Ser Pro Gln
705 710 715 720
Pro Gly Glu Gln Leu Pro Pro Glu Met Thr Val Ala Arg Ser Ser Val
725 730 735
Lys Glu Thr Ser Arg Glu Gly Thr Ser Ser Phe His Thr Arg Gln Lys
740 745 750
Ser Glu Gly Gly Val Tyr His Asp Pro His Ser Asp Asp Gly Thr Ala
755 760 765
Pro Lys Glu Asn Arg His Leu Tyr Asn Asp Pro Val Pro Arg Arg Val
770 775 780
Gly Ser Phe Tyr Arg Val Pro Ser Pro Arg Pro Asp Asn Ser Phe His
785 790 795 800
Glu Asn Asn Val Ser Thr Arg Val Ser Ser Leu Pro Ser Glu Ser Ser
805 810 815
Ser Gly Thr Asn His Ser Lys Arg Gln Pro Ala Phe Asp Pro Trp Lys
820 825 830
Ser Pro Glu Asn Ile Ser His Ser Glu Gln Leu Lys Glu Lys Glu Lys
835 840 845
Gln Gly Phe Phe Arg Ser Met Lys Lys Lys Lys Lys Lys Ser Gln Thr
850 855 860
Val Pro Asn Ser Asp Ser Pro Asp Leu Leu Thr Leu Gln Lys Ser Ile
865 870 875 880
His Ser Ala Ser Thr Pro Ser Ser Arg Pro Lys Glu Trp Arg Pro Glu
885 890 895
Lys Ile Ser Asp Leu Gln Thr Gln Ser Gln Pro Leu Lys Ser Leu Arg
900 905 910
Lys Leu Leu His Leu Ser Ser Ala Ser Asn His Pro Ala Ser Ser Asp
915 920 925
Pro Arg Phe Gln Pro Leu Thr Ala Gln Gln Thr Lys Asn Ser Phe Ser
930 935 940
Glu Ile Arg Ile His Pro Leu Ser Gln Ala Ser Gly Gly Ser Ser Asn
945 950 955 960
Ile Arg Gln Glu Pro Ala Pro Lys Gly Arg Pro Ala Leu Gln Leu Pro
965 970 975
Gly Gln Met Asp Pro Gly Trp His Val Ser Ser Val Thr Arg Ser Ala
980 985 990
Thr Glu Gly Pro Ser Tyr Ser Glu Gln Leu Gly Ala Lys Ser Gly Pro
995 1000 1005
Asn Gly His Pro Tyr Asn Arg Thr Asn Arg Ser Arg Met Pro Asn
1010 1015 1020
Leu Asn Asp Leu Lys Glu Thr Ala Leu Gly Ala Gly Gly Gly Gly
1025 1030 1035
Ser Leu Glu Val Leu Phe Gln Gly Pro Asp Tyr Lys Asp His Asp
1040 1045 1050
Gly Asp Tyr Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Asp
1055 1060 1065
Lys Asp Gly Ala Pro His His His His His His Ser Ala Trp Ser
1070 1075 1080
His Pro Gln Phe Glu Lys Gly Gly Gly Ser Gly Gly Gly Ser Gly
1085 1090 1095
Gly Ser Ala Trp Ser His Pro Gln Phe Glu Lys
1100 1105
<210> 177
<211> 3330
<212> DNA
<213> 人工序列
<220>
<223> TwinStrep-3cV2-TATκ28-hCDKL5-Flag-His-TwinStrep (DNA
序列)
<400> 177
atgtcagcgt ggtcgcatcc tcaattcgaa aagggcggcg gttcgggtgg aggaagtggc 60
ggatcggcct ggtctcaccc gcaattcgaa aagggttccc tcgaggtcct gtttcagggc 120
