TW202306975A

TW202306975A - 對ｅｒｂｂ４而非ｅｒｂｂ３具有改善的選擇性的工程化ｎｒｇ－１變體

Info

Publication number: TW202306975A
Application number: TW111121403A
Authority: TW
Inventors: 達倫Ｌ貝茲; 劉智; 泰源李; 馬克里歐麥克斯; 祖倫王
Original assignee: 美商安進公司
Priority date: 2021-06-10
Filing date: 2022-06-09
Publication date: 2023-02-16
Also published as: MX2023014680A; EP4351722A1; JP2024522579A; AU2022289721A1; WO2022261299A1; US20220402985A1; AR126114A1; CA3222782A1; UY39807A

Abstract

本發明關於工程化神經調節蛋白-1變體，其選擇性地激活ErbB4受體而不激活ErbB3受體。本發明還提供了使用此類變體治療心臟衰竭之方法。

Description

對ErbB4而非ErbB3具有改善的選擇性的工程化NRG-1變體

本發明關於工程化神經調節蛋白-1變體，其選擇性地激活ErbB4受體而不激活或微弱地激活ErbB3受體。本發明還提供使用此類神經調節蛋白變體治療心臟衰竭之方法。 序列表

本申請含有電腦可讀形式的序列表（檔案名：A-2828-WO-PCT Seq List_ST25.txt，創建於2020年5月9日，其大小為334 KB），作為本揭露的一個單獨部分，並且藉由援引以其全文併入。

包含四個成員（EGFR、ErbB2、ErbB3和ErbB4）的表皮生長因子受體家族已經證明在多種細胞功能（包括細胞生長、分化和存活）中起重要作用。它們係蛋白質酪胺酸激酶受體，由細胞外配體結合結構域、跨膜結構域和細胞質酪胺酸激酶結構域組成。已經鑒定了多種受體配體，該等受體配體在結合後介導受體同二聚化或異二聚化。特異性受體締合導致不同的磷酸化模式、複雜的傳訊級聯和多種生物功能（包括細胞增殖、防止細胞凋亡和促進腫瘤細胞移動、黏附和侵襲）。表現ErbB受體之示例性細胞包括膠質細胞、神經膠質母細胞瘤細胞、施旺氏（Schwann）細胞、肝細胞、上皮細胞和肌細胞。膠質細胞來源於中樞神經系統，並且包括寡樹突細胞和星狀細胞。表現ErbB受體的肌細胞包括肌細胞先質（成肌細胞）以及更特化的骨骼肌細胞、心肌細胞和平滑肌細胞。

神經調節蛋白（也稱為調蛋白、膠質生長因子（GGF）和新的分化因子（NDF））係重要的生長因子，尤其對於心臟和神經系統而言。已經鑒定了神經調節蛋白-1（NRG-1）的超過15種不同的同種型，並且基於它們必需EGF樣結構域的序列差異將其分成兩組，稱為α型和β型。神經調節蛋白-1係ErbB3和ErbB4受體的配體。已經顯示，神經調節蛋白-1的EGF樣結構域（大小範圍為50至64個胺基酸）足以結合和激活該等受體。參見，例如，Jones等人, 1999, FEBS Lett.[歐洲生物化學會聯盟通訊]26:447:227-231。先前的研究已經顯示，神經調節蛋白-1β（NRG-1β）可以以高親和力直接結合ErbB3和ErbB4。孤兒受體ErbB2具有預激活的構象，以促進以比ErbB3和ErbB4同二聚體高大約100倍的親和力與ErbB3或ErbB4異二聚化。異質性受體在不同的細胞類型中起作用：周圍神經系統中的ErbB2/ErbB3和心臟中的ErbB2/ErbB4。神經發育的研究已經表明交感神經系統的形成需要完整的NRG-1β、ErbB2和ErbB3傳訊系統。ErbB2/ErbB4受體激活促進心肌細胞生長和存活。NRG-1β、或ErbB2或ErbB4的靶向破壞導致心臟發育缺陷而引起胚胎死亡。最近的研究還強調了NRG-1β、ErbB2和ErbB4在心血管發育以及在維持成人正常心臟功能中的作用。

藉由重組NRG-1激活ErbB4係心臟衰竭的潛在治療選擇，因為神經調節蛋白刺激的ErbB2/ErbB4異二聚化對早期心臟發育中的心肌功能係至關重要的，並且還防止成人心臟的嚴重功能障礙。在三個不同的心臟衰竭動物模型中，短期投與重組NRG-1β EGF結構域顯著改善或防止心肌性能惡化。更重要的是，NRG-1β顯著延長心臟衰竭動物的存活。參見，例如，De Keulenaer等人, 2019, Circulation: Heart Failure [循環：心臟衰竭] 12:e006288。該等作用使NRG-1β有希望成為用於由多種常見疾病引起的心臟衰竭的廣譜治療劑或先導化合物。

已經有幾種基於NRG-1的候選藥物，該等候選藥物在通過結合ErbB4治療心臟病的臨床試驗中已取得進展。然而，認為通過ErbB3的結合促進某些癌症的發展或進展，並且還可能引起胃腸毒性。

61聚體肽（來自野生型hNRG-1的S177至Q237）已經顯示出對ErbB4和ErbB3兩者的有效活性。參見Liu等人, 2006, J Amer Coll Cardiol [美國心臟病學會雜誌] 48:1438-1447；和美國專利案號7,226,907。還參見國際專利申請公開案號WO 2010060265；WO 2009007332；WO 2009033373；WO 2006030241；Jay等人, 2013; Circulation [循環] 128:152-161；以及Wali等人, 2014, Mol Cancer Res [分子癌症研究] 12:1140-1155。美國專利案號7,115,554和7,063,961描述了調蛋白β1變體，該等變體顯示出對ErbB3和ErbB4受體增加的親和力。美國專利申請公開案號2007/0213264描述了神經調節蛋白-1β變體，該等變體顯示出對ErbB3和/或ErbB4增加或降低的結合親和力。

然而，仍然需要NRG-1變體用於心臟衰竭的治療用途，該等變體對ErbB4的選擇性高於對ErbB3的選擇性。

本揭露提供了神經調節蛋白-1β的多肽變體，與野生型序列相比，該等變體對ErbB4而非ErbB3具有選擇性。在某些實施方式中，與野生型序列相比，變體對ErbB4具有增加的結合親和力，並且對ErbB3具有降低的結合親和力。在某些實施方式中，與野生型序列相比，變體對ErbB4具有增加的結合親和力，並且對ErbB3具有相似的結合親和力。在某些實施方式中，與野生型序列相比，變體對ErbB4具有相似的結合親和力，並且對ErbB3具有降低的結合親和力。

本揭露還包括NRG-1變體，相對於ErbB3受體，該等NRG-1變體對ErbB4受體具有比衍生該NRG-1變體的NRG-1更高的特異性。在某些實施方式中，NRG-1變體對ErbB4具有比對ErbB3高2x、3x、4x的結合親和力。

本揭露還包括NRG-1變體，與ErbB3受體相比，該等NRG-1變體對ErbB4受體具有更高的選擇性。在某些實施方式中，NRG-1變體對ErbB4/ErbB3的選擇性大於等於1000或大於等於10000。

在某些實施方式中，NRG-1變體具有促效劑活性，該促效劑活性係相應的野生型序列的至少50%、60%、70%或80%。

在一個實施方式中，本揭露提供了多肽變體，其包含具有下式的胺基酸序列： SHLVKCX ₁₈₃EX ₁₈₅X ₁₈₆KX ₁₈₈FCVNGGECX ₁₉₇X ₁₉₈X ₁₉₉X ₂₀₀X ₂₀₁X ₂₀₂SX ₂₀₄PSRX ₂₀₈LCKCPNEFTGDRCX ₂₂₂X ₂₂₃X ₂₂₄X ₂₂₅X ₂₂₆ASX ₂₂₉（SEQ ID NO:177）其中 X ₁₈₃係A或G； X ₁₈₅X ₁₈₆係KD、KE、KH、ND、NE、NH、RD、RE、RH、RQ、SD、SE或SH； X ₁₈₈係S或T； X ₁₉₇X ₁₉₈X ₁₉₉X ₂₀₀X ₂₀₁X ₂₀₂係FMIEDS（SEQ ID NO:178）、FMIEGP（SEQ ID NO:179）、FMIEHL（SEQ ID NO:180）、FMVEDL（SEQ ID NO:181）、FMVERS（SEQ ID NO:182）、FMVKRP（SEQ ID NO:183）、FVIEDP（SEQ ID NO:184）、FVIEGS（SEQ ID NO:185）、FVVEGL（SEQ ID NO:186）、YMIEDL（SEQ ID NO:187）、YMIEGL（SEQ ID NO:188）、YMIEHP（SEQ ID NO:189）、YMVEDL（SEQ ID NO:190）、YMVEGS（SEQ ID NO:191）、YMVERP（SEQ ID NO:192）、YVIEDS（SEQ ID NO:193）、YVIEGS（SEQ ID NO:194）、YVIEHL（SEQ ID NO:195）、YVVEDL（SEQ ID NO:196）、YVVEHS（SEQ ID NO:197）或YVVERP（SEQ ID NO:198）； X ₂₀₄係I或N； X ₂₀₈係F或Y； X ₂₂₂X ₂₂₃X ₂₂₄X ₂₂₅X ₂₂₆係EKDVM（SEQ ID NO:199）、QAPHI（SEQ ID NO:200）、QDDFM（SEQ ID NO:201）、QDFFL（SEQ ID NO:202）、QDFFM（SEQ ID NO:203）、QDVFL（SEQ ID NO:204）、QDVFM（SEQ ID NO:205）、QEDFM（SEQ ID NO:206）、QETQI（SEQ ID NO:207）、QKDFL（SEQ ID NO:208）、QKDFM（SEQ ID NO:209）、QKDVM（SEQ ID NO:210）、QKFFL（SEQ ID NO:211）、QKFFM（SEQ ID NO:212）、QKLDI（SEQ ID NO:213）、QKTSL（SEQ ID NO:214）、QKVFL（SEQ ID NO:215）、QKVFM（SEQ ID NO:216）、QKVVM（SEQ ID NO:217）、QNDFL（SEQ ID NO:218）、QNDFM（SEQ ID NO:219）、QNVFL（SEQ ID NO:220）、QNVFM（SEQ ID NO:221）、QNYVM（SEQ ID NO:222）、QQSFP（SEQ ID NO:223）、QSALT（SEQ ID NO:224）、QSSEL（SEQ ID NO:225）、QSTRV（SEQ ID NO:226）、QTSLL（SEQ ID NO:227）或QVTRL（SEQ ID NO:228）；並且 X ₂₂₉不存在，係F或FYKAEELYQ（SEQ ID NO:229）。

