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一种融合蛋白及其应用

文献发布时间:2023-06-19 11:26:00



技术领域

本发明涉及生物医药领域,具体而言,涉及一种融合蛋白及其应用。

背景技术

所有病毒都有核酸(包括DNA和RNA),并且都以核酸作为寄生存活的根本。目前应对病毒传染病(例如新冠病毒、HIV等等)主要寄希望于疫苗。疫苗开发难度大,时间长,效果也因人而异,在特殊情况下,疫苗可能不起应有的作用甚至起反作用。故有必要开发一种以直接杀灭病毒为主的组合型预防和治疗病毒疾病的方法。

有鉴于此,特提出本发明。

发明内容

这种方法的关键特点是通过蛋白融合(核酸酶-病毒识别蛋白融合体)或者载体结合(核酸酶-病毒识别载体)的方式,将一般性降解病毒核酸的工具酶与病毒的特异性受体以及抗体有机结合在一起,直接针对性地杀灭特定病毒。这种方法以核酸酶降解病毒核酸为主攻武器,以病毒的特异性受体以及抗体为主要开关,配合以病毒特异性融膜分子、病毒特异性融膜载体(包括脂质体、纳米颗粒、红细胞,功能性活细胞等)作为病毒攻击通道。

本方法使用的核酸酶包括所有能够降解病毒核酸的工具酶,例如各种RNase,DNase,ribozyme,siRNA,CRISPR介导的DNA酶和RNA酶等等。

本方法使用的病毒的特异性受体以及抗体包括所有能够与特定病毒组成成分特异性能够结合的一般分子,其中特别包括病毒的受体以及所有能够与特定病毒组成成分特异性结合的抗体,例如新冠病毒的受体ACE2以及各种抗新冠病毒S蛋白,E蛋白,M蛋白,N蛋白抗体等等。

本方法使用的蛋白融合(核酸酶-病毒识别蛋白融合体)方式包括将核酸酶通过共价键融合连接到各种特定病毒识别蛋白体的N端或者C端。例如特定病毒受体的N端或者C端,以及将核酸酶通过共价键融合连接到特定病毒抗体轻链的N端或者C端,或者连接到特定病毒抗体重链的N端或者C端。

本方法使用的病毒特异性融膜载体包括脂质体、纳米颗粒、红细胞,各种功能性活细胞等等。

本方法使用的载体结合(核酸酶-病毒识别载体)方式包括将针对特定病毒核酸的核酸酶放入病毒特异性融膜载体内部,将特定病毒识别蛋白体(例如病毒受体和抗体等等)放到病毒特异性融膜载体表面。

在使用各种功能性活细胞作为核酸酶-病毒识别载体的方式中,一般采用基因表达载体的方式将针对特定病毒中特定核酸序列的特异性核酸酶(例如ribozyme,siRNA,CRISPR介导的DNA酶和RNA酶等等)放入病毒特异性融膜载体内部,将特定病毒识别蛋白体(例如病毒受体和抗体等等)放到病毒特异性融膜载体表面。

本发明采用了如下技术方案:

本发明提供一种预防和治疗病毒性传染病的融合蛋白,其特征在于,包括:核酸酶、病毒抗体或病毒受体。

进一步,本发明的预防和治疗病毒性传染病的融合蛋白,其特征在于,还包括:病毒特异性融膜载体。

本发明还提供一种预防和治疗新冠状病毒传染病的融合蛋白,其特征在于,包括:核酸酶、新冠病毒抗体或病毒受体。

进一步,本发明的预防和治疗新冠状病毒传染病的融合蛋白,其特征在于,包括:新冠病毒受体。

进一步,本发明的预防和治疗新冠状病毒传染病的融合蛋白,其特征在于:所述新冠病毒受体为ACE2及其改造形式,新冠病毒抗体为CR3022及其改造形式。

进一步,本发明的预防和治疗新冠状病毒传染病的融合蛋白,其特征在于,还包括:核糖核酸酶。

进一步,本发明的预防和治疗新冠状病毒传染病的融合蛋白,其特征在于:所述核糖核酸酶为RNase7、RNase2、RNaseK、RNaseT2、XRN2、XRN1或新冠状病毒RNA序列特异性的RNaseP。

进一步,本发明的预防和治疗新冠状病毒传染病的融合蛋白,其特征在于,还包括:co-receptors(受体):为CD147、DC-SIGN(CD209)、L-SIGN(CD209L)、CLEC4G、ANPEP、ENPEP或DPP4。

进一步,本发明的预防和治疗新冠状病毒传染病的融合蛋白,其特征在于,融合蛋白的序列如本文二十三个实施例(1-23)所示。

进一步,本发明的预防和治疗新冠状病毒传染病的融合蛋白,融合蛋白为新冠病毒受体-新冠病毒抗体-核糖核酸酶形式。

本发明还提供一种识别新冠病毒的RNA酶-红细胞载体,首先通过基因表达载体将新冠病毒的受体ACE2m(H374D,H378D)和CD147以及抗新冠病毒的抗体(IgM完整形式)表达在人脐带血中的CD34阳性细胞hematopoietic stem cells(HSCs)表面,然后诱导生成成熟的无核红细胞,然后采用短暂低渗透压的方法将RNase7,RNase2,XRN2,XRN1放到红细胞内部。

本发明还提供一种识别新冠病毒的RNA酶-功能性活细胞载体,首先通过基因表达载体将新冠病毒的受体ACE2m(H374D,H378D),CD147,抗新冠病毒的抗体,以及专门识别并且特异性切断新冠病毒RNA保守序列的RNase P在人脐带血或者其他有核细胞中表达。

本发明的预防和治疗病毒性传染病的多功能融合蛋白和多功能载体,开发速度比疫苗更快而且更容易,安全性和有效性把握性更大。可以推广应用到各种病毒传染病的预防和治疗中。

具体实施方式

下面以新冠病毒为主进行具体说明,当然,相似的蛋白结构和开发方式开发所得到的成果可以应用到其它各种细胞特异性病毒传染病。

实施例一

本实施例的融合蛋白ACE2-huFc(G1)-RNase7,用于鼻腔和眼睛点滴而预防新冠病毒传染,融合蛋白序列如下:

STIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWS

AFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQE

CLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVN

GVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYS

LTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKS

IGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEP

VPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRL

GKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYAD

QSIKVRISLKSALGD

RAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKPRISFNFFVTAPKNVSDIIPRTEV

EKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQPPVS

GSGG

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGSGG

KPKGMTSSQWFKIQHMQPSPQACNSAMKNINKHTKRCKDLNT

FLHEPFSSVAATCQTPKIACKNGDKNCHQSHGAVSLTMCKLTSGKHPNCRYKEKRQNKSYVVACKPPQKK

DSQQFHLVPVHLDRVL

本实施例及以下一些实施例中,每个融合蛋白分子的第一行是用于细胞分泌的信号肽,最终的纯化产品不包括信号肽。如果用昆虫细胞表达可以换成gp64或者gp67信号肽,如果用细菌表达需要将信号肽替换成起始密码。融合蛋白的各部分以GSGG或者GGSGG的连接序列进行连接。

实施例二

本实施例的融合蛋白ACE2-huFc(G1+M)-RNase7,用于鼻腔和眼睛点滴而预防新冠病毒传染,融合蛋白序列如下:

STIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWS

AFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQE

CLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVN

GVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYS

LTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKS

IGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEP

VPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRL

GKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYAD

QSIKVRISLKSALGD

RAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKPRISFNFFVTAPKNVSDIIPRTEV

EKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQPPVS

GSGG

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

PDVYLLPPAREQLNLRESATITCLVTGFSPADVFVQWMQRGQPLSPEKYVTSAPMPEPQAPGRYFAHSIL

TVSEEEWNTGETYTCVVAHEALPNRVTERTVD

KSTGKPTLYNVSLVMSDTAGTCY

GGSGG

KPKGMTSSQWFKIQHMQPSPQACNSAMKNINKHTKRCKDLNT

FLHEPFSSVAATCQTPKIACKNGDKNCHQSHGAVSLTMCKLTSGKHPNCRYKEKRQNKSYVVACKPPQKK

DSQQFHLVPVHLDRVL

实施例三

本实施例的融合蛋白ACE2m(H374D,H378D)-huFc(G1)-RNase7,用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:(ACE2序列中374位的H,修改为D,378位的H,也修改为D):

MSSSSWLLLSLVAVTAAQ(信号肽)

STIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWS

AFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQE

CLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVN

GVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYS

LTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHdEMGdIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKS

IGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEP

VPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRL

GKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYAD

QSIKVRISLKSALGD

RAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKPRISFNFFVTAPKNVSDIIPRTEV

EKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQPPVS

GSGG

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGSGG

KPKGMTSSQWFKIQHMQPSPQACNSAMKNINKHTKRCKDLNT

FLHEPFSSVAATCQTPKIACKNGDKNCHQSHGAVSLTMCKLTSGKHPNCRYKEKRQNKSYVVACKPPQKK

DSQQFHLVPVHLDRVL

实施例四

本实施例的融合蛋白ACE2m(H374D,H378D)-huFc(G1+M)-RNase7,用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:(ACE2序列中374位的H,修改为D,378位的H,也修改为D):

MSSSSWLLLSLVAVTAAQ(信号肽)

STIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWS

AFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQE

CLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVN

GVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYS

LTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHdEMGdIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKS

IGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEP

VPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRL

GKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYAD

QSIKVRISLKSALGD

RAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKPRISFNFFVTAPKNVSDIIPRTEV

EKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQPPVS

GSGG

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

PDVYLLPPAREQLNLRESATITCLVTGFSPADVFVQWMQRGQPLSPEKYVTSAPMPEPQAPGRYFAHSIL

TVSEEEWNTGETYTCVVAHEALPNRVTERTVD

KSTGKPTLYNVSLVMSDTAGTCY

GGSGG

KPKGMTSSQWFKIQHMQPSPQACNSAMKNINKHTKRCKDLNT

FLHEPFSSVAATCQTPKIACKNGDKNCHQSHGAVSLTMCKLTSGKHPNCRYKEKRQNKSYVVACKPPQKK

DSQQFHLVPVHLDRVL

实施例五

本实施例的融合蛋白ACE2-huFc(G1)-RNase2,用于鼻腔和眼睛点滴而预防新冠病毒传染,融合蛋白序列如下:

STIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWS

AFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQE

CLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVN

GVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYS

LTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKS

IGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEP

VPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRL

GKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYAD

QSIKVRISLKSALGD

RAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKPRISFNFFVTAPKNVSDIIPRTEV

EKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQPPVS

GSGG

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGSGG

SLHVKPPQFTWAQWFETQHINMTSQQCTNAMQVINNYQRRCKNQNTF

LLTTFANVVNVCGNPNMTCPSNKTRKNCHHSGSQVPLIHCNLTTPSPQNISNCRYAQTPANMFYIVACDN

RDQRRDPPQYPVVPVHLDRII

实施例六

本实施例的融合蛋白ACE2-huFc(G1+M)-RNase2,用于鼻腔和眼睛点滴而预防新冠病毒传染,融合蛋白序列如下:

STIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWS

AFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQE

CLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVN

GVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYS

LTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKS

IGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEP

VPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRL

GKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYAD

QSIKVRISLKSALGD

RAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKPRISFNFFVTAPKNVSDIIPRTEV

EKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQPPVS

GSGG

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

PDVYLLPPAREQLNLRESATITCLVTGFSPADVFVQWMQRGQPLSPEKYVTSAPMPEPQAPGRYFAHSIL

TVSEEEWNTGETYTCVVAHEALPNRVTERTVD

KSTGKPTLYNVSLVMSDTAGTCY

GGSGG

SLHVKPPQFTWAQWFETQHINMTSQQCTNAMQVINNYQRRCKNQNTF

LLTTFANVVNVCGNPNMTCPSNKTRKNCHHSGSQVPLIHCNLTTPSPQNISNCRYAQTPANMFYIVACDN

RDQRRDPPQYPVVPVHLDRII

实施例七

本实施例的融合蛋白Anti-SARS-CoV2-hIgG1+Anti-SARS-CoV2-hK-RNase7,用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:

Anti-SARS-CoV2-hIgG1:

QMQLVQSGTEVKKPGESLKISCKGSGYGFITYWIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTI

SADKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDVWGQGTTVTVSS

ASTKGPSVFPLAPSSK

STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS

SLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF

SCSVMHEALHNHYTQKSLSLSPGK

Anti-SARS-CoV2-hK-RNase7:

DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSG

SGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKVEIKR

TVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST

LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

GGSGG

KPKGMTSSQWFKIQHMQPSPQACNSAMKNINKHTKRCKDLNT

FLHEPFSSVAATCQTPKIACKNGDKNCHQSHGAVSLTMCKLTSGKHPNCRYKEKRQNKSYVVACKPPQKK

DSQQFHLVPVHLDRVL

实施例八

本实施例的融合蛋白Anti-SARS-CoV2-hIgG1+M+Anti-SARS-CoV2-hK-RNase7,用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:

Anti-SARS-CoV2-hIgG1+M:

QMQLVQSGTEVKKPGESLKISCKGSGYGFITYWIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTI

SADKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDVWGQGTTVTVSS

ASTKGPSVFPLAPSSK

STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS

SLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF

SCSVMHEALHNHYTQKSLSLSPGK

PDVYLLPPAREQLNLRESATITCLVTGFSPADVFVQWMQRGQPLSPEKYVTSAPMPEPQAPGRYFAHSIL

TVSEEEWNTGETYTCVVAHEALPNRVTERTVD

KSTGKPTLYNVSLVMSDTAGTCY

Anti-SARS-CoV2-hK-RNase7:

DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSG

SGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKVEIKR

TVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST

LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

GGSGG

KPKGMTSSQWFKIQHMQPSPQACNSAMKNINKHTKRCKDLNT

FLHEPFSSVAATCQTPKIACKNGDKNCHQSHGAVSLTMCKLTSGKHPNCRYKEKRQNKSYVVACKPPQKK

DSQQFHLVPVHLDRVL

实施例九

本实施例的融合蛋白Anti-SARS-CoV2-hIgG1+Anti-SARS-CoV2-hK-RNaseK,用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:

Anti-SARS-CoV2-hIgG1:

QMQLVQSGTEVKKPGESLKISCKGSGYGFITYWIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTI

SADKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDVWGQGTTVTVSS

ASTKGPSVFPLAPSSK

STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS

SLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF

SCSVMHEALHNHYTQKSLSLSPGK

Anti-SARS-CoV2-hK-RNaseK:

DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSG

SGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKVEIKR

TVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST

LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

GGSGG

MASLLCCGPKLAACGIVLSAWGVIMLIMLGIFFNVHSAVLIEDVPFTEKDFENGPQNIYNLYEQVSYNCF

IAAGLYLLLGGFSFCQVRLNKRKEYMVR

实施例十

本实施例的融合蛋白Anti-SARS-CoV2-hIgG1+M+Anti-SARS-CoV2-hK-RNaseK,用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:

Anti-SARS-CoV2-hIgG1+M:

QMQLVQSGTEVKKPGESLKISCKGSGYGFITYWIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTI

SADKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDVWGQGTTVTVSS

ASTKGPSVFPLAPSSK

STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS

SLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF

SCSVMHEALHNHYTQKSLSLSPGK

PDVYLLPPAREQLNLRESATITCLVTGFSPADVFVQWMQRGQPLSPEKYVTSAPMPEPQAPGRYFAHSIL

TVSEEEWNTGETYTCVVAHEALPNRVTERTVD

KSTGKPTLYNVSLVMSDTAGTCY

Anti-SARS-CoV2-hK-RNaseK:

DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSG

SGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKVEIKR

TVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST

LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

GGSGG

MASLLCCGPKLAACGIVLSAWGVIMLIMLGIFFNVHSAVLIEDVPFTEKDFENGPQNIYNLYEQVSYNCF

IAAGLYLLLGGFSFCQVRLNKRKEYMVR

实施例十一

本实施例的融合蛋白Anti-SARS-CoV2-hIgG1+Anti-SARS-CoV2-hK-ribonucleaseT2,用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:

Anti-SARS-CoV2-hIgG1:

QMQLVQSGTEVKKPGESLKISCKGSGYGFITYWIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTI

SADKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDVWGQGTTVTVSS

ASTKGPSVFPLAPSSK

STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS

SLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF

SCSVMHEALHNHYTQKSLSLSPGK

Anti-SARS-CoV2-hK-ribonuclease T2:

DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSG

SGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKVEIKR

TVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST

LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

GGSGG

MRAYWPDVIHSFPNRSRFWKHEWEKHGTCAAQVDALNSQKKYFGRSLELYRELDLNSVLLKLGIKPSINY

YQVADFKDALARVYGVIPKIQCLPPSQDEEVQTIGQIELCLTKQDQQLQNCTEPGEQPSPKQEVWLANGA

AESRGLRVCEDGPVFYPPPKKTKH

实施例十二

本实施例的融合蛋白Anti-SARS-CoV2-hIgG1+RNase2-Anti-SARS-CoV2-hK,用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:

Anti-SARS-CoV2-hIgG1:

QMQLVQSGTEVKKPGESLKISCKGSGYGFITYWIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTI

SADKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDVWGQGTTVTVSS

ASTKGPSVFPLAPSSK

STSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSS

SLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF

SCSVMHEALHNHYTQKSLSLSPGK

RNase2-Anti-SARS-CoV2-hK:

SLHVKPPQFTWAQWFETQHINMTSQQCTNAMQVINNYQRRCKNQNTF

LLTTFANVVNVCGNPNMTCPSNKTRKNCHHSGSQVPLIHCNLTTPSPQNISNCRYAQTPANMFYIVACDN

RDQRRDPPQYPVVPVHLDRII

GGSGG

DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSG

SGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKVEIKR

TVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST

LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

实施例十三

本实施例的融合蛋白ACE2p1-CR3022vLvH-hFc(G1)-RNase7,用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:

MGS

STIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWS

AFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQE

CLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVN

GVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYS

LTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRIL

GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKVEIKR

GGSGGGGSGGGSGGGSGGSG

QMQLVQSGTEVKKPGESLKISCKGSGYGFITYWIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDVWGQGTTVTVSS

GGGSGG

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGSGGG

KPKGMTSSQWFKIQHMQPSPQACNSAMKNINKHTKRCKDLNT

FLHEPFSSVAATCQTPKIACKNGDKNCHQSHGAVSLTMCKLTSGKHPNCRYKEKRQNKSYVVACKPPQKK

DSQQFHLVPVHLDRVL

实施例十四

本实施例的融合蛋白ACE2 p1m1-CR3022vLvH-hFc(G1)-RNase7,用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:

MGS

STIEEQAKTFLDLFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWS

AFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQE

CLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVN

GVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYS

LTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRIL

GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKVEIKR

GGSGGGGSGGGSGGGSGGSG

QMQLVQSGTEVKKPGESLKISCKGSGYGFITYWIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDVWGQGTTVTVSS

GGGSGG

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGSGGG

KPKGMTSSQWFKIQHMQPSPQACNSAMKNINKHTKRCKDLNT

FLHEPFSSVAATCQTPKIACKNGDKNCHQSHGAVSLTMCKLTSGKHPNCRYKEKRQNKSYVVACKPPQKK

DSQQFHLVPVHLDRVL

实施例十五

本实施例的融合蛋白ACE2p1-CR3022vHvL-CD147-hFc(G1)-RNase2,用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:

MGS

STIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWS

AFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQE

CLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVN

GVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYS

LTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRIL

GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

QMQLVQSGTEVKKPGESLKISCKGSGYGFITYWIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDVWGQGTTVTVSS

GGSGGGGSGGGSGGGSGGSG

DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKVEIKR

GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

AAGTVFTTVEDLGSKILLTCSLNDSATEVTGHRWLKGGVVLKEDALPGQ

KTEFKVDSDDQWGEYSCVFLPEPMGTANIQLHGPPRVKAVKSSEHINEGETAMLVCKSESVPPVTDWAWY

KITDSE

DKALMNGSESRFFVSSSQGRSELHIENLNMEADPGQYRCNGTSSKGSDQAIITLRVRSHLAALW

PLLGIVAEVLVLVTIIFIYEKRRKPEDVLDDDDAGSAPLKSSGQHQNDKGKNVRQRNSS

GGGSGGGSGGG

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGSGG

SLHVKPPQFTWAQWFETQHINMTSQQCTNAMQVINNYQRRCKNQNTF

LLTTFANVVNVCGNPNMTCPSNKTRKNCHHSGSQVPLIHCNLTTPSPQNISNCRYAQTPANMFYIVACDN

RDQRRDPPQYPVVPVHLDRII

实施例十六

本实施例的融合蛋白ACE2 p1m2-CR3022vHvL-CD147-hFc(G1)-RNase2,用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:

MGS

STIEEQAKTFLDKFNFEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWS

AFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQE

CLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVN

GVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYS

LTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRIL

GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

QMQLVQSGTEVKKPGESLKISCKGSGYGFITYWIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDVWGQGTTVTVSS

GGSGGGGSGGGSGGGSGGSG

DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKVEIKR

GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

AAGTVFTTVEDLGSKILLTCSLNDSATEVTGHRWLKGGVVLKEDALPGQ

KTEFKVDSDDQWGEYSCVFLPEPMGTANIQLHGPPRVKAVKSSEHINEGETAMLVCKSESVPPVTDWAWY

KITDSE

DKALMNGSESRFFVSSSQGRSELHIENLNMEADPGQYRCNGTSSKGSDQAIITLRVRSHLAALW

PLLGIVAEVLVLVTIIFIYEKRRKPEDVLDDDDAGSAPLKSSGQHQNDKGKNVRQRNSS

GGGSGGGSGGG

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGSGG

SLHVKPPQFTWAQWFETQHINMTSQQCTNAMQVINNYQRRCKNQNTF

LLTTFANVVNVCGNPNMTCPSNKTRKNCHHSGSQVPLIHCNLTTPSPQNISNCRYAQTPANMFYIVACDN

RDQRRDPPQYPVVPVHLDRII

实施例十七

本实施例的融合蛋白ACE2 p2m1-CR3022vLvH-hFc(G1)-RNase7,用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:

MGS

STIEEQAKTFLDLFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWS

AFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTG

GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKVEIKR

GGSGGGGSGGGSGGGSGGSG

QMQLVQSGTEVKKPGESLKISCKGSGYGFITYWIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDVWGQGTTVTVSS

GGGSGG

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGSGG

KPKGMTSSQWFKIQHMQPSPQACNSAMKNINKHTKRCKDLNT

FLHEPFSSVAATCQTPKIACKNGDKNCHQSHGAVSLTMCKLTSGKHPNCRYKEKRQNKSYVVACKPPQKK

DSQQFHLVPVHLDRVL

实施例十八

本实施例的融合蛋白ACE2p2-CR3022vLvH-hFc(G1)-RNase7,用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:

MGS

STIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWS

AFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTG

GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKVEIKR

GGSGGGGSGGGSGGGSGGSG

QMQLVQSGTEVKKPGESLKISCKGSGYGFITYWIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDVWGQGTTVTVSS

GGGSGG

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGSGG

KPKGMTSSQWFKIQHMQPSPQACNSAMKNINKHTKRCKDLNT

FLHEPFSSVAATCQTPKIACKNGDKNCHQSHGAVSLTMCKLTSGKHPNCRYKEKRQNKSYVVACKPPQKK

DSQQFHLVPVHLDRVL

实施例十九

本实施例的融合蛋白ACE2 p2 m-CR3022vLvH-CD147-hFc(G1)-RNase7用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:

MGS

STIEEQAKTFLDLFNFEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWS

AFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTG

GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKVEIKR

GGSGGGGSGGGSGGGSGGSG

QMQLVQSGTEVKKPGESLKISCKGSGYGFITYWIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDVWGQGTTVTVSS

GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

AAGTVFTTVEDLGSKILLTCSLNDSATEVTGHRWLKGGVVLKEDALPGQ

KTEFKVDSDDQWGEYSCVFLPEPMGTANIQLHGPPRVKAVKSSEHINEGETAMLVCKSESVPPVTDWAWY

KITDSE

DKALMNGSESRFFVSSSQGRSELHIENLNMEADPGQYRCNGTSSKGSDQAIITLRVRSHLAALW

PLLGIVAEVLVLVTIIFIYEKRRKPEDVLDDDDAGSAPLKSSGQHQNDKGKNVRQRNSS

GGGSGGGSGGG

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGSGG

KPKGMTSSQWFKIQHMQPSPQACNSAMKNINKHTKRCKDLNT

FLHEPFSSVAATCQTPKIACKNGDKNCHQSHGAVSLTMCKLTSGKHPNCRYKEKRQNKSYVVACKPPQKK

DSQQFHLVPVHLDRVL

实施例二十

本实施例的融合蛋白ACE2p2-CR3022vLvH-CD147-hFc(G1)-RNase7,用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:

MGS

STIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWS

AFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTG

GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKVEIKR

GGSGGGGSGGGSGGGSGGSG

QMQLVQSGTEVKKPGESLKISCKGSGYGFITYWIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDVWGQGTTVTVSS

GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

AAGTVFTTVEDLGSKILLTCSLNDSATEVTGHRWLKGGVVLKEDALPGQ

KTEFKVDSDDQWGEYSCVFLPEPMGTANIQLHGPPRVKAVKSSEHINEGETAMLVCKSESVPPVTDWAWY

KITDSE

DKALMNGSESRFFVSSSQGRSELHIENLNMEADPGQYRCNGTSSKGSDQAIITLRVRSHLAALW

PLLGIVAEVLVLVTIIFIYEKRRKPEDVLDDDDAGSAPLKSSGQHQNDKGKNVRQRNSS

GGGSGGGSGGG

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGSGG

KPKGMTSSQWFKIQHMQPSPQACNSAMKNINKHTKRCKDLNT

FLHEPFSSVAATCQTPKIACKNGDKNCHQSHGAVSLTMCKLTSGKHPNCRYKEKRQNKSYVVACKPPQKK

DSQQFHLVPVHLDRVL

实施例二十一

本实施例的融合蛋白ACE2 p2m2-CR3022vHvL-CD147-hFc(G1)-RNaseT2,用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:

MGS

STIEEQAKTFLDKFNFEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWS

AFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTG

GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

QMQLVQSGTEVKKPGESLKISCKGSGYGFITYWIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDVWGQGTTVTVSS

GGSGGGGSGGGSGGGSGGSG

DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKVEIKR

GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

AAGTVFTTVEDLGSKILLTCSLNDSATEVTGHRWLKGGVVLKEDALPGQ

KTEFKVDSDDQWGEYSCVFLPEPMGTANIQLHGPPRVKAVKSSEHINEGETAMLVCKSESVPPVTDWAWY

KITDSE

DKALMNGSESRFFVSSSQGRSELHIENLNMEADPGQYRCNGTSSKGSDQAIITLRVRSHLAALW

PLLGIVAEVLVLVTIIFIYEKRRKPEDVLDDDDAGSAPLKSSGQHQNDKGKNVRQRNSS

GGGSGGGSGGG

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGSGG

MRAYWPDVIHSFPNRSRFWKHEWEKHGTCAAQVDALNSQKKYFGRSLELYRELDLNSVLLKLGIKPSINY

YQVADFKDALARVYGVIPKIQCLPPSQDEEVQTIGQIELCLTKQDQQLQNCTEPGEQPSPKQEVWLANGA

AESRGLRVCEDGPVFYPPPKKTKH

实施例二十二

本实施例的融合蛋白ACE2p2-CR3022vHvL-CD147-hFc(G1)-RNaseT2,用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:

MGS

STIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWS

AFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTG

GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

QMQLVQSGTEVKKPGESLKISCKGSGYGFITYWIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDVWGQGTTVTVSS

GGSGGGGSGGGSGGGSGGSG

DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKVEIKR

GGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGS

AAGTVFTTVEDLGSKILLTCSLNDSATEVTGHRWLKGGVVLKEDALPGQ

KTEFKVDSDDQWGEYSCVFLPEPMGTANIQLHGPPRVKAVKSSEHINEGETAMLVCKSESVPPVTDWAWY

KITDSE

DKALMNGSESRFFVSSSQGRSELHIENLNMEADPGQYRCNGTSSKGSDQAIITLRVRSHLAALW

PLLGIVAEVLVLVTIIFIYEKRRKPEDVLDDDDAGSAPLKSSGQHQNDKGKNVRQRNSS

GGGSGGGSGGG

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGSGG

MRAYWPDVIHSFPNRSRFWKHEWEKHGTCAAQVDALNSQKKYFGRSLELYRELDLNSVLLKLGIKPSINY

YQVADFKDALARVYGVIPKIQCLPPSQDEEVQTIGQIELCLTKQDQQLQNCTEPGEQPSPKQEVWLANGA

AESRGLRVCEDGPVFYPPPKKTKH

实施例二十三

本实施例的融合蛋白ACE2p2m-CR3022vHvL-CD147-hFc(G1)-RNaseK,用于鼻腔和眼睛点滴而预防新冠病毒传染或者静脉注射治疗,融合蛋白序列如下:

MGS

STIEEQAKTFLDLFNFEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWS

AFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTG

GGGGSGGGGSGGGGS

QMQLVQSGTEVKKPGESLKISCKGSGYGFITYWIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDVWGQGTTVTVSS

GGSGGGGSGGGSGGGSGGSG

DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKVEIKR

GGGSGGGSGGGSGGG

AAGTVFTTVEDLGSKILLTCSLNDSATEVTGHRWLKGGVVLKEDALPGQ

KTEFKVDSDDQWGEYSCVFLPEPMGTANIQLHGPPRVKAVKSSEHINEGETAMLVCKSESVPPVTDWAWY

KITDSE

DKALMNGSESRFFVSSSQGRSELHIENLNMEADPGQYRCNGTSSKGSDQAIITLRVRSHLAALW

PLLGIVAEVLVLVTIIFIYEKRRKPEDVLDDDDAGSAPLKSSGQHQNDKGKNVRQRNSS

GGGSGGGSGGG

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

GGSGGG

MASLLCCGPKLAACGIVLSAWGVIMLIMLGIFFNVHSAVLIEDVPFTEKDFENGPQNIYNLYEQVSYNCF

IAAGLYLLLGGFSFCQVRLNKRKEYMVR

实施例二十四

识别新冠病毒的RNA酶-红细胞载体

在GMP条件下,首先通过基因表达载体将新冠病毒的受体ACE2m(H374D,H378D)和CD147以及抗新冠病毒的抗体(IgM完整形式)表达在人脐带血中的CD34阳性细胞hematopoietic stem cells(HSCs)表面,然后诱导生成成熟的无核红细胞。然后采用短暂低渗透压的方法将RNase7,RNase2,XRN2,XRN1放到红细胞内部。组装好的细胞经过鉴定和政府批准后静脉注射用于治疗新冠病毒传染病人。

>NP_001304889.1 5'-3'exoribonuclease 2isoform 1[Homo sapiens]XRN2

MGSAACPRGALPELAPCCQPREQSQPHTRWDAGCGIQHPGGEEFRTLGGARAYRVPNSQEGRSSPTRFFP

APEGPAHCFVSSPDRAFWVSEEVQRLLLSNACQPKECNGVKIPVDASKPNPNDVEFDNLYLDMNGIIHPC

THPEDKPAPKNEDEMMVAIFEYIDRLFSIVRPRRLLYMAIDGVAPRAKMNQQRSRRFRASKEGMEAAVEK

QRVREEILAKGGFLPPEEIKERFDSNCITPGTEFMDNLAKCLRYYIADRLNNDPGWKNLTVILSDASAPG

EGEHKIMDYIRRQRAQPNHDPNTHHCLCGADADLIMLGLATHEPNFTIIREEFKPNKPKPCGLCNQFGHE

VKDCEGLPREKKGKHDELADSLPCAEGEFIFLRLNVLREYLERELTMASLPFTFDVERSIDDWVFMCFFV

GNDFLPHLPSLEIRENAIDRLVNIYKNVVHKTGGYLTESGYVNLQRVQMIMLAVGEVEDSIFKKRKDDED

SFRRRQKEKRKRMKRDQPAFTPSGILTPHALGSRNSPGSQVASNPRQAAYEMRMQNNSSPSISPNTSFTS

DGSPSPLGGIKRKAEDSDSEPEPEDNVRLWEAGWKQRYYKNKFDVDAADEKFRRKVVQSYVEGLCWVLRY

YYQGCASWKWYYPFHYAPFASDFEGIADMPSDFEKGTKPFKPLEQLMGVFPAASGNFLPPSWRKLMSDPD

SSIIDFYPEDFAIDLNGKKYAWQGVALLPFVDERRLRAALEEVYPDLTPEETRRNSLGGDVLFVGKHHPL

HDFILELYQTGSTEPVEVPPELCHGIQGKFSLDEEAILPDQIVCSPVPMLRDLTQNTVVSINFKDPQFAE

DYIFKAVMLPGARKPAAVLKPSDWEKSSNGRQWKPQLGFNRDRRPVHLDQAAFRTLGHVMPRGSGTGIYS

NAAPPPVTYQGNLYRPLLRGQAQIPKLMSNMRPQDSWRGPPPLFQQQRFDRGVGAEPLLPWNRMLQTQNA

AFQPNQYQMLAGPGGYPPRRDDRGGRQGYPREGRKYPLPPPSGRYNWN

>NP_001269786.1 5'-3'exoribonuclease 1 isoform c[Homo sapiens]XRN1

MGVPKFYRWISERYPCLSEVVKEHQIPEFDNLYLDMNGIIHQCSHPNDDDVHFRISDDKIFTDIFHYLEV

LFRIIKPRKVFFMAVDGVAPRAKMNQQRGRRFRSAKEAEDKIKKAIEKGETLPTEARFDSNCITPGTEFM

ARLHEHLKYFVNMKISTDKSWQGVTIYFSGHETPGEGEHKIMEFIRSEKAKPDHDPNTRHCLYGLDADLI

MLGLTSHEAHFSLLREEVRFGGKKTQRVCAPEETTFHLLHLSLMREYIDYEFSVLKEKITFKYDIERIID

DWILMGFLVGNDFIPHLPHLHINHDALPLLYGTYVTILPELGGYINESGHLNLPRFEKYLVKLSDFDREH

FSEVFVDLKWFESKVGNKYLNEAAGVAAEEARNYKEKKKLKGQENSLCWTALDKNEGEMITSKDNLEDET

EDDDLFETEFRQYKRTYYMTKMGVDVVSDDFLADQAACYVQAIQWILHYYYHGVQSWSWYYPYHYAPFLS

DIHNISTLKIHFELGKPFKPFEQLLAVLPAASKNLLPACYQHLMTNEDSPIIEYYPPDFKTDLNGKQQEW

EAVVLIPFIDEKRLLEAMETCNHSLKKEERKRNQHSECLMCWYDRDTEFIYPSPWPEKFPAIERCCTRYK

IISLDAWRVDINKNKITRIDQKALYFCGFPTLKHIRHKFFLKKSGVQVFQQSSRGENMMLEILVDAESDE

LTVENVASSVLGKSVFVNWPHLEEARVVAVSDGETKFYLEEPPGTQKLYSGRTAPPSKVVHLGDKEQSNW

AKEVQGISEHYLRRKGIIINETSAVVYAQLLTGRKYQINQNGEVRLEKQWSKQVVPFVYQTIVKDIRAFD

SRFSNIKTLDDLFPLRSMVFMLGTPYYGCTGEVQDSGDVITEGRIRVIFSIPCEPNLDALIQNQHKYSIK

YNPGYVLASRLGVSGYLVSRFTGSIFIGRGSRRNPHGDHKANVGLNLKFNKKNEEVPGYTKKVGSEWMYS

SAAEQLLAEYLERAPELFSYIAKNSQEDVFYEDDIWPGENENGAEKVQEIITWLKGHPVSTLSRSSCDLQ

ILDAAIVEKIEEEVEKCKQRKNNKKVRVTVKPHLLYRPLEQQHGVIPDRDAEFCLFDRVVNVRENFSVPV

GLRGTIIGIKGANREADVLFEVLFDEEFPGGLTIRCSPGRGYRLPTSALVNLSHGSRSETGNQKLTAIVK

PQPAVHQHSSSSSVSSGHLGALNHSPQSLFVPTQVPTKDDDEFCNIWQSLQGSGKMQYFQPTIQEKGAVL

PQEISQVNQHHKSGFNDNSVKYQQRKHDPHRKFKEECKSPKAECWSQKMSNKQPNSGIENFLASLNISKE

NEVQSSHHGEPPSEEHLSPQSFAMKGTRMLKEILKIDGSNTVDHKNEIKQIANEIPVSSNRRDEYGLPSQ

PKQNKKLASYMNKPHSANEYHNVQSMDNMCWPAPSQIPPVSTPVTELSRICSLVGMPQPDFSFLRMPQTM

TVCQVKLSNGLLVHGPQCHSENEAKEKAALFALQQLGSLGMNFPLPSQVFANYPSAVPPGTIPPAFPPPT

ANIMPSSSHLFGSMPWGPSVPVPGKPFHHTLYSGTMPMAGGIPGGVHNQFIPLQVTKKRVANKKNFENKE

AQSSQATPVQTSQPDSSNIVKVSPRESSSASLKSSPIAQPASSFQVETASQGHSISHHKSTPISSSRRKS

RKLAVNFGVSKPSE

>BAC76828.1 CD147[Homo sapiens]

MAAALFVLLGFALLGTHGASG

AAGTVFTTVEDLGSKILLTCSLNDSATEVTGHRWLKGGVVLKEDALPGQ

KTEFKVDSDDQWGEYSCVFLPEPMGTANIQLHGPPRVKAVKSSEHINEGETAMLVCKSESVPPVTDWAWY

KITDSE

DKALMNGSESRFFVSSSQGRSELHIENLNMEADPGQYRCNGTSSKGSDQAIITLRVRSHLAALW

PLLGIVAEVLVLVTIIFIYEKRRKPEDVLDDDDAGSAPLKSSGQHQNDKGKNVRQRNSS

ACE2m(H374D,H378D)

MSSSSWLLLSLVAVTAAQ

STIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWS

AFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQE

CLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVN

GVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYS

LTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHdEMGdIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKS

IGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEP

VPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRL

GKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYAD

QSIKVRISLKSALGD

RAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKPRISFNFFVTAPKNVSDIIPRTEV

EKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQPPVS

IWLIVFGVVMGVIVVGIVILIFTGIRDRKK

KNKARSGENPYASIDISKGENNPGFQNTDDVQTSF

SMCVPDQDTAIRVFAIPPSFASIFLTKSTKLTCLVTDLTTYDSVTISWTRQNGEAVKTHTNISESHPNAT

FSAVGEASICEDDWNSGERFTCTVTHTDLPSPLKQTISRPKGVALHRPDVYLLPPAREQLNLRESATITC

LVTGFSPADVFVQWMQRGQPLSPEKYVTSAPMPEPQAPGRYFAHSILTVSEEEWNTGETYTCVVAHEALP

NRVTERTVDKSTGKPTLYNVSLVMSDTAGTCY

KPKGMTSSQWFKIQHMQPSPQACNSAMKNINKHTKRCKDLNT

FLHEPFSSVAATCQTPKIACKNGDKNCHQSHGAVSLTMCKLTSGKHPNCRYKEKRQNKSYVVACKPPQKK

DSQQFHLVPVHLDRVL

Anti-SARS-CoV2-scFv-huFc(G-M)

MPLLLLLPLLWAGALA

DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSINKNYLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSTPYTFGQGTKVEIKGGSGGGGSGGGSGGGGSGGGSGMQMQLVQSGTEVKKPGESLKISCKGSGYGFITYWIGWVRQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCAGGSGISTPMDVWGQGTTVTVSS

GSGG

DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

PDVYLLPPAREQLNLRESATITCLVTGFSPADVFVQWMQRGQPLSPEKYVTSAPMPEPQAPGRYFAHSIL

TVSEEEWNTGETYTCVVAHEALPNRVTERTVD

KSTGKPTLYNVSLVMSDTAGTCY

实施例二十五

识别新冠病毒的RNA酶-功能性活细胞载体

在GMP条件下,首先通过基因表达载体将新冠病毒的受体ACE2m(H374D,H378D),CD147,抗新冠病毒的抗体,以及专门识别并且特异性切断新冠病毒RNA保守序列的RNase P在人脐带血或者其他合适的有核细胞中表达。组装好的细胞经过鉴定和政府批准后静脉注射用于治疗新冠病毒传染病人。

ACE2m(H374D,H378D),CD147,抗新冠病毒的抗体序列与上面相同,专门识别并且特异性切断新冠病毒RNA保守序列的RNase P序列如下:

(用U6或者H1 promoter表达)

M1(G33C G205C C326T)RNaseP RdRp1

GAAGCTGACCAGACAGTCGCCGCTTCGTCGTCcTCCTCTTCGGGGGAGACGGGCGGAGGGGAGGAAAGTCCGGGCTCCATAGGGCAGGGTGCCAGGTAACGCCTGGGGGGGAAACCCACGACCAGTGCAACAGAGAGCAAACCGCCGATGGCCCGCGCAAGCGGGATCAGGTAAGGGTGAAAGGGTGCGGTAagAGCGCACCGCcCGGCTGGTAACAGTCCGTGGCACGGTAAACTCCACCCGGAGCAAGGCCAAATAGGGGTTCATAAGGTACGGCCCGTACTGAACCCGGGTAGGCTGCTTGAGCCAGTGAGCGATTGCTGGCtTAGATGAATGACTGTCCACGACAGAACCCGGCTTATCGGTCAGTTTCACCT

CAAAGAAGAAGTG CCA

M1(G33C G205C C326T)RNaseP RdRp2

GAAGCTGACCAGACAGTCGCCGCTTCGTCGTCcTCCTCTTCGGGGGAGACGGGCGGAGGGGAGGAAAGTCCGGGCTCCATAGGGCAGGGTGCCAGGTAACGCCTGGGGGGGAAACCCACGACCAGTGCAACAGAGAGCAAACCGCCGATGGCCCGCGCAAGCGGGATCAGGTAAGGGTGAAAGGGTGCGGTAagAGCGCACCGCcCGGCTGGTAACAGTCCGTGGCACGGTAAACTCCACCCGGAGCAAGGCCAAATAGGGGTTCATAAGGTACGGCCCGTACTGAACCCGGGTAGGCTGCTTGAGCCAGTGAGCGATTGCTGGCtTAGATGAATGACTGTCCACGACAGAACCCGGCTTATCGGTCAGTTTCACCT

CTGATATCACACAT CCA

M1(G33C G205C C326T)RNaseP RdRp3

GAAGCTGACCAGACAGTCGCCGCTTCGTCGTCcTCCTCTTCGGGGGAGACGGGCGGAGGGGAGGAAAGTCCGGGCTCCATAGGGCAGGGTGCCAGGTAACGCCTGGGGGGGAAACCCACGACCAGTGCAACAGAGAGCAAACCGCCGATGGCCCGCGCAAGCGGGATCAGGTAAGGGTGAAAGGGTGCGGTAagAGCGCACCGCcCGGCTGGTAACAGTCCGTGGCACGGTAAACTCCACCCGGAGCAAGGCCAAATAGGGGTTCATAAGGTACGGCCCGTACTGAACCCGGGTAGGCTGCTTGAGCCAGTGAGCGATTGCTGGCtTAGATGAATGACTGTCCACGACAGAACCCGGCTTATCGGTCAGTTTCACCT

TCTGATCCCAATAT CCA

M1(G33C G205C C326T)RNaseP RdRp4

GAAGCTGACCAGACAGTCGCCGCTTCGTCGTCcTCCTCTTCGGGGGAGACGGGCGGAGGGGAGGAAAGTCCGGGCTCCATAGGGCAGGGTGCCAGGTAACGCCTGGGGGGGAAACCCACGACCAGTGCAACAGAGAGCAAACCGCCGATGGCCCGCGCAAGCGGGATCAGGTAAGGGTGAAAGGGTGCGGTAagAGCGCACCGCcCGGCTGGTAACAGTCCGTGGCACGGTAAACTCCACCCGGAGCAAGGCCAAATAGGGGTTCATAAGGTACGGCCCGTACTGAACCCGGGTAGGCTGCTTGAGCCAGTGAGCGATTGCTGGCtTAGATGAATGACTGTCCACGACAGAACCCGGCTTATCGGTCAGTTTCACCT

GTCTCTTAACTACA CCA

M1(G33C G205C C326T)RNaseP RdRp5

GAAGCTGACCAGACAGTCGCCGCTTCGTCGTCcTCCTCTTCGGGGGAGACGGGCGGAGGGGAGGAAAGTCCGGGCTCCATAGGGCAGGGTGCCAGGTAACGCCTGGGGGGGAAACCCACGACCAGTGCAACAGAGAGCAAACCGCCGATGGCCCGCGCAAGCGGGATCAGGTAAGGGTGAAAGGGTGCGGTAagAGCGCACCGCcCGGCTGGTAACAGTCCGTGGCACGGTAAACTCCACCCGGAGCAAGGCCAAATAGGGGTTCATAAGGTACGGCCCGTACTGAACCCGGGTAGGCTGCTTGAGCCAGTGAGCGATTGCTGGCtTAGATGAATGACTGTCCACGACAGAACCCGGCTTATCGGTCAGTTTCACCT

GCGAGCTCTATTCT CCA

M1(G33C G205C C326T)RNaseP RdRp6

GAAGCTGACCAGACAGTCGCCGCTTCGTCGTCcTCCTCTTCGGGGGAGACGGGCGGAGGGGAGGAAAGTCCGGGCTCCATAGGGCAGGGTGCCAGGTAACGCCTGGGGGGGAAACCCACGACCAGTGCAACAGAGAGCAAACCGCCGATGGCCCGCGCAAGCGGGATCAGGTAAGGGTGAAAGGGTGCGGTAagAGCGCACCGCcCGGCTGGTAACAGTCCGTGGCACGGTAAACTCCACCCGGAGCAAGGCCAAATAGGGGTTCATAAGGTACGGCCCGTACTGAACCCGGGTAGGCTGCTTGAGCCAGTGAGCGATTGCTGGCtTAGATGAATGACTGTCCACGACAGAACCCGGCTTATCGGTCAGTTTCACCT

CACACTCATTAGCT CCA

尽管已用具体实施例来说明和描述了本发明,然而应意识到,在不背离本发明的精神和范围的情况下可以作出许多其它的更改和修改。因此,这意味着在所附权利要求中包括属于本发明范围内的所有这些变化和修改。