cccgacgctg ctcagcctgc tcgccgtgcc aggagaacca agctggctgc ctacgctcgt 180
aaggctgcta gacaagctag ggccggtggc ggaggtagca agatcccaaa catcggtaac 240
gtgatgaaca agttcgagat cctgggcgtg gtcggtgaag gcgcttacgg agtggtcctg 300
aagtgcaggc acaaggagac ccacgaaatc gtggccatca agaagttcaa ggactctgag 360
gaaaacgagg aagtcaaaga gaccactctg cgtgaactga agatgctgag gactctgaag 420
caggagaaca tcgtcgagct gaaggaagct ttccgccgta ggggaaagct gtacctggtg 480
ttcgagtacg tcgaaaagaa catgctggag ctgctggagg aaatgccaaa cggtgtgcct 540
cccgaaaagg tcaagagcta catctaccag ctgatcaagg ccatccactg gtgccacaag 600
aacgacatcg tgcaccgtga catcaagcct gagaacctgc tgatcagcca caacgacgtc 660
ctgaagctgt gcgacttcgg tttcgctagg aacctgtctg agggcaacaa cgctaactac 720
actgaatacg tggccacccg ttggtacagg tctccagagc tgctgctggg tgccccttac 780
ggcaagtctg tggacatgtg gtctgtcgga tgcatcctgg gtgaactgag cgacggacag 840
cccctgttcc caggagagtc tgaaatcgac cagctgttca ccatccagaa ggtcctgggc 900
cccctgccaa gcgagcagat gaagctgttc tactctaacc cccgtttcca cggactgagg 960
ttccctgctg tgaaccaccc ccagagcctg gaaagacgct acctgggtat cctgaactct 1020
gtcctgctgg acctgatgaa gaacctgctg aagctggacc ctgctgaccg ctacctgacc 1080
gagcagtgcc tgaaccaccc cactttccag acccagagac tgctggaccg cagcccctct 1140
cgttcagcca agaggaagcc ataccacgtg gaatccagca ccctgagcaa ccgtaaccag 1200
gctggcaagt ccactgccct gcagagccac cacaggtcca acagcaagga catccaaaac 1260
ctgtcagtgg gactgccaag ggctgacgag ggactgccag ccaacgaatc cttcctgaac 1320
ggcaacctgg ctggagcctc tctgtcacca ctgcacacta agacctacca ggcttcttca 1380
cagcctggtt ccactagcaa ggacctgacc aacaacaaca tcccacacct gctgtctcct 1440
aaggaagcta aatcaaagac cgagttcgac ttcaacatcg accctaagcc ctccgaggga 1500
cctggtacta agtacctgaa gtctaactca agatcccagc agaaccgcca ctcattcatg 1560
gagtccagcc agtccaaggc tggtaccctg cagcccaacg aaaagcagtc ccgccacagc 1620
tacatcgaca ccatccctca gtcttcacgt agcccctctt acaggactaa ggctaagagc 1680
cacggcgccc tgtcagactc caagagcgtg tctaacctgt ctgaggctag agcccagatc 1740
gccgaacctt caacctcccg ctacttcccc tccagctgcc tggacctgaa ctctcccact 1800
tcaccaactc ctaccagaca ctccgacact cgcaccctgc tgagcccatc tggtagaaac 1860
aaccgcaacg agggcaccct ggactcacgt aggaccacta cccgtcactc caagactatg 1920
gaggaactga agctgccaga gcacatggac tcttcacact cacactccct gagcgctcct 1980