在本實施方式的一個方面，多肽變體包含SEQ ID No: 114至176中任一個的胺基酸序列。

在一個實施方式中，本揭露提供了多肽變體，其中 X ₁₈₃係A或G； X ₁₈₅X ₁₈₆係KD、KE、KH、ND、NH、RD、RE、RH、RQ、SD、SE或SH； X ₁₈₈係S或T； X ₁₉₇X ₁₉₈X ₁₉₉X ₂₀₀X ₂₀₁X ₂₀₂係FMIEDS（SEQ ID NO:178）、FMIEGP（SEQ ID NO:179）、FMIEHL（SEQ ID NO:180）、FMVEDL（SEQ ID NO:181）、FMVERS（SEQ ID NO:182）、FMVKRP（SEQ ID NO:183）、FVIEDP（SEQ ID NO:184）、FVIEGS（SEQ ID NO:185）、YMIEDL（SEQ ID NO:187）、YMIEGL（SEQ ID NO:188）、YMIEHP（SEQ ID NO:189）、YMVEDL（SEQ ID NO:190）、YMVEGS（SEQ ID NO:191）、YMVERP（SEQ ID NO:192）、YVIEDS（SEQ ID NO:193）、YVIEGS（SEQ ID NO:194）、YVIEHL（SEQ ID NO:195）、YVVEHS（SEQ ID NO:197）或YVVERP（SEQ ID NO:198）； X ₂₀₄係I或N； X ₂₀₈係F或Y； X ₂₂₂X ₂₂₃X ₂₂₄X ₂₂₅X ₂₂₆係EKDVM（SEQ ID NO:199）、QAPHI（SEQ ID NO:200）、QDFFL（SEQ ID NO:202）、QDFFM（SEQ ID NO:203）、QDVFL（SEQ ID NO:204）、QEDFM（SEQ ID NO:206）、QETQI（SEQ ID NO:207）、QKDFL（SEQ ID NO:208）、QKDFM（SEQ ID NO:209）、QKDVM（SEQ ID NO:210）、QKFFL（SEQ ID NO:211）、QKFFM（SEQ ID NO:212）、QKLDI（SEQ ID NO:213）、QKTSL（SEQ ID NO:214）、QKVFL（SEQ ID NO:215）、QNDFL（SEQ ID NO:218）、QNDFM（SEQ ID NO:219）、QNVFL（SEQ ID NO:220）、QNVFM（SEQ ID NO:221）、QNYVM（SEQ ID NO:222）、QQSFP（SEQ ID NO:223）、QSALT（SEQ ID NO:224）、QSSEL（SEQ ID NO:225）、QSTRV（SEQ ID NO:226）、QTSLL（SEQ ID NO:227）或QVTRL（SEQ ID NO:228）；並且 X ₂₂₉係F或FYKAEELYQ（SEQ ID NO:229）。

在本實施方式的一個方面，多肽變體包含SEQ ID No: 114、115、117至124、126至135、138、139、144至147、149至156、160至168、或171至176中任一個的胺基酸序列。

在一個實施方式中，本揭露提供了多肽變體，其中 X ₁₈₃係A或G； X ₁₈₅係KE、KH、ND、RD、RH、RQ、SD、SE或SH； X ₁₈₈係S或T； X ₁₉₇X ₁₉₈X ₁₉₉X ₂₀₀X ₂₀₁X ₂₀₂係FMIEDS（SEQ ID NO:178）、FMIEGP（SEQ ID NO:179）、FMVEDL（SEQ ID NO:181）、FMVKRP（SEQ ID NO:183）、FVIEDP（SEQ ID NO:184）、FVIEGS（SEQ ID NO:185）、YMIEDL（SEQ ID NO:187）、YMIEHP（SEQ ID NO:189）、YMVEDL（SEQ ID NO:190）、YMVEGS（SEQ ID NO:191）、YMVERP（SEQ ID NO:192）、YVIEDS（SEQ ID NO:193）、YVIEGS（SEQ ID NO:194）、YVIEHL（SEQ ID NO:195）、YVVEHS（SEQ ID NO:197）或YVVERP（SEQ ID NO:198）； X ₂₀₄係I或N； X ₂₀₈係F或Y； X ₂₂₂X ₂₂₃X ₂₂₄X ₂₂₅X ₂₂₆係EKDVM（SEQ ID NO:199）、QAPHI（SEQ ID NO:200）、QEDFM（SEQ ID NO:206）、QETQI（SEQ ID NO:207）、QKDFL（SEQ ID NO:208）、QKDFM（SEQ ID NO:209）、QKDVM（SEQ ID NO:210）、QKFFL（SEQ ID NO:211）、QKFFM（SEQ ID NO:212）、QKLDI（SEQ ID NO:213）、QKTSL（SEQ ID NO:214）、QKVFL（SEQ ID NO:215）、QNDFL（SEQ ID NO:218）、QNDFM（SEQ ID NO:219）、QNVFL（SEQ ID NO:220）、QNVFM（SEQ ID NO:221）、QNYVM（SEQ ID NO:222）、QQSFP（SEQ ID NO:223）、QSALT（SEQ ID NO:224）、QSSEL（SEQ ID NO:225）、QSTRV（SEQ ID NO:226）、QTSLL（SEQ ID NO:227）或QVTRL（SEQ ID NO:228）；並且 X ₂₂₉係F或FYKAEELYQ（SEQ ID NO:229）。

在本實施方式的一個方面，多肽變體包含SEQ ID No: 117至124、126至135、144至147、149至152、154至156、163、167、168、或171至176中任一個的胺基酸序列。

在一個實施方式中，本揭露提供了多肽變體其中 X ₁₈₃係A或G； X ₁₈₅X ₁₈₆係KH、ND、RD、RH或SH； X ₁₈₈係S或T； X ₁₉₇X ₁₉₈X ₁₉₉X ₂₀₀X ₂₀₁X ₂₀₂係FMIEDS（SEQ ID NO:178）、FMIEGP（SEQ ID NO:179）、FMVEDL（SEQ ID NO:181）、FVIEDP（SEQ ID NO:184）、YMIEDL（SEQ ID NO:187）、YMVEGS（SEQ ID NO:191）、YVIEGS（SEQ ID NO:194）、YVIEHL（SEQ ID NO:195）或YVVERP（SEQ ID NO:198）； X ₂₀₄係I或N； X ₂₀₈係F或Y； X ₂₂₂X ₂₂₃X ₂₂₄X ₂₂₅X ₂₂₆係QAPHI（SEQ ID NO:200）、QEDFM（SEQ ID NO:206）、QETQI（SEQ ID NO:207）、QKDFL（SEQ ID NO:208）、QKDFM（SEQ ID NO:209）、QKTSL（SEQ ID NO:214）、QNDFL（SEQ ID NO:218）、QNDFM（SEQ ID NO:219）、QQSFP（SEQ ID NO:223）、QSALT（SEQ ID NO:224）、QSSEL（SEQ ID NO:225）、QSTRV（SEQ ID NO:226）、QTSLL（SEQ ID NO:227）或QVTRL（SEQ ID NO:228）；並且 X ₂₂₉係F或FYKAEELYQ（SEQ ID NO:229）。

在本實施方式的一個方面，多肽變體包含SEQ ID No: 117至124、126、128至135、146、147、150、151、163、167、168或171中任一個的胺基酸序列。

在本實施方式的另一方面，多肽變體包含SEQ ID No: 117、118、119、120、122、123、124、126、128、129、130、131、133或135中任一個的胺基酸序列。

在任一實施方式中，多肽變體進一步包含第二胺基酸序列，以充當訊息序列、增加半衰期或幫助純化。在某些方面，多肽變體可以與胺基酸序列融合以延長其半衰期。在一方面，胺基酸序列係Fc區。在一方面，胺基酸序列與多肽變體的C末端融合。在一方面，胺基酸序列與多肽變體的N末端融合。在某些方面，胺基酸序列經由連接子與多肽變體融合。在某些方面，多肽變體可以與His標籤融合以幫助純化。在一方面，His標籤與多肽變體的C末端融合。在一方面，His標籤與多肽變體的N末端融合。

在其他方面，多肽變體包含SEQ ID No: 1至24、29至54、56至67、69至80、82至111中任一個的胺基酸序列。在其他方面，多肽變體包含SEQ ID No: 1至15、19、20、22、23、29至34、37、38、43至54、56至59、61至67、69至80、82至85、87至93、或97至111中任一個的胺基酸序列。在一方面，多肽變體包含SEQ ID No: 3、4、6、9、11至13、19、22、31至34、43至48、52、54、56至59、61至63、65至67、71、72、75至80、84、85、88、100、或104至106中任一個的胺基酸序列。在一方面，多肽變體包含SEQ ID No: 3、4、6、9、11至13、19、22、31至34、43至48、52、54、56至59、61至63、65至67、71、72、75至80、84、85、88、100、或104至106中任一個的胺基酸序列。在一方面，多肽變體包含SEQ ID NO:4、11、13、32、34、45、46、48、52、72、75、76、77、78、79或80的胺基酸序列。在一方面，多肽變體包含SEQ ID NO:56、57、58、59、61、62、63、65、66或67的胺基酸序列。

本揭露還提供了包含本文描述的多肽變體和藥學上可接受的載劑之藥物組成物。

本揭露還提供了在有需要的受試者中治療心血管疾病或病症之方法，該方法包括投與治療有效量的多肽變體或藥物組成物。在本實施方式的某些方面，心血管疾病或病症係心臟衰竭、心肌梗塞、擴張型心肌病、心肌炎或心臟毒性。在某些方面，受試者係人。

本揭露還提供了上述的多肽變體，其用於在治療心血管疾病或病症中使用或用於製備用於治療心血管疾病或病症的藥物。在一個實施方式中，本揭露提供了神經調節蛋白多肽變體，其用於在治療心血管疾病或病症中使用。在另一個實施方式中，本揭露提供了神經調節蛋白多肽用於製備用於治療心血管疾病或病症的藥物之用途。