SEQUENCE LISTING

<110> 维亚生物科技(上海)有限公司

<120> 一种融合蛋白及其应用

<130> JSP12001319

<160> 39

<170> PatentIn version 3.3

<210> 1

<211> 1086

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 1

Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Lys Phe Asn His

1 5 10 15

Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser Trp Asn Tyr

20 25 30

Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn Asn Ala Gly

35 40 45

Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu Ala Gln Met

50 55 60

Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu Gln Leu Gln

65 70 75 80

Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp Lys Ser Lys

85 90 95

Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr Ser Thr Gly

100 105 110

Lys Val Cys Asn Pro Asp Asn Pro Gln Glu Cys Leu Leu Leu Glu Pro

115 120 125

Gly Leu Asn Glu Ile Met Ala Asn Ser Leu Asp Tyr Asn Glu Arg Leu

130 135 140

Trp Ala Trp Glu Ser Trp Arg Ser Glu Val Gly Lys Gln Leu Arg Pro

145 150 155 160

Leu Tyr Glu Glu Tyr Val Val Leu Lys Asn Glu Met Ala Arg Ala Asn

165 170 175

His Tyr Glu Asp Tyr Gly Asp Tyr Trp Arg Gly Asp Tyr Glu Val Asn

180 185 190

Gly Val Asp Gly Tyr Asp Tyr Ser Arg Gly Gln Leu Ile Glu Asp Val

195 200 205

Glu His Thr Phe Glu Glu Ile Lys Pro Leu Tyr Glu His Leu His Ala

210 215 220

Tyr Val Arg Ala Lys Leu Met Asn Ala Tyr Pro Ser Tyr Ile Ser Pro

225 230 235 240

Ile Gly Cys Leu Pro Ala His Leu Leu Gly Asp Met Trp Gly Arg Phe

245 250 255

Trp Thr Asn Leu Tyr Ser Leu Thr Val Pro Phe Gly Gln Lys Pro Asn

260 265 270

Ile Asp Val Thr Asp Ala Met Val Asp Gln Ala Trp Asp Ala Gln Arg

275 280 285

Ile Phe Lys Glu Ala Glu Lys Phe Phe Val Ser Val Gly Leu Pro Asn

290 295 300

Met Thr Gln Gly Phe Trp Glu Asn Ser Met Leu Thr Asp Pro Gly Asn

305 310 315 320

Val Gln Lys Ala Val Cys His Pro Thr Ala Trp Asp Leu Gly Lys Gly

325 330 335

Asp Phe Arg Ile Leu Met Cys Thr Lys Val Thr Met Asp Asp Phe Leu

340 345 350

Thr Ala His His Glu Met Gly His Ile Gln Tyr Asp Met Ala Tyr Ala

355 360 365

Ala Gln Pro Phe Leu Leu Arg Asn Gly Ala Asn Glu Gly Phe His Glu

370 375 380

Ala Val Gly Glu Ile Met Ser Leu Ser Ala Ala Thr Pro Lys His Leu

385 390 395 400

Lys Ser Ile Gly Leu Leu Ser Pro Asp Phe Gln Glu Asp Asn Glu Thr

405 410 415

Glu Ile Asn Phe Leu Leu Lys Gln Ala Leu Thr Ile Val Gly Thr Leu

420 425 430

Pro Phe Thr Tyr Met Leu Glu Lys Trp Arg Trp Met Val Phe Lys Gly

435 440 445

Glu Ile Pro Lys Asp Gln Trp Met Lys Lys Trp Trp Glu Met Lys Arg

450 455 460

Glu Ile Val Gly Val Val Glu Pro Val Pro His Asp Glu Thr Tyr Cys

465 470 475 480

Asp Pro Ala Ser Leu Phe His Val Ser Asn Asp Tyr Ser Phe Ile Arg

485 490 495

Tyr Tyr Thr Arg Thr Leu Tyr Gln Phe Gln Phe Gln Glu Ala Leu Cys

500 505 510

Gln Ala Ala Lys His Glu Gly Pro Leu His Lys Cys Asp Ile Ser Asn

515 520 525

Ser Thr Glu Ala Gly Gln Lys Leu Phe Asn Met Leu Arg Leu Gly Lys

530 535 540

Ser Glu Pro Trp Thr Leu Ala Leu Glu Asn Val Val Gly Ala Lys Asn

545 550 555 560

Met Asn Val Arg Pro Leu Leu Asn Tyr Phe Glu Pro Leu Phe Thr Trp

565 570 575

Leu Lys Asp Gln Asn Lys Asn Ser Phe Val Gly Trp Ser Thr Asp Trp

580 585 590

Ser Pro Tyr Ala Asp Gln Ser Ile Lys Val Arg Ile Ser Leu Lys Ser

595 600 605

Ala Leu Gly Asp Arg Ala Tyr Glu Trp Asn Asp Asn Glu Met Tyr Leu

610 615 620

Phe Arg Ser Ser Val Ala Tyr Ala Met Arg Gln Tyr Phe Leu Lys Val

625 630 635 640

Lys Asn Gln Met Ile Leu Phe Gly Glu Glu Asp Val Arg Val Ala Asn

645 650 655

Leu Lys Pro Arg Ile Ser Phe Asn Phe Phe Val Thr Ala Pro Lys Asn

660 665 670

Val Ser Asp Ile Ile Pro Arg Thr Glu Val Glu Lys Ala Ile Arg Met

675 680 685

Ser Arg Ser Arg Ile Asn Asp Ala Phe Arg Leu Asn Asp Asn Ser Leu

690 695 700

Glu Phe Leu Gly Ile Gln Pro Thr Leu Gly Pro Pro Asn Gln Pro Pro

705 710 715 720

Val Ser Gly Ser Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro

725 730 735

Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys

740 745 750

Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val

755 760 765

Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr

770 775 780

Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu

785 790 795 800

Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His

805 810 815

Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys

820 825 830

Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln

835 840 845

Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu

850 855 860

Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro

865 870 875 880

Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn

885 890 895

Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu

900 905 910

Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val

915 920 925

Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln

930 935 940

Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Ser Gly Gly Lys Pro

945 950 955 960

Lys Gly Met Thr Ser Ser Gln Trp Phe Lys Ile Gln His Met Gln Pro

965 970 975

Ser Pro Gln Ala Cys Asn Ser Ala Met Lys Asn Ile Asn Lys His Thr

980 985 990

Lys Arg Cys Lys Asp Leu Asn Thr Phe Leu His Glu Pro Phe Ser Ser

995 1000 1005

Val Ala Ala Thr Cys Gln Thr Pro Lys Ile Ala Cys Lys Asn Gly

1010 1015 1020

Asp Lys Asn Cys His Gln Ser His Gly Ala Val Ser Leu Thr Met

1025 1030 1035

Cys Lys Leu Thr Ser Gly Lys His Pro Asn Cys Arg Tyr Lys Glu

1040 1045 1050

Lys Arg Gln Asn Lys Ser Tyr Val Val Ala Cys Lys Pro Pro Gln

1055 1060 1065

Lys Lys Asp Ser Gln Gln Phe His Leu Val Pro Val His Leu Asp

1070 1075 1080

Arg Val Leu

1085

<210> 2

<211> 1211

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 2

Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Lys Phe Asn His

1 5 10 15

Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser Trp Asn Tyr

20 25 30

Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn Asn Ala Gly

35 40 45

Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu Ala Gln Met

50 55 60

Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu Gln Leu Gln

65 70 75 80

Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp Lys Ser Lys

85 90 95

Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr Ser Thr Gly

100 105 110

Lys Val Cys Asn Pro Asp Asn Pro Gln Glu Cys Leu Leu Leu Glu Pro

115 120 125

Gly Leu Asn Glu Ile Met Ala Asn Ser Leu Asp Tyr Asn Glu Arg Leu

130 135 140

Trp Ala Trp Glu Ser Trp Arg Ser Glu Val Gly Lys Gln Leu Arg Pro

145 150 155 160

Leu Tyr Glu Glu Tyr Val Val Leu Lys Asn Glu Met Ala Arg Ala Asn

165 170 175

His Tyr Glu Asp Tyr Gly Asp Tyr Trp Arg Gly Asp Tyr Glu Val Asn

180 185 190

Gly Val Asp Gly Tyr Asp Tyr Ser Arg Gly Gln Leu Ile Glu Asp Val

195 200 205

Glu His Thr Phe Glu Glu Ile Lys Pro Leu Tyr Glu His Leu His Ala

210 215 220

Tyr Val Arg Ala Lys Leu Met Asn Ala Tyr Pro Ser Tyr Ile Ser Pro

225 230 235 240

Ile Gly Cys Leu Pro Ala His Leu Leu Gly Asp Met Trp Gly Arg Phe

245 250 255

Trp Thr Asn Leu Tyr Ser Leu Thr Val Pro Phe Gly Gln Lys Pro Asn

260 265 270

Ile Asp Val Thr Asp Ala Met Val Asp Gln Ala Trp Asp Ala Gln Arg

275 280 285

Ile Phe Lys Glu Ala Glu Lys Phe Phe Val Ser Val Gly Leu Pro Asn

290 295 300

Met Thr Gln Gly Phe Trp Glu Asn Ser Met Leu Thr Asp Pro Gly Asn

305 310 315 320

Val Gln Lys Ala Val Cys His Pro Thr Ala Trp Asp Leu Gly Lys Gly

325 330 335

Asp Phe Arg Ile Leu Met Cys Thr Lys Val Thr Met Asp Asp Phe Leu

340 345 350

Thr Ala His His Glu Met Gly His Ile Gln Tyr Asp Met Ala Tyr Ala

355 360 365

Ala Gln Pro Phe Leu Leu Arg Asn Gly Ala Asn Glu Gly Phe His Glu

370 375 380

Ala Val Gly Glu Ile Met Ser Leu Ser Ala Ala Thr Pro Lys His Leu

385 390 395 400

Lys Ser Ile Gly Leu Leu Ser Pro Asp Phe Gln Glu Asp Asn Glu Thr

405 410 415

Glu Ile Asn Phe Leu Leu Lys Gln Ala Leu Thr Ile Val Gly Thr Leu

420 425 430

Pro Phe Thr Tyr Met Leu Glu Lys Trp Arg Trp Met Val Phe Lys Gly

435 440 445

Glu Ile Pro Lys Asp Gln Trp Met Lys Lys Trp Trp Glu Met Lys Arg

450 455 460

Glu Ile Val Gly Val Val Glu Pro Val Pro His Asp Glu Thr Tyr Cys

465 470 475 480

Asp Pro Ala Ser Leu Phe His Val Ser Asn Asp Tyr Ser Phe Ile Arg

485 490 495

Tyr Tyr Thr Arg Thr Leu Tyr Gln Phe Gln Phe Gln Glu Ala Leu Cys

500 505 510

Gln Ala Ala Lys His Glu Gly Pro Leu His Lys Cys Asp Ile Ser Asn

515 520 525

Ser Thr Glu Ala Gly Gln Lys Leu Phe Asn Met Leu Arg Leu Gly Lys

530 535 540

Ser Glu Pro Trp Thr Leu Ala Leu Glu Asn Val Val Gly Ala Lys Asn

545 550 555 560

Met Asn Val Arg Pro Leu Leu Asn Tyr Phe Glu Pro Leu Phe Thr Trp

565 570 575

Leu Lys Asp Gln Asn Lys Asn Ser Phe Val Gly Trp Ser Thr Asp Trp

580 585 590

Ser Pro Tyr Ala Asp Gln Ser Ile Lys Val Arg Ile Ser Leu Lys Ser

595 600 605

Ala Leu Gly Asp Arg Ala Tyr Glu Trp Asn Asp Asn Glu Met Tyr Leu

610 615 620

Phe Arg Ser Ser Val Ala Tyr Ala Met Arg Gln Tyr Phe Leu Lys Val

625 630 635 640

Lys Asn Gln Met Ile Leu Phe Gly Glu Glu Asp Val Arg Val Ala Asn

645 650 655

Leu Lys Pro Arg Ile Ser Phe Asn Phe Phe Val Thr Ala Pro Lys Asn

660 665 670

Val Ser Asp Ile Ile Pro Arg Thr Glu Val Glu Lys Ala Ile Arg Met

675 680 685

Ser Arg Ser Arg Ile Asn Asp Ala Phe Arg Leu Asn Asp Asn Ser Leu

690 695 700

Glu Phe Leu Gly Ile Gln Pro Thr Leu Gly Pro Pro Asn Gln Pro Pro

705 710 715 720

Val Ser Gly Ser Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro

725 730 735

Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys

740 745 750

Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val

755 760 765

Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr

770 775 780

Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu

785 790 795 800

Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His

805 810 815

Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys

820 825 830

Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln

835 840 845

Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu

850 855 860

Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro

865 870 875 880

Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn

885 890 895

Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu

900 905 910

Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val

915 920 925

Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln

930 935 940

Lys Ser Leu Ser Leu Ser Pro Gly Lys Pro Asp Val Tyr Leu Leu Pro

945 950 955 960

Pro Ala Arg Glu Gln Leu Asn Leu Arg Glu Ser Ala Thr Ile Thr Cys

965 970 975

Leu Val Thr Gly Phe Ser Pro Ala Asp Val Phe Val Gln Trp Met Gln

980 985 990

Arg Gly Gln Pro Leu Ser Pro Glu Lys Tyr Val Thr Ser Ala Pro Met

995 1000 1005

Pro Glu Pro Gln Ala Pro Gly Arg Tyr Phe Ala His Ser Ile Leu

1010 1015 1020

Thr Val Ser Glu Glu Glu Trp Asn Thr Gly Glu Thr Tyr Thr Cys

1025 1030 1035

Val Val Ala His Glu Ala Leu Pro Asn Arg Val Thr Glu Arg Thr

1040 1045 1050

Val Asp Lys Ser Thr Gly Lys Pro Thr Leu Tyr Asn Val Ser Leu

1055 1060 1065

Val Met Ser Asp Thr Ala Gly Thr Cys Tyr Gly Gly Ser Gly Gly

1070 1075 1080

Lys Pro Lys Gly Met Thr Ser Ser Gln Trp Phe Lys Ile Gln His

1085 1090 1095

Met Gln Pro Ser Pro Gln Ala Cys Asn Ser Ala Met Lys Asn Ile

1100 1105 1110

Asn Lys His Thr Lys Arg Cys Lys Asp Leu Asn Thr Phe Leu His

1115 1120 1125

Glu Pro Phe Ser Ser Val Ala Ala Thr Cys Gln Thr Pro Lys Ile

1130 1135 1140

Ala Cys Lys Asn Gly Asp Lys Asn Cys His Gln Ser His Gly Ala

1145 1150 1155

Val Ser Leu Thr Met Cys Lys Leu Thr Ser Gly Lys His Pro Asn

1160 1165 1170

Cys Arg Tyr Lys Glu Lys Arg Gln Asn Lys Ser Tyr Val Val Ala

1175 1180 1185

Cys Lys Pro Pro Gln Lys Lys Asp Ser Gln Gln Phe His Leu Val

1190 1195 1200

Pro Val His Leu Asp Arg Val Leu

1205 1210

<210> 3

<211> 1104

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 3

Met Ser Ser Ser Ser Trp Leu Leu Leu Ser Leu Val Ala Val Thr Ala

1 5 10 15

Ala Gln Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Lys Phe

20 25 30

Asn His Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser Trp

35 40 45

Asn Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn Asn

50 55 60

Ala Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu Ala

65 70 75 80

Gln Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu Gln

85 90 95

Leu Gln Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp Lys

100 105 110

Ser Lys Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr Ser

115 120 125

Thr Gly Lys Val Cys Asn Pro Asp Asn Pro Gln Glu Cys Leu Leu Leu

130 135 140

Glu Pro Gly Leu Asn Glu Ile Met Ala Asn Ser Leu Asp Tyr Asn Glu

145 150 155 160

Arg Leu Trp Ala Trp Glu Ser Trp Arg Ser Glu Val Gly Lys Gln Leu

165 170 175

Arg Pro Leu Tyr Glu Glu Tyr Val Val Leu Lys Asn Glu Met Ala Arg

180 185 190

Ala Asn His Tyr Glu Asp Tyr Gly Asp Tyr Trp Arg Gly Asp Tyr Glu

195 200 205

Val Asn Gly Val Asp Gly Tyr Asp Tyr Ser Arg Gly Gln Leu Ile Glu

210 215 220

Asp Val Glu His Thr Phe Glu Glu Ile Lys Pro Leu Tyr Glu His Leu

225 230 235 240

His Ala Tyr Val Arg Ala Lys Leu Met Asn Ala Tyr Pro Ser Tyr Ile

245 250 255

Ser Pro Ile Gly Cys Leu Pro Ala His Leu Leu Gly Asp Met Trp Gly

260 265 270

Arg Phe Trp Thr Asn Leu Tyr Ser Leu Thr Val Pro Phe Gly Gln Lys

275 280 285

Pro Asn Ile Asp Val Thr Asp Ala Met Val Asp Gln Ala Trp Asp Ala

290 295 300

Gln Arg Ile Phe Lys Glu Ala Glu Lys Phe Phe Val Ser Val Gly Leu

305 310 315 320

Pro Asn Met Thr Gln Gly Phe Trp Glu Asn Ser Met Leu Thr Asp Pro

325 330 335

Gly Asn Val Gln Lys Ala Val Cys His Pro Thr Ala Trp Asp Leu Gly

340 345 350

Lys Gly Asp Phe Arg Ile Leu Met Cys Thr Lys Val Thr Met Asp Asp

355 360 365

Phe Leu Thr Ala His Asp Glu Met Gly Asp Ile Gln Tyr Asp Met Ala

370 375 380

Tyr Ala Ala Gln Pro Phe Leu Leu Arg Asn Gly Ala Asn Glu Gly Phe

385 390 395 400

His Glu Ala Val Gly Glu Ile Met Ser Leu Ser Ala Ala Thr Pro Lys

405 410 415

His Leu Lys Ser Ile Gly Leu Leu Ser Pro Asp Phe Gln Glu Asp Asn

420 425 430

Glu Thr Glu Ile Asn Phe Leu Leu Lys Gln Ala Leu Thr Ile Val Gly

435 440 445

Thr Leu Pro Phe Thr Tyr Met Leu Glu Lys Trp Arg Trp Met Val Phe

450 455 460

Lys Gly Glu Ile Pro Lys Asp Gln Trp Met Lys Lys Trp Trp Glu Met

465 470 475 480

Lys Arg Glu Ile Val Gly Val Val Glu Pro Val Pro His Asp Glu Thr

485 490 495

Tyr Cys Asp Pro Ala Ser Leu Phe His Val Ser Asn Asp Tyr Ser Phe

500 505 510

Ile Arg Tyr Tyr Thr Arg Thr Leu Tyr Gln Phe Gln Phe Gln Glu Ala

515 520 525

Leu Cys Gln Ala Ala Lys His Glu Gly Pro Leu His Lys Cys Asp Ile

530 535 540

Ser Asn Ser Thr Glu Ala Gly Gln Lys Leu Phe Asn Met Leu Arg Leu

545 550 555 560

Gly Lys Ser Glu Pro Trp Thr Leu Ala Leu Glu Asn Val Val Gly Ala

565 570 575

Lys Asn Met Asn Val Arg Pro Leu Leu Asn Tyr Phe Glu Pro Leu Phe

580 585 590

Thr Trp Leu Lys Asp Gln Asn Lys Asn Ser Phe Val Gly Trp Ser Thr

595 600 605

Asp Trp Ser Pro Tyr Ala Asp Gln Ser Ile Lys Val Arg Ile Ser Leu

610 615 620

Lys Ser Ala Leu Gly Asp Arg Ala Tyr Glu Trp Asn Asp Asn Glu Met

625 630 635 640

Tyr Leu Phe Arg Ser Ser Val Ala Tyr Ala Met Arg Gln Tyr Phe Leu

645 650 655

Lys Val Lys Asn Gln Met Ile Leu Phe Gly Glu Glu Asp Val Arg Val

660 665 670

Ala Asn Leu Lys Pro Arg Ile Ser Phe Asn Phe Phe Val Thr Ala Pro

675 680 685

Lys Asn Val Ser Asp Ile Ile Pro Arg Thr Glu Val Glu Lys Ala Ile

690 695 700

Arg Met Ser Arg Ser Arg Ile Asn Asp Ala Phe Arg Leu Asn Asp Asn

705 710 715 720

Ser Leu Glu Phe Leu Gly Ile Gln Pro Thr Leu Gly Pro Pro Asn Gln

725 730 735

Pro Pro Val Ser Gly Ser Gly Gly Asp Lys Thr His Thr Cys Pro Pro

740 745 750

Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro

755 760 765

Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr

770 775 780

Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn

785 790 795 800

Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg

805 810 815

Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val

820 825 830

Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser

835 840 845

Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys

850 855 860

Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp

865 870 875 880

Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe

885 890 895

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu

900 905 910

Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe

915 920 925

Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly

930 935 940

Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr

945 950 955 960

Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Ser Gly Gly

965 970 975

Lys Pro Lys Gly Met Thr Ser Ser Gln Trp Phe Lys Ile Gln His Met

980 985 990

Gln Pro Ser Pro Gln Ala Cys Asn Ser Ala Met Lys Asn Ile Asn Lys

995 1000 1005

His Thr Lys Arg Cys Lys Asp Leu Asn Thr Phe Leu His Glu Pro

1010 1015 1020

Phe Ser Ser Val Ala Ala Thr Cys Gln Thr Pro Lys Ile Ala Cys

1025 1030 1035

Lys Asn Gly Asp Lys Asn Cys His Gln Ser His Gly Ala Val Ser

1040 1045 1050

Leu Thr Met Cys Lys Leu Thr Ser Gly Lys His Pro Asn Cys Arg

1055 1060 1065

Tyr Lys Glu Lys Arg Gln Asn Lys Ser Tyr Val Val Ala Cys Lys

1070 1075 1080

Pro Pro Gln Lys Lys Asp Ser Gln Gln Phe His Leu Val Pro Val

1085 1090 1095

His Leu Asp Arg Val Leu

1100

<210> 4

<211> 1229

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 4

Met Ser Ser Ser Ser Trp Leu Leu Leu Ser Leu Val Ala Val Thr Ala

1 5 10 15

Ala Gln Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Lys Phe

20 25 30

Asn His Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser Trp

35 40 45

Asn Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn Asn

50 55 60

Ala Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu Ala

65 70 75 80

Gln Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu Gln

85 90 95

Leu Gln Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp Lys

100 105 110

Ser Lys Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr Ser

115 120 125

Thr Gly Lys Val Cys Asn Pro Asp Asn Pro Gln Glu Cys Leu Leu Leu

130 135 140

Glu Pro Gly Leu Asn Glu Ile Met Ala Asn Ser Leu Asp Tyr Asn Glu

145 150 155 160

Arg Leu Trp Ala Trp Glu Ser Trp Arg Ser Glu Val Gly Lys Gln Leu

165 170 175

Arg Pro Leu Tyr Glu Glu Tyr Val Val Leu Lys Asn Glu Met Ala Arg

180 185 190

Ala Asn His Tyr Glu Asp Tyr Gly Asp Tyr Trp Arg Gly Asp Tyr Glu

195 200 205

Val Asn Gly Val Asp Gly Tyr Asp Tyr Ser Arg Gly Gln Leu Ile Glu

210 215 220

Asp Val Glu His Thr Phe Glu Glu Ile Lys Pro Leu Tyr Glu His Leu

225 230 235 240

His Ala Tyr Val Arg Ala Lys Leu Met Asn Ala Tyr Pro Ser Tyr Ile

245 250 255

Ser Pro Ile Gly Cys Leu Pro Ala His Leu Leu Gly Asp Met Trp Gly

260 265 270

Arg Phe Trp Thr Asn Leu Tyr Ser Leu Thr Val Pro Phe Gly Gln Lys

275 280 285

Pro Asn Ile Asp Val Thr Asp Ala Met Val Asp Gln Ala Trp Asp Ala

290 295 300

Gln Arg Ile Phe Lys Glu Ala Glu Lys Phe Phe Val Ser Val Gly Leu

305 310 315 320

Pro Asn Met Thr Gln Gly Phe Trp Glu Asn Ser Met Leu Thr Asp Pro

325 330 335

Gly Asn Val Gln Lys Ala Val Cys His Pro Thr Ala Trp Asp Leu Gly

340 345 350

Lys Gly Asp Phe Arg Ile Leu Met Cys Thr Lys Val Thr Met Asp Asp

355 360 365

Phe Leu Thr Ala His Asp Glu Met Gly Asp Ile Gln Tyr Asp Met Ala

370 375 380

Tyr Ala Ala Gln Pro Phe Leu Leu Arg Asn Gly Ala Asn Glu Gly Phe

385 390 395 400

His Glu Ala Val Gly Glu Ile Met Ser Leu Ser Ala Ala Thr Pro Lys

405 410 415

His Leu Lys Ser Ile Gly Leu Leu Ser Pro Asp Phe Gln Glu Asp Asn

420 425 430

Glu Thr Glu Ile Asn Phe Leu Leu Lys Gln Ala Leu Thr Ile Val Gly

435 440 445

Thr Leu Pro Phe Thr Tyr Met Leu Glu Lys Trp Arg Trp Met Val Phe

450 455 460

Lys Gly Glu Ile Pro Lys Asp Gln Trp Met Lys Lys Trp Trp Glu Met

465 470 475 480

Lys Arg Glu Ile Val Gly Val Val Glu Pro Val Pro His Asp Glu Thr

485 490 495

Tyr Cys Asp Pro Ala Ser Leu Phe His Val Ser Asn Asp Tyr Ser Phe

500 505 510

Ile Arg Tyr Tyr Thr Arg Thr Leu Tyr Gln Phe Gln Phe Gln Glu Ala

515 520 525

Leu Cys Gln Ala Ala Lys His Glu Gly Pro Leu His Lys Cys Asp Ile

530 535 540

Ser Asn Ser Thr Glu Ala Gly Gln Lys Leu Phe Asn Met Leu Arg Leu

545 550 555 560

Gly Lys Ser Glu Pro Trp Thr Leu Ala Leu Glu Asn Val Val Gly Ala

565 570 575

Lys Asn Met Asn Val Arg Pro Leu Leu Asn Tyr Phe Glu Pro Leu Phe

580 585 590

Thr Trp Leu Lys Asp Gln Asn Lys Asn Ser Phe Val Gly Trp Ser Thr

595 600 605

Asp Trp Ser Pro Tyr Ala Asp Gln Ser Ile Lys Val Arg Ile Ser Leu

610 615 620

Lys Ser Ala Leu Gly Asp Arg Ala Tyr Glu Trp Asn Asp Asn Glu Met

625 630 635 640

Tyr Leu Phe Arg Ser Ser Val Ala Tyr Ala Met Arg Gln Tyr Phe Leu

645 650 655

Lys Val Lys Asn Gln Met Ile Leu Phe Gly Glu Glu Asp Val Arg Val

660 665 670

Ala Asn Leu Lys Pro Arg Ile Ser Phe Asn Phe Phe Val Thr Ala Pro

675 680 685

Lys Asn Val Ser Asp Ile Ile Pro Arg Thr Glu Val Glu Lys Ala Ile

690 695 700

Arg Met Ser Arg Ser Arg Ile Asn Asp Ala Phe Arg Leu Asn Asp Asn

705 710 715 720

Ser Leu Glu Phe Leu Gly Ile Gln Pro Thr Leu Gly Pro Pro Asn Gln

725 730 735

Pro Pro Val Ser Gly Ser Gly Gly Asp Lys Thr His Thr Cys Pro Pro

740 745 750

Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro

755 760 765

Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr

770 775 780

Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn

785 790 795 800

Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg

805 810 815

Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val

820 825 830

Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser

835 840 845

Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys

850 855 860

Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp

865 870 875 880

Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe

885 890 895

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu

900 905 910

Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe

915 920 925

Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly

930 935 940

Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr

945 950 955 960

Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Pro Asp Val Tyr Leu

965 970 975

Leu Pro Pro Ala Arg Glu Gln Leu Asn Leu Arg Glu Ser Ala Thr Ile

980 985 990

Thr Cys Leu Val Thr Gly Phe Ser Pro Ala Asp Val Phe Val Gln Trp

995 1000 1005

Met Gln Arg Gly Gln Pro Leu Ser Pro Glu Lys Tyr Val Thr Ser

1010 1015 1020

Ala Pro Met Pro Glu Pro Gln Ala Pro Gly Arg Tyr Phe Ala His

1025 1030 1035

Ser Ile Leu Thr Val Ser Glu Glu Glu Trp Asn Thr Gly Glu Thr

1040 1045 1050

Tyr Thr Cys Val Val Ala His Glu Ala Leu Pro Asn Arg Val Thr

1055 1060 1065

Glu Arg Thr Val Asp Lys Ser Thr Gly Lys Pro Thr Leu Tyr Asn

1070 1075 1080

Val Ser Leu Val Met Ser Asp Thr Ala Gly Thr Cys Tyr Gly Gly

1085 1090 1095

Ser Gly Gly Lys Pro Lys Gly Met Thr Ser Ser Gln Trp Phe Lys

1100 1105 1110

Ile Gln His Met Gln Pro Ser Pro Gln Ala Cys Asn Ser Ala Met

1115 1120 1125

Lys Asn Ile Asn Lys His Thr Lys Arg Cys Lys Asp Leu Asn Thr

1130 1135 1140

Phe Leu His Glu Pro Phe Ser Ser Val Ala Ala Thr Cys Gln Thr

1145 1150 1155

Pro Lys Ile Ala Cys Lys Asn Gly Asp Lys Asn Cys His Gln Ser

1160 1165 1170

His Gly Ala Val Ser Leu Thr Met Cys Lys Leu Thr Ser Gly Lys

1175 1180 1185

His Pro Asn Cys Arg Tyr Lys Glu Lys Arg Gln Asn Lys Ser Tyr

1190 1195 1200

Val Val Ala Cys Lys Pro Pro Gln Lys Lys Asp Ser Gln Gln Phe

1205 1210 1215

His Leu Val Pro Val His Leu Asp Arg Val Leu

1220 1225

<210> 5

<211> 1096

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 5

Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Lys Phe Asn His

1 5 10 15

Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser Trp Asn Tyr

20 25 30

Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn Asn Ala Gly

35 40 45

Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu Ala Gln Met

50 55 60

Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu Gln Leu Gln

65 70 75 80

Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp Lys Ser Lys

85 90 95

Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr Ser Thr Gly

100 105 110

Lys Val Cys Asn Pro Asp Asn Pro Gln Glu Cys Leu Leu Leu Glu Pro

115 120 125

Gly Leu Asn Glu Ile Met Ala Asn Ser Leu Asp Tyr Asn Glu Arg Leu

130 135 140

Trp Ala Trp Glu Ser Trp Arg Ser Glu Val Gly Lys Gln Leu Arg Pro

145 150 155 160

Leu Tyr Glu Glu Tyr Val Val Leu Lys Asn Glu Met Ala Arg Ala Asn

165 170 175

His Tyr Glu Asp Tyr Gly Asp Tyr Trp Arg Gly Asp Tyr Glu Val Asn

180 185 190

Gly Val Asp Gly Tyr Asp Tyr Ser Arg Gly Gln Leu Ile Glu Asp Val

195 200 205

Glu His Thr Phe Glu Glu Ile Lys Pro Leu Tyr Glu His Leu His Ala

210 215 220

Tyr Val Arg Ala Lys Leu Met Asn Ala Tyr Pro Ser Tyr Ile Ser Pro

225 230 235 240

Ile Gly Cys Leu Pro Ala His Leu Leu Gly Asp Met Trp Gly Arg Phe

245 250 255

Trp Thr Asn Leu Tyr Ser Leu Thr Val Pro Phe Gly Gln Lys Pro Asn

260 265 270

Ile Asp Val Thr Asp Ala Met Val Asp Gln Ala Trp Asp Ala Gln Arg

275 280 285

Ile Phe Lys Glu Ala Glu Lys Phe Phe Val Ser Val Gly Leu Pro Asn

290 295 300

Met Thr Gln Gly Phe Trp Glu Asn Ser Met Leu Thr Asp Pro Gly Asn

305 310 315 320