cacgaatctt tctcatacgg cctgggatac accagcccat tctccagcca gcagcgtcct 2040
cacaggcact ctatgtacgt gactagagac aaggtccgcg ctaagggact ggacggttcc 2100
ctgtctatcg gtcagggaat ggctgctagg gccaactctc tgcagctgct gtcaccccag 2160
ccaggagagc agctgccacc tgaaatgacc gtggctagat cttcagtcaa ggagacttcc 2220
cgcgaaggca cctccagctt ccacactaga cagaagtcag agggcggagt gtaccacgac 2280
cctcactctg acgacggaac tgctcccaag gaaaaccgcc acctgtacaa cgaccctgtg 2340
cccagacgcg tcggatcctt ctaccgtgtc ccaagcccta ggcccgacaa ctctttccac 2400
gagaacaacg tgagcaccag agtctcttca ctgccctctg aatccagctc tggcactaac 2460
cactcaaagc gccagcctgc tttcgacccc tggaagtccc cagagaacat ctctcactca 2520
gaacagctga aggagaagga aaagcaggga ttcttccgct caatgaagaa gaagaagaag 2580
aagtcccaga ccgtgcccaa ctccgacagc ccagacctgc tgaccctgca gaagtcaatc 2640
cactctgcct caactccttc atccagaccc aaggagtggc gccccgaaaa gatctccgac 2700
ctgcagactc agtcccagcc actgaagagc ctgcgtaagc tgctgcacct gagctctgct 2760
tccaaccacc ctgcctcatc cgacccacgt ttccagcctc tgactgctca gcagaccaag 2820
aactccttca gcgagatcag gatccaccca ctgtcccagg ctagcggtgg cagctctaac 2880
atccgtcagg aaccagctcc taagggacgt ccagctctgc agctgcctgg tcagatggac 2940
ccaggctggc acgtgtcatc cgtcactaga tcagctaccg agggaccatc ttactcagaa 3000
cagctgggtg ccaagtcagg ccccaacgga cacccataca accgcaccaa ccgttccagg 3060
atgcctaacc tgaacgacct gaaggagact gctctggggg ccggaggtgg cggatccctg 3120
gaagtgcttt tccaaggtcc cgactacaag gaccacgacg gtgactacaa agatcacgac 3180
atcgactaca aggacgacga cgacaaggac ggtgccccac accaccacca ccaccactct 3240
gcatggtcgc atcctcaatt cgagaagggg ggtggcagcg gagggggttc cggcggatca 3300
gcctggagtc acccacagtt tgaaaaataa 3330

Claims (77)

1.一种组合物，所述组合物包含：
基因疗法递送系统；以及
编码CDKL5多肽的CDKL5多核苷酸，其中所述CDKL5多肽与SEQ ID NO:1、SEQ ID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQ ID NO:26具有至少98％的序列同一性。
2.如权利要求1所述的组合物，其中所述CDKL5多肽与SEQ ID NO:1或SEQ ID NO:26具有至少98％的序列同一性。
3.如权利要求1或2所述的组合物，其中所述CDKL5多核苷酸与SEQ ID NO:123具有至少90％的序列同一性。
4.如权利要求1所述的组合物，其中所述CDKL5多肽与SEQ ID NO:2、SEQ ID NO:3、SEQID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ ID NO:9、SEQ IDNO:10、SEQ ID NO:11或SEQ ID NO:12具有至少98％的序列同一性。
5.如权利要求1所述的组合物，其中所述CDKL5多肽与SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24或SEQ ID NO:25具有至少98％的序列同一性。