本發明部分基於以下發現：可以設計對ErbB4具有高度選擇性同時對ErbB3具有降低的或沒有結合親和力的神經調節蛋白變體。此類變體係用於心臟相關疾病的候選治療劑，同時最小化針對其他細胞類型的交叉反應性。本發明部分源於改善心臟衰竭藥物功效的努力。因此，本揭露還關於治療患有心臟病和相關病症（例如，心臟衰竭）或具有發展該等疾病和病症的風險的受試者。定義

儘管在本申請中使用的術語係本領域中的標準術語，但是本文提供了某些術語的定義以確保請求項的含義的清楚性和確定性。單位、前綴和符號可能會用它們的國際單位制（SI）接受形式表示。本文列舉的數字範圍包括定義範圍的數字，並且包括並支持所定義範圍內的每個整數。除非另外指示，否則本文描述的方法和技術可根據本領域中熟知的常規方法且如貫穿本說明書所引用及論述的各種通用和更特定參考文獻中所描述來進行。參見例如，Sambrook等人, Molecular Cloning: A Laboratory Manual [分子選殖：實驗室手冊], 第3版, Cold Spring Harbor Laboratory Press [冷泉港實驗室出版社], 冷泉港, 紐約(2001) 和Ausubel等人, Current Protocols in Molecular Biology [分子生物學現代方法], Greene Publishing Associates [格林出版聯合公司] (1992)；以及Harlow和Lane Antibodies: A Laboratory Manual [抗體：實驗室手冊] Cold Spring Harbor Laboratory Press [冷泉港實驗室出版社], 冷泉港, 紐約(1990)。

如本文所用，除非另外明確說明，否則術語「一」和「一個（種）」意指一或多個。此外，除非上下文另有要求，否則單數術語將包括複數且複數術語將包括單數。通常，結合本文中所描述的細胞及組織培養、分子生物學、免疫學、微生物學、遺傳學以及蛋白質及核酸化學及雜交而使用的命名法及其技術係本領域中所熟知且通常使用的那些命名法及技術。

在本申請中所引用的所有文件或文件的部分，包括但不限於專利、專利申請、文章、書籍和專著，都藉由援引清楚地特此併入。在本發明之實施方式中描述的內容可以與本發明之其他實施方式組合。

如本文所用，術語「神經調節蛋白-1」或「NRG-1」或「神經調節蛋白」係指可以結合並且激活ErbB2/ErbB4或ErbB2/ErbB3異二聚體蛋白激酶的蛋白質或肽，例如所有神經調節蛋白同種型、僅神經調節蛋白EGF結構域、神經調節蛋白突變體以及還激活上述受體的任何類型的神經調節蛋白樣基因產物。神經調節蛋白還包括NRG-1、NRG-2、NRG-3和NRG-4。該等蛋白質和多肽可以激活上述ErbB受體並且調節其生物反應，例如，刺激乳癌細胞分化和乳蛋白分泌；誘導神經脊細胞分化成施旺氏細胞；刺激骨骼肌細胞中的乙醯膽鹼合成；以及改善心肌細胞存活和DNA合成。神經調節蛋白還包括那些具有保守胺基酸取代的變體，該等變體基本上不會改變它們的生物活性。合適的保守胺基酸取代係熟悉該項技術者已知的，並且通常可以在不改變所得分子的生物活性的情況下進行。熟悉該項技術者意識到，一般而言，多肽的非必需區中的單一胺基酸取代基本上不會改變生物活性（參見例如，Watson等人 Molecular Biology of the Gene [基因分子生物學], 第4版, 1987.The Benjamin/Cummings Pub. Co.[本傑明/柯明斯出版有限公司] 第224頁）。短語「神經調節蛋白」涵蓋全長神經調節蛋白以及神經調節蛋白肽（例如，全長神經調節蛋白的截短形式）。神經調節蛋白核酸涵蓋神經調節蛋白核酸和神經調節蛋白寡核苷酸。

如本文所用，「神經調節蛋白變體」係指具有經修飾的序列的神經調節蛋白，該經修飾的序列改變或改善神經調節蛋白對ErbB4的選擇性和/或降低神經調節蛋白對ErbB3的選擇性。

如本文所用，術語「表皮生長因子樣結構域」或「EGF樣結構域」係指由神經調節蛋白基因編碼的多肽模體，該神經調節蛋白基因結合並激活ErbB2、ErbB3、ErbB4或其組合，並且與以下中揭露的EGF受體結合結構域具有結構相似性：國際專利申請公開案號WO 00/64400和WO 97/09425，Holmes等人, 1992, Science [科學], 256:1205-1210；美國專利案號5,530,109和5,716, 930；Hijazi等人, 1998, Int. J. Oncol.[國際腫瘤學雜誌], 13:1061-1067；Chang等人, 1997, Nature [自然], 387:509-512；Carraway等人, 1997, Nature [自然], 387:512-516；Higashiyama等人, 1997, J. Bio Chem.[生物化學雜誌], 122:675-680。EGF樣結構域可以源自NRG-1、NRG-2、NRG-3或NRF-4。EGF樣結構域可為C或B亞型。

如本文所用，術語「ErbB2」、「ErbB2（HER2）」、「HER2」係指相同的蛋白質（或在其中引用時相同的基因）並且在本文中可互換使用。ErbB2（erb-b2受體酪胺酸激酶2）在本領域還稱為NEU、NGL、TKR1、CD340、HER-2、MLN 19和HER-2/neu。

如本文所用，術語「ErbB3」、「ErbB3（HER3）」、「HER3」係指相同的蛋白質（或在其中引用時相同的基因）並且在本文中可互換使用。ErbB3（erb-b2受體酪胺酸激酶3）在本領域還稱為FERLK、LCCS2、ErbB-3、c-erbB3、erbB3-S、MDA-BF-1、c-erbB-3、p180-ErbB3、p45-sErbB3和p85-sErbB3。

如本文所用，術語「ErbB4」、「ErbB4（HER4）」、「HER4」係指相同的蛋白質（或在其中引用時相同的基因）並且在本文中可互換使用。ErbB4（erb-b2受體酪胺酸激酶4）在本領域還稱為ALS19和p180erbB4。

如本文所用，術語「有效量」或「治療有效量」意指足以產生期望的結果的劑量或量。期望的結果可以包含受試者的劑量或量的客觀或主觀改善（例如，長期存活、改善的心臟功能、疾病狀態的有效預防等）。

如本文所用，術語「射出分率」係指隨著每次收縮，左心室泵出的血液量的射出分率（EF），測量值通常以百分比表示。例如，50%的射出分率意指隨著每次心臟跳動泵出左心室中血液總量的50%。

如本文所用，術語「心臟衰竭」意指心臟輸出量不能滿足代謝組織要求的心臟功能異常。心臟衰竭包括廣泛的疾病狀態，例如鬱血性心臟衰竭、心肌梗塞、心動過速、家族性肥厚型心肌病、缺血性心臟病、特發性擴張型心肌病和心肌炎。心臟衰竭可以由許多因素引起，包括缺血性、先天性、風濕性或特發性形式。慢性心臟肥大係重要的疾病狀態，其係鬱血性心臟衰竭和心跳停止的前兆。

如本文所用，術語「多肽」和「蛋白質」在本文中可互換用於指胺基酸殘基的聚合物。該等術語還適用於其中一或多個胺基酸殘基係相應天然存在胺基酸的類似物或模擬物的胺基酸聚合物，以及天然存在的胺基酸聚合物。該等術語還可涵蓋已例如藉由添加碳水化合物殘基以形成糖蛋白而經修飾或經磷酸化的胺基酸聚合物。多肽和蛋白可由天然存在的和非重組的細胞產生，或者多肽和蛋白可由基因工程改造的或重組的細胞產生。多肽和蛋白質還可以藉由合成方式產生。多肽和蛋白可包含具有天然蛋白的胺基酸序列的分子，或具有天然序列的一或多個胺基酸的缺失、添加和/或取代的分子。

術語「多肽」和「蛋白」涵蓋僅包含天然存在的胺基酸的分子，以及包含非天然存在的胺基酸的分子。非天然存在的胺基酸（其可以根據需要取代在本文揭露的任何序列中發現的天然存在的胺基酸）之實例包括：4-羥基脯胺酸、γ-羧基麩胺酸、ε-N,N,N-三甲基離胺酸、ε-N-乙醯基離胺酸、O-磷酸絲胺酸、N-乙醯絲胺酸、N-甲醯基甲硫胺酸、3-甲基組胺酸、5-羥基離胺酸、σ-N-甲基精胺酸、和其他類似的胺基酸和亞胺基酸（例如，4-羥基脯胺酸）。本文使用的多肽標記法中，按照標準用法和慣例，左手方向係胺基末端方向，右手方向係羧基末端方向。

可插入蛋白或多肽序列中或取代蛋白或多肽序列中的野生型殘基的非天然存在的胺基酸之實例的非限制性清單包括β-胺基酸、高胺基酸、環狀胺基酸及具有衍生化側鏈的胺基酸。實例包括（呈L形式或D形式；縮寫如括號中所示）：瓜胺酸（Cit）、高瓜胺酸（hCit）、Nα-甲基瓜胺酸（NMeCit）、Nα-甲基高瓜胺酸（Nα-MeHoCit）、鳥胺酸（Orn）、Nα-甲基鳥胺酸（Nα-MeOrn或NMeOrn）、肌胺酸（Sar）、高離胺酸（hLys或hK）、高精胺酸（hArg或hR）、高麩醯胺酸（hQ）、Nα-甲基精胺酸（NMeR）、Nα-甲基白胺酸（Nα-MeL或NMeL）、N-甲基高離胺酸（NMeHoK）、Nα-甲基麩醯胺酸（NMeQ）、正白胺酸（Nle）、正纈胺酸（Nva）、1,2,3,4-四氫異喹啉（Tic）、八氫吲哚-2-甲酸（Oic）、3-(1-萘基)丙胺酸（1-Nal）、3-(2-萘基)丙胺酸（2-Nal）、1,2,3,4-四氫異喹啉（Tic）、2-二氫茚基甘胺酸（IgI）、對碘苯丙胺酸（pI-Phe）、對胺基苯丙胺酸（4AmP或4-胺基-Phe）、4-胍基苯丙胺酸（Guf）、甘胺醯基離胺酸（縮寫「K（Nε-甘胺醯基）」或「K（甘胺醯基）」或「K（gly）」）、硝基苯丙胺酸（硝基phe）、胺基苯丙胺酸（胺基phe或胺基-Phe）、苯甲基苯丙胺酸（苯甲基phe）、γ-羧基麩胺酸（γ-羧基glu）、羥基脯胺酸（羥基pro）、對羧基苯丙胺酸（Cpa）、α-胺基己二酸（Aad）、Nα-甲基纈胺酸（NMeVal）、N-α-甲基白胺酸（NMeLeu）、Nα-甲基正白胺酸（NMeNle）、環戊基甘胺酸（Cpg）、環己基甘胺酸（Chg）、乙醯基精胺酸（乙醯基arg）、α,β-二胺基丙酸（Dpr）、α,γ-二胺基丁酸（Dab）、二胺基丙酸（Dap）、環己基丙胺酸（Cha）、4-甲基-苯丙胺酸（MePhe）、β,β-二苯基丙胺酸（BiPhA）、胺基丁酸（Abu）、4-苯基-苯丙胺酸（或聯苯丙胺酸；4Bip）、α-胺基-異丁酸（Aib）、β-丙胺酸、β-胺基丙酸、哌啶甲酸、胺基己酸、胺基庚酸、胺基庚二酸、鎖鏈素、二胺基庚二酸、N-乙基甘胺酸、N-乙基精胺酸、羥基離胺酸、別羥基離胺酸、異鎖鏈素、別異白胺酸、N-甲基甘胺酸、N-甲基異白胺酸、N-甲基纈胺酸、4-羥基脯胺酸（Hyp）、γ-羧基麩胺酸、ε-N,N,N-三甲基離胺酸、ε-N-乙醯基離胺酸、O-磷酸絲胺酸、N-乙醯基絲胺酸、N-甲醯基甲硫胺酸、3-甲基組胺酸、5-羥基離胺酸、ω-甲基精胺酸、4-胺基-O-鄰苯二甲酸（4APA）及其他類似胺基酸，以及特別列出的那些胺基酸中的任一者的衍生化形式。