Val Gln Lys Ala Val Cys His Pro Thr Ala Trp Asp Leu Gly Lys Gly

325 330 335

Asp Phe Arg Ile Leu Met Cys Thr Lys Val Thr Met Asp Asp Phe Leu

340 345 350

Thr Ala His His Glu Met Gly His Ile Gln Tyr Asp Met Ala Tyr Ala

355 360 365

Ala Gln Pro Phe Leu Leu Arg Asn Gly Ala Asn Glu Gly Phe His Glu

370 375 380

Ala Val Gly Glu Ile Met Ser Leu Ser Ala Ala Thr Pro Lys His Leu

385 390 395 400

Lys Ser Ile Gly Leu Leu Ser Pro Asp Phe Gln Glu Asp Asn Glu Thr

405 410 415

Glu Ile Asn Phe Leu Leu Lys Gln Ala Leu Thr Ile Val Gly Thr Leu

420 425 430

Pro Phe Thr Tyr Met Leu Glu Lys Trp Arg Trp Met Val Phe Lys Gly

435 440 445

Glu Ile Pro Lys Asp Gln Trp Met Lys Lys Trp Trp Glu Met Lys Arg

450 455 460

Glu Ile Val Gly Val Val Glu Pro Val Pro His Asp Glu Thr Tyr Cys

465 470 475 480

Asp Pro Ala Ser Leu Phe His Val Ser Asn Asp Tyr Ser Phe Ile Arg

485 490 495

Tyr Tyr Thr Arg Thr Leu Tyr Gln Phe Gln Phe Gln Glu Ala Leu Cys

500 505 510

Gln Ala Ala Lys His Glu Gly Pro Leu His Lys Cys Asp Ile Ser Asn

515 520 525

Ser Thr Glu Ala Gly Gln Lys Leu Phe Asn Met Leu Arg Leu Gly Lys

530 535 540

Ser Glu Pro Trp Thr Leu Ala Leu Glu Asn Val Val Gly Ala Lys Asn

545 550 555 560

Met Asn Val Arg Pro Leu Leu Asn Tyr Phe Glu Pro Leu Phe Thr Trp

565 570 575

Leu Lys Asp Gln Asn Lys Asn Ser Phe Val Gly Trp Ser Thr Asp Trp

580 585 590

Ser Pro Tyr Ala Asp Gln Ser Ile Lys Val Arg Ile Ser Leu Lys Ser

595 600 605

Ala Leu Gly Asp Arg Ala Tyr Glu Trp Asn Asp Asn Glu Met Tyr Leu

610 615 620

Phe Arg Ser Ser Val Ala Tyr Ala Met Arg Gln Tyr Phe Leu Lys Val

625 630 635 640

Lys Asn Gln Met Ile Leu Phe Gly Glu Glu Asp Val Arg Val Ala Asn

645 650 655

Leu Lys Pro Arg Ile Ser Phe Asn Phe Phe Val Thr Ala Pro Lys Asn

660 665 670

Val Ser Asp Ile Ile Pro Arg Thr Glu Val Glu Lys Ala Ile Arg Met

675 680 685

Ser Arg Ser Arg Ile Asn Asp Ala Phe Arg Leu Asn Asp Asn Ser Leu

690 695 700

Glu Phe Leu Gly Ile Gln Pro Thr Leu Gly Pro Pro Asn Gln Pro Pro

705 710 715 720

Val Ser Gly Ser Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro

725 730 735

Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys

740 745 750

Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val

755 760 765

Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr

770 775 780

Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu

785 790 795 800

Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His

805 810 815

Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys

820 825 830

Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln

835 840 845

Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu

850 855 860

Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro

865 870 875 880

Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn

885 890 895

Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu

900 905 910

Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val

915 920 925

Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln

930 935 940

Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Ser Gly Gly Ser Leu

945 950 955 960

His Val Lys Pro Pro Gln Phe Thr Trp Ala Gln Trp Phe Glu Thr Gln

965 970 975

His Ile Asn Met Thr Ser Gln Gln Cys Thr Asn Ala Met Gln Val Ile

980 985 990

Asn Asn Tyr Gln Arg Arg Cys Lys Asn Gln Asn Thr Phe Leu Leu Thr

995 1000 1005

Thr Phe Ala Asn Val Val Asn Val Cys Gly Asn Pro Asn Met Thr

1010 1015 1020

Cys Pro Ser Asn Lys Thr Arg Lys Asn Cys His His Ser Gly Ser

1025 1030 1035

Gln Val Pro Leu Ile His Cys Asn Leu Thr Thr Pro Ser Pro Gln

1040 1045 1050

Asn Ile Ser Asn Cys Arg Tyr Ala Gln Thr Pro Ala Asn Met Phe

1055 1060 1065

Tyr Ile Val Ala Cys Asp Asn Arg Asp Gln Arg Arg Asp Pro Pro

1070 1075 1080

Gln Tyr Pro Val Val Pro Val His Leu Asp Arg Ile Ile

1085 1090 1095

<210> 6

<211> 1221

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 6

Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Lys Phe Asn His

1 5 10 15

Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser Trp Asn Tyr

20 25 30

Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn Asn Ala Gly

35 40 45

Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu Ala Gln Met

50 55 60

Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu Gln Leu Gln

65 70 75 80

Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp Lys Ser Lys

85 90 95

Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr Ser Thr Gly

100 105 110

Lys Val Cys Asn Pro Asp Asn Pro Gln Glu Cys Leu Leu Leu Glu Pro

115 120 125

Gly Leu Asn Glu Ile Met Ala Asn Ser Leu Asp Tyr Asn Glu Arg Leu

130 135 140

Trp Ala Trp Glu Ser Trp Arg Ser Glu Val Gly Lys Gln Leu Arg Pro

145 150 155 160

Leu Tyr Glu Glu Tyr Val Val Leu Lys Asn Glu Met Ala Arg Ala Asn

165 170 175

His Tyr Glu Asp Tyr Gly Asp Tyr Trp Arg Gly Asp Tyr Glu Val Asn

180 185 190

Gly Val Asp Gly Tyr Asp Tyr Ser Arg Gly Gln Leu Ile Glu Asp Val

195 200 205

Glu His Thr Phe Glu Glu Ile Lys Pro Leu Tyr Glu His Leu His Ala

210 215 220

Tyr Val Arg Ala Lys Leu Met Asn Ala Tyr Pro Ser Tyr Ile Ser Pro

225 230 235 240

Ile Gly Cys Leu Pro Ala His Leu Leu Gly Asp Met Trp Gly Arg Phe

245 250 255

Trp Thr Asn Leu Tyr Ser Leu Thr Val Pro Phe Gly Gln Lys Pro Asn

260 265 270

Ile Asp Val Thr Asp Ala Met Val Asp Gln Ala Trp Asp Ala Gln Arg

275 280 285

Ile Phe Lys Glu Ala Glu Lys Phe Phe Val Ser Val Gly Leu Pro Asn

290 295 300

Met Thr Gln Gly Phe Trp Glu Asn Ser Met Leu Thr Asp Pro Gly Asn

305 310 315 320

Val Gln Lys Ala Val Cys His Pro Thr Ala Trp Asp Leu Gly Lys Gly

325 330 335

Asp Phe Arg Ile Leu Met Cys Thr Lys Val Thr Met Asp Asp Phe Leu

340 345 350

Thr Ala His His Glu Met Gly His Ile Gln Tyr Asp Met Ala Tyr Ala

355 360 365

Ala Gln Pro Phe Leu Leu Arg Asn Gly Ala Asn Glu Gly Phe His Glu

370 375 380

Ala Val Gly Glu Ile Met Ser Leu Ser Ala Ala Thr Pro Lys His Leu

385 390 395 400

Lys Ser Ile Gly Leu Leu Ser Pro Asp Phe Gln Glu Asp Asn Glu Thr

405 410 415

Glu Ile Asn Phe Leu Leu Lys Gln Ala Leu Thr Ile Val Gly Thr Leu

420 425 430

Pro Phe Thr Tyr Met Leu Glu Lys Trp Arg Trp Met Val Phe Lys Gly

435 440 445

Glu Ile Pro Lys Asp Gln Trp Met Lys Lys Trp Trp Glu Met Lys Arg

450 455 460

Glu Ile Val Gly Val Val Glu Pro Val Pro His Asp Glu Thr Tyr Cys

465 470 475 480

Asp Pro Ala Ser Leu Phe His Val Ser Asn Asp Tyr Ser Phe Ile Arg

485 490 495

Tyr Tyr Thr Arg Thr Leu Tyr Gln Phe Gln Phe Gln Glu Ala Leu Cys

500 505 510

Gln Ala Ala Lys His Glu Gly Pro Leu His Lys Cys Asp Ile Ser Asn

515 520 525

Ser Thr Glu Ala Gly Gln Lys Leu Phe Asn Met Leu Arg Leu Gly Lys

530 535 540

Ser Glu Pro Trp Thr Leu Ala Leu Glu Asn Val Val Gly Ala Lys Asn

545 550 555 560

Met Asn Val Arg Pro Leu Leu Asn Tyr Phe Glu Pro Leu Phe Thr Trp

565 570 575

Leu Lys Asp Gln Asn Lys Asn Ser Phe Val Gly Trp Ser Thr Asp Trp

580 585 590

Ser Pro Tyr Ala Asp Gln Ser Ile Lys Val Arg Ile Ser Leu Lys Ser

595 600 605

Ala Leu Gly Asp Arg Ala Tyr Glu Trp Asn Asp Asn Glu Met Tyr Leu

610 615 620

Phe Arg Ser Ser Val Ala Tyr Ala Met Arg Gln Tyr Phe Leu Lys Val

625 630 635 640

Lys Asn Gln Met Ile Leu Phe Gly Glu Glu Asp Val Arg Val Ala Asn

645 650 655

Leu Lys Pro Arg Ile Ser Phe Asn Phe Phe Val Thr Ala Pro Lys Asn

660 665 670

Val Ser Asp Ile Ile Pro Arg Thr Glu Val Glu Lys Ala Ile Arg Met

675 680 685

Ser Arg Ser Arg Ile Asn Asp Ala Phe Arg Leu Asn Asp Asn Ser Leu

690 695 700

Glu Phe Leu Gly Ile Gln Pro Thr Leu Gly Pro Pro Asn Gln Pro Pro

705 710 715 720

Val Ser Gly Ser Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro

725 730 735

Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys

740 745 750

Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val

755 760 765

Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr

770 775 780

Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu

785 790 795 800

Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His

805 810 815

Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys

820 825 830

Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln

835 840 845

Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu

850 855 860

Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro

865 870 875 880

Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn

885 890 895

Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu

900 905 910

Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val

915 920 925

Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln

930 935 940

Lys Ser Leu Ser Leu Ser Pro Gly Lys Pro Asp Val Tyr Leu Leu Pro

945 950 955 960

Pro Ala Arg Glu Gln Leu Asn Leu Arg Glu Ser Ala Thr Ile Thr Cys

965 970 975

Leu Val Thr Gly Phe Ser Pro Ala Asp Val Phe Val Gln Trp Met Gln

980 985 990

Arg Gly Gln Pro Leu Ser Pro Glu Lys Tyr Val Thr Ser Ala Pro Met

995 1000 1005

Pro Glu Pro Gln Ala Pro Gly Arg Tyr Phe Ala His Ser Ile Leu

1010 1015 1020

Thr Val Ser Glu Glu Glu Trp Asn Thr Gly Glu Thr Tyr Thr Cys

1025 1030 1035

Val Val Ala His Glu Ala Leu Pro Asn Arg Val Thr Glu Arg Thr

1040 1045 1050

Val Asp Lys Ser Thr Gly Lys Pro Thr Leu Tyr Asn Val Ser Leu

1055 1060 1065

Val Met Ser Asp Thr Ala Gly Thr Cys Tyr Gly Gly Ser Gly Gly

1070 1075 1080

Ser Leu His Val Lys Pro Pro Gln Phe Thr Trp Ala Gln Trp Phe

1085 1090 1095

Glu Thr Gln His Ile Asn Met Thr Ser Gln Gln Cys Thr Asn Ala

1100 1105 1110

Met Gln Val Ile Asn Asn Tyr Gln Arg Arg Cys Lys Asn Gln Asn

1115 1120 1125

Thr Phe Leu Leu Thr Thr Phe Ala Asn Val Val Asn Val Cys Gly

1130 1135 1140

Asn Pro Asn Met Thr Cys Pro Ser Asn Lys Thr Arg Lys Asn Cys

1145 1150 1155

His His Ser Gly Ser Gln Val Pro Leu Ile His Cys Asn Leu Thr

1160 1165 1170

Thr Pro Ser Pro Gln Asn Ile Ser Asn Cys Arg Tyr Ala Gln Thr

1175 1180 1185

Pro Ala Asn Met Phe Tyr Ile Val Ala Cys Asp Asn Arg Asp Gln

1190 1195 1200

Arg Arg Asp Pro Pro Gln Tyr Pro Val Val Pro Val His Leu Asp

1205 1210 1215

Arg Ile Ile

1220

<210> 7

<211> 449

<212> PRT

<213> Artificial

<220>

<223> fuison protein

<400> 7

Gln Met Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile Thr Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr Tyr Cys

85 90 95

Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly Gln Gly

100 105 110

Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

115 120 125

Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys

210 215 220

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro

225 230 235 240

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

245 250 255

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp

260 265 270

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

275 280 285

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val

290 295 300

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

305 310 315 320

Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys

325 330 335

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr

340 345 350

Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr

355 360 365

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu

370 375 380

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu

385 390 395 400

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys

405 410 415

Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu

420 425 430

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

435 440 445

Lys

<210> 8

<211> 353

<212> PRT

<213> Artificial

<220>

<223> fuison protein

<400> 8

Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

Ser Ile Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp

115 120 125

Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn

130 135 140

Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu

145 150 155 160

Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp

165 170 175

Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr

180 185 190

Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser

195 200 205

Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Ser Gly

210 215 220

Gly Lys Pro Lys Gly Met Thr Ser Ser Gln Trp Phe Lys Ile Gln His

225 230 235 240

Met Gln Pro Ser Pro Gln Ala Cys Asn Ser Ala Met Lys Asn Ile Asn

245 250 255

Lys His Thr Lys Arg Cys Lys Asp Leu Asn Thr Phe Leu His Glu Pro

260 265 270

Phe Ser Ser Val Ala Ala Thr Cys Gln Thr Pro Lys Ile Ala Cys Lys

275 280 285

Asn Gly Asp Lys Asn Cys His Gln Ser His Gly Ala Val Ser Leu Thr

290 295 300

Met Cys Lys Leu Thr Ser Gly Lys His Pro Asn Cys Arg Tyr Lys Glu

305 310 315 320

Lys Arg Gln Asn Lys Ser Tyr Val Val Ala Cys Lys Pro Pro Gln Lys

325 330 335

Lys Asp Ser Gln Gln Phe His Leu Val Pro Val His Leu Asp Arg Val

340 345 350

Leu

<210> 9

<211> 574

<212> PRT

<213> Artificial

<220>

<223> fuison protein

<400> 9

Gln Met Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile Thr Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr Tyr Cys

85 90 95

Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly Gln Gly

100 105 110

Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

115 120 125

Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys

210 215 220

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro

225 230 235 240

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

245 250 255

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp

260 265 270

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

275 280 285

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val

290 295 300

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

305 310 315 320

Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys

325 330 335

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr

340 345 350

Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr

355 360 365

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu

370 375 380

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu

385 390 395 400

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys

405 410 415

Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu

420 425 430

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

435 440 445

Lys Pro Asp Val Tyr Leu Leu Pro Pro Ala Arg Glu Gln Leu Asn Leu

450 455 460

Arg Glu Ser Ala Thr Ile Thr Cys Leu Val Thr Gly Phe Ser Pro Ala

465 470 475 480

Asp Val Phe Val Gln Trp Met Gln Arg Gly Gln Pro Leu Ser Pro Glu

485 490 495

Lys Tyr Val Thr Ser Ala Pro Met Pro Glu Pro Gln Ala Pro Gly Arg

500 505 510

Tyr Phe Ala His Ser Ile Leu Thr Val Ser Glu Glu Glu Trp Asn Thr

515 520 525

Gly Glu Thr Tyr Thr Cys Val Val Ala His Glu Ala Leu Pro Asn Arg

530 535 540

Val Thr Glu Arg Thr Val Asp Lys Ser Thr Gly Lys Pro Thr Leu Tyr

545 550 555 560

Asn Val Ser Leu Val Met Ser Asp Thr Ala Gly Thr Cys Tyr

565 570

<210> 10

<211> 353

<212> PRT

<213> Artificial

<220>

<223> fuison protein

<400> 10

Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

Ser Ile Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp

115 120 125

Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn

130 135 140

Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu

145 150 155 160

Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp

165 170 175

Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr

180 185 190

Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser

195 200 205

Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Ser Gly

210 215 220

Gly Lys Pro Lys Gly Met Thr Ser Ser Gln Trp Phe Lys Ile Gln His

225 230 235 240

Met Gln Pro Ser Pro Gln Ala Cys Asn Ser Ala Met Lys Asn Ile Asn

245 250 255

Lys His Thr Lys Arg Cys Lys Asp Leu Asn Thr Phe Leu His Glu Pro

260 265 270

Phe Ser Ser Val Ala Ala Thr Cys Gln Thr Pro Lys Ile Ala Cys Lys

275 280 285

Asn Gly Asp Lys Asn Cys His Gln Ser His Gly Ala Val Ser Leu Thr

290 295 300

Met Cys Lys Leu Thr Ser Gly Lys His Pro Asn Cys Arg Tyr Lys Glu

305 310 315 320

Lys Arg Gln Asn Lys Ser Tyr Val Val Ala Cys Lys Pro Pro Gln Lys

325 330 335

Lys Asp Ser Gln Gln Phe His Leu Val Pro Val His Leu Asp Arg Val

340 345 350

Leu

<210> 11

<211> 449

<212> PRT

<213> Artificial

<220>

<223> fuison protein

<400> 11

Gln Met Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile Thr Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr Tyr Cys

85 90 95

Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly Gln Gly

100 105 110

Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

115 120 125

Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys

210 215 220

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro

225 230 235 240

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

245 250 255

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp

260 265 270

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

275 280 285

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val

290 295 300

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

305 310 315 320

Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys

325 330 335

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr

340 345 350

Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr

355 360 365

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu

370 375 380

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu

385 390 395 400

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys

405 410 415

Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu

420 425 430

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

435 440 445

Lys

<210> 12

<211> 323

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 12

Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

Ser Ile Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp

115 120 125

Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn

130 135 140

Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu

145 150 155 160

Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp

165 170 175

Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr

180 185 190

Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser

195 200 205

Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Ser Gly

210 215 220

Gly Met Ala Ser Leu Leu Cys Cys Gly Pro Lys Leu Ala Ala Cys Gly

225 230 235 240

Ile Val Leu Ser Ala Trp Gly Val Ile Met Leu Ile Met Leu Gly Ile

245 250 255

Phe Phe Asn Val His Ser Ala Val Leu Ile Glu Asp Val Pro Phe Thr

260 265 270

Glu Lys Asp Phe Glu Asn Gly Pro Gln Asn Ile Tyr Asn Leu Tyr Glu

275 280 285

Gln Val Ser Tyr Asn Cys Phe Ile Ala Ala Gly Leu Tyr Leu Leu Leu

290 295 300

Gly Gly Phe Ser Phe Cys Gln Val Arg Leu Asn Lys Arg Lys Glu Tyr

305 310 315 320

Met Val Arg

<210> 13

<211> 574

<212> PRT

<213> Artificial

<220>

<223> fuison protein

<400> 13

Gln Met Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile Thr Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr Tyr Cys

85 90 95

Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly Gln Gly

100 105 110

Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

115 120 125

Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys

210 215 220

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro

225 230 235 240

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

245 250 255

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp

260 265 270

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

275 280 285

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val

290 295 300

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

305 310 315 320

Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys

325 330 335

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr

340 345 350

Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr

355 360 365

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu

370 375 380

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu

385 390 395 400

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys

405 410 415

Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu

420 425 430

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

435 440 445

Lys Pro Asp Val Tyr Leu Leu Pro Pro Ala Arg Glu Gln Leu Asn Leu

450 455 460

Arg Glu Ser Ala Thr Ile Thr Cys Leu Val Thr Gly Phe Ser Pro Ala

465 470 475 480

Asp Val Phe Val Gln Trp Met Gln Arg Gly Gln Pro Leu Ser Pro Glu

485 490 495

Lys Tyr Val Thr Ser Ala Pro Met Pro Glu Pro Gln Ala Pro Gly Arg

500 505 510

Tyr Phe Ala His Ser Ile Leu Thr Val Ser Glu Glu Glu Trp Asn Thr

515 520 525

Gly Glu Thr Tyr Thr Cys Val Val Ala His Glu Ala Leu Pro Asn Arg

530 535 540

Val Thr Glu Arg Thr Val Asp Lys Ser Thr Gly Lys Pro Thr Leu Tyr

545 550 555 560

Asn Val Ser Leu Val Met Ser Asp Thr Ala Gly Thr Cys Tyr

565 570

<210> 14

<211> 323

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 14

Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

Ser Ile Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp

115 120 125

Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn

130 135 140

Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu

145 150 155 160

Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp

165 170 175

Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr

180 185 190

Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser

195 200 205

Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Ser Gly

210 215 220

Gly Met Ala Ser Leu Leu Cys Cys Gly Pro Lys Leu Ala Ala Cys Gly

225 230 235 240

Ile Val Leu Ser Ala Trp Gly Val Ile Met Leu Ile Met Leu Gly Ile

245 250 255

Phe Phe Asn Val His Ser Ala Val Leu Ile Glu Asp Val Pro Phe Thr

260 265 270

Glu Lys Asp Phe Glu Asn Gly Pro Gln Asn Ile Tyr Asn Leu Tyr Glu

275 280 285

Gln Val Ser Tyr Asn Cys Phe Ile Ala Ala Gly Leu Tyr Leu Leu Leu

290 295 300

Gly Gly Phe Ser Phe Cys Gln Val Arg Leu Asn Lys Arg Lys Glu Tyr

305 310 315 320

Met Val Arg

<210> 15

<211> 449

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 15

Gln Met Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile Thr Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr Tyr Cys

85 90 95

Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly Gln Gly

100 105 110

Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

115 120 125

Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys

210 215 220

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro

225 230 235 240

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

245 250 255

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp

260 265 270

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

275 280 285

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val

290 295 300

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

305 310 315 320

Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys

325 330 335

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr

340 345 350

Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr

355 360 365

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu

370 375 380

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu

385 390 395 400

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys

405 410 415

Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu

420 425 430

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

435 440 445

Lys

<210> 16

<211> 389

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 16

Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

Ser Ile Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp

115 120 125

Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn

130 135 140

Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu

145 150 155 160

Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp

165 170 175

Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr

180 185 190

Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser

195 200 205

Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Ser Gly

210 215 220

Gly Met Arg Ala Tyr Trp Pro Asp Val Ile His Ser Phe Pro Asn Arg

225 230 235 240

Ser Arg Phe Trp Lys His Glu Trp Glu Lys His Gly Thr Cys Ala Ala

245 250 255

Gln Val Asp Ala Leu Asn Ser Gln Lys Lys Tyr Phe Gly Arg Ser Leu

260 265 270

Glu Leu Tyr Arg Glu Leu Asp Leu Asn Ser Val Leu Leu Lys Leu Gly

275 280 285

Ile Lys Pro Ser Ile Asn Tyr Tyr Gln Val Ala Asp Phe Lys Asp Ala

290 295 300

Leu Ala Arg Val Tyr Gly Val Ile Pro Lys Ile Gln Cys Leu Pro Pro

305 310 315 320

Ser Gln Asp Glu Glu Val Gln Thr Ile Gly Gln Ile Glu Leu Cys Leu

325 330 335

Thr Lys Gln Asp Gln Gln Leu Gln Asn Cys Thr Glu Pro Gly Glu Gln

340 345 350

Pro Ser Pro Lys Gln Glu Val Trp Leu Ala Asn Gly Ala Ala Glu Ser

355 360 365

Arg Gly Leu Arg Val Cys Glu Asp Gly Pro Val Phe Tyr Pro Pro Pro

370 375 380

Lys Lys Thr Lys His

385

<210> 17

<211> 449

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 17

Gln Met Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile Thr Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr Tyr Cys