6.如权利要求1或5所述的组合物，其中所述CDKL5多核苷酸与SEQ ID NO:125、SEQ IDNO:127、SEQ ID NO:129、SEQ ID NO:131、SEQ ID NO:133、SEQ ID NO:135、SEQ ID NO:137、SEQ ID NO:139、SEQ ID NO:141、SEQ ID NO:143、SEQ ID NO:145、SEQ ID NO:147或1SEQID NO:149具有至少90％的序列同一性。
7.如权利要求1-6中任一项所述的组合物，其中所述基因疗法递送系统包含病毒载体、脂质体、脂质-核酸纳米粒子、外来体和基因编辑系统中的一项或多项。
8.如权利要求7所述的组合物，其中所述基因编辑系统包含规律间隔成簇短回文重复(CRISPR)相关蛋白9(CRISPR-Cas-9)、转录激活因子样效应核酸酶(TALEN)或ZNF(锌指蛋白)中的一项或多项。
9.如权利要求1-7中任一项所述的组合物，其中所述基因疗法递送系统包含病毒载体。
10.如权利要求9所述的组合物，其中所述病毒载体包含腺病毒载体、腺相关病毒载体、慢病毒载体、逆转录病毒载体、痘病毒载体或单纯疱疹病毒载体中的一项或多项。
11.如权利要求9或10所述的组合物，其中所述病毒载体包含与所述CDKL5多核苷酸可操作地连接的病毒多核苷酸。
12.如权利要求9-11中任一项所述的组合物，其中所述病毒载体包含至少一个反向末端重复(ITR)。
13.如权利要求9-12中任一项所述的组合物，所述组合物进一步包含SV40内含子、聚腺苷酸化信号或稳定元件中的一项或多项。
14.如权利要求9-13中任一项所述的组合物，所述组合物进一步包含启动子。
15.如权利要求14所述的组合物，其中所述启动子与SEQ ID NO:29或SEQ ID NO:30具有至少90％的序列同一性。
16.如权利要求1-15中任一项所述的组合物，所述组合物进一步包含编码细胞穿透多肽的多核苷酸。
17.如权利要求16所述的组合物，其中所述细胞穿透多肽与SEQ ID NO:32、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37或SEQ ID NO:167具有至少90％的序列同一性。
18.如权利要求16或17所述的组合物，其中编码所述细胞穿透肽的多核苷酸与SEQ IDNO:150、SEQ ID NO:151、SEQ ID NO:152、SEQ ID NO:153、SEQ ID NO:154、SEQ ID NO:170、SEQ ID NO:171、SEQ ID NO:172或SEQ ID NO:173具有至少90％的序列同一性。
19.如权利要求1-18中任一项所述的组合物，所述组合物进一步包含编码前导信号多肽的多核苷酸。
20.如权利要求19所述的组合物，其中所述前导信号多肽与SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42、SEQ ID NO:156、SEQ ID NO:157、SEQ IDNO:158、SEQ ID NO:159、SEQ ID NO:160、SEQ ID NO:161、SEQ ID NO:162、SEQ ID NO:163、SEQ ID NO:164、SEQ ID NO:165、SEQ ID NO:166或SEQ ID NO:168具有至少90％的序列同一性。
21.如权利要求19或20所述的组合物，其中编码所述前导信号多肽的多核苷酸与SEQID NO:155或SEQ ID NO:169具有至少90％的序列同一性。
22.一种药物配制品，所述药物配制品包含如权利要求1-21中任一项所述的组合物；以及药学上可接受的载剂。
23.一种治疗CDKL5介导的神经性障碍的方法，所述方法包括将如权利要求1-21中任一项所述的组合物或如权利要求22所述的配制品施用至对其有需要的患者。
24.如权利要求23所述的方法，其中所述组合物或所述配制品是鞘内、静脉内、脑池内、脑室内或实质内施用的。
25.如权利要求23或24所述的方法，其中所述CDKL5介导的神经性障碍是CDKL5缺乏或者由CDKL5突变或缺乏引起的非典型雷特综合征中的一项或多项。
26.一种治疗CDKL5介导的神经性障碍的方法，所述方法包括将如权利要求1-21中任一项所述的组合物或如权利要求22所述的配制品施用至离体细胞，并将所述离体细胞施用至对其有需要的患者。
27.如权利要求26所述的方法，其中所述离体细胞是鞘内、静脉内、脑池内、脑室内或实质内施用的。
28.如权利要求26或27所述的方法，其中所述CDKL5介导的神经性障碍是CDKL5缺乏或者由CDKL5突变或缺乏引起的非典型雷特综合征中的一项或多项。
29.一种CDKL5多肽，其中所述CDKL5多肽包含与SEQ ID NO:13、SEQ ID NO:14、SEQ IDNO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ IDNO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24或SEQ ID NO:25具有至少99％序列同一性的序列。