「Fc」區，當該術語在本文所用時，可以包含含有抗體的C _H2和C _H3結構域的兩個重鏈片段。這兩個重鏈片段由兩個或更多個二硫鍵及C _H3結構域的疏水性相互作用維持在一起。包含Fc區的目的蛋白（包括抗原結合蛋白和Fc融合蛋白）形成本揭露的另一方面。 NRG-1β 變體

本揭露提供了NRG-1的多肽變體，該等多肽變體對ErbB4具有選擇性。如本文所揭露的神經調節蛋白變體具有自然界中未發現的胺基酸序列，其中天然神經調節蛋白中的一或多個野生型胺基酸殘基被不同的胺基酸殘基取代。至少一個取代係非保守的以改變功能，例如，改善對ErbB4的選擇性。

對應於人NRG-1的胺基酸177-237並且含有EGF樣結構域的功能性人NRG-1片段具有胺基酸序列 SHLVKCAEKEKTFCVNGGECFMVKDLSNPSRYLCKCPNEFTGDRCQNYVMASFYK AEELYQ（SEQ ID NO: 112）

在一些實施方式中，含有EGF樣結構域的神經調節蛋白片段係指NRG-1的胺基酸殘基177-226、177-228、177-229、177-237或177-240（SEQ ID NO: 112）。

包含經修飾的神經調節蛋白序列和一或多個連接子、Fc序列和His標籤的代表性神經調節蛋白變體在下表1中顯示。 [表1]