85 90 95

Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly Gln Gly

100 105 110

Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

115 120 125

Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu

130 135 140

Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp

145 150 155 160

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

165 170 175

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185 190

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

195 200 205

Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys

210 215 220

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro

225 230 235 240

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

245 250 255

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp

260 265 270

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

275 280 285

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val

290 295 300

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

305 310 315 320

Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys

325 330 335

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr

340 345 350

Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr

355 360 365

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu

370 375 380

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu

385 390 395 400

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys

405 410 415

Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu

420 425 430

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

435 440 445

Lys

<210> 18

<211> 363

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 18

Ser Leu His Val Lys Pro Pro Gln Phe Thr Trp Ala Gln Trp Phe Glu

1 5 10 15

Thr Gln His Ile Asn Met Thr Ser Gln Gln Cys Thr Asn Ala Met Gln

20 25 30

Val Ile Asn Asn Tyr Gln Arg Arg Cys Lys Asn Gln Asn Thr Phe Leu

35 40 45

Leu Thr Thr Phe Ala Asn Val Val Asn Val Cys Gly Asn Pro Asn Met

50 55 60

Thr Cys Pro Ser Asn Lys Thr Arg Lys Asn Cys His His Ser Gly Ser

65 70 75 80

Gln Val Pro Leu Ile His Cys Asn Leu Thr Thr Pro Ser Pro Gln Asn

85 90 95

Ile Ser Asn Cys Arg Tyr Ala Gln Thr Pro Ala Asn Met Phe Tyr Ile

100 105 110

Val Ala Cys Asp Asn Arg Asp Gln Arg Arg Asp Pro Pro Gln Tyr Pro

115 120 125

Val Val Pro Val His Leu Asp Arg Ile Ile Gly Gly Ser Gly Gly Asp

130 135 140

Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu

145 150 155 160

Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser Ser

165 170 175

Ile Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro

180 185 190

Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro

195 200 205

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile

210 215 220

Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr

225 230 235 240

Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

245 250 255

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu

260 265 270

Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe

275 280 285

Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln

290 295 300

Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser

305 310 315 320

Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu

325 330 335

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser

340 345 350

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys

355 360

<210> 19

<211> 1009

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 19

Met Gly Ser Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Lys

1 5 10 15

Phe Asn His Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser

20 25 30

Trp Asn Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn

35 40 45

Asn Ala Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu

50 55 60

Ala Gln Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu

65 70 75 80

Gln Leu Gln Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp

85 90 95

Lys Ser Lys Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr

100 105 110

Ser Thr Gly Lys Val Cys Asn Pro Asp Asn Pro Gln Glu Cys Leu Leu

115 120 125

Leu Glu Pro Gly Leu Asn Glu Ile Met Ala Asn Ser Leu Asp Tyr Asn

130 135 140

Glu Arg Leu Trp Ala Trp Glu Ser Trp Arg Ser Glu Val Gly Lys Gln

145 150 155 160

Leu Arg Pro Leu Tyr Glu Glu Tyr Val Val Leu Lys Asn Glu Met Ala

165 170 175

Arg Ala Asn His Tyr Glu Asp Tyr Gly Asp Tyr Trp Arg Gly Asp Tyr

180 185 190

Glu Val Asn Gly Val Asp Gly Tyr Asp Tyr Ser Arg Gly Gln Leu Ile

195 200 205

Glu Asp Val Glu His Thr Phe Glu Glu Ile Lys Pro Leu Tyr Glu His

210 215 220

Leu His Ala Tyr Val Arg Ala Lys Leu Met Asn Ala Tyr Pro Ser Tyr

225 230 235 240

Ile Ser Pro Ile Gly Cys Leu Pro Ala His Leu Leu Gly Asp Met Trp

245 250 255

Gly Arg Phe Trp Thr Asn Leu Tyr Ser Leu Thr Val Pro Phe Gly Gln

260 265 270

Lys Pro Asn Ile Asp Val Thr Asp Ala Met Val Asp Gln Ala Trp Asp

275 280 285

Ala Gln Arg Ile Phe Lys Glu Ala Glu Lys Phe Phe Val Ser Val Gly

290 295 300

Leu Pro Asn Met Thr Gln Gly Phe Trp Glu Asn Ser Met Leu Thr Asp

305 310 315 320

Pro Gly Asn Val Gln Lys Ala Val Cys His Pro Thr Ala Trp Asp Leu

325 330 335

Gly Lys Gly Asp Phe Arg Ile Leu Gly Gly Gly Gly Ser Gly Gly Gly

340 345 350

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

355 360 365

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

370 375 380

Gly Gly Gly Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu

385 390 395 400

Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln

405 410 415

Ser Val Leu Tyr Ser Ser Ile Asn Lys Asn Tyr Leu Ala Trp Tyr Gln

420 425 430

Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr

435 440 445

Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr

450 455 460

Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val

465 470 475 480

Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly

485 490 495

Thr Lys Val Glu Ile Lys Arg Gly Gly Ser Gly Gly Gly Gly Ser Gly

500 505 510

Gly Gly Ser Gly Gly Gly Ser Gly Gly Ser Gly Gln Met Gln Leu Val

515 520 525

Gln Ser Gly Thr Glu Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser

530 535 540

Cys Lys Gly Ser Gly Tyr Gly Phe Ile Thr Tyr Trp Ile Gly Trp Val

545 550 555 560

Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met Gly Ile Ile Tyr Pro

565 570 575

Gly Asp Ser Glu Thr Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr

580 585 590

Ile Ser Ala Asp Lys Ser Ile Asn Thr Ala Tyr Leu Gln Trp Ser Ser

595 600 605

Leu Lys Ala Ser Asp Thr Ala Ile Tyr Tyr Cys Ala Gly Gly Ser Gly

610 615 620

Ile Ser Thr Pro Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

625 630 635 640

Ser Ser Gly Gly Gly Ser Gly Gly Asp Lys Thr His Thr Cys Pro Pro

645 650 655

Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro

660 665 670

Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr

675 680 685

Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn

690 695 700

Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg

705 710 715 720

Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val

725 730 735

Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser

740 745 750

Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys

755 760 765

Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp

770 775 780

Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe

785 790 795 800

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu

805 810 815

Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe

820 825 830

Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly

835 840 845

Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr

850 855 860

Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Ser Gly Gly

865 870 875 880

Gly Lys Pro Lys Gly Met Thr Ser Ser Gln Trp Phe Lys Ile Gln His

885 890 895

Met Gln Pro Ser Pro Gln Ala Cys Asn Ser Ala Met Lys Asn Ile Asn

900 905 910

Lys His Thr Lys Arg Cys Lys Asp Leu Asn Thr Phe Leu His Glu Pro

915 920 925

Phe Ser Ser Val Ala Ala Thr Cys Gln Thr Pro Lys Ile Ala Cys Lys

930 935 940

Asn Gly Asp Lys Asn Cys His Gln Ser His Gly Ala Val Ser Leu Thr

945 950 955 960

Met Cys Lys Leu Thr Ser Gly Lys His Pro Asn Cys Arg Tyr Lys Glu

965 970 975

Lys Arg Gln Asn Lys Ser Tyr Val Val Ala Cys Lys Pro Pro Gln Lys

980 985 990

Lys Asp Ser Gln Gln Phe His Leu Val Pro Val His Leu Asp Arg Val

995 1000 1005

Leu

<210> 20

<211> 1009

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 20

Met Gly Ser Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Leu

1 5 10 15

Phe Asn His Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser

20 25 30

Trp Asn Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn

35 40 45

Asn Ala Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu

50 55 60

Ala Gln Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu

65 70 75 80

Gln Leu Gln Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp

85 90 95

Lys Ser Lys Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr

100 105 110

Ser Thr Gly Lys Val Cys Asn Pro Asp Asn Pro Gln Glu Cys Leu Leu

115 120 125

Leu Glu Pro Gly Leu Asn Glu Ile Met Ala Asn Ser Leu Asp Tyr Asn

130 135 140

Glu Arg Leu Trp Ala Trp Glu Ser Trp Arg Ser Glu Val Gly Lys Gln

145 150 155 160

Leu Arg Pro Leu Tyr Glu Glu Tyr Val Val Leu Lys Asn Glu Met Ala

165 170 175

Arg Ala Asn His Tyr Glu Asp Tyr Gly Asp Tyr Trp Arg Gly Asp Tyr

180 185 190

Glu Val Asn Gly Val Asp Gly Tyr Asp Tyr Ser Arg Gly Gln Leu Ile

195 200 205

Glu Asp Val Glu His Thr Phe Glu Glu Ile Lys Pro Leu Tyr Glu His

210 215 220

Leu His Ala Tyr Val Arg Ala Lys Leu Met Asn Ala Tyr Pro Ser Tyr

225 230 235 240

Ile Ser Pro Ile Gly Cys Leu Pro Ala His Leu Leu Gly Asp Met Trp

245 250 255

Gly Arg Phe Trp Thr Asn Leu Tyr Ser Leu Thr Val Pro Phe Gly Gln

260 265 270

Lys Pro Asn Ile Asp Val Thr Asp Ala Met Val Asp Gln Ala Trp Asp

275 280 285

Ala Gln Arg Ile Phe Lys Glu Ala Glu Lys Phe Phe Val Ser Val Gly

290 295 300

Leu Pro Asn Met Thr Gln Gly Phe Trp Glu Asn Ser Met Leu Thr Asp

305 310 315 320

Pro Gly Asn Val Gln Lys Ala Val Cys His Pro Thr Ala Trp Asp Leu

325 330 335

Gly Lys Gly Asp Phe Arg Ile Leu Gly Gly Gly Gly Ser Gly Gly Gly

340 345 350

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

355 360 365

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

370 375 380

Gly Gly Gly Gly Ser Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu

385 390 395 400

Ala Val Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln

405 410 415

Ser Val Leu Tyr Ser Ser Ile Asn Lys Asn Tyr Leu Ala Trp Tyr Gln

420 425 430

Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr

435 440 445

Arg Glu Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr

450 455 460

Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val

465 470 475 480

Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly

485 490 495

Thr Lys Val Glu Ile Lys Arg Gly Gly Ser Gly Gly Gly Gly Ser Gly

500 505 510

Gly Gly Ser Gly Gly Gly Ser Gly Gly Ser Gly Gln Met Gln Leu Val

515 520 525

Gln Ser Gly Thr Glu Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser

530 535 540

Cys Lys Gly Ser Gly Tyr Gly Phe Ile Thr Tyr Trp Ile Gly Trp Val

545 550 555 560

Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met Gly Ile Ile Tyr Pro

565 570 575

Gly Asp Ser Glu Thr Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr

580 585 590

Ile Ser Ala Asp Lys Ser Ile Asn Thr Ala Tyr Leu Gln Trp Ser Ser

595 600 605

Leu Lys Ala Ser Asp Thr Ala Ile Tyr Tyr Cys Ala Gly Gly Ser Gly

610 615 620

Ile Ser Thr Pro Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

625 630 635 640

Ser Ser Gly Gly Gly Ser Gly Gly Asp Lys Thr His Thr Cys Pro Pro

645 650 655

Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro

660 665 670

Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr

675 680 685

Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn

690 695 700

Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg

705 710 715 720

Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val

725 730 735

Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser

740 745 750

Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys

755 760 765

Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp

770 775 780

Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe

785 790 795 800

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu

805 810 815

Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe

820 825 830

Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly

835 840 845

Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr

850 855 860

Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Gly Ser Gly Gly

865 870 875 880

Gly Lys Pro Lys Gly Met Thr Ser Ser Gln Trp Phe Lys Ile Gln His

885 890 895

Met Gln Pro Ser Pro Gln Ala Cys Asn Ser Ala Met Lys Asn Ile Asn

900 905 910

Lys His Thr Lys Arg Cys Lys Asp Leu Asn Thr Phe Leu His Glu Pro

915 920 925

Phe Ser Ser Val Ala Ala Thr Cys Gln Thr Pro Lys Ile Ala Cys Lys

930 935 940

Asn Gly Asp Lys Asn Cys His Gln Ser His Gly Ala Val Ser Leu Thr

945 950 955 960

Met Cys Lys Leu Thr Ser Gly Lys His Pro Asn Cys Arg Tyr Lys Glu

965 970 975

Lys Arg Gln Asn Lys Ser Tyr Val Val Ala Cys Lys Pro Pro Gln Lys

980 985 990

Lys Asp Ser Gln Gln Phe His Leu Val Pro Val His Leu Asp Arg Val

995 1000 1005

Leu

<210> 21

<211> 1316

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 21

Met Gly Ser Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Lys

1 5 10 15

Phe Asn His Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser

20 25 30

Trp Asn Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn

35 40 45

Asn Ala Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu

50 55 60

Ala Gln Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu

65 70 75 80

Gln Leu Gln Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp

85 90 95

Lys Ser Lys Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr

100 105 110

Ser Thr Gly Lys Val Cys Asn Pro Asp Asn Pro Gln Glu Cys Leu Leu

115 120 125

Leu Glu Pro Gly Leu Asn Glu Ile Met Ala Asn Ser Leu Asp Tyr Asn

130 135 140

Glu Arg Leu Trp Ala Trp Glu Ser Trp Arg Ser Glu Val Gly Lys Gln

145 150 155 160

Leu Arg Pro Leu Tyr Glu Glu Tyr Val Val Leu Lys Asn Glu Met Ala

165 170 175

Arg Ala Asn His Tyr Glu Asp Tyr Gly Asp Tyr Trp Arg Gly Asp Tyr

180 185 190

Glu Val Asn Gly Val Asp Gly Tyr Asp Tyr Ser Arg Gly Gln Leu Ile

195 200 205

Glu Asp Val Glu His Thr Phe Glu Glu Ile Lys Pro Leu Tyr Glu His

210 215 220

Leu His Ala Tyr Val Arg Ala Lys Leu Met Asn Ala Tyr Pro Ser Tyr

225 230 235 240

Ile Ser Pro Ile Gly Cys Leu Pro Ala His Leu Leu Gly Asp Met Trp

245 250 255

Gly Arg Phe Trp Thr Asn Leu Tyr Ser Leu Thr Val Pro Phe Gly Gln

260 265 270

Lys Pro Asn Ile Asp Val Thr Asp Ala Met Val Asp Gln Ala Trp Asp

275 280 285

Ala Gln Arg Ile Phe Lys Glu Ala Glu Lys Phe Phe Val Ser Val Gly

290 295 300

Leu Pro Asn Met Thr Gln Gly Phe Trp Glu Asn Ser Met Leu Thr Asp

305 310 315 320

Pro Gly Asn Val Gln Lys Ala Val Cys His Pro Thr Ala Trp Asp Leu

325 330 335

Gly Lys Gly Asp Phe Arg Ile Leu Gly Gly Gly Gly Ser Gly Gly Gly

340 345 350

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

355 360 365

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

370 375 380

Gly Gly Gly Gly Ser Gln Met Gln Leu Val Gln Ser Gly Thr Glu Val

385 390 395 400

Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr

405 410 415

Gly Phe Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys

420 425 430

Gly Leu Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg

435 440 445

Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser

450 455 460

Ile Asn Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr

465 470 475 480

Ala Ile Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp

485 490 495

Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Ser Gly

500 505 510

Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Ser Gly

515 520 525

Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

530 535 540

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

545 550 555 560

Ser Ile Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

565 570 575

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

580 585 590

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

595 600 605

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

610 615 620

Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

625 630 635 640

Lys Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

645 650 655

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

660 665 670

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala

675 680 685

Ala Gly Thr Val Phe Thr Thr Val Glu Asp Leu Gly Ser Lys Ile Leu

690 695 700

Leu Thr Cys Ser Leu Asn Asp Ser Ala Thr Glu Val Thr Gly His Arg

705 710 715 720

Trp Leu Lys Gly Gly Val Val Leu Lys Glu Asp Ala Leu Pro Gly Gln

725 730 735

Lys Thr Glu Phe Lys Val Asp Ser Asp Asp Gln Trp Gly Glu Tyr Ser

740 745 750

Cys Val Phe Leu Pro Glu Pro Met Gly Thr Ala Asn Ile Gln Leu His

755 760 765

Gly Pro Pro Arg Val Lys Ala Val Lys Ser Ser Glu His Ile Asn Glu

770 775 780

Gly Glu Thr Ala Met Leu Val Cys Lys Ser Glu Ser Val Pro Pro Val

785 790 795 800

Thr Asp Trp Ala Trp Tyr Lys Ile Thr Asp Ser Glu Asp Lys Ala Leu

805 810 815

Met Asn Gly Ser Glu Ser Arg Phe Phe Val Ser Ser Ser Gln Gly Arg

820 825 830

Ser Glu Leu His Ile Glu Asn Leu Asn Met Glu Ala Asp Pro Gly Gln

835 840 845

Tyr Arg Cys Asn Gly Thr Ser Ser Lys Gly Ser Asp Gln Ala Ile Ile

850 855 860

Thr Leu Arg Val Arg Ser His Leu Ala Ala Leu Trp Pro Leu Leu Gly

865 870 875 880

Ile Val Ala Glu Val Leu Val Leu Val Thr Ile Ile Phe Ile Tyr Glu

885 890 895

Lys Arg Arg Lys Pro Glu Asp Val Leu Asp Asp Asp Asp Ala Gly Ser

900 905 910

Ala Pro Leu Lys Ser Ser Gly Gln His Gln Asn Asp Lys Gly Lys Asn

915 920 925

Val Arg Gln Arg Asn Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly

930 935 940

Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu

945 950 955 960

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

965 970 975

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

980 985 990

Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

995 1000 1005

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn

1010 1015 1020

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp

1025 1030 1035

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala

1040 1045 1050

Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln

1055 1060 1065

Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu

1070 1075 1080

Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe

1085 1090 1095

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro

1100 1105 1110

Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

1115 1120 1125

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp

1130 1135 1140

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

1145 1150 1155

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

1160 1165 1170

Gly Gly Ser Gly Gly Ser Leu His Val Lys Pro Pro Gln Phe Thr

1175 1180 1185

Trp Ala Gln Trp Phe Glu Thr Gln His Ile Asn Met Thr Ser Gln

1190 1195 1200

Gln Cys Thr Asn Ala Met Gln Val Ile Asn Asn Tyr Gln Arg Arg

1205 1210 1215

Cys Lys Asn Gln Asn Thr Phe Leu Leu Thr Thr Phe Ala Asn Val

1220 1225 1230

Val Asn Val Cys Gly Asn Pro Asn Met Thr Cys Pro Ser Asn Lys

1235 1240 1245

Thr Arg Lys Asn Cys His His Ser Gly Ser Gln Val Pro Leu Ile

1250 1255 1260

His Cys Asn Leu Thr Thr Pro Ser Pro Gln Asn Ile Ser Asn Cys

1265 1270 1275

Arg Tyr Ala Gln Thr Pro Ala Asn Met Phe Tyr Ile Val Ala Cys

1280 1285 1290

Asp Asn Arg Asp Gln Arg Arg Asp Pro Pro Gln Tyr Pro Val Val

1295 1300 1305

Pro Val His Leu Asp Arg Ile Ile

1310 1315

<210> 22

<211> 1316

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 22

Met Gly Ser Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Lys

1 5 10 15

Phe Asn Phe Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser

20 25 30

Trp Asn Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn

35 40 45

Asn Ala Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu

50 55 60

Ala Gln Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu

65 70 75 80

Gln Leu Gln Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp

85 90 95

Lys Ser Lys Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr

100 105 110

Ser Thr Gly Lys Val Cys Asn Pro Asp Asn Pro Gln Glu Cys Leu Leu

115 120 125

Leu Glu Pro Gly Leu Asn Glu Ile Met Ala Asn Ser Leu Asp Tyr Asn

130 135 140

Glu Arg Leu Trp Ala Trp Glu Ser Trp Arg Ser Glu Val Gly Lys Gln

145 150 155 160

Leu Arg Pro Leu Tyr Glu Glu Tyr Val Val Leu Lys Asn Glu Met Ala

165 170 175

Arg Ala Asn His Tyr Glu Asp Tyr Gly Asp Tyr Trp Arg Gly Asp Tyr

180 185 190

Glu Val Asn Gly Val Asp Gly Tyr Asp Tyr Ser Arg Gly Gln Leu Ile

195 200 205

Glu Asp Val Glu His Thr Phe Glu Glu Ile Lys Pro Leu Tyr Glu His

210 215 220

Leu His Ala Tyr Val Arg Ala Lys Leu Met Asn Ala Tyr Pro Ser Tyr

225 230 235 240

Ile Ser Pro Ile Gly Cys Leu Pro Ala His Leu Leu Gly Asp Met Trp

245 250 255

Gly Arg Phe Trp Thr Asn Leu Tyr Ser Leu Thr Val Pro Phe Gly Gln

260 265 270

Lys Pro Asn Ile Asp Val Thr Asp Ala Met Val Asp Gln Ala Trp Asp

275 280 285

Ala Gln Arg Ile Phe Lys Glu Ala Glu Lys Phe Phe Val Ser Val Gly

290 295 300

Leu Pro Asn Met Thr Gln Gly Phe Trp Glu Asn Ser Met Leu Thr Asp

305 310 315 320

Pro Gly Asn Val Gln Lys Ala Val Cys His Pro Thr Ala Trp Asp Leu

325 330 335

Gly Lys Gly Asp Phe Arg Ile Leu Gly Gly Gly Gly Ser Gly Gly Gly

340 345 350

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

355 360 365

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

370 375 380

Gly Gly Gly Gly Ser Gln Met Gln Leu Val Gln Ser Gly Thr Glu Val

385 390 395 400

Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr

405 410 415

Gly Phe Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys

420 425 430

Gly Leu Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg

435 440 445

Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser

450 455 460

Ile Asn Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr

465 470 475 480

Ala Ile Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp

485 490 495

Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Ser Gly

500 505 510

Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Ser Gly

515 520 525

Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

530 535 540

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

545 550 555 560

Ser Ile Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

565 570 575

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

580 585 590

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

595 600 605

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

610 615 620

Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

625 630 635 640

Lys Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

645 650 655

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

660 665 670

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala

675 680 685

Ala Gly Thr Val Phe Thr Thr Val Glu Asp Leu Gly Ser Lys Ile Leu

690 695 700

Leu Thr Cys Ser Leu Asn Asp Ser Ala Thr Glu Val Thr Gly His Arg

705 710 715 720

Trp Leu Lys Gly Gly Val Val Leu Lys Glu Asp Ala Leu Pro Gly Gln

725 730 735

Lys Thr Glu Phe Lys Val Asp Ser Asp Asp Gln Trp Gly Glu Tyr Ser

740 745 750