30.如权利要求29所述的CDKL5多肽，其中所述CDKL5多肽包含SEQ ID NO:13、SEQ IDNO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ IDNO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24或SEQ ID NO:25的序列。
31.如权利要求29所述的CDKL5多肽，其中所述CDKL5多肽包含SEQ ID NO:13的序列。
32.如权利要求29所述的CDKL5多肽，其中所述CDKL5多肽包含SEQ ID NO:14的序列。
33.如权利要求29所述的CDKL5多肽，其中所述CDKL5多肽包含SEQ ID NO:15的序列。
34.如权利要求29所述的CDKL5多肽，其中所述CDKL5多肽包含SEQ ID NO:16的序列。
35.如权利要求29所述的CDKL5多肽，其中所述CDKL5多肽包含SEQ ID NO:17的序列。
36.如权利要求29所述的CDKL5多肽，其中所述CDKL5多肽包含SEQ ID NO:18的序列。
37.如权利要求29所述的CDKL5多肽，其中所述CDKL5多肽包含SEQ ID NO:19的序列。
38.如权利要求29所述的CDKL5多肽，其中所述CDKL5多肽包含SEQ ID NO:20的序列。
39.如权利要求29所述的CDKL5多肽，其中所述CDKL5多肽包含SEQ ID NO:21的序列。
40.如权利要求29所述的CDKL5多肽，其中所述CDKL5多肽包含SEQ ID NO:22的序列。
41.如权利要求29所述的CDKL5多肽，其中所述CDKL5多肽包含SEQ ID NO:23的序列。
42.如权利要求29所述的CDKL5多肽，其中所述CDKL5多肽包含SEQ ID NO:24的序列。
43.如权利要求29所述的CDKL5多肽，其中所述CDKL5多肽包含SEQ ID NO:25的序列。
44.一种CDKL5多肽，其中所述CDKL5多肽包含具有相对于SEQ ID NO:1或SEQ ID NO:26的一个或多个突变以除去一个或多个N-连接糖基化位点的序列。
45.如权利要求44所述的CDKL5多肽，其中所述序列与SEQ ID NO:1或SEQ ID NO:26具有至少99％的序列同一性。
46.如权利要求44或45所述的CDKL5多肽，其中SEQ ID NO:1或SEQ ID NO:26的至少一个天冬酰胺残基已被不同的氨基酸取代。
47.如权利要求44-46中任一项所述的CDKL5多肽，其中SEQ ID NO:1或SEQ ID NO:26的至少一个天冬酰胺残基已被谷氨酰胺取代。
48.如权利要求44-47中任一项所述的CDKL5多肽，其中SEQ ID NO:1或SEQ ID NO:26的至少一个丝氨酸或苏氨酸残基已被不同的氨基酸取代。
49.如权利要求44-48中任一项所述的CDKL5多肽，其中SEQ ID NO:1或SEQ ID NO:26的天冬酰胺-X-丝氨酸序列或天冬酰胺-X-苏氨酸序列中的至少一个氨基酸已被脯氨酸或组氨酸取代。
50.一种融合蛋白，所述融合蛋白包含如权利要求29-49中任一项所述的CDKL5多肽和可操作地偶联至所述CDKL5多肽的前导信号多肽。
51.如权利要求50所述的融合蛋白，其中所述前导信号多肽与SEQ ID NO:38、SEQ IDNO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42或SEQ ID NO:168具有至少90％的序列同一性。
52.如权利要求50或51所述的融合蛋白，其中所述前导信号多肽包含SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42或SEQ ID NO:168的序列。
53.一种融合蛋白，所述融合蛋白包含如权利要求29-49中任一项所述的CDKL5多肽和可操作地偶联至所述CDKL5多肽的细胞穿透多肽。
54.如权利要求53所述的融合蛋白，其中所述细胞穿透多肽与SEQ ID NO:31、SEQ IDNO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37或SEQID NO:167具有至少90％的序列同一性。
55.如权利要求53或54所述的融合蛋白，其中所述细胞穿透多肽包含SEQ ID NO:31、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:36、SEQ ID NO:37或SEQ ID NO:167的序列。
56.如权利要求53-55中任一项所述的融合蛋白，所述融合蛋白进一步包含前导信号多肽。
57.如权利要求56所述的融合蛋白，其中所述前导信号多肽与SEQ ID NO:38、SEQ IDNO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42或SEQ ID NO:168具有至少90％的序列同一性。