名稱	序列	SEQ ID NO.
huNRG1(S177-F229)(NRGE1C)::3x(G4Q)::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFGGGGQGGGGQGGGGQDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	1
huNRG1(S177-F229)(NRGE1C)::1KmodT482V，M493L)::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFGSGSATGGSGSVASSGSGSATHLDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	2
huNRG1(S177-F229)(NRGE1C)::(G4A)2:G4::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFGGGGAGGGGAGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	3
huNRG1(S177-F229)(NRGE1C)((G4E)2)::G4::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFGGGGEGGGGEGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	4
huNRG1(S177-F229)(NRGE1C)::(G4S)2::G4::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFGGGGSGGGGSGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	5
huNRG1(S177-F229)(NRGE1C)(G4E)::G4S::G4::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFGGGGEGGGGSGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	6
huNRG1(S177-F229)(NRGE1C)(NRGmod)::G4::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFAAAEELYQGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	7
huNRG1(S177-F229)(NRGE1D)::3x(G4Q)::huFcSEFL2（Pb）	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFGGGGQGGGGQGGGGQDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	8
huNRG1(S177-F229)(NRGE1D)::1KmodT482V，M493L)::huFcSEFL2（Pb）	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFGSGSATGGSGSVASSGSGSATHLDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	9
huNRG1(S177-F229)(NRGE1D)::(G4A)2:G4::huFcSEFL2（Pb）	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFGGGGAGGGGAGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	10
huNRG1(S177-F229)(NRGE1D)((G4E)2)::G4::huFcSEFL2（Pb）	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFGGGGEGGGGEGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	11
huNRG1(S177-F229)(NRGE1D)::(G4S)2::G4::huFcSEFL2（Pb）	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFGGGGSGGGGSGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	12
huNRG1(S177-F229)(NRGE1D)(G4E)::G4S::G4::huFcSEFL2（Pb）	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFGGGGEGGGGSGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	13
huNRG1(S177-F229)(NRGE1D)(NRGmod)::G4::huFcSEFL2（Pb）	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFAAAEELYQGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	14
huNRG1(S177-Q237)(3H8)::3xG4S::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	15
huNRG1(S177-F229)(3H8)::3x(G4Q)::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFGGGGQGGGGQGGGGQDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	16
huNRG1(S177-Q237)(3H8)::3x(G4Q)::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQGGGGQGGGGQGGGGQDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	17
huNRG1(S177-S228)(3H8)::3x(G4Q)::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASGGGGQGGGGQGGGGQDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	18
huNRG1(S177-Q237)(NRGE1C)::GG::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	19
huNRG1(S177-F229)(NRGE1C)::3x(G4Q)::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFGGGGQGGGGQGGGGQDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	1
huNRG1(S177-Q237)(NRGE1C)::3x(G4Q)::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQGGGGQGGGGQGGGGQDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	20
huNRG1(S177-S228)(NRGE1C)::3x(G4Q)::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASGGGGQGGGGQGGGGQDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	21
huNRG1(S177-Q237)(NRGE1D)::GG::huFcSEFL2（Pb）	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	22
huNRG1(S177-F229)(NRGE1D)::3x(G4Q)::huFcSEFL2（Pb）	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFGGGGQGGGGQGGGGQDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	8
huNRG1(S177-Q237)(NRGE1D)::3x(G4Q)::huFcSEFL2（Pb）	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQGGGGQGGGGQGGGGQDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	23
huNRG1(S177-S228)(NRGE1D)::3x(G4Q)::huFcSEFL2（Pb）	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASGGGGQGGGGQGGGGQDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	24
huNRG1(S177-Q237)(wt)::GG::huFcSEFL2（Pb）	SHLVKCAEKEKTFCVNGGECFMVKDLSNPSRYLCKCPNEFTGDRCQNYVMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	25
huNRG1(S177-F229)(wt)::3x(G4Q)::huFcSEFL2（Pb）	SHLVKCAEKEKTFCVNGGECFMVKDLSNPSRYLCKCPNEFTGDRCQNYVMASFGGGGQGGGGQGGGGQDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	26
huNRG1(S177-Q237)(wt)::3x(G4Q)::huFcSEFL2（Pb）	SHLVKCAEKEKTFCVNGGECFMVKDLSNPSRYLCKCPNEFTGDRCQNYVMASFYKAEELYQGGGGQGGGGQGGGGQDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	27
huNRG1(S177-S228)(wt)::3x(G4Q)::huFcSEFL2（Pb）	SHLVKCAEKEKTFCVNGGECFMVKDLSNPSRYLCKCPNEFTGDRCQNYVMASGGGGQGGGGQGGGGQDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	28
huNRG1(S177-Q237)(NRGE1A)::GG::huFcSEFL2（Pb）	SHLVKCAENDKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	29
huNRG1(S177-Q237)(NRGE1B)::GG::huFcSEFL2（Pb）	SHLVKCGENDKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	30
huNRG1(S177-Q237)(NRGE1C)::GG::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	19
huNRG1(S177-Q237)(NRGE1D)::GG::huFcSEFL2（Pb）	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	22
huNRG1(S177-Q237)(NRGE1E)::GG::huFcSEFL2（Pb）	SHLVKCGENDKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQNDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	31
huNRG1(S177-Q237)(NRGE1F)::GG::huFcSEFL2（Pb）	SHLVKCAENDKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQNDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	32
huNRG1(S177-Q237)(NRGE1G)::GG::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQNDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	33
huNRG1(S177-Q237)(NRGE1H)::GG::huFcSEFL2（Pb）	SHLVKCGESHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQNDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	34
huNRG1(S177-Q237)(NRGE1I)::GG::huFcSEFL2（Pb）	SHLVKCGENDKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQDDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	35
huNRG1(S177-Q237)(NRGE1J)::GG::huFcSEFL2（Pb）	SHLVKCGENDKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQDDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	36
huNRG1(S177-Q237)(NRGE1K)::GG::huFcSEFL2（Pb）	SHLVKCAEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQDDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	37
huNRG1(S177-Q237)(NRGE1L)::GG::huFcSEFL2（Pb）	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQDDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	38
huNRG1(S177-Q237)(NRGE1M)::GG::huFcSEFL2（Pb）	SHLVKCGENDKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQDFFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	39
huNRG1(S177-Q237)(NRGE1N)::GG::huFcSEFL2（Pb）	SHLVKCGENDKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQDFFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	40
huNRG1(S177-Q237)(NRGE1O)::GG::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQDFFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	41
huNRG1(S177-Q237)(NRGE1P)::GG::huFcSEFL2（Pb）	SHLVKCAESHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQDFFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	42
huNRG1(S177-Q237)(1D3)::GG::huFcSEFL2（Pb）	SHLVKCGENDKSFCVNGGECFVIEDPSIPSRYLCKCPNEFTGDRCQNDFLASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	43
huNRG1(S177-F229)(NRGE1C) (D48T_F49Q_M50I) huIgG1z SELF2 Fc	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQETQIASFGGGGEGGGGAGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	44
huNRG1(S177-F229)(NRGE1C) (E47A_D48P_F49H_M50I) huIgG1z SELF2 Fc	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQAPHIASFGGGGEGGGGAGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	45
huNRG1(S177-F229)(NRGE1C) (E47K_D48T_F49S_M50L) huIgG1z SELF2 Fc	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQKTSLASFGGGGEGGGGAGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	46
huNRG1(S177-F229)(NRGE1C) (E47Q_D48S_M50P) huIgG1z SELF2 Fc	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQQSFPASFGGGGEGGGGAGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	47
huNRG1(S177-F229)(NRGE1C) (E47S_D48A_F49L_M50T) huIgG1z SELF2 Fc	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQSALTASFGGGGEGGGGAGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	48
huNRG1(S177-F229)(NRGE1C) (E47S_D48T_F49R_M50V) huIgG1z SELF2 Fc	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQSTRVASFGGGGEGGGGAGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	49
huNRG1(S177-F229)(NRGE1C) huIgG1z SELF2 Fc	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFGGGGEGGGGAGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	50
huNRG1(S177-F229)(NRGE1D) (E47K_D48L_F49D_M50I) huIgG1z SELF2 Fc	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQKLDIASFGGGGEGGGGAGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	51
huNRG1(S177-F229)(NRGE1D) (E47S_D48S_F49E_M50L) huIgG1z SELF2 Fc	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQSSELASFGGGGEGGGGAGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	52
huNRG1(S177-F229)(NRGE1D) (E47T_D48S_F49L_M50L) huIgG1z SELF2 Fc	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQTSLLASFGGGGEGGGGAGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	53
huNRG1(S177-F229)(NRGE1D) huIgG1z SELF2 Fc	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFGGGGEGGGGAGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	54
huNRG1(S177-F229) huIgG1z SELF2 Fc	SHLVKCAEKEKTFCVNGGECFMVKDLSNPSRYLCKCPNEFTGDRCQNYVMASFGGGGEGGGGAGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	55
huNRG1(S177-F229)(NRGE1C) 6xHis	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFGGGGEGGGGAGGGGHHHHHH	56
huNRG1(S177-F229)(NRGE1C) (D48T_F49Q_M50I) 6xHis	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQETQIASFGGGGEGGGGAGGGGHHHHHH	57
huNRG1(S177-F229)(NRGE1C) (E47A_D48P_F49H_M50I) 6xHis	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQAPHIASFGGGGEGGGGAGGGGHHHHHH	58
huNRG1(S177-F229)(NRGE1C) (E47K_D48T_F49S_M50L) 6xHis	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQKTSLASFGGGGEGGGGAGGGGHHHHHH	59
huNRG1(S177-F229)(NRGE1C) (E47Q_D48S_M50P) 6xHis	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQQSFPASFGGGGEGGGGAGGGGHHHHHH	60
huNRG1(S177-F229)(NRGE1C) (E47S_D48A_F49L_M50T) 6xHis	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQSALTASFGGGGEGGGGAGGGGHHHHHH	61
huNRG1(S177-F229)(NRGE1C) (E47S_D48T_F49R_M50V) 6xHis	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQSTRVASFGGGGEGGGGAGGGGHHHHHH	62
huNRG1(S177-F229)(NRGE1D) 6xHis	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFGGGGEGGGGAGGGGHHHHHH	63
huNRG1(S177-F229)(NRGE1D) (E47K_D48L_F49D_M50I) 6xHis	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQKLDIASFGGGGEGGGGAGGGGHHHHHH	64
huNRG1(S177-F229)(NRGE1D) (E47S_D48S_F49E_M50L) 6xHis	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQSSELASFGGGGEGGGGAGGGGHHHHHH	65
huNRG1(S177-F229)(NRGE1D) (E47T_D48S_F49L_M50L) 6xHis	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQTSLLASFGGGGEGGGGAGGGGHHHHHH	66
huNRG1(S177-F229)(NRGE1D) (E47V_D48T_F49R_M50L) 6xHis	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQVTRLASFGGGGEGGGGAGGGGHHHHHH	67
huNRG1(S177-F229) 6xHis	SHLVKCAEKEKTFCVNGGECFMVKDLSNPSRYLCKCPNEFTGDRCQNYVMASFGGGGEGGGGAGGGGHHHHHH	68
:huFcSEFL2(desK):G4SG4:huNRG1(S177-F229)(NRGE1C)	DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGG SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGG SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASF	69
:huFcSEFL2(desK):G4SG4:huNRG1(S177-F229)(NRGE1D)	DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGG SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGG SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASF	70
:huFcSEFL2(desK):G4SG4:huNRG1(S177-Q237)(NRGE1C)	DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGG SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGG SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQ	71
:huFcSEFL2(desK):G4SG4:huNRG1(S177-Q237)(NRGE1D)	DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGG SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGG SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQ	72
:huFcSEFL2(desK)v131(+):G4SG4:huNRG1(S177-F229)(NRGE1C)	DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREKMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLKSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGG SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTENQVSLTCLVEGFYPSDIAVEWESNGQPENNYETTPPVLDSDGSFFLYSDLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	73
:huFcSEFL2(desK)v131(+):G4SG4:huNRG1(S177-F229)(NRGE1D)	DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREKMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLKSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGG SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTENQVSLTCLVEGFYPSDIAVEWESNGQPENNYETTPPVLDSDGSFFLYSDLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	74
:huFcSEFL2(desK)v131(+):G4SG4:huNRG1(S177-Q237)(NRGE1C)	DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREKMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLKSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGG SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQ DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTENQVSLTCLVEGFYPSDIAVEWESNGQPENNYETTPPVLDSDGSFFLYSDLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	75
:huFcSEFL2(desK)v131(+):G4SG4:huNRG1(S177-Q237)(NRGE1D)	DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREKMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLKSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGG SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQ DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTENQVSLTCLVEGFYPSDIAVEWESNGQPENNYETTPPVLDSDGSFFLYSDLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	76
:huNRG1(S177-F229)(NRGE1C) ::2X(G4A)G4::huFcSEFL2v131(+)	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFGGGGAGGGGAGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREKMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLKSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTENQVSLTCLVEGFYPSDIAVEWESNGQPENNYETTPPVLDSDGSFFLYSDLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	77
:huNRG1(S177-F229)(NRGE1C) ::2X(G4E)G4::huFcSEFL2v131(+)	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFGGGGEGGGGEGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREKMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLKSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTENQVSLTCLVEGFYPSDIAVEWESNGQPENNYETTPPVLDSDGSFFLYSDLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	78
:huNRG1(S177-F229)(NRGE1D) ::2X(G4A)G4::huFcSEFL2v131(+)	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFGGGGAGGGGAGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREKMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLKSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTENQVSLTCLVEGFYPSDIAVEWESNGQPENNYETTPPVLDSDGSFFLYSDLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	79
:huNRG1(S177-F229)(NRGE1D) ::2X(G4E)G4::huFcSEFL2v131(+)	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFGGGGEGGGGEGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREKMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLKSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTENQVSLTCLVEGFYPSDIAVEWESNGQPENNYETTPPVLDSDGSFFLYSDLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	80
huNRG1(S177-S228)(wt)((G4E)2:G4)::huFcSEFL2（Pb）	SHLVKCAEKEKTFCVNGGECFMVKDLSNPSRYLCKCPNEFTGDRCQNYVMASFGGGGEGGGGEGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	81
huNRG1(S177-F229)(NRGE1C)((G4E)2，GGT-＞GGC 末端離胺酸前緘默突變)::G4::huFcSEFL2	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFGGGGEGGGGEGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	4
huNRG1(S177-F229)(NRGE1D)((G4E)2:G4)::huFcSEFL2（Pb）	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFGGGGEGGGGEGGGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	11
huNRG1(S177-Q237)(1A1)::GG::huFcSEFL2（Pb）	SHLVKCGESEKSFCVNGGECYVIEDSSIPSRFLCKCPNEFTGDRCQNVFLASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	82
huNRG1(S177-Q237)(1A12)::GG::huFcSEFL2（Pb）	SHLVKCAEKHKSFCVNGGECYVVERPSIPSRYLCKCPNEFTGDRCQKFFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	83
huNRG1(S177-Q237)(1A7)::GG::huFcSEFL2（Pb）	SHLVKCAERDKSFCVNGGECYVIEHLSNPSRFLCKCPNEFTGDRCQKDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	84
huNRG1(S177-Q237)(1B4)::GG::huFcSEFL2（Pb）	SHLVKCGERDKTFCVNGGECFMIEDSSNPSRYLCKCPNEFTGDRCQKDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	85
huNRG1(S177-Q237)(1B9)::GG::huFcSEFL2（Pb）	SHLVKCAEKHKSFCVNGGECFMVEDLSIPSRYLCKCPNEFTGDRCQDVFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	86
huNRG1(S177-Q237)(1C11)::GG::huFcSEFL2（Pb）	SHLVKCGEKEKTFCVNGGECYMVERPSIPSRFLCKCPNEFTGDRCQKFFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	87
huNRG1(S177-Q237)(1D10)::GG::huFcSEFL2（Pb）	SHLVKCAERDKTFCVNGGECYMIEDLSIPSRYLCKCPNEFTGDRCQKDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	88
huNRG1(S177-Q237)(1D3)::GG::huFcSEFL2（Pb）	SHLVKCGENDKSFCVNGGECFVIEDPSIPSRYLCKCPNEFTGDRCQNDFLASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	43
huNRG1(S177-Q237)(1D4)::GG::huFcSEFL2（Pb）	SHLVKCGERDKTFCVNGGECYVVEHSSNPSRYLCKCPNEFTGDRCQKFFLASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	89
huNRG1(S177-Q237)(1D4)::GG::huFcSEFL2（Pb）	SHLVKCGERDKTFCVNGGECYVVEHSSNPSRYLCKCPNEFTGDRCQKFFLASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	89
huNRG1(S177-Q237)(2E3)::GG::huFcSEFL2（Pb）	SHLVKCGEKEKSFCVNGGECYMIEGLSIPSRFLCKCPNEFTGDRCQDVFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	90
huNRG1(S177-Q237)(2E4)::GG::huFcSEFL2（Pb）	SHLVKCGESDKSFCVNGGECFMVKRPSNPSRYLCKCPNEFTGDRCQKVFLASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	91
huNRG1(S177-Q237)(2F2)::GG::huFcSEFL2（Pb）	SHLVKCAESEKTFCVNGGECYMIEHPSNPSRFLCKCPNEFTGDRCQNVFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	92
huNRG1(S177-Q237)(2G3)::GG::huFcSEFL2（Pb）	SHLVKCGERQKSFCVNGGECYMVEDLSIPSRYLCKCPNEFTGDRCQKVFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	93
huNRG1(S177-Q237)(2G4)::GG::huFcSEFL2（Pb）	SHLVKCAENEKTFCVNGGECFVVEGLSIPSRYLCKCPNEFTGDRCQDVFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	94
huNRG1(S177-Q237)(2H7)::GG::huFcSEFL2（Pb）	SHLVKCGEKEKSFCVNGGECYVVEDLSIPSRFLCKCPNEFTGDRCQKVVMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	95
huNRG1(S177-Q237)(3A7)::GG::huFcSEFL2（Pb）	SHLVKCAEKEKSFCVNGGECFVIEGSSIPSRFLCKCPNEFTGDRCQKVVMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	96
huNRG1(S177-Q237)(3B8)::GG::huFcSEFL2（Pb）	SHLVKCGERDKSFCVNGGECFMVERSSIPSRYLCKCPNEFTGDRCQDFFLASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	97
huNRG1(S177-Q237)(3D6)::GG::huFcSEFL2（Pb）	SHLVKCGESDKSFCVNGGECFVIEGSSIPSRFLCKCPNEFTGDRCQDFFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	98
huNRG1(S177-Q237)(3D8)::GG::huFcSEFL2（Pb）	SHLVKCGEKDKTFCVNGGECFMVEDLSIPSRFLCKCPNEFTGDRCQDFFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	99
huNRG1(S177-Q237)(3E6)::GG::huFcSEFL2（Pb）	SHLVKCAEKHKSFCVNGGECYVIEGSSIPSRFLCKCPNEFTGDRCQKDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	100
huNRG1(S177-Q237)(3E9)::GG::huFcSEFL2（Pb）	SHLVKCAENHKTFCVNGGECFVIEGSSNPSRYLCKCPNEFTGDRCQDVFLASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	101
huNRG1(S177-Q237)(3F2)::GG::huFcSEFL2（Pb）	SHLVKCGESHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQDDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	102
huNRG1(S177-Q237)(3G3)::GG::huFcSEFL2（Pb）	SHLVKCGEREKTFCVNGGECFMIEHLSIPSRFLCKCPNEFTGDRCQEDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	103
huNRG1(S177-Q237)(3G9)::GG::huFcSEFL2（Pb）	SHLVKCGESHKSFCVNGGECFMVEDLSNPSRFLCKCPNEFTGDRCQKDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	104
huNRG1(S177-Q237)(3H5)::GG::huFcSEFL2（Pb）	SHLVKCGERHKSFCVNGGECYVVERPSIPSRFLCKCPNEFTGDRCQKDFLASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	105
huNRG1(S177-Q237)(3H8)::GG::huFcSEFL2（Pb）	SHLVKCGEKHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	106
huNRG1(S177-Q237)(_200E)::GG::huFcSEFL2（Pb）	SHLVKCAEKEKTFCVNGGECFMVEDLSNPSRYLCKCPNEFTGDRCQNYVMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	107
huNRG1(S177-Q237)(_200E_KDF)::GG::huFcSEFL2（Pb）	SHLVKCAEKEKTFCVNGGECFMVEDLSNPSRYLCKCPNEFTGDRCQKDFMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	108
huNRG1(S177-Q237)(_FVIEDPSI)::GG::huFcSEFL2（Pb）	SHLVKCAEKEKTFCVNGGECFVIEDPSIPSRYLCKCPNEFTGDRCQNYVMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	109
huNRG1(S177-Q237)(wt)::GG::huFcSEFL2（Pb）	SHLVKCAEKEKTFCVNGGECFMVKDLSNPSRYLCKCPNEFTGDRCQNYVMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	25
huNRG1(S177-Q237)(v80)::GG::huFcSEFL2（Pb）	SHLVKCAESHKSFCVNGGECFVIEGSSIPSRYLCKCPNEFTGDRCQKDVMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	110
huNRG1(S177-Q237)(v80.3)::GG::huFcSEFL2（Pb）	SHLVKCAERHKSFCVNGGECFVIEGSSIPSRYLCKCPNEFTGDRCEKDVMASFYKAEELYQGGDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPCEEQYGSTYRCVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK	111