Cys Val Phe Leu Pro Glu Pro Met Gly Thr Ala Asn Ile Gln Leu His

755 760 765

Gly Pro Pro Arg Val Lys Ala Val Lys Ser Ser Glu His Ile Asn Glu

770 775 780

Gly Glu Thr Ala Met Leu Val Cys Lys Ser Glu Ser Val Pro Pro Val

785 790 795 800

Thr Asp Trp Ala Trp Tyr Lys Ile Thr Asp Ser Glu Asp Lys Ala Leu

805 810 815

Met Asn Gly Ser Glu Ser Arg Phe Phe Val Ser Ser Ser Gln Gly Arg

820 825 830

Ser Glu Leu His Ile Glu Asn Leu Asn Met Glu Ala Asp Pro Gly Gln

835 840 845

Tyr Arg Cys Asn Gly Thr Ser Ser Lys Gly Ser Asp Gln Ala Ile Ile

850 855 860

Thr Leu Arg Val Arg Ser His Leu Ala Ala Leu Trp Pro Leu Leu Gly

865 870 875 880

Ile Val Ala Glu Val Leu Val Leu Val Thr Ile Ile Phe Ile Tyr Glu

885 890 895

Lys Arg Arg Lys Pro Glu Asp Val Leu Asp Asp Asp Asp Ala Gly Ser

900 905 910

Ala Pro Leu Lys Ser Ser Gly Gln His Gln Asn Asp Lys Gly Lys Asn

915 920 925

Val Arg Gln Arg Asn Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly

930 935 940

Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu

945 950 955 960

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

965 970 975

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

980 985 990

Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

995 1000 1005

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn

1010 1015 1020

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp

1025 1030 1035

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala

1040 1045 1050

Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln

1055 1060 1065

Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu

1070 1075 1080

Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe

1085 1090 1095

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro

1100 1105 1110

Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

1115 1120 1125

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp

1130 1135 1140

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

1145 1150 1155

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

1160 1165 1170

Gly Gly Ser Gly Gly Ser Leu His Val Lys Pro Pro Gln Phe Thr

1175 1180 1185

Trp Ala Gln Trp Phe Glu Thr Gln His Ile Asn Met Thr Ser Gln

1190 1195 1200

Gln Cys Thr Asn Ala Met Gln Val Ile Asn Asn Tyr Gln Arg Arg

1205 1210 1215

Cys Lys Asn Gln Asn Thr Phe Leu Leu Thr Thr Phe Ala Asn Val

1220 1225 1230

Val Asn Val Cys Gly Asn Pro Asn Met Thr Cys Pro Ser Asn Lys

1235 1240 1245

Thr Arg Lys Asn Cys His His Ser Gly Ser Gln Val Pro Leu Ile

1250 1255 1260

His Cys Asn Leu Thr Thr Pro Ser Pro Gln Asn Ile Ser Asn Cys

1265 1270 1275

Arg Tyr Ala Gln Thr Pro Ala Asn Met Phe Tyr Ile Val Ala Cys

1280 1285 1290

Asp Asn Arg Asp Gln Arg Arg Asp Pro Pro Gln Tyr Pro Val Val

1295 1300 1305

Pro Val His Leu Asp Arg Ile Ile

1310 1315

<210> 23

<211> 779

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 23

Met Gly Ser Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Leu

1 5 10 15

Phe Asn His Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser

20 25 30

Trp Asn Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn

35 40 45

Asn Ala Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu

50 55 60

Ala Gln Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu

65 70 75 80

Gln Leu Gln Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp

85 90 95

Lys Ser Lys Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr

100 105 110

Ser Thr Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

130 135 140

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

145 150 155 160

Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

165 170 175

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

180 185 190

Ser Ile Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

195 200 205

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

210 215 220

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

225 230 235 240

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

245 250 255

Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

260 265 270

Lys Arg Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly

275 280 285

Gly Ser Gly Gly Ser Gly Gln Met Gln Leu Val Gln Ser Gly Thr Glu

290 295 300

Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly

305 310 315 320

Tyr Gly Phe Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly

325 330 335

Lys Gly Leu Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr

340 345 350

Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys

355 360 365

Ser Ile Asn Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp

370 375 380

Thr Ala Ile Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met

385 390 395 400

Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly

405 410 415

Ser Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu

420 425 430

Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp

435 440 445

Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp

450 455 460

Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly

465 470 475 480

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn

485 490 495

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp

500 505 510

Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro

515 520 525

Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu

530 535 540

Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn

545 550 555 560

Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile

565 570 575

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr

580 585 590

Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys

595 600 605

Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys

610 615 620

Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu

625 630 635 640

Ser Leu Ser Pro Gly Lys Gly Gly Ser Gly Gly Lys Pro Lys Gly Met

645 650 655

Thr Ser Ser Gln Trp Phe Lys Ile Gln His Met Gln Pro Ser Pro Gln

660 665 670

Ala Cys Asn Ser Ala Met Lys Asn Ile Asn Lys His Thr Lys Arg Cys

675 680 685

Lys Asp Leu Asn Thr Phe Leu His Glu Pro Phe Ser Ser Val Ala Ala

690 695 700

Thr Cys Gln Thr Pro Lys Ile Ala Cys Lys Asn Gly Asp Lys Asn Cys

705 710 715 720

His Gln Ser His Gly Ala Val Ser Leu Thr Met Cys Lys Leu Thr Ser

725 730 735

Gly Lys His Pro Asn Cys Arg Tyr Lys Glu Lys Arg Gln Asn Lys Ser

740 745 750

Tyr Val Val Ala Cys Lys Pro Pro Gln Lys Lys Asp Ser Gln Gln Phe

755 760 765

His Leu Val Pro Val His Leu Asp Arg Val Leu

770 775

<210> 24

<211> 779

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 24

Met Gly Ser Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Lys

1 5 10 15

Phe Asn His Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser

20 25 30

Trp Asn Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn

35 40 45

Asn Ala Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu

50 55 60

Ala Gln Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu

65 70 75 80

Gln Leu Gln Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp

85 90 95

Lys Ser Lys Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr

100 105 110

Ser Thr Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

130 135 140

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

145 150 155 160

Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

165 170 175

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

180 185 190

Ser Ile Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

195 200 205

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

210 215 220

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

225 230 235 240

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

245 250 255

Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

260 265 270

Lys Arg Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly

275 280 285

Gly Ser Gly Gly Ser Gly Gln Met Gln Leu Val Gln Ser Gly Thr Glu

290 295 300

Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly

305 310 315 320

Tyr Gly Phe Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly

325 330 335

Lys Gly Leu Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr

340 345 350

Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys

355 360 365

Ser Ile Asn Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp

370 375 380

Thr Ala Ile Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met

385 390 395 400

Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly

405 410 415

Ser Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu

420 425 430

Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp

435 440 445

Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp

450 455 460

Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly

465 470 475 480

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn

485 490 495

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp

500 505 510

Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro

515 520 525

Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu

530 535 540

Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn

545 550 555 560

Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile

565 570 575

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr

580 585 590

Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys

595 600 605

Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys

610 615 620

Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu

625 630 635 640

Ser Leu Ser Pro Gly Lys Gly Gly Ser Gly Gly Lys Pro Lys Gly Met

645 650 655

Thr Ser Ser Gln Trp Phe Lys Ile Gln His Met Gln Pro Ser Pro Gln

660 665 670

Ala Cys Asn Ser Ala Met Lys Asn Ile Asn Lys His Thr Lys Arg Cys

675 680 685

Lys Asp Leu Asn Thr Phe Leu His Glu Pro Phe Ser Ser Val Ala Ala

690 695 700

Thr Cys Gln Thr Pro Lys Ile Ala Cys Lys Asn Gly Asp Lys Asn Cys

705 710 715 720

His Gln Ser His Gly Ala Val Ser Leu Thr Met Cys Lys Leu Thr Ser

725 730 735

Gly Lys His Pro Asn Cys Arg Tyr Lys Glu Lys Arg Gln Asn Lys Ser

740 745 750

Tyr Val Val Ala Cys Lys Pro Pro Gln Lys Lys Asp Ser Gln Gln Phe

755 760 765

His Leu Val Pro Val His Leu Asp Arg Val Leu

770 775

<210> 25

<211> 1077

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 25

Met Gly Ser Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Leu

1 5 10 15

Phe Asn Phe Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser

20 25 30

Trp Asn Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn

35 40 45

Asn Ala Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu

50 55 60

Ala Gln Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu

65 70 75 80

Gln Leu Gln Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp

85 90 95

Lys Ser Lys Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr

100 105 110

Ser Thr Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

130 135 140

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

145 150 155 160

Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

165 170 175

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

180 185 190

Ser Ile Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

195 200 205

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

210 215 220

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

225 230 235 240

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

245 250 255

Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

260 265 270

Lys Arg Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly

275 280 285

Gly Ser Gly Gly Ser Gly Gln Met Gln Leu Val Gln Ser Gly Thr Glu

290 295 300

Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly

305 310 315 320

Tyr Gly Phe Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly

325 330 335

Lys Gly Leu Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr

340 345 350

Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys

355 360 365

Ser Ile Asn Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp

370 375 380

Thr Ala Ile Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met

385 390 395 400

Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly

405 410 415

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

420 425 430

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

435 440 445

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala Gly Thr Val Phe

450 455 460

Thr Thr Val Glu Asp Leu Gly Ser Lys Ile Leu Leu Thr Cys Ser Leu

465 470 475 480

Asn Asp Ser Ala Thr Glu Val Thr Gly His Arg Trp Leu Lys Gly Gly

485 490 495

Val Val Leu Lys Glu Asp Ala Leu Pro Gly Gln Lys Thr Glu Phe Lys

500 505 510

Val Asp Ser Asp Asp Gln Trp Gly Glu Tyr Ser Cys Val Phe Leu Pro

515 520 525

Glu Pro Met Gly Thr Ala Asn Ile Gln Leu His Gly Pro Pro Arg Val

530 535 540

Lys Ala Val Lys Ser Ser Glu His Ile Asn Glu Gly Glu Thr Ala Met

545 550 555 560

Leu Val Cys Lys Ser Glu Ser Val Pro Pro Val Thr Asp Trp Ala Trp

565 570 575

Tyr Lys Ile Thr Asp Ser Glu Asp Lys Ala Leu Met Asn Gly Ser Glu

580 585 590

Ser Arg Phe Phe Val Ser Ser Ser Gln Gly Arg Ser Glu Leu His Ile

595 600 605

Glu Asn Leu Asn Met Glu Ala Asp Pro Gly Gln Tyr Arg Cys Asn Gly

610 615 620

Thr Ser Ser Lys Gly Ser Asp Gln Ala Ile Ile Thr Leu Arg Val Arg

625 630 635 640

Ser His Leu Ala Ala Leu Trp Pro Leu Leu Gly Ile Val Ala Glu Val

645 650 655

Leu Val Leu Val Thr Ile Ile Phe Ile Tyr Glu Lys Arg Arg Lys Pro

660 665 670

Glu Asp Val Leu Asp Asp Asp Asp Ala Gly Ser Ala Pro Leu Lys Ser

675 680 685

Ser Gly Gln His Gln Asn Asp Lys Gly Lys Asn Val Arg Gln Arg Asn

690 695 700

Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Asp Lys Thr

705 710 715 720

His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser

725 730 735

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

740 745 750

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro

755 760 765

Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

770 775 780

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val

785 790 795 800

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

805 810 815

Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr

820 825 830

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

835 840 845

Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys

850 855 860

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

865 870 875 880

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

885 890 895

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser

900 905 910

Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

915 920 925

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

930 935 940

Gly Gly Ser Gly Gly Lys Pro Lys Gly Met Thr Ser Ser Gln Trp Phe

945 950 955 960

Lys Ile Gln His Met Gln Pro Ser Pro Gln Ala Cys Asn Ser Ala Met

965 970 975

Lys Asn Ile Asn Lys His Thr Lys Arg Cys Lys Asp Leu Asn Thr Phe

980 985 990

Leu His Glu Pro Phe Ser Ser Val Ala Ala Thr Cys Gln Thr Pro Lys

995 1000 1005

Ile Ala Cys Lys Asn Gly Asp Lys Asn Cys His Gln Ser His Gly

1010 1015 1020

Ala Val Ser Leu Thr Met Cys Lys Leu Thr Ser Gly Lys His Pro

1025 1030 1035

Asn Cys Arg Tyr Lys Glu Lys Arg Gln Asn Lys Ser Tyr Val Val

1040 1045 1050

Ala Cys Lys Pro Pro Gln Lys Lys Asp Ser Gln Gln Phe His Leu

1055 1060 1065

Val Pro Val His Leu Asp Arg Val Leu

1070 1075

<210> 26

<211> 1077

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 26

Met Gly Ser Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Lys

1 5 10 15

Phe Asn His Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser

20 25 30

Trp Asn Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn

35 40 45

Asn Ala Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu

50 55 60

Ala Gln Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu

65 70 75 80

Gln Leu Gln Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp

85 90 95

Lys Ser Lys Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr

100 105 110

Ser Thr Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

130 135 140

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

145 150 155 160

Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

165 170 175

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

180 185 190

Ser Ile Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

195 200 205

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

210 215 220

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

225 230 235 240

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

245 250 255

Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

260 265 270

Lys Arg Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly

275 280 285

Gly Ser Gly Gly Ser Gly Gln Met Gln Leu Val Gln Ser Gly Thr Glu

290 295 300

Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly

305 310 315 320

Tyr Gly Phe Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly

325 330 335

Lys Gly Leu Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr

340 345 350

Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys

355 360 365

Ser Ile Asn Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp

370 375 380

Thr Ala Ile Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met

385 390 395 400

Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Gly

405 410 415

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

420 425 430

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

435 440 445

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala Gly Thr Val Phe

450 455 460

Thr Thr Val Glu Asp Leu Gly Ser Lys Ile Leu Leu Thr Cys Ser Leu

465 470 475 480

Asn Asp Ser Ala Thr Glu Val Thr Gly His Arg Trp Leu Lys Gly Gly

485 490 495

Val Val Leu Lys Glu Asp Ala Leu Pro Gly Gln Lys Thr Glu Phe Lys

500 505 510

Val Asp Ser Asp Asp Gln Trp Gly Glu Tyr Ser Cys Val Phe Leu Pro

515 520 525

Glu Pro Met Gly Thr Ala Asn Ile Gln Leu His Gly Pro Pro Arg Val

530 535 540

Lys Ala Val Lys Ser Ser Glu His Ile Asn Glu Gly Glu Thr Ala Met

545 550 555 560

Leu Val Cys Lys Ser Glu Ser Val Pro Pro Val Thr Asp Trp Ala Trp

565 570 575

Tyr Lys Ile Thr Asp Ser Glu Asp Lys Ala Leu Met Asn Gly Ser Glu

580 585 590

Ser Arg Phe Phe Val Ser Ser Ser Gln Gly Arg Ser Glu Leu His Ile

595 600 605

Glu Asn Leu Asn Met Glu Ala Asp Pro Gly Gln Tyr Arg Cys Asn Gly

610 615 620

Thr Ser Ser Lys Gly Ser Asp Gln Ala Ile Ile Thr Leu Arg Val Arg

625 630 635 640

Ser His Leu Ala Ala Leu Trp Pro Leu Leu Gly Ile Val Ala Glu Val

645 650 655

Leu Val Leu Val Thr Ile Ile Phe Ile Tyr Glu Lys Arg Arg Lys Pro

660 665 670

Glu Asp Val Leu Asp Asp Asp Asp Ala Gly Ser Ala Pro Leu Lys Ser

675 680 685

Ser Gly Gln His Gln Asn Asp Lys Gly Lys Asn Val Arg Gln Arg Asn

690 695 700

Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Asp Lys Thr

705 710 715 720

His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser

725 730 735

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

740 745 750

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro

755 760 765

Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

770 775 780

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val

785 790 795 800

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

805 810 815

Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr

820 825 830

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

835 840 845

Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys

850 855 860

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

865 870 875 880

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

885 890 895

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser

900 905 910

Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

915 920 925

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

930 935 940

Gly Gly Ser Gly Gly Lys Pro Lys Gly Met Thr Ser Ser Gln Trp Phe

945 950 955 960

Lys Ile Gln His Met Gln Pro Ser Pro Gln Ala Cys Asn Ser Ala Met

965 970 975

Lys Asn Ile Asn Lys His Thr Lys Arg Cys Lys Asp Leu Asn Thr Phe

980 985 990

Leu His Glu Pro Phe Ser Ser Val Ala Ala Thr Cys Gln Thr Pro Lys

995 1000 1005

Ile Ala Cys Lys Asn Gly Asp Lys Asn Cys His Gln Ser His Gly

1010 1015 1020

Ala Val Ser Leu Thr Met Cys Lys Leu Thr Ser Gly Lys His Pro

1025 1030 1035

Asn Cys Arg Tyr Lys Glu Lys Arg Gln Asn Lys Ser Tyr Val Val

1040 1045 1050

Ala Cys Lys Pro Pro Gln Lys Lys Asp Ser Gln Gln Phe His Leu

1055 1060 1065

Val Pro Val His Leu Asp Arg Val Leu

1070 1075

<210> 27

<211> 1113

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 27

Met Gly Ser Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Lys

1 5 10 15

Phe Asn Phe Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser

20 25 30

Trp Asn Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn

35 40 45

Asn Ala Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu

50 55 60

Ala Gln Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu

65 70 75 80

Gln Leu Gln Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp

85 90 95

Lys Ser Lys Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr

100 105 110

Ser Thr Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

130 135 140

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

145 150 155 160

Gln Met Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro Gly Glu

165 170 175

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile Thr Tyr

180 185 190

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

195 200 205

Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro Ser Phe

210 215 220

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr Ala Tyr

225 230 235 240

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr Tyr Cys

245 250 255

Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly Gln Gly

260 265 270

Thr Thr Val Thr Val Ser Ser Gly Gly Ser Gly Gly Gly Gly Ser Gly

275 280 285

Gly Gly Ser Gly Gly Gly Ser Gly Gly Ser Gly Asp Ile Gln Leu Thr

290 295 300

Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile

305 310 315 320

Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser Ser Ile Asn Lys Asn

325 330 335

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu

340 345 350

Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser

355 360 365

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln

370 375 380

Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro

385 390 395 400

Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Gly Gly Gly

405 410 415

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

420 425 430

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

435 440 445

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala Gly Thr Val Phe

450 455 460

Thr Thr Val Glu Asp Leu Gly Ser Lys Ile Leu Leu Thr Cys Ser Leu

465 470 475 480

Asn Asp Ser Ala Thr Glu Val Thr Gly His Arg Trp Leu Lys Gly Gly

485 490 495

Val Val Leu Lys Glu Asp Ala Leu Pro Gly Gln Lys Thr Glu Phe Lys

500 505 510

Val Asp Ser Asp Asp Gln Trp Gly Glu Tyr Ser Cys Val Phe Leu Pro

515 520 525

Glu Pro Met Gly Thr Ala Asn Ile Gln Leu His Gly Pro Pro Arg Val

530 535 540

Lys Ala Val Lys Ser Ser Glu His Ile Asn Glu Gly Glu Thr Ala Met

545 550 555 560

Leu Val Cys Lys Ser Glu Ser Val Pro Pro Val Thr Asp Trp Ala Trp

565 570 575

Tyr Lys Ile Thr Asp Ser Glu Asp Lys Ala Leu Met Asn Gly Ser Glu

580 585 590

Ser Arg Phe Phe Val Ser Ser Ser Gln Gly Arg Ser Glu Leu His Ile

595 600 605

Glu Asn Leu Asn Met Glu Ala Asp Pro Gly Gln Tyr Arg Cys Asn Gly

610 615 620

Thr Ser Ser Lys Gly Ser Asp Gln Ala Ile Ile Thr Leu Arg Val Arg