58.如权利要求56或57所述的融合蛋白，其中所述前导信号多肽包含SEQ ID NO:38、SEQ ID NO:39、SEQ ID NO:40、SEQ ID NO:41、SEQ ID NO:42或SEQ ID NO:168的序列。
59.如权利要求29-58中任一项所述的融合蛋白，所述融合蛋白进一步包含一个或多个亲和标签、一个或多个蛋白酶切割位点或其组合。
60.如权利要求59所述的融合蛋白，其中所述亲和标签包含MYC、HA、V5、NE、StrepII、
Figure FDA0003721100630000081
谷胱甘肽S-转移酶(GST)、麦芽糖结合蛋白(MBP)、钙调蛋白结合肽(CBP)、
Figure FDA0003721100630000082
多组氨酸(His)、HPC4或其组合中的一项或多项。
61.如权利要求59或60所述的融合蛋白，其中所述蛋白酶切割位点对凝血酶、弗林蛋白酶、因子Xa、金属蛋白酶、肠激酶、组织蛋白酶、HRV3C、TEV或其组合中的一项或多项敏感。
62.一种药物配制品，所述药物配制品包含
如权利要求29-49中任一项所述的CDKL5多肽或如权利要求50-61中任一项所述的融合蛋白；以及
药学上可接受的载剂。
63.一种治疗CDKL5介导的神经性障碍的方法，所述方法包括将如权利要求29-49中任一项所述的CDKL5多肽、或如权利要求50-61中任一项所述的融合蛋白、或如权利要求62所述的配制品施用至对其有需要的患者。
64.如权利要求63所述的方法，其中CDKL5多肽、所述融合蛋白或所述配制品是鞘内、静脉内、脑池内、脑室内或实质内施用的。
65.如权利要求63或64所述的方法，其中所述CDKL5介导的神经性障碍是CDKL5缺乏或者由CDKL5突变或缺乏引起的非典型雷特综合征中的一项或多项。
66.一种生产如权利要求29-49中任一项所述的CDKL5多肽或如权利要求50-61中任一项所述的融合蛋白的方法，所述方法包括：
表达所述CDKL5多肽或所述融合蛋白；以及
纯化所述CDKL5多肽或所述融合蛋白。
67.如权利要求66所述的方法，其中所述CDKL5多肽或所述融合蛋白在中国仓鼠卵巢(CHO)细胞、HeLa细胞、人胚肾(HEK)细胞、昆虫细胞或大肠杆菌细胞中表达。
68.一种生产包含CDKL5多肽的蛋白的方法，所述方法包括：
在昆虫细胞中表达所述蛋白；以及
从所述昆虫细胞中纯化所述蛋白。
69.如权利要求68所述的方法，其中所述昆虫细胞是Sf9细胞或BTI-Tn-5B1-4细胞。
70.如权利要求68或69所述的方法，其中所述蛋白包括含有所述CDKL5多肽和可操作地偶联至所述CDKL5多肽的细胞穿透多肽的融合蛋白。
71.如权利要求70所述的方法，其中所述融合蛋白进一步包含前导信号多肽。
72.如权利要求68-71中任一项所述的方法，其中所述融合蛋白进一步包含亲和标签、一个或多个蛋白酶切割位点或其组合中的一项或多项。
73.如权利要求72所述的方法，其中所述亲和标签包含MYC、HA、V5、NE、StrepII、
Figure FDA0003721100630000101
谷胱甘肽S-转移酶(GST)、麦芽糖结合蛋白(MBP)、钙调蛋白结合肽(CBP)、
Figure FDA0003721100630000102
多组氨酸(His)、HPC4或其组合中的一项或多项。
74.如权利要求72或73所述的方法，其中所述蛋白酶切割位点对凝血酶、弗林蛋白酶、因子Xa、金属蛋白酶、肠激酶、组织蛋白酶、HRV3C、TEV或其组合中的一项或多项敏感。
75.如权利要求68-74中任一项所述的方法，其中所述CDKL5多肽与SEQ ID NO:1、SEQID NO:2、SEQ ID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ IDNO:8、SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:11、SEQ ID NO:12、SEQ ID NO:13、SEQ IDNO:14、SEQ ID NO:15、SEQ ID NO:16、SEQ ID NO:17、SEQ ID NO:18、SEQ ID NO:19、SEQ IDNO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:24、SEQ ID NO:25或SEQID NO:26具有至少98％的序列同一性。
76.如权利要求68-75中任一项所述的方法，其中所述CDKL5多肽与SEQ ID NO:1或SEQID NO:26具有至少98％的序列同一性。
77.如权利要求68-76中任一项所述的方法，其中所述CDKL5多肽与SEQ ID NO:2、SEQID NO:3、SEQ ID NO:4、SEQ ID NO:5、SEQ ID NO:6、SEQ ID NO:7、SEQ ID NO:8、SEQ IDNO:9、SEQ ID NO:10、SEQ ID NO:11或SEQ ID NO:12具有至少98％的序列同一性。
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