神經調節蛋白變體序列以粗體表示。

人神經調節蛋白變體序列（沒有連接子、Fc序列或His標籤）在下表2中顯示。 [表2]

變體名稱	HuNRG1變體序列	SEQ ID NO:
NRG1(S177-Q237) (NRGE1A)	SHLVKCAENDKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQ	114
NRG1(S177-Q237) (NRGE1B)	SHLVKCGENDKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQ	115
NRG1(S177-S228) (NRGE1C)	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMAS	116
NRG1(S177-F229) (NRGE1C)	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASF	117
NRG1(S177-F229) (NRGE1C TQI)	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQETQIASF	118
NRG1(S177-F229) (NRGE1C APHI)	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQAPHIASF	119
NRG1(S177-F229) (NRGE1C KTSL)	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQKTSLASF	120
NRG1(S177-F229) (NRGE1C QSP)	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQQSFPASF	121
NRG1(S177-F229) (NRGE1C SALT)	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQSALTASF	122
NRG1(S177-F229) (NRGE1C STRV)	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQSTRVASF	123
NRG1(S177-Q237) (NRGE1C)	SHLVKCGEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQ	124
NRG1(S177-S228) (NRGE1D)	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMAS	125
NRG1(S177-F229) (NRGE1D)	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASF	126
NRG1(S177-F229) (NRGE1D KLDI)	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQKLDIASF	127
NRG1(S177-F229) (NRGE1D SSEL)	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQSSELASF	128
NRG1(S177-F229) (NRGE1D TSLL)	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQTSLLASF	129
NRG1(S177-F229) (NRGE1D VTRL)	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQVTRLASF	130
NRG1(S177-Q237) (NRGE1D)	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQ	131
NRG1(S177-Q237) (NRGE1E)	SHLVKCGENDKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQNDFMASFYKAEELYQ	132
NRG1(S177-Q237) (NRGE1F)	SHLVKCAENDKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQNDFMASFYKAEELYQ	133
NRG1(S177-Q237) (NRGE1G)	SHLVKCGEKHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQNDFMASFYKAEELYQ	134
NRG1(S177-Q237) (NRGE1H)	SHLVKCGESHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQNDFMASFYKAEELYQ	135
NRG1(S177-Q237) (NRGE1I)	SHLVKCGENDKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQDDFMASFYKAEELYQ	136
NRG1(S177-Q237) (NRGE1J)	SHLVKCGENDKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQDDFMASFYKAEELYQ	137
NRG1(S177-Q237) (NRGE1K)	SHLVKCAEKHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQDDFMASFYKAEELYQ	138
NRG1(S177-Q237) (NRGE1L)	SHLVKCGESHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQDDFMASFYKAEELYQ	139
NRG1(S177-Q237) (NRGE1M)	SHLVKCGENDKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQDFFMASFYKAEELYQ	140
NRG1(S177-Q237) (NRGE1N)	SHLVKCGENDKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQDFFMASFYKAEELYQ	141
NRG1(S177-Q237) (NRGE1O)	SHLVKCGEKHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQDFFMASFYKAEELYQ	142
NRG1(S177-Q237) (NRGE1P)	SHLVKCAESHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQDFFMASFYKAEELYQ	143
NRG1(S177-Q237) (1A1)	SHLVKCGESEKSFCVNGGECYVIEDSSIPSRFLCKCPNEFTGDRCQNVFLASFYKAEELYQ	144
NRG1(S177-Q237) (1A12)	SHLVKCAEKHKSFCVNGGECYVVERPSIPSRYLCKCPNEFTGDRCQKFFMASFYKAEELYQ	145
NRG1(S177-Q237) (1A7)	SHLVKCAERDKSFCVNGGECYVIEHLSNPSRFLCKCPNEFTGDRCQKDFMASFYKAEELYQ	146
NRG1(S177-Q237) (1B4)	SHLVKCGERDKTFCVNGGECFMIEDSSNPSRYLCKCPNEFTGDRCQKDFMASFYKAEELYQ	147
NRG1(S177-Q237) (1B9)	SHLVKCAEKHKSFCVNGGECFMVEDLSIPSRYLCKCPNEFTGDRCQDVFMASFYKAEELYQ	148
NRG1(S177-Q237) (1C11)	SHLVKCGEKEKTFCVNGGECYMVERPSIPSRFLCKCPNEFTGDRCQKFFMASFYKAEELYQ	149
NRG1(S177-Q237) (1D10)	SHLVKCAERDKTFCVNGGECYMIEDLSIPSRYLCKCPNEFTGDRCQKDFMASFYKAEELYQ	150
NRG1(S177-Q237) (1D3)	SHLVKCGENDKSFCVNGGECFVIEDPSIPSRYLCKCPNEFTGDRCQNDFLASFYKAEELYQ	151
NRG1(S177-Q237) (1D4)	SHLVKCGERDKTFCVNGGECYVVEHSSNPSRYLCKCPNEFTGDRCQKFFLASFYKAEELYQ	152
NRG1(S177-Q237)(2E3)	SHLVKCGEKEKSFCVNGGECYMIEGLSIPSRFLCKCPNEFTGDRCQDVFMASFYKAEELYQ	153
NRG1(S177-Q237) (2E4)	SHLVKCGESDKSFCVNGGECFMVKRPSNPSRYLCKCPNEFTGDRCQKVFLASFYKAEELYQ	154
NRG1(S177-Q237) (2F2)	SHLVKCAESEKTFCVNGGECYMIEHPSNPSRFLCKCPNEFTGDRCQNVFMASFYKAEELYQ	155
NRG1(S177-Q237) (2G3)	SHLVKCGERQKSFCVNGGECYMVEDLSIPSRYLCKCPNEFTGDRCQKVFMASFYKAEELYQ	156
NRG1(S177-Q237) (2G4)	SHLVKCAENEKTFCVNGGECFVVEGLSIPSRYLCKCPNEFTGDRCQDVFMASFYKAEELYQ	157
NRG1(S177-Q237) (2H7)	SHLVKCGEKEKSFCVNGGECYVVEDLSIPSRFLCKCPNEFTGDRCQKVVMASFYKAEELYQ	158
NRG1(S177-Q237) (3A7)	SHLVKCAEKEKSFCVNGGECFVIEGSSIPSRFLCKCPNEFTGDRCQKVVMASFYKAEELYQ	159
NRG1(S177-Q237) (3B8)	SHLVKCGERDKSFCVNGGECFMVERSSIPSRYLCKCPNEFTGDRCQDFFLASFYKAEELYQ	160
NRG1(S177-Q237) (3D6)	SHLVKCGESDKSFCVNGGECFVIEGSSIPSRFLCKCPNEFTGDRCQDFFMASFYKAEELYQ	161
NRG1(S177-Q237) (3D8)	SHLVKCGEKDKTFCVNGGECFMVEDLSIPSRFLCKCPNEFTGDRCQDFFMASFYKAEELYQ	162
NRG1(S177-Q237)(3E6)	SHLVKCAEKHKSFCVNGGECYVIEGSSIPSRFLCKCPNEFTGDRCQKDFMASFYKAEELYQ	163
NRG1(S177-Q237)(3E9)	SHLVKCAENHKTFCVNGGECFVIEGSSNPSRYLCKCPNEFTGDRCQDVFLASFYKAEELYQ	164
NRG1(S177-Q237) (3F2)	SHLVKCGESHKSFCVNGGECFMIEGPSNPSRYLCKCPNEFTGDRCQDDFMASFYKAEELYQ	165
NRG1(S177-Q237) (3G3)	SHLVKCGEREKTFCVNGGECFMIEHLSIPSRFLCKCPNEFTGDRCQEDFMASFYKAEELYQ	166
NRG1(S177-Q237) (3G9)	SHLVKCGESHKSFCVNGGECFMVEDLSNPSRFLCKCPNEFTGDRCQKDFMASFYKAEELYQ	167
NRG1(S177-Q237) (3H5)	SHLVKCGERHKSFCVNGGECYVVERPSIPSRFLCKCPNEFTGDRCQKDFLASFYKAEELYQ	168
NRG1(S177-S228) (3H8)	SHLVKCGEKHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMAS	169
NRG1(S177-F229) (3H8)	SHLVKCGEKHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASF	170
NRG1(S177-Q237) (3H8)	SHLVKCGEKHKSFCVNGGECYMVEGSSIPSRYLCKCPNEFTGDRCQEDFMASFYKAEELYQ	171
NRG1(S177-Q237) (200E)	SHLVKCAEKEKTFCVNGGECFMVEDLSNPSRYLCKCPNEFTGDRCQNYVMASFYKAEELYQ	172
NRG1(S177-Q237) (200E_KDF)	SHLVKCAEKEKTFCVNGGECFMVEDLSNPSRYLCKCPNEFTGDRCQKDFMASFYKAEELYQ	173
NRG1(S177-Q237) (FVIEDPSI)	SHLVKCAEKEKTFCVNGGECFVIEDPSIPSRYLCKCPNEFTGDRCQNYVMASFYKAEELYQ	174
NRG1(S177-Q237) (v80)	SHLVKCAESHKSFCVNGGECFVIEGSSIPSRYLCKCPNEFTGDRCQKDVMASFYKAEELYQ	175
NRG1(S177-Q237) (v80.3)	SHLVKCAERHKSFCVNGGECFVIEGSSIPSRYLCKCPNEFTGDRCEKDVMASFYKAEELYQ	176