625 630 635 640

Ser His Leu Ala Ala Leu Trp Pro Leu Leu Gly Ile Val Ala Glu Val

645 650 655

Leu Val Leu Val Thr Ile Ile Phe Ile Tyr Glu Lys Arg Arg Lys Pro

660 665 670

Glu Asp Val Leu Asp Asp Asp Asp Ala Gly Ser Ala Pro Leu Lys Ser

675 680 685

Ser Gly Gln His Gln Asn Asp Lys Gly Lys Asn Val Arg Gln Arg Asn

690 695 700

Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Asp Lys Thr

705 710 715 720

His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser

725 730 735

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

740 745 750

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro

755 760 765

Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

770 775 780

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val

785 790 795 800

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

805 810 815

Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr

820 825 830

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

835 840 845

Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys

850 855 860

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

865 870 875 880

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

885 890 895

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser

900 905 910

Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

915 920 925

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

930 935 940

Gly Gly Ser Gly Gly Met Arg Ala Tyr Trp Pro Asp Val Ile His Ser

945 950 955 960

Phe Pro Asn Arg Ser Arg Phe Trp Lys His Glu Trp Glu Lys His Gly

965 970 975

Thr Cys Ala Ala Gln Val Asp Ala Leu Asn Ser Gln Lys Lys Tyr Phe

980 985 990

Gly Arg Ser Leu Glu Leu Tyr Arg Glu Leu Asp Leu Asn Ser Val Leu

995 1000 1005

Leu Lys Leu Gly Ile Lys Pro Ser Ile Asn Tyr Tyr Gln Val Ala

1010 1015 1020

Asp Phe Lys Asp Ala Leu Ala Arg Val Tyr Gly Val Ile Pro Lys

1025 1030 1035

Ile Gln Cys Leu Pro Pro Ser Gln Asp Glu Glu Val Gln Thr Ile

1040 1045 1050

Gly Gln Ile Glu Leu Cys Leu Thr Lys Gln Asp Gln Gln Leu Gln

1055 1060 1065

Asn Cys Thr Glu Pro Gly Glu Gln Pro Ser Pro Lys Gln Glu Val

1070 1075 1080

Trp Leu Ala Asn Gly Ala Ala Glu Ser Arg Gly Leu Arg Val Cys

1085 1090 1095

Glu Asp Gly Pro Val Phe Tyr Pro Pro Pro Lys Lys Thr Lys His

1100 1105 1110

<210> 28

<211> 1113

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 28

Met Gly Ser Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Lys

1 5 10 15

Phe Asn His Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser

20 25 30

Trp Asn Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn

35 40 45

Asn Ala Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu

50 55 60

Ala Gln Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu

65 70 75 80

Gln Leu Gln Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp

85 90 95

Lys Ser Lys Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr

100 105 110

Ser Thr Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

130 135 140

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

145 150 155 160

Gln Met Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro Gly Glu

165 170 175

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile Thr Tyr

180 185 190

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

195 200 205

Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro Ser Phe

210 215 220

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr Ala Tyr

225 230 235 240

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr Tyr Cys

245 250 255

Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly Gln Gly

260 265 270

Thr Thr Val Thr Val Ser Ser Gly Gly Ser Gly Gly Gly Gly Ser Gly

275 280 285

Gly Gly Ser Gly Gly Gly Ser Gly Gly Ser Gly Asp Ile Gln Leu Thr

290 295 300

Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala Thr Ile

305 310 315 320

Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser Ser Ile Asn Lys Asn

325 330 335

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu

340 345 350

Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Ser

355 360 365

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln

370 375 380

Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser Thr Pro

385 390 395 400

Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Gly Gly Gly

405 410 415

Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

420 425 430

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

435 440 445

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala Gly Thr Val Phe

450 455 460

Thr Thr Val Glu Asp Leu Gly Ser Lys Ile Leu Leu Thr Cys Ser Leu

465 470 475 480

Asn Asp Ser Ala Thr Glu Val Thr Gly His Arg Trp Leu Lys Gly Gly

485 490 495

Val Val Leu Lys Glu Asp Ala Leu Pro Gly Gln Lys Thr Glu Phe Lys

500 505 510

Val Asp Ser Asp Asp Gln Trp Gly Glu Tyr Ser Cys Val Phe Leu Pro

515 520 525

Glu Pro Met Gly Thr Ala Asn Ile Gln Leu His Gly Pro Pro Arg Val

530 535 540

Lys Ala Val Lys Ser Ser Glu His Ile Asn Glu Gly Glu Thr Ala Met

545 550 555 560

Leu Val Cys Lys Ser Glu Ser Val Pro Pro Val Thr Asp Trp Ala Trp

565 570 575

Tyr Lys Ile Thr Asp Ser Glu Asp Lys Ala Leu Met Asn Gly Ser Glu

580 585 590

Ser Arg Phe Phe Val Ser Ser Ser Gln Gly Arg Ser Glu Leu His Ile

595 600 605

Glu Asn Leu Asn Met Glu Ala Asp Pro Gly Gln Tyr Arg Cys Asn Gly

610 615 620

Thr Ser Ser Lys Gly Ser Asp Gln Ala Ile Ile Thr Leu Arg Val Arg

625 630 635 640

Ser His Leu Ala Ala Leu Trp Pro Leu Leu Gly Ile Val Ala Glu Val

645 650 655

Leu Val Leu Val Thr Ile Ile Phe Ile Tyr Glu Lys Arg Arg Lys Pro

660 665 670

Glu Asp Val Leu Asp Asp Asp Asp Ala Gly Ser Ala Pro Leu Lys Ser

675 680 685

Ser Gly Gln His Gln Asn Asp Lys Gly Lys Asn Val Arg Gln Arg Asn

690 695 700

Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Asp Lys Thr

705 710 715 720

His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser

725 730 735

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

740 745 750

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro

755 760 765

Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

770 775 780

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val

785 790 795 800

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

805 810 815

Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr

820 825 830

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

835 840 845

Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys

850 855 860

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

865 870 875 880

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

885 890 895

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser

900 905 910

Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

915 920 925

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

930 935 940

Gly Gly Ser Gly Gly Met Arg Ala Tyr Trp Pro Asp Val Ile His Ser

945 950 955 960

Phe Pro Asn Arg Ser Arg Phe Trp Lys His Glu Trp Glu Lys His Gly

965 970 975

Thr Cys Ala Ala Gln Val Asp Ala Leu Asn Ser Gln Lys Lys Tyr Phe

980 985 990

Gly Arg Ser Leu Glu Leu Tyr Arg Glu Leu Asp Leu Asn Ser Val Leu

995 1000 1005

Leu Lys Leu Gly Ile Lys Pro Ser Ile Asn Tyr Tyr Gln Val Ala

1010 1015 1020

Asp Phe Lys Asp Ala Leu Ala Arg Val Tyr Gly Val Ile Pro Lys

1025 1030 1035

Ile Gln Cys Leu Pro Pro Ser Gln Asp Glu Glu Val Gln Thr Ile

1040 1045 1050

Gly Gln Ile Glu Leu Cys Leu Thr Lys Gln Asp Gln Gln Leu Gln

1055 1060 1065

Asn Cys Thr Glu Pro Gly Glu Gln Pro Ser Pro Lys Gln Glu Val

1070 1075 1080

Trp Leu Ala Asn Gly Ala Ala Glu Ser Arg Gly Leu Arg Val Cys

1085 1090 1095

Glu Asp Gly Pro Val Phe Tyr Pro Pro Pro Lys Lys Thr Lys His

1100 1105 1110

<210> 29

<211> 988

<212> PRT

<213> Artificial

<220>

<223> fuiosn protein

<400> 29

Met Gly Ser Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Leu

1 5 10 15

Phe Asn Phe Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser

20 25 30

Trp Asn Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn

35 40 45

Asn Ala Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu

50 55 60

Ala Gln Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu

65 70 75 80

Gln Leu Gln Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp

85 90 95

Lys Ser Lys Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr

100 105 110

Ser Thr Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly

115 120 125

Gly Ser Gln Met Gln Leu Val Gln Ser Gly Thr Glu Val Lys Lys Pro

130 135 140

Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Gly Phe Ile

145 150 155 160

Thr Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu

165 170 175

Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser Glu Thr Arg Tyr Ser Pro

180 185 190

Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Asn Thr

195 200 205

Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Ile Tyr

210 215 220

Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr Pro Met Asp Val Trp Gly

225 230 235 240

Gln Gly Thr Thr Val Thr Val Ser Ser Gly Gly Ser Gly Gly Gly Gly

245 250 255

Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Ser Gly Asp Ile Gln

260 265 270

Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly Glu Arg Ala

275 280 285

Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser Ser Ile Asn

290 295 300

Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys

305 310 315 320

Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val Pro Asp Arg

325 330 335

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser

340 345 350

Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln Tyr Tyr Ser

355 360 365

Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Gly

370 375 380

Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ala Ala

385 390 395 400

Gly Thr Val Phe Thr Thr Val Glu Asp Leu Gly Ser Lys Ile Leu Leu

405 410 415

Thr Cys Ser Leu Asn Asp Ser Ala Thr Glu Val Thr Gly His Arg Trp

420 425 430

Leu Lys Gly Gly Val Val Leu Lys Glu Asp Ala Leu Pro Gly Gln Lys

435 440 445

Thr Glu Phe Lys Val Asp Ser Asp Asp Gln Trp Gly Glu Tyr Ser Cys

450 455 460

Val Phe Leu Pro Glu Pro Met Gly Thr Ala Asn Ile Gln Leu His Gly

465 470 475 480

Pro Pro Arg Val Lys Ala Val Lys Ser Ser Glu His Ile Asn Glu Gly

485 490 495

Glu Thr Ala Met Leu Val Cys Lys Ser Glu Ser Val Pro Pro Val Thr

500 505 510

Asp Trp Ala Trp Tyr Lys Ile Thr Asp Ser Glu Asp Lys Ala Leu Met

515 520 525

Asn Gly Ser Glu Ser Arg Phe Phe Val Ser Ser Ser Gln Gly Arg Ser

530 535 540

Glu Leu His Ile Glu Asn Leu Asn Met Glu Ala Asp Pro Gly Gln Tyr

545 550 555 560

Arg Cys Asn Gly Thr Ser Ser Lys Gly Ser Asp Gln Ala Ile Ile Thr

565 570 575

Leu Arg Val Arg Ser His Leu Ala Ala Leu Trp Pro Leu Leu Gly Ile

580 585 590

Val Ala Glu Val Leu Val Leu Val Thr Ile Ile Phe Ile Tyr Glu Lys

595 600 605

Arg Arg Lys Pro Glu Asp Val Leu Asp Asp Asp Asp Ala Gly Ser Ala

610 615 620

Pro Leu Lys Ser Ser Gly Gln His Gln Asn Asp Lys Gly Lys Asn Val

625 630 635 640

Arg Gln Arg Asn Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly

645 650 655

Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

660 665 670

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

675 680 685

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

690 695 700

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

705 710 715 720

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

725 730 735

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

740 745 750

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

755 760 765

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

770 775 780

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

785 790 795 800

Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val

805 810 815

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

820 825 830

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

835 840 845

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

850 855 860

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

865 870 875 880

Ser Pro Gly Lys Gly Gly Ser Gly Gly Gly Met Ala Ser Leu Leu Cys

885 890 895

Cys Gly Pro Lys Leu Ala Ala Cys Gly Ile Val Leu Ser Ala Trp Gly

900 905 910

Val Ile Met Leu Ile Met Leu Gly Ile Phe Phe Asn Val His Ser Ala

915 920 925

Val Leu Ile Glu Asp Val Pro Phe Thr Glu Lys Asp Phe Glu Asn Gly

930 935 940

Pro Gln Asn Ile Tyr Asn Leu Tyr Glu Gln Val Ser Tyr Asn Cys Phe

945 950 955 960

Ile Ala Ala Gly Leu Tyr Leu Leu Leu Gly Gly Phe Ser Phe Cys Gln

965 970 975

Val Arg Leu Asn Lys Arg Lys Glu Tyr Met Val Arg

980 985

<210> 30

<211> 1028

<212> PRT

<213> Homo sapiens

<400> 30

Met Gly Ser Ala Ala Cys Pro Arg Gly Ala Leu Pro Glu Leu Ala Pro

1 5 10 15

Cys Cys Gln Pro Arg Glu Gln Ser Gln Pro His Thr Arg Trp Asp Ala

20 25 30

Gly Cys Gly Ile Gln His Pro Gly Gly Glu Glu Phe Arg Thr Leu Gly

35 40 45

Gly Ala Arg Ala Tyr Arg Val Pro Asn Ser Gln Glu Gly Arg Ser Ser

50 55 60

Pro Thr Arg Phe Phe Pro Ala Pro Glu Gly Pro Ala His Cys Phe Val

65 70 75 80

Ser Ser Pro Asp Arg Ala Phe Trp Val Ser Glu Glu Val Gln Arg Leu

85 90 95

Leu Leu Ser Asn Ala Cys Gln Pro Lys Glu Cys Asn Gly Val Lys Ile

100 105 110

Pro Val Asp Ala Ser Lys Pro Asn Pro Asn Asp Val Glu Phe Asp Asn

115 120 125

Leu Tyr Leu Asp Met Asn Gly Ile Ile His Pro Cys Thr His Pro Glu

130 135 140

Asp Lys Pro Ala Pro Lys Asn Glu Asp Glu Met Met Val Ala Ile Phe

145 150 155 160

Glu Tyr Ile Asp Arg Leu Phe Ser Ile Val Arg Pro Arg Arg Leu Leu

165 170 175

Tyr Met Ala Ile Asp Gly Val Ala Pro Arg Ala Lys Met Asn Gln Gln

180 185 190

Arg Ser Arg Arg Phe Arg Ala Ser Lys Glu Gly Met Glu Ala Ala Val

195 200 205

Glu Lys Gln Arg Val Arg Glu Glu Ile Leu Ala Lys Gly Gly Phe Leu

210 215 220

Pro Pro Glu Glu Ile Lys Glu Arg Phe Asp Ser Asn Cys Ile Thr Pro

225 230 235 240

Gly Thr Glu Phe Met Asp Asn Leu Ala Lys Cys Leu Arg Tyr Tyr Ile

245 250 255

Ala Asp Arg Leu Asn Asn Asp Pro Gly Trp Lys Asn Leu Thr Val Ile

260 265 270

Leu Ser Asp Ala Ser Ala Pro Gly Glu Gly Glu His Lys Ile Met Asp

275 280 285

Tyr Ile Arg Arg Gln Arg Ala Gln Pro Asn His Asp Pro Asn Thr His

290 295 300

His Cys Leu Cys Gly Ala Asp Ala Asp Leu Ile Met Leu Gly Leu Ala

305 310 315 320

Thr His Glu Pro Asn Phe Thr Ile Ile Arg Glu Glu Phe Lys Pro Asn

325 330 335

Lys Pro Lys Pro Cys Gly Leu Cys Asn Gln Phe Gly His Glu Val Lys

340 345 350

Asp Cys Glu Gly Leu Pro Arg Glu Lys Lys Gly Lys His Asp Glu Leu

355 360 365

Ala Asp Ser Leu Pro Cys Ala Glu Gly Glu Phe Ile Phe Leu Arg Leu

370 375 380

Asn Val Leu Arg Glu Tyr Leu Glu Arg Glu Leu Thr Met Ala Ser Leu

385 390 395 400

Pro Phe Thr Phe Asp Val Glu Arg Ser Ile Asp Asp Trp Val Phe Met

405 410 415

Cys Phe Phe Val Gly Asn Asp Phe Leu Pro His Leu Pro Ser Leu Glu

420 425 430

Ile Arg Glu Asn Ala Ile Asp Arg Leu Val Asn Ile Tyr Lys Asn Val

435 440 445

Val His Lys Thr Gly Gly Tyr Leu Thr Glu Ser Gly Tyr Val Asn Leu

450 455 460

Gln Arg Val Gln Met Ile Met Leu Ala Val Gly Glu Val Glu Asp Ser

465 470 475 480

Ile Phe Lys Lys Arg Lys Asp Asp Glu Asp Ser Phe Arg Arg Arg Gln

485 490 495

Lys Glu Lys Arg Lys Arg Met Lys Arg Asp Gln Pro Ala Phe Thr Pro

500 505 510

Ser Gly Ile Leu Thr Pro His Ala Leu Gly Ser Arg Asn Ser Pro Gly

515 520 525

Ser Gln Val Ala Ser Asn Pro Arg Gln Ala Ala Tyr Glu Met Arg Met

530 535 540

Gln Asn Asn Ser Ser Pro Ser Ile Ser Pro Asn Thr Ser Phe Thr Ser

545 550 555 560

Asp Gly Ser Pro Ser Pro Leu Gly Gly Ile Lys Arg Lys Ala Glu Asp

565 570 575

Ser Asp Ser Glu Pro Glu Pro Glu Asp Asn Val Arg Leu Trp Glu Ala

580 585 590

Gly Trp Lys Gln Arg Tyr Tyr Lys Asn Lys Phe Asp Val Asp Ala Ala

595 600 605

Asp Glu Lys Phe Arg Arg Lys Val Val Gln Ser Tyr Val Glu Gly Leu

610 615 620

Cys Trp Val Leu Arg Tyr Tyr Tyr Gln Gly Cys Ala Ser Trp Lys Trp

625 630 635 640

Tyr Tyr Pro Phe His Tyr Ala Pro Phe Ala Ser Asp Phe Glu Gly Ile

645 650 655

Ala Asp Met Pro Ser Asp Phe Glu Lys Gly Thr Lys Pro Phe Lys Pro

660 665 670

Leu Glu Gln Leu Met Gly Val Phe Pro Ala Ala Ser Gly Asn Phe Leu

675 680 685

Pro Pro Ser Trp Arg Lys Leu Met Ser Asp Pro Asp Ser Ser Ile Ile

690 695 700

Asp Phe Tyr Pro Glu Asp Phe Ala Ile Asp Leu Asn Gly Lys Lys Tyr

705 710 715 720

Ala Trp Gln Gly Val Ala Leu Leu Pro Phe Val Asp Glu Arg Arg Leu

725 730 735

Arg Ala Ala Leu Glu Glu Val Tyr Pro Asp Leu Thr Pro Glu Glu Thr

740 745 750

Arg Arg Asn Ser Leu Gly Gly Asp Val Leu Phe Val Gly Lys His His

755 760 765

Pro Leu His Asp Phe Ile Leu Glu Leu Tyr Gln Thr Gly Ser Thr Glu

770 775 780

Pro Val Glu Val Pro Pro Glu Leu Cys His Gly Ile Gln Gly Lys Phe

785 790 795 800

Ser Leu Asp Glu Glu Ala Ile Leu Pro Asp Gln Ile Val Cys Ser Pro

805 810 815

Val Pro Met Leu Arg Asp Leu Thr Gln Asn Thr Val Val Ser Ile Asn

820 825 830

Phe Lys Asp Pro Gln Phe Ala Glu Asp Tyr Ile Phe Lys Ala Val Met

835 840 845

Leu Pro Gly Ala Arg Lys Pro Ala Ala Val Leu Lys Pro Ser Asp Trp

850 855 860

Glu Lys Ser Ser Asn Gly Arg Gln Trp Lys Pro Gln Leu Gly Phe Asn

865 870 875 880

Arg Asp Arg Arg Pro Val His Leu Asp Gln Ala Ala Phe Arg Thr Leu

885 890 895

Gly His Val Met Pro Arg Gly Ser Gly Thr Gly Ile Tyr Ser Asn Ala

900 905 910

Ala Pro Pro Pro Val Thr Tyr Gln Gly Asn Leu Tyr Arg Pro Leu Leu

915 920 925

Arg Gly Gln Ala Gln Ile Pro Lys Leu Met Ser Asn Met Arg Pro Gln

930 935 940

Asp Ser Trp Arg Gly Pro Pro Pro Leu Phe Gln Gln Gln Arg Phe Asp

945 950 955 960

Arg Gly Val Gly Ala Glu Pro Leu Leu Pro Trp Asn Arg Met Leu Gln

965 970 975

Thr Gln Asn Ala Ala Phe Gln Pro Asn Gln Tyr Gln Met Leu Ala Gly

980 985 990

Pro Gly Gly Tyr Pro Pro Arg Arg Asp Asp Arg Gly Gly Arg Gln Gly

995 1000 1005

Tyr Pro Arg Glu Gly Arg Lys Tyr Pro Leu Pro Pro Pro Ser Gly

1010 1015 1020

Arg Tyr Asn Trp Asn

1025

<210> 31

<211> 1694

<212> PRT

<213> Homo sapiens

<400> 31

Met Gly Val Pro Lys Phe Tyr Arg Trp Ile Ser Glu Arg Tyr Pro Cys

1 5 10 15

Leu Ser Glu Val Val Lys Glu His Gln Ile Pro Glu Phe Asp Asn Leu

20 25 30

Tyr Leu Asp Met Asn Gly Ile Ile His Gln Cys Ser His Pro Asn Asp

35 40 45

Asp Asp Val His Phe Arg Ile Ser Asp Asp Lys Ile Phe Thr Asp Ile

50 55 60

Phe His Tyr Leu Glu Val Leu Phe Arg Ile Ile Lys Pro Arg Lys Val

65 70 75 80

Phe Phe Met Ala Val Asp Gly Val Ala Pro Arg Ala Lys Met Asn Gln

85 90 95

Gln Arg Gly Arg Arg Phe Arg Ser Ala Lys Glu Ala Glu Asp Lys Ile

100 105 110

Lys Lys Ala Ile Glu Lys Gly Glu Thr Leu Pro Thr Glu Ala Arg Phe

115 120 125

Asp Ser Asn Cys Ile Thr Pro Gly Thr Glu Phe Met Ala Arg Leu His

130 135 140

Glu His Leu Lys Tyr Phe Val Asn Met Lys Ile Ser Thr Asp Lys Ser

145 150 155 160

Trp Gln Gly Val Thr Ile Tyr Phe Ser Gly His Glu Thr Pro Gly Glu

165 170 175

Gly Glu His Lys Ile Met Glu Phe Ile Arg Ser Glu Lys Ala Lys Pro

180 185 190

Asp His Asp Pro Asn Thr Arg His Cys Leu Tyr Gly Leu Asp Ala Asp

195 200 205

Leu Ile Met Leu Gly Leu Thr Ser His Glu Ala His Phe Ser Leu Leu

210 215 220

Arg Glu Glu Val Arg Phe Gly Gly Lys Lys Thr Gln Arg Val Cys Ala

225 230 235 240

Pro Glu Glu Thr Thr Phe His Leu Leu His Leu Ser Leu Met Arg Glu

245 250 255

Tyr Ile Asp Tyr Glu Phe Ser Val Leu Lys Glu Lys Ile Thr Phe Lys

260 265 270

Tyr Asp Ile Glu Arg Ile Ile Asp Asp Trp Ile Leu Met Gly Phe Leu

275 280 285

Val Gly Asn Asp Phe Ile Pro His Leu Pro His Leu His Ile Asn His

290 295 300

Asp Ala Leu Pro Leu Leu Tyr Gly Thr Tyr Val Thr Ile Leu Pro Glu

305 310 315 320

Leu Gly Gly Tyr Ile Asn Glu Ser Gly His Leu Asn Leu Pro Arg Phe

325 330 335

Glu Lys Tyr Leu Val Lys Leu Ser Asp Phe Asp Arg Glu His Phe Ser

340 345 350

Glu Val Phe Val Asp Leu Lys Trp Phe Glu Ser Lys Val Gly Asn Lys

355 360 365

Tyr Leu Asn Glu Ala Ala Gly Val Ala Ala Glu Glu Ala Arg Asn Tyr

370 375 380

Lys Glu Lys Lys Lys Leu Lys Gly Gln Glu Asn Ser Leu Cys Trp Thr

385 390 395 400

Ala Leu Asp Lys Asn Glu Gly Glu Met Ile Thr Ser Lys Asp Asn Leu

405 410 415

Glu Asp Glu Thr Glu Asp Asp Asp Leu Phe Glu Thr Glu Phe Arg Gln

420 425 430

Tyr Lys Arg Thr Tyr Tyr Met Thr Lys Met Gly Val Asp Val Val Ser

435 440 445

Asp Asp Phe Leu Ala Asp Gln Ala Ala Cys Tyr Val Gln Ala Ile Gln

450 455 460

Trp Ile Leu His Tyr Tyr Tyr His Gly Val Gln Ser Trp Ser Trp Tyr

465 470 475 480

Tyr Pro Tyr His Tyr Ala Pro Phe Leu Ser Asp Ile His Asn Ile Ser

485 490 495

Thr Leu Lys Ile His Phe Glu Leu Gly Lys Pro Phe Lys Pro Phe Glu

500 505 510

Gln Leu Leu Ala Val Leu Pro Ala Ala Ser Lys Asn Leu Leu Pro Ala

515 520 525

Cys Tyr Gln His Leu Met Thr Asn Glu Asp Ser Pro Ile Ile Glu Tyr

530 535 540

Tyr Pro Pro Asp Phe Lys Thr Asp Leu Asn Gly Lys Gln Gln Glu Trp

545 550 555 560

Glu Ala Val Val Leu Ile Pro Phe Ile Asp Glu Lys Arg Leu Leu Glu

565 570 575

Ala Met Glu Thr Cys Asn His Ser Leu Lys Lys Glu Glu Arg Lys Arg

580 585 590

Asn Gln His Ser Glu Cys Leu Met Cys Trp Tyr Asp Arg Asp Thr Glu

595 600 605

Phe Ile Tyr Pro Ser Pro Trp Pro Glu Lys Phe Pro Ala Ile Glu Arg

610 615 620

Cys Cys Thr Arg Tyr Lys Ile Ile Ser Leu Asp Ala Trp Arg Val Asp

625 630 635 640

Ile Asn Lys Asn Lys Ile Thr Arg Ile Asp Gln Lys Ala Leu Tyr Phe

645 650 655

Cys Gly Phe Pro Thr Leu Lys His Ile Arg His Lys Phe Phe Leu Lys

660 665 670

Lys Ser Gly Val Gln Val Phe Gln Gln Ser Ser Arg Gly Glu Asn Met

675 680 685

Met Leu Glu Ile Leu Val Asp Ala Glu Ser Asp Glu Leu Thr Val Glu

690 695 700

Asn Val Ala Ser Ser Val Leu Gly Lys Ser Val Phe Val Asn Trp Pro

705 710 715 720

His Leu Glu Glu Ala Arg Val Val Ala Val Ser Asp Gly Glu Thr Lys

725 730 735

Phe Tyr Leu Glu Glu Pro Pro Gly Thr Gln Lys Leu Tyr Ser Gly Arg

740 745 750

Thr Ala Pro Pro Ser Lys Val Val His Leu Gly Asp Lys Glu Gln Ser

755 760 765

Asn Trp Ala Lys Glu Val Gln Gly Ile Ser Glu His Tyr Leu Arg Arg

770 775 780

Lys Gly Ile Ile Ile Asn Glu Thr Ser Ala Val Val Tyr Ala Gln Leu

785 790 795 800

Leu Thr Gly Arg Lys Tyr Gln Ile Asn Gln Asn Gly Glu Val Arg Leu

805 810 815

Glu Lys Gln Trp Ser Lys Gln Val Val Pro Phe Val Tyr Gln Thr Ile

820 825 830

Val Lys Asp Ile Arg Ala Phe Asp Ser Arg Phe Ser Asn Ile Lys Thr

835 840 845

Leu Asp Asp Leu Phe Pro Leu Arg Ser Met Val Phe Met Leu Gly Thr

850 855 860

Pro Tyr Tyr Gly Cys Thr Gly Glu Val Gln Asp Ser Gly Asp Val Ile

865 870 875 880

Thr Glu Gly Arg Ile Arg Val Ile Phe Ser Ile Pro Cys Glu Pro Asn

885 890 895

Leu Asp Ala Leu Ile Gln Asn Gln His Lys Tyr Ser Ile Lys Tyr Asn

900 905 910

Pro Gly Tyr Val Leu Ala Ser Arg Leu Gly Val Ser Gly Tyr Leu Val

915 920 925

Ser Arg Phe Thr Gly Ser Ile Phe Ile Gly Arg Gly Ser Arg Arg Asn

930 935 940

Pro His Gly Asp His Lys Ala Asn Val Gly Leu Asn Leu Lys Phe Asn

945 950 955 960

Lys Lys Asn Glu Glu Val Pro Gly Tyr Thr Lys Lys Val Gly Ser Glu

965 970 975

Trp Met Tyr Ser Ser Ala Ala Glu Gln Leu Leu Ala Glu Tyr Leu Glu

980 985 990

Arg Ala Pro Glu Leu Phe Ser Tyr Ile Ala Lys Asn Ser Gln Glu Asp

995 1000 1005

Val Phe Tyr Glu Asp Asp Ile Trp Pro Gly Glu Asn Glu Asn Gly

1010 1015 1020

Ala Glu Lys Val Gln Glu Ile Ile Thr Trp Leu Lys Gly His Pro

1025 1030 1035

Val Ser Thr Leu Ser Arg Ser Ser Cys Asp Leu Gln Ile Leu Asp

1040 1045 1050

Ala Ala Ile Val Glu Lys Ile Glu Glu Glu Val Glu Lys Cys Lys

1055 1060 1065

Gln Arg Lys Asn Asn Lys Lys Val Arg Val Thr Val Lys Pro His

1070 1075 1080

Leu Leu Tyr Arg Pro Leu Glu Gln Gln His Gly Val Ile Pro Asp

1085 1090 1095

Arg Asp Ala Glu Phe Cys Leu Phe Asp Arg Val Val Asn Val Arg

1100 1105 1110

Glu Asn Phe Ser Val Pro Val Gly Leu Arg Gly Thr Ile Ile Gly

1115 1120 1125