在某些實施方式中，多肽變體包含具有下式的胺基酸序列： SHLVKCX ₁₈₃EX ₁₈₅X ₁₈₆KX ₁₈₈FCVNGGECX ₁₉₇X ₁₉₈X ₁₉₉X ₂₀₀X ₂₀₁X ₂₀₂SX ₂₀₄PSRX ₂₀₈LCKCPNEFTGDRCX ₂₂₂X ₂₂₃X ₂₂₄X ₂₂₅X ₂₂₆ASX ₂₂₉（SEQ ID NO: 177）

其中

X ₁₈₃係A或G；

X ₁₈₅X ₁₈₆係KD、KE、KH、ND、NE、NH、RD、RE、RH、RQ、SD、SE或SH；

X ₁₈₈係S或T；

X ₁₉₇X ₁₉₈X ₁₉₉X ₂₀₀X ₂₀₁X ₂₀₂係FMIEDS（SEQ ID NO:178）、FMIEGP（SEQ ID NO:179）、FMIEHL（SEQ ID NO:180）、FMVEDL（SEQ ID NO:181）、FMVERS（SEQ ID NO:182）、FMVKRP（SEQ ID NO:183）、FVIEDP（SEQ ID NO:184）、FVIEGS（SEQ ID NO:185）、FVVEGL（SEQ ID NO:186）、YMIEDL（SEQ ID NO:187）、YMIEGL（SEQ ID NO:188）、YMIEHP（SEQ ID NO:189）、YMVEDL（SEQ ID NO:190）、YMVEGS（SEQ ID NO:191）、YMVERP（SEQ ID NO:192）、YVIEDS（SEQ ID NO:193）、YVIEGS（SEQ ID NO:194）、YVIEHL（SEQ ID NO:195）、YVVEDL（SEQ ID NO:196）、YVVEHS（SEQ ID NO:197）或YVVERP（SEQ ID NO:198）；

X ₂₀₄係I或N；

X ₂₀₈係F或Y；

X ₂₂₂X ₂₂₃X ₂₂₄X ₂₂₅X ₂₂₆係EKDVM（SEQ ID NO:199）、QAPHI（SEQ ID NO:200）、QDDFM（SEQ ID NO:201）、QDFFL（SEQ ID NO:202）、QDFFM（SEQ ID NO:203）、QDVFL（SEQ ID NO:204）、QDVFM（SEQ ID NO:205）、QEDFM（SEQ ID NO:206）、QETQI（SEQ ID NO:207）、QKDFL（SEQ ID NO:208）、QKDFM（SEQ ID NO:209）、QKDVM（SEQ ID NO:210）、QKFFL（SEQ ID NO:211）、QKFFM（SEQ ID NO:212）、QKLDI（SEQ ID NO:213）、QKTSL（SEQ ID NO:214）、QKVFL（SEQ ID NO:215）、QKVFM（SEQ ID NO:216）、QKVVM（SEQ ID NO:217）、QNDFL（SEQ ID NO:218）、QNDFM（SEQ ID NO:219）、QNVFL（SEQ ID NO:220）、QNVFM（SEQ ID NO:221）、QNYVM（SEQ ID NO:222）、QQSFP（SEQ ID NO:223）、QSALT（SEQ ID NO:224）、QSSEL（SEQ ID NO:225）、QSTRV（SEQ ID NO:226）、QTSLL（SEQ ID NO:227）或QVTRL（SEQ ID NO:228）；並且

X ₂₂₉不存在，係F或FYKAEELYQ（SEQ ID NO:229）。

在上式和下式中，野生型序列加下劃線。

在某些實施方式中，多肽變體包含SEQ ID No: 114至176中任一個的胺基酸序列。

在某些實施方式中，多肽變體包含SEQ ID No: 1至24、29至54、56至67、69至80、或82至111中任一個的胺基酸序列。

在某些實施方式中，多肽變體包含具有下式的胺基酸序列： SHLVKCX ₁₈₃EX ₁₈₅X ₁₈₆KX ₁₈₈FCVNGGECX ₁₉₇X ₁₉₈X ₁₉₉X ₂₀₀X ₂₀₁X ₂₀₂SX ₂₀₄PSRX ₂₀₈LCKCPNEFTGDRCX ₂₂₂X ₂₂₃X ₂₂₄X ₂₂₅X ₂₂₆ASX ₂₂₉[SEQ ID NO: 177]

其中

X ₁₈₃係A或G；

X ₁₈₅X ₁₈₆係KD、KE、KH、ND、NH、RD、RE、RH、RQ、SD、SE或SH；

X ₁₈₈係S或T；

X ₁₉₇X ₁₉₈X ₁₉₉X ₂₀₀X ₂₀₁X ₂₀₂係FMIEDS（SEQ ID NO:178）、FMIEGP（SEQ ID NO:179）、FMIEHL（SEQ ID NO:180）、FMVEDL（SEQ ID NO:181）、FMVERS（SEQ ID NO:182）、FMVKRP（SEQ ID NO:183）、FVIEDP（SEQ ID NO:184）、FVIEGS（SEQ ID NO:185）、YMIEDL（SEQ ID NO:187）、YMIEGL（SEQ ID NO:188）、YMIEHP（SEQ ID NO:189）、YMVEDL（SEQ ID NO:190）、YMVEGS（SEQ ID NO:191）、YMVERP（SEQ ID NO:192）、YVIEDS（SEQ ID NO:193）、YVIEGS（SEQ ID NO:194）、YVIEHL（SEQ ID NO:195）、YVVEHS（SEQ ID NO:197）或YVVERP（SEQ ID NO:198）；

X ₂₀₄係I或N；

X ₂₀₈係F或Y；

X ₂₂₂X ₂₂₃X ₂₂₄X ₂₂₅X ₂₂₆係EKDVM（SEQ ID NO:199）、QAPHI（SEQ ID NO:200）、QDFFL（SEQ ID NO:202）、QDFFM（SEQ ID NO:203）、QDVFL（SEQ ID NO:204）、QEDFM（SEQ ID NO:206）、QETQI（SEQ ID NO:207）、QKDFL（SEQ ID NO:208）、QKDFM（SEQ ID NO:209）、QKDVM（SEQ ID NO:210）、QKFFL（SEQ ID NO:211）、QKFFM（SEQ ID NO:212）、QKLDI（SEQ ID NO:213）、QKTSL（SEQ ID NO:214）、QKVFL（SEQ ID NO:215）、QNDFL（SEQ ID NO:218）、QNDFM（SEQ ID NO:219）、QNVFL（SEQ ID NO:220）、QNVFM（SEQ ID NO:221）、QNYVM（SEQ ID NO:222）、QQSFP（SEQ ID NO:223）、QSALT（SEQ ID NO:224）、QSSEL（SEQ ID NO:225）、QSTRV（SEQ ID NO:226）、QTSLL（SEQ ID NO:227）或QVTRL（SEQ ID NO:228）；並且

X ₂₂₉係F或FYKAEELYQ（SEQ ID NO:229）。

在某些實施方式中，多肽變體包含SEQ ID No: 114、115、117至124、126至135、138、139、144至147、149至156、160至168、或171至176中任一個的胺基酸序列。

在某些實施方式中，多肽變體包含SEQ ID No: 1至15、19、20、22、23、29至34、37、38、43至54、56至59、61至67、69至80、82至85、87至93、或97至111中任一個的胺基酸序列。