Ile Lys Gly Ala Asn Arg Glu Ala Asp Val Leu Phe Glu Val Leu

1130 1135 1140

Phe Asp Glu Glu Phe Pro Gly Gly Leu Thr Ile Arg Cys Ser Pro

1145 1150 1155

Gly Arg Gly Tyr Arg Leu Pro Thr Ser Ala Leu Val Asn Leu Ser

1160 1165 1170

His Gly Ser Arg Ser Glu Thr Gly Asn Gln Lys Leu Thr Ala Ile

1175 1180 1185

Val Lys Pro Gln Pro Ala Val His Gln His Ser Ser Ser Ser Ser

1190 1195 1200

Val Ser Ser Gly His Leu Gly Ala Leu Asn His Ser Pro Gln Ser

1205 1210 1215

Leu Phe Val Pro Thr Gln Val Pro Thr Lys Asp Asp Asp Glu Phe

1220 1225 1230

Cys Asn Ile Trp Gln Ser Leu Gln Gly Ser Gly Lys Met Gln Tyr

1235 1240 1245

Phe Gln Pro Thr Ile Gln Glu Lys Gly Ala Val Leu Pro Gln Glu

1250 1255 1260

Ile Ser Gln Val Asn Gln His His Lys Ser Gly Phe Asn Asp Asn

1265 1270 1275

Ser Val Lys Tyr Gln Gln Arg Lys His Asp Pro His Arg Lys Phe

1280 1285 1290

Lys Glu Glu Cys Lys Ser Pro Lys Ala Glu Cys Trp Ser Gln Lys

1295 1300 1305

Met Ser Asn Lys Gln Pro Asn Ser Gly Ile Glu Asn Phe Leu Ala

1310 1315 1320

Ser Leu Asn Ile Ser Lys Glu Asn Glu Val Gln Ser Ser His His

1325 1330 1335

Gly Glu Pro Pro Ser Glu Glu His Leu Ser Pro Gln Ser Phe Ala

1340 1345 1350

Met Lys Gly Thr Arg Met Leu Lys Glu Ile Leu Lys Ile Asp Gly

1355 1360 1365

Ser Asn Thr Val Asp His Lys Asn Glu Ile Lys Gln Ile Ala Asn

1370 1375 1380

Glu Ile Pro Val Ser Ser Asn Arg Arg Asp Glu Tyr Gly Leu Pro

1385 1390 1395

Ser Gln Pro Lys Gln Asn Lys Lys Leu Ala Ser Tyr Met Asn Lys

1400 1405 1410

Pro His Ser Ala Asn Glu Tyr His Asn Val Gln Ser Met Asp Asn

1415 1420 1425

Met Cys Trp Pro Ala Pro Ser Gln Ile Pro Pro Val Ser Thr Pro

1430 1435 1440

Val Thr Glu Leu Ser Arg Ile Cys Ser Leu Val Gly Met Pro Gln

1445 1450 1455

Pro Asp Phe Ser Phe Leu Arg Met Pro Gln Thr Met Thr Val Cys

1460 1465 1470

Gln Val Lys Leu Ser Asn Gly Leu Leu Val His Gly Pro Gln Cys

1475 1480 1485

His Ser Glu Asn Glu Ala Lys Glu Lys Ala Ala Leu Phe Ala Leu

1490 1495 1500

Gln Gln Leu Gly Ser Leu Gly Met Asn Phe Pro Leu Pro Ser Gln

1505 1510 1515

Val Phe Ala Asn Tyr Pro Ser Ala Val Pro Pro Gly Thr Ile Pro

1520 1525 1530

Pro Ala Phe Pro Pro Pro Thr Ala Asn Ile Met Pro Ser Ser Ser

1535 1540 1545

His Leu Phe Gly Ser Met Pro Trp Gly Pro Ser Val Pro Val Pro

1550 1555 1560

Gly Lys Pro Phe His His Thr Leu Tyr Ser Gly Thr Met Pro Met

1565 1570 1575

Ala Gly Gly Ile Pro Gly Gly Val His Asn Gln Phe Ile Pro Leu

1580 1585 1590

Gln Val Thr Lys Lys Arg Val Ala Asn Lys Lys Asn Phe Glu Asn

1595 1600 1605

Lys Glu Ala Gln Ser Ser Gln Ala Thr Pro Val Gln Thr Ser Gln

1610 1615 1620

Pro Asp Ser Ser Asn Ile Val Lys Val Ser Pro Arg Glu Ser Ser

1625 1630 1635

Ser Ala Ser Leu Lys Ser Ser Pro Ile Ala Gln Pro Ala Ser Ser

1640 1645 1650

Phe Gln Val Glu Thr Ala Ser Gln Gly His Ser Ile Ser His His

1655 1660 1665

Lys Ser Thr Pro Ile Ser Ser Ser Arg Arg Lys Ser Arg Lys Leu

1670 1675 1680

Ala Val Asn Phe Gly Val Ser Lys Pro Ser Glu

1685 1690

<210> 32

<211> 269

<212> PRT

<213> Homo sapiens

<400> 32

Met Ala Ala Ala Leu Phe Val Leu Leu Gly Phe Ala Leu Leu Gly Thr

1 5 10 15

His Gly Ala Ser Gly Ala Ala Gly Thr Val Phe Thr Thr Val Glu Asp

20 25 30

Leu Gly Ser Lys Ile Leu Leu Thr Cys Ser Leu Asn Asp Ser Ala Thr

35 40 45

Glu Val Thr Gly His Arg Trp Leu Lys Gly Gly Val Val Leu Lys Glu

50 55 60

Asp Ala Leu Pro Gly Gln Lys Thr Glu Phe Lys Val Asp Ser Asp Asp

65 70 75 80

Gln Trp Gly Glu Tyr Ser Cys Val Phe Leu Pro Glu Pro Met Gly Thr

85 90 95

Ala Asn Ile Gln Leu His Gly Pro Pro Arg Val Lys Ala Val Lys Ser

100 105 110

Ser Glu His Ile Asn Glu Gly Glu Thr Ala Met Leu Val Cys Lys Ser

115 120 125

Glu Ser Val Pro Pro Val Thr Asp Trp Ala Trp Tyr Lys Ile Thr Asp

130 135 140

Ser Glu Asp Lys Ala Leu Met Asn Gly Ser Glu Ser Arg Phe Phe Val

145 150 155 160

Ser Ser Ser Gln Gly Arg Ser Glu Leu His Ile Glu Asn Leu Asn Met

165 170 175

Glu Ala Asp Pro Gly Gln Tyr Arg Cys Asn Gly Thr Ser Ser Lys Gly

180 185 190

Ser Asp Gln Ala Ile Ile Thr Leu Arg Val Arg Ser His Leu Ala Ala

195 200 205

Leu Trp Pro Leu Leu Gly Ile Val Ala Glu Val Leu Val Leu Val Thr

210 215 220

Ile Ile Phe Ile Tyr Glu Lys Arg Arg Lys Pro Glu Asp Val Leu Asp

225 230 235 240

Asp Asp Asp Ala Gly Ser Ala Pro Leu Lys Ser Ser Gly Gln His Gln

245 250 255

Asn Asp Lys Gly Lys Asn Val Arg Gln Arg Asn Ser Ser

260 265

<210> 33

<211> 1175

<212> PRT

<213> Artificial

<220>

<223> ACE2m mutation

<400> 33

Met Ser Ser Ser Ser Trp Leu Leu Leu Ser Leu Val Ala Val Thr Ala

1 5 10 15

Ala Gln Ser Thr Ile Glu Glu Gln Ala Lys Thr Phe Leu Asp Lys Phe

20 25 30

Asn His Glu Ala Glu Asp Leu Phe Tyr Gln Ser Ser Leu Ala Ser Trp

35 40 45

Asn Tyr Asn Thr Asn Ile Thr Glu Glu Asn Val Gln Asn Met Asn Asn

50 55 60

Ala Gly Asp Lys Trp Ser Ala Phe Leu Lys Glu Gln Ser Thr Leu Ala

65 70 75 80

Gln Met Tyr Pro Leu Gln Glu Ile Gln Asn Leu Thr Val Lys Leu Gln

85 90 95

Leu Gln Ala Leu Gln Gln Asn Gly Ser Ser Val Leu Ser Glu Asp Lys

100 105 110

Ser Lys Arg Leu Asn Thr Ile Leu Asn Thr Met Ser Thr Ile Tyr Ser

115 120 125

Thr Gly Lys Val Cys Asn Pro Asp Asn Pro Gln Glu Cys Leu Leu Leu

130 135 140

Glu Pro Gly Leu Asn Glu Ile Met Ala Asn Ser Leu Asp Tyr Asn Glu

145 150 155 160

Arg Leu Trp Ala Trp Glu Ser Trp Arg Ser Glu Val Gly Lys Gln Leu

165 170 175

Arg Pro Leu Tyr Glu Glu Tyr Val Val Leu Lys Asn Glu Met Ala Arg

180 185 190

Ala Asn His Tyr Glu Asp Tyr Gly Asp Tyr Trp Arg Gly Asp Tyr Glu

195 200 205

Val Asn Gly Val Asp Gly Tyr Asp Tyr Ser Arg Gly Gln Leu Ile Glu

210 215 220

Asp Val Glu His Thr Phe Glu Glu Ile Lys Pro Leu Tyr Glu His Leu

225 230 235 240

His Ala Tyr Val Arg Ala Lys Leu Met Asn Ala Tyr Pro Ser Tyr Ile

245 250 255

Ser Pro Ile Gly Cys Leu Pro Ala His Leu Leu Gly Asp Met Trp Gly

260 265 270

Arg Phe Trp Thr Asn Leu Tyr Ser Leu Thr Val Pro Phe Gly Gln Lys

275 280 285

Pro Asn Ile Asp Val Thr Asp Ala Met Val Asp Gln Ala Trp Asp Ala

290 295 300

Gln Arg Ile Phe Lys Glu Ala Glu Lys Phe Phe Val Ser Val Gly Leu

305 310 315 320

Pro Asn Met Thr Gln Gly Phe Trp Glu Asn Ser Met Leu Thr Asp Pro

325 330 335

Gly Asn Val Gln Lys Ala Val Cys His Pro Thr Ala Trp Asp Leu Gly

340 345 350

Lys Gly Asp Phe Arg Ile Leu Met Cys Thr Lys Val Thr Met Asp Asp

355 360 365

Phe Leu Thr Ala His Asp Glu Met Gly Asp Ile Gln Tyr Asp Met Ala

370 375 380

Tyr Ala Ala Gln Pro Phe Leu Leu Arg Asn Gly Ala Asn Glu Gly Phe

385 390 395 400

His Glu Ala Val Gly Glu Ile Met Ser Leu Ser Ala Ala Thr Pro Lys

405 410 415

His Leu Lys Ser Ile Gly Leu Leu Ser Pro Asp Phe Gln Glu Asp Asn

420 425 430

Glu Thr Glu Ile Asn Phe Leu Leu Lys Gln Ala Leu Thr Ile Val Gly

435 440 445

Thr Leu Pro Phe Thr Tyr Met Leu Glu Lys Trp Arg Trp Met Val Phe

450 455 460

Lys Gly Glu Ile Pro Lys Asp Gln Trp Met Lys Lys Trp Trp Glu Met

465 470 475 480

Lys Arg Glu Ile Val Gly Val Val Glu Pro Val Pro His Asp Glu Thr

485 490 495

Tyr Cys Asp Pro Ala Ser Leu Phe His Val Ser Asn Asp Tyr Ser Phe

500 505 510

Ile Arg Tyr Tyr Thr Arg Thr Leu Tyr Gln Phe Gln Phe Gln Glu Ala

515 520 525

Leu Cys Gln Ala Ala Lys His Glu Gly Pro Leu His Lys Cys Asp Ile

530 535 540

Ser Asn Ser Thr Glu Ala Gly Gln Lys Leu Phe Asn Met Leu Arg Leu

545 550 555 560

Gly Lys Ser Glu Pro Trp Thr Leu Ala Leu Glu Asn Val Val Gly Ala

565 570 575

Lys Asn Met Asn Val Arg Pro Leu Leu Asn Tyr Phe Glu Pro Leu Phe

580 585 590

Thr Trp Leu Lys Asp Gln Asn Lys Asn Ser Phe Val Gly Trp Ser Thr

595 600 605

Asp Trp Ser Pro Tyr Ala Asp Gln Ser Ile Lys Val Arg Ile Ser Leu

610 615 620

Lys Ser Ala Leu Gly Asp Arg Ala Tyr Glu Trp Asn Asp Asn Glu Met

625 630 635 640

Tyr Leu Phe Arg Ser Ser Val Ala Tyr Ala Met Arg Gln Tyr Phe Leu

645 650 655

Lys Val Lys Asn Gln Met Ile Leu Phe Gly Glu Glu Asp Val Arg Val

660 665 670

Ala Asn Leu Lys Pro Arg Ile Ser Phe Asn Phe Phe Val Thr Ala Pro

675 680 685

Lys Asn Val Ser Asp Ile Ile Pro Arg Thr Glu Val Glu Lys Ala Ile

690 695 700

Arg Met Ser Arg Ser Arg Ile Asn Asp Ala Phe Arg Leu Asn Asp Asn

705 710 715 720

Ser Leu Glu Phe Leu Gly Ile Gln Pro Thr Leu Gly Pro Pro Asn Gln

725 730 735

Pro Pro Val Ser Ile Trp Leu Ile Val Phe Gly Val Val Met Gly Val

740 745 750

Ile Val Val Gly Ile Val Ile Leu Ile Phe Thr Gly Ile Arg Asp Arg

755 760 765

Lys Lys Lys Asn Lys Ala Arg Ser Gly Glu Asn Pro Tyr Ala Ser Ile

770 775 780

Asp Ile Ser Lys Gly Glu Asn Asn Pro Gly Phe Gln Asn Thr Asp Asp

785 790 795 800

Val Gln Thr Ser Phe Ser Met Cys Val Pro Asp Gln Asp Thr Ala Ile

805 810 815

Arg Val Phe Ala Ile Pro Pro Ser Phe Ala Ser Ile Phe Leu Thr Lys

820 825 830

Ser Thr Lys Leu Thr Cys Leu Val Thr Asp Leu Thr Thr Tyr Asp Ser

835 840 845

Val Thr Ile Ser Trp Thr Arg Gln Asn Gly Glu Ala Val Lys Thr His

850 855 860

Thr Asn Ile Ser Glu Ser His Pro Asn Ala Thr Phe Ser Ala Val Gly

865 870 875 880

Glu Ala Ser Ile Cys Glu Asp Asp Trp Asn Ser Gly Glu Arg Phe Thr

885 890 895

Cys Thr Val Thr His Thr Asp Leu Pro Ser Pro Leu Lys Gln Thr Ile

900 905 910

Ser Arg Pro Lys Gly Val Ala Leu His Arg Pro Asp Val Tyr Leu Leu

915 920 925

Pro Pro Ala Arg Glu Gln Leu Asn Leu Arg Glu Ser Ala Thr Ile Thr

930 935 940

Cys Leu Val Thr Gly Phe Ser Pro Ala Asp Val Phe Val Gln Trp Met

945 950 955 960

Gln Arg Gly Gln Pro Leu Ser Pro Glu Lys Tyr Val Thr Ser Ala Pro

965 970 975

Met Pro Glu Pro Gln Ala Pro Gly Arg Tyr Phe Ala His Ser Ile Leu

980 985 990

Thr Val Ser Glu Glu Glu Trp Asn Thr Gly Glu Thr Tyr Thr Cys Val

995 1000 1005

Val Ala His Glu Ala Leu Pro Asn Arg Val Thr Glu Arg Thr Val

1010 1015 1020

Asp Lys Ser Thr Gly Lys Pro Thr Leu Tyr Asn Val Ser Leu Val

1025 1030 1035

Met Ser Asp Thr Ala Gly Thr Cys Tyr Lys Pro Lys Gly Met Thr

1040 1045 1050

Ser Ser Gln Trp Phe Lys Ile Gln His Met Gln Pro Ser Pro Gln

1055 1060 1065

Ala Cys Asn Ser Ala Met Lys Asn Ile Asn Lys His Thr Lys Arg

1070 1075 1080

Cys Lys Asp Leu Asn Thr Phe Leu His Glu Pro Phe Ser Ser Val

1085 1090 1095

Ala Ala Thr Cys Gln Thr Pro Lys Ile Ala Cys Lys Asn Gly Asp

1100 1105 1110

Lys Asn Cys His Gln Ser His Gly Ala Val Ser Leu Thr Met Cys

1115 1120 1125

Lys Leu Thr Ser Gly Lys His Pro Asn Cys Arg Tyr Lys Glu Lys

1130 1135 1140

Arg Gln Asn Lys Ser Tyr Val Val Ala Cys Lys Pro Pro Gln Lys

1145 1150 1155

Lys Asp Ser Gln Gln Phe His Leu Val Pro Val His Leu Asp Arg

1160 1165 1170

Val Leu

1175

<210> 34

<211> 627

<212> PRT

<213> Artificial

<220>

<223> fusion protein

<400> 34

Met Pro Leu Leu Leu Leu Leu Pro Leu Leu Trp Ala Gly Ala Leu Ala

1 5 10 15

Asp Ile Gln Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

20 25 30

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

35 40 45

Ser Ile Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

50 55 60

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

65 70 75 80

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

85 90 95

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

100 105 110

Tyr Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

115 120 125

Lys Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly

130 135 140

Gly Ser Gly Gly Gly Ser Gly Met Gln Met Gln Leu Val Gln Ser Gly

145 150 155 160

Thr Glu Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly

165 170 175

Ser Gly Tyr Gly Phe Ile Thr Tyr Trp Ile Gly Trp Val Arg Gln Met

180 185 190

Pro Gly Lys Gly Leu Glu Trp Met Gly Ile Ile Tyr Pro Gly Asp Ser

195 200 205

Glu Thr Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Ile Ser Ala

210 215 220

Asp Lys Ser Ile Asn Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala

225 230 235 240

Ser Asp Thr Ala Ile Tyr Tyr Cys Ala Gly Gly Ser Gly Ile Ser Thr

245 250 255

Pro Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Gly

260 265 270

Ser Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu

275 280 285

Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp

290 295 300

Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp

305 310 315 320

Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly

325 330 335

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn

340 345 350

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp

355 360 365

Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro

370 375 380

Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu

385 390 395 400

Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn

405 410 415

Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile

420 425 430

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr

435 440 445

Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys

450 455 460

Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys

465 470 475 480

Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu

485 490 495

Ser Leu Ser Pro Gly Lys Pro Asp Val Tyr Leu Leu Pro Pro Ala Arg

500 505 510

Glu Gln Leu Asn Leu Arg Glu Ser Ala Thr Ile Thr Cys Leu Val Thr

515 520 525

Gly Phe Ser Pro Ala Asp Val Phe Val Gln Trp Met Gln Arg Gly Gln

530 535 540

Pro Leu Ser Pro Glu Lys Tyr Val Thr Ser Ala Pro Met Pro Glu Pro

545 550 555 560

Gln Ala Pro Gly Arg Tyr Phe Ala His Ser Ile Leu Thr Val Ser Glu

565 570 575

Glu Glu Trp Asn Thr Gly Glu Thr Tyr Thr Cys Val Val Ala His Glu

580 585 590

Ala Leu Pro Asn Arg Val Thr Glu Arg Thr Val Asp Lys Ser Thr Gly

595 600 605

Lys Pro Thr Leu Tyr Asn Val Ser Leu Val Met Ser Asp Thr Ala Gly

610 615 620

Thr Cys Tyr

625

<210> 35

<211> 393

<212> PRT

<213> Artificial

<220>

<223> RNaseP

<400> 35

Gly Ala Ala Gly Cys Thr Gly Ala Cys Cys Ala Gly Ala Cys Ala Gly

1 5 10 15

Thr Cys Gly Cys Cys Gly Cys Thr Thr Cys Gly Thr Cys Gly Thr Cys

20 25 30

Cys Thr Cys Cys Thr Cys Thr Thr Cys Gly Gly Gly Gly Gly Ala Gly

35 40 45

Ala Cys Gly Gly Gly Cys Gly Gly Ala Gly Gly Gly Gly Ala Gly Gly

50 55 60

Ala Ala Ala Gly Thr Cys Cys Gly Gly Gly Cys Thr Cys Cys Ala Thr

65 70 75 80

Ala Gly Gly Gly Cys Ala Gly Gly Gly Thr Gly Cys Cys Ala Gly Gly

85 90 95

Thr Ala Ala Cys Gly Cys Cys Thr Gly Gly Gly Gly Gly Gly Gly Ala

100 105 110

Ala Ala Cys Cys Cys Ala Cys Gly Ala Cys Cys Ala Gly Thr Gly Cys

115 120 125

Ala Ala Cys Ala Gly Ala Gly Ala Gly Cys Ala Ala Ala Cys Cys Gly

130 135 140

Cys Cys Gly Ala Thr Gly Gly Cys Cys Cys Gly Cys Gly Cys Ala Ala

145 150 155 160

Gly Cys Gly Gly Gly Ala Thr Cys Ala Gly Gly Thr Ala Ala Gly Gly

165 170 175

Gly Thr Gly Ala Ala Ala Gly Gly Gly Thr Gly Cys Gly Gly Thr Ala

180 185 190

Ala Gly Ala Gly Cys Gly Cys Ala Cys Cys Gly Cys Cys Cys Gly Gly

195 200 205

Cys Thr Gly Gly Thr Ala Ala Cys Ala Gly Thr Cys Cys Gly Thr Gly

210 215 220

Gly Cys Ala Cys Gly Gly Thr Ala Ala Ala Cys Thr Cys Cys Ala Cys

225 230 235 240

Cys Cys Gly Gly Ala Gly Cys Ala Ala Gly Gly Cys Cys Ala Ala Ala

245 250 255

Thr Ala Gly Gly Gly Gly Thr Thr Cys Ala Thr Ala Ala Gly Gly Thr

260 265 270

Ala Cys Gly Gly Cys Cys Cys Gly Thr Ala Cys Thr Gly Ala Ala Cys

275 280 285

Cys Cys Gly Gly Gly Thr Ala Gly Gly Cys Thr Gly Cys Thr Thr Gly

290 295 300

Ala Gly Cys Cys Ala Gly Thr Gly Ala Gly Cys Gly Ala Thr Thr Gly

305 310 315 320

Cys Thr Gly Gly Cys Thr Thr Ala Gly Ala Thr Gly Ala Ala Thr Gly

325 330 335

Ala Cys Thr Gly Thr Cys Cys Ala Cys Gly Ala Cys Ala Gly Ala Ala

340 345 350

Cys Cys Cys Gly Gly Cys Thr Thr Ala Thr Cys Gly Gly Thr Cys Ala

355 360 365

Gly Thr Thr Thr Cys Ala Cys Cys Thr Cys Ala Ala Ala Gly Ala Ala

370 375 380

Gly Ala Ala Gly Thr Gly Cys Cys Ala

385 390

<210> 36

<211> 394

<212> PRT

<213> Artificial

<220>

<223> RNaseP

<400> 36

Gly Ala Ala Gly Cys Thr Gly Ala Cys Cys Ala Gly Ala Cys Ala Gly

1 5 10 15

Thr Cys Gly Cys Cys Gly Cys Thr Thr Cys Gly Thr Cys Gly Thr Cys

20 25 30

Cys Thr Cys Cys Thr Cys Thr Thr Cys Gly Gly Gly Gly Gly Ala Gly

35 40 45

Ala Cys Gly Gly Gly Cys Gly Gly Ala Gly Gly Gly Gly Ala Gly Gly

50 55 60

Ala Ala Ala Gly Thr Cys Cys Gly Gly Gly Cys Thr Cys Cys Ala Thr

65 70 75 80

Ala Gly Gly Gly Cys Ala Gly Gly Gly Thr Gly Cys Cys Ala Gly Gly

85 90 95

Thr Ala Ala Cys Gly Cys Cys Thr Gly Gly Gly Gly Gly Gly Gly Ala

100 105 110

Ala Ala Cys Cys Cys Ala Cys Gly Ala Cys Cys Ala Gly Thr Gly Cys

115 120 125

Ala Ala Cys Ala Gly Ala Gly Ala Gly Cys Ala Ala Ala Cys Cys Gly

130 135 140

Cys Cys Gly Ala Thr Gly Gly Cys Cys Cys Gly Cys Gly Cys Ala Ala

145 150 155 160

Gly Cys Gly Gly Gly Ala Thr Cys Ala Gly Gly Thr Ala Ala Gly Gly

165 170 175

Gly Thr Gly Ala Ala Ala Gly Gly Gly Thr Gly Cys Gly Gly Thr Ala

180 185 190

Ala Gly Ala Gly Cys Gly Cys Ala Cys Cys Gly Cys Cys Cys Gly Gly

195 200 205

Cys Thr Gly Gly Thr Ala Ala Cys Ala Gly Thr Cys Cys Gly Thr Gly

210 215 220

Gly Cys Ala Cys Gly Gly Thr Ala Ala Ala Cys Thr Cys Cys Ala Cys

225 230 235 240

Cys Cys Gly Gly Ala Gly Cys Ala Ala Gly Gly Cys Cys Ala Ala Ala

245 250 255

Thr Ala Gly Gly Gly Gly Thr Thr Cys Ala Thr Ala Ala Gly Gly Thr

260 265 270

Ala Cys Gly Gly Cys Cys Cys Gly Thr Ala Cys Thr Gly Ala Ala Cys

275 280 285

Cys Cys Gly Gly Gly Thr Ala Gly Gly Cys Thr Gly Cys Thr Thr Gly

290 295 300

Ala Gly Cys Cys Ala Gly Thr Gly Ala Gly Cys Gly Ala Thr Thr Gly

305 310 315 320

Cys Thr Gly Gly Cys Thr Thr Ala Gly Ala Thr Gly Ala Ala Thr Gly

325 330 335

Ala Cys Thr Gly Thr Cys Cys Ala Cys Gly Ala Cys Ala Gly Ala Ala

340 345 350

Cys Cys Cys Gly Gly Cys Thr Thr Ala Thr Cys Gly Gly Thr Cys Ala

355 360 365

Gly Thr Thr Thr Cys Ala Cys Cys Thr Cys Thr Gly Ala Thr Ala Thr

370 375 380

Cys Ala Cys Ala Cys Ala Thr Cys Cys Ala

385 390

<210> 37

<211> 394

<212> PRT

<213> Artificial

<220>

<223> RNaseP

<400> 37

Gly Ala Ala Gly Cys Thr Gly Ala Cys Cys Ala Gly Ala Cys Ala Gly

1 5 10 15

Thr Cys Gly Cys Cys Gly Cys Thr Thr Cys Gly Thr Cys Gly Thr Cys

20 25 30

Cys Thr Cys Cys Thr Cys Thr Thr Cys Gly Gly Gly Gly Gly Ala Gly

35 40 45

Ala Cys Gly Gly Gly Cys Gly Gly Ala Gly Gly Gly Gly Ala Gly Gly

50 55 60

Ala Ala Ala Gly Thr Cys Cys Gly Gly Gly Cys Thr Cys Cys Ala Thr

65 70 75 80

Ala Gly Gly Gly Cys Ala Gly Gly Gly Thr Gly Cys Cys Ala Gly Gly

85 90 95

Thr Ala Ala Cys Gly Cys Cys Thr Gly Gly Gly Gly Gly Gly Gly Ala

100 105 110

Ala Ala Cys Cys Cys Ala Cys Gly Ala Cys Cys Ala Gly Thr Gly Cys

115 120 125

Ala Ala Cys Ala Gly Ala Gly Ala Gly Cys Ala Ala Ala Cys Cys Gly

130 135 140

Cys Cys Gly Ala Thr Gly Gly Cys Cys Cys Gly Cys Gly Cys Ala Ala

145 150 155 160

Gly Cys Gly Gly Gly Ala Thr Cys Ala Gly Gly Thr Ala Ala Gly Gly

165 170 175

Gly Thr Gly Ala Ala Ala Gly Gly Gly Thr Gly Cys Gly Gly Thr Ala

180 185 190

Ala Gly Ala Gly Cys Gly Cys Ala Cys Cys Gly Cys Cys Cys Gly Gly

195 200 205

Cys Thr Gly Gly Thr Ala Ala Cys Ala Gly Thr Cys Cys Gly Thr Gly

210 215 220

Gly Cys Ala Cys Gly Gly Thr Ala Ala Ala Cys Thr Cys Cys Ala Cys

225 230 235 240

Cys Cys Gly Gly Ala Gly Cys Ala Ala Gly Gly Cys Cys Ala Ala Ala

245 250 255

Thr Ala Gly Gly Gly Gly Thr Thr Cys Ala Thr Ala Ala Gly Gly Thr

260 265 270

Ala Cys Gly Gly Cys Cys Cys Gly Thr Ala Cys Thr Gly Ala Ala Cys

275 280 285

Cys Cys Gly Gly Gly Thr Ala Gly Gly Cys Thr Gly Cys Thr Thr Gly

290 295 300

Ala Gly Cys Cys Ala Gly Thr Gly Ala Gly Cys Gly Ala Thr Thr Gly

305 310 315 320

Cys Thr Gly Gly Cys Thr Thr Ala Gly Ala Thr Gly Ala Ala Thr Gly

325 330 335

Ala Cys Thr Gly Thr Cys Cys Ala Cys Gly Ala Cys Ala Gly Ala Ala

340 345 350

Cys Cys Cys Gly Gly Cys Thr Thr Ala Thr Cys Gly Gly Thr Cys Ala

355 360 365

Gly Thr Thr Thr Cys Ala Cys Cys Thr Thr Cys Thr Gly Ala Thr Cys

370 375 380

Cys Cys Ala Ala Thr Ala Thr Cys Cys Ala

385 390

<210> 38

<211> 394

<212> PRT

<213> Artificial

<220>

<223> RNaseP

<400> 38

Gly Ala Ala Gly Cys Thr Gly Ala Cys Cys Ala Gly Ala Cys Ala Gly

1 5 10 15

Thr Cys Gly Cys Cys Gly Cys Thr Thr Cys Gly Thr Cys Gly Thr Cys

20 25 30

Cys Thr Cys Cys Thr Cys Thr Thr Cys Gly Gly Gly Gly Gly Ala Gly

35 40 45

Ala Cys Gly Gly Gly Cys Gly Gly Ala Gly Gly Gly Gly Ala Gly Gly

50 55 60

Ala Ala Ala Gly Thr Cys Cys Gly Gly Gly Cys Thr Cys Cys Ala Thr

65 70 75 80

Ala Gly Gly Gly Cys Ala Gly Gly Gly Thr Gly Cys Cys Ala Gly Gly

85 90 95

Thr Ala Ala Cys Gly Cys Cys Thr Gly Gly Gly Gly Gly Gly Gly Ala

100 105 110

Ala Ala Cys Cys Cys Ala Cys Gly Ala Cys Cys Ala Gly Thr Gly Cys

115 120 125

Ala Ala Cys Ala Gly Ala Gly Ala Gly Cys Ala Ala Ala Cys Cys Gly

130 135 140

Cys Cys Gly Ala Thr Gly Gly Cys Cys Cys Gly Cys Gly Cys Ala Ala

145 150 155 160

Gly Cys Gly Gly Gly Ala Thr Cys Ala Gly Gly Thr Ala Ala Gly Gly

165 170 175

Gly Thr Gly Ala Ala Ala Gly Gly Gly Thr Gly Cys Gly Gly Thr Ala

180 185 190

Ala Gly Ala Gly Cys Gly Cys Ala Cys Cys Gly Cys Cys Cys Gly Gly

195 200 205

Cys Thr Gly Gly Thr Ala Ala Cys Ala Gly Thr Cys Cys Gly Thr Gly

210 215 220

Gly Cys Ala Cys Gly Gly Thr Ala Ala Ala Cys Thr Cys Cys Ala Cys

225 230 235 240

Cys Cys Gly Gly Ala Gly Cys Ala Ala Gly Gly Cys Cys Ala Ala Ala

245 250 255

Thr Ala Gly Gly Gly Gly Thr Thr Cys Ala Thr Ala Ala Gly Gly Thr

260 265 270

Ala Cys Gly Gly Cys Cys Cys Gly Thr Ala Cys Thr Gly Ala Ala Cys

275 280 285

Cys Cys Gly Gly Gly Thr Ala Gly Gly Cys Thr Gly Cys Thr Thr Gly

290 295 300

Ala Gly Cys Cys Ala Gly Thr Gly Ala Gly Cys Gly Ala Thr Thr Gly

305 310 315 320

Cys Thr Gly Gly Cys Thr Thr Ala Gly Ala Thr Gly Ala Ala Thr Gly

325 330 335

Ala Cys Thr Gly Thr Cys Cys Ala Cys Gly Ala Cys Ala Gly Ala Ala

340 345 350

Cys Cys Cys Gly Gly Cys Thr Thr Ala Thr Cys Gly Gly Thr Cys Ala

355 360 365

Gly Thr Thr Thr Cys Ala Cys Cys Thr Gly Cys Gly Ala Gly Cys Thr

370 375 380

Cys Thr Ala Thr Thr Cys Thr Cys Cys Ala

385 390

<210> 39

<211> 394

<212> PRT

<213> Artificial

<220>

<223> RNaseP

<400> 39

Gly Ala Ala Gly Cys Thr Gly Ala Cys Cys Ala Gly Ala Cys Ala Gly

1 5 10 15

Thr Cys Gly Cys Cys Gly Cys Thr Thr Cys Gly Thr Cys Gly Thr Cys

20 25 30

Cys Thr Cys Cys Thr Cys Thr Thr Cys Gly Gly Gly Gly Gly Ala Gly

35 40 45

Ala Cys Gly Gly Gly Cys Gly Gly Ala Gly Gly Gly Gly Ala Gly Gly

50 55 60

Ala Ala Ala Gly Thr Cys Cys Gly Gly Gly Cys Thr Cys Cys Ala Thr

65 70 75 80

Ala Gly Gly Gly Cys Ala Gly Gly Gly Thr Gly Cys Cys Ala Gly Gly

85 90 95

Thr Ala Ala Cys Gly Cys Cys Thr Gly Gly Gly Gly Gly Gly Gly Ala

100 105 110

Ala Ala Cys Cys Cys Ala Cys Gly Ala Cys Cys Ala Gly Thr Gly Cys

115 120 125

Ala Ala Cys Ala Gly Ala Gly Ala Gly Cys Ala Ala Ala Cys Cys Gly

130 135 140

Cys Cys Gly Ala Thr Gly Gly Cys Cys Cys Gly Cys Gly Cys Ala Ala

145 150 155 160

Gly Cys Gly Gly Gly Ala Thr Cys Ala Gly Gly Thr Ala Ala Gly Gly

165 170 175

Gly Thr Gly Ala Ala Ala Gly Gly Gly Thr Gly Cys Gly Gly Thr Ala

180 185 190

Ala Gly Ala Gly Cys Gly Cys Ala Cys Cys Gly Cys Cys Cys Gly Gly

195 200 205

Cys Thr Gly Gly Thr Ala Ala Cys Ala Gly Thr Cys Cys Gly Thr Gly

210 215 220

Gly Cys Ala Cys Gly Gly Thr Ala Ala Ala Cys Thr Cys Cys Ala Cys

225 230 235 240

Cys Cys Gly Gly Ala Gly Cys Ala Ala Gly Gly Cys Cys Ala Ala Ala

245 250 255

Thr Ala Gly Gly Gly Gly Thr Thr Cys Ala Thr Ala Ala Gly Gly Thr

260 265 270

Ala Cys Gly Gly Cys Cys Cys Gly Thr Ala Cys Thr Gly Ala Ala Cys

275 280 285

Cys Cys Gly Gly Gly Thr Ala Gly Gly Cys Thr Gly Cys Thr Thr Gly

290 295 300

Ala Gly Cys Cys Ala Gly Thr Gly Ala Gly Cys Gly Ala Thr Thr Gly

305 310 315 320

Cys Thr Gly Gly Cys Thr Thr Ala Gly Ala Thr Gly Ala Ala Thr Gly

325 330 335

Ala Cys Thr Gly Thr Cys Cys Ala Cys Gly Ala Cys Ala Gly Ala Ala

340 345 350

Cys Cys Cys Gly Gly Cys Thr Thr Ala Thr Cys Gly Gly Thr Cys Ala

355 360 365

Gly Thr Thr Thr Cys Ala Cys Cys Thr Cys Ala Cys Ala Cys Thr Cys

370 375 380

Ala Thr Thr Ala Gly Cys Thr Cys Cys Ala

385 390

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