其中

X ₁₈₃係A或G；

X ₁₈₅係KE、KH、ND、RD、RH、RQ、SD、SE或SH；

X ₁₈₈係S或T；

X ₁₉₇X ₁₉₈X ₁₉₉X ₂₀₀X ₂₀₁X ₂₀₂係FMIEDS（SEQ ID NO:178）、FMIEGP（SEQ ID NO:179）、FMVEDL（SEQ ID NO:181）、FMVKRP（SEQ ID NO:183）、FVIEDP（SEQ ID NO:184）、FVIEGS（SEQ ID NO:185）、YMIEDL（SEQ ID NO:187）、YMIEHP（SEQ ID NO:189）、YMVEDL（SEQ ID NO:190）、YMVEGS（SEQ ID NO:191）、YMVERP（SEQ ID NO:192）、YVIEDS（SEQ ID NO:193）、YVIEGS（SEQ ID NO:194）、YVIEHL（SEQ ID NO:195）、YVVEHS（SEQ ID NO:197）或YVVERP（SEQ ID NO:198）；

X ₂₀₄係I或N；

X ₂₀₈係F或Y；

X ₂₂₂X ₂₂₃X ₂₂₄X ₂₂₅X ₂₂₆係EKDVM（SEQ ID NO:199）、QAPHI（SEQ ID NO:200）、QEDFM（SEQ ID NO:206）、QETQI（SEQ ID NO:207）、QKDFL（SEQ ID NO:208）、QKDFM（SEQ ID NO:209）、QKDVM（SEQ ID NO:210）、QKFFL（SEQ ID NO:211）、QKFFM（SEQ ID NO:212）、QKLDI（SEQ ID NO:213）、QKTSL（SEQ ID NO:214）、QKVFL（SEQ ID NO:215）、QNDFL（SEQ ID NO:218）、QNDFM（SEQ ID NO:219）、QNVFL（SEQ ID NO:220）、QNVFM（SEQ ID NO:221）、QNYVM（SEQ ID NO:222）、QQSFP（SEQ ID NO:223）、QSALT（SEQ ID NO:224）、QSSEL（SEQ ID NO:225）、QSTRV（SEQ ID NO:226）、QTSLL（SEQ ID NO:227）或QVTRL（SEQ ID NO:228）；並且

X ₈係F或FYKAEELYQ（SEQ ID NO:229）。

在某些實施方式中，多肽變體包含SEQ ID No: 117至124、126至135、144至147、149至152、154至156、163、167、168、或171至176中任一個的胺基酸序列。

在某些實施方式中，多肽變體包含SEQ ID No: 3、4、6、9、11至13、19、22、31至34、43至48、52、54、56至59、61至63、65至67、71、72、75至80、84、85、88、100、或104至106中任一個的胺基酸序列。

其中

X ₁₈₃係A或G；

X ₁₈₅X ₁₈₆係KH、ND、RD、RH或SH；

X ₁₈₈係S或T；

X ₁₉₇X ₁₉₈X ₁₉₉X ₂₀₀X ₂₀₁X ₂₀₂係FMIEDS（SEQ ID NO:178）、FMIEGP（SEQ ID NO:179）、FMVEDL（SEQ ID NO:181）、FVIEDP（SEQ ID NO:184）、YMIEDL（SEQ ID NO:187）、YMVEGS（SEQ ID NO:191）、YVIEGS（SEQ ID NO:194）、YVIEHL（SEQ ID NO:195）或YVVERP（SEQ ID NO:198）；

X ₂₀₄係I或N；

X ₂₀₈係F或Y；

X ₂₂₂X ₂₂₃X ₂₂₄X ₂₂₅X ₂₂₆係QAPHI（SEQ ID NO:200）、QEDFM（SEQ ID NO:206）、QETQI（SEQ ID NO:207）、QKDFL（SEQ ID NO:208）、QKDFM（SEQ ID NO:209）、QKTSL（SEQ ID NO:214）、QNDFL（SEQ ID NO:218）、QNDFM（SEQ ID NO:219）、QQSFP（SEQ ID NO:223）、QSALT（SEQ ID NO:224）、QSSEL（SEQ ID NO:225）、QSTRV（SEQ ID NO:226）、QTSLL（SEQ ID NO:227）或QVTRL（SEQ ID NO:228）；並且；

X ₂₂₉係F或FYKAEELYQ（SEQ D NO:229）。

在某些實施方式中，多肽變體包含SEQ ID No: 117至124、126、128至135、146、147、150、151、163、167、168或171中任一個的胺基酸序列。

在某些實施方式中，與SEQ ID NO: 112的多肽相比，多肽變體對ErbB4具有增強的結合親和力。

在某些實施方式中，與SEQ ID NO:112的多肽相比，多肽變體對ErbB3具有降低的結合親和力。

在某些實施方式中，與SEQ ID NO:112的多肽相比，多肽變體對ErbB4具有增加的結合親和力，同時對ErbB3具有相似的結合親和力。

在某些實施方式中，與SEQ ID NO: 112的多肽相比，多肽變體對ErbB4具有增加的結合親和力，同時對ErbB3具有降低的結合親和力。

在某些實施方式中，與SEQ ID NO: 124的多肽相比，多肽變體對ErbB4具有相似的結合，同時對ErbB3具有降低的結合。

在某些實施方式中，多肽變體對ErbB4/ErbB3具有至少500、至少1000、至少5000或至少10,000的選擇性。對ErbB4/ErbB3的選擇性可以藉由熟悉該項技術者已知的方法（例如實例1中描述的Akt測定）測量。例如，選擇性能以施旺氏細胞/心肌細胞中EC50的比率表示。這個比率提供了與心臟細胞相比的神經細胞中的活性。

在某些實施方式中，多肽變體具有促效劑活性，該促效劑活性係對野生型序列活性的至少50%、60%、70%或80%。這可以藉由Akt的磷酸化測量。

上文描述的神經調節蛋白變體中任一個可以藉由融合到異源多肽來修飾，以產生「嵌合神經調節蛋白變體」或融合蛋白。典型地，異源多肽在神經調節蛋白變體的N末端或C末端融合以維持神經調節蛋白變體的生物活性。然而，還可以將異源多肽引入對生物活性不是關鍵的神經調節蛋白變體區。通常，藉由重組技術或化學合成產生嵌合神經調節蛋白變體。嵌合神經調節蛋白變體之實例包括融合至「訊息序列」、「純化柄」、免疫球蛋白序列或其任何組合的神經調節蛋白變體。可以使用連接子將神經調節蛋白多肽與異源多肽連接。

「訊息序列」係胺基酸序列，該胺基酸序列指導表現嵌合蛋白的細胞分泌與其融合的多肽。因此，神經調節蛋白變體與訊息序列的融合促進神經調節蛋白變體的重組產生，因為嵌合神經調節蛋白變體分泌到宿主細胞培養基中，從該宿主細胞培養基中可以相對容易地回收嵌合神經調節蛋白變體。合適的訊息序列可以從任何蛋白質中獲得，該蛋白質具有訊息序列並且典型地（但不總是）與神經調節蛋白變體的N末端融合。編碼原核訊息序列的DNA可以例如從lamB或ompF、MalE、PhoA和其他基因中獲得。其他合適的原核訊息序列係大腸桿菌耐熱腸毒素II（STII）訊息序列。哺乳動物訊息序列在下面討論。

「純化柄」係與另一種多肽結合的多肽或多肽序列的一部分，稱為「結合配偶體」。純化柄與神經調節蛋白變體的融合賦予變體與結合配偶體結合的能力，從而促進所得嵌合神經調節蛋白變體的純化。通常，選擇純化柄以使結合配偶體基本上不與混合物中存在的其他組分發生交叉反應，嵌合神經調節蛋白變體將從該混合物中純化。示例性「純化柄」係His標籤序列。如本文所用，術語「基本上不發生交叉反應」意指結合配偶體對純化柄的親和力係對混合物中存在的任何其他組分的任何親和力的至少約20倍、通常至少約100倍、更通常至少約1000倍。

嵌合神經調節蛋白變體包括與免疫球蛋白序列融合的神經調節蛋白變體。在一個實施方式中，免疫球蛋白序列係IgG分子（例如，IgG1、IgG2、IgG3或IgG4）的Fc區，其增加IgG的體內血清半衰期。參見例如，美國專利申請公開案號US 2006/0140934。

在一個實施方式中，神經調節蛋白變體經由神經調節蛋白變體的N末端上的第一（第1）胺基酸附接至連接子，該胺基酸在一個實施方式中係絲胺酸（S或Ser）胺基酸。

在某些實施方式中，Fc區具有至少一個突變，較佳的是降低效應子功能和/或延長分子的半衰期。在某些方面，Fc區在胺基酸234、239、434或其組合（根據EU編號進行編號）中包含至少一個突變，其中在某些方面，胺基酸突變包含以下取代突變中的至少一個：L234F、S239A、N434A或其組合。胺基酸234和/或239的突變敲低了Fc區的效應子功能。胺基酸434的突變延長了受試者中融合蛋白的半衰期。其他突變係本領域已知的，例如SEFL2.0和SEFL2.2突變。參見例如，Jacobsen等人, 2017, J Biol Chem [生物化學雜誌] 292:1865-1875以及Yang等人, 2018, Front Immunol [免疫學前沿] 第8卷, 第1860條。

在某些實施方式中，Fc區中的一或多個突變降低效應子功能。在一些實施方式中，降低的效應子功能包含融合蛋白對一或多個Fc受體的降低的親和力。FcR可為FcyRI、FcyRIIa、FcyRIib、FcyRIIIa（158F）、FcyRIIIa（158V）和Clq。

在一個實施方式中，融合蛋白包含神經調節蛋白變體，該神經調節蛋白變體經由GGGGSGGGGS（G4S）連接子（SEQ ID NO: 113）與Fc區的C末端融合或可操作地連接。在一些實施方式中，可以使用連接子的一或多個拷貝。在其他實施方式中，可以在本文使用G4S連接子的2、3、4或5個拷貝或本領域已知的和/或如本文所描述的適用於本文揭露的組成物之任何其他連接子。

術語「連接子」係本領域公認的並且係指連接兩種化合物（例如兩種多肽）的分子（包括但不限於不經修飾的或經修飾的核苷酸或胺基酸）或分子之群組（例如，2個或更多個，例如，2、3、4、5、6、7、8、9、10、15、20、25、30、35、40、45、50、55、60、65、70、75、80、85、90、95、100個或更多個）。連接子可以由單個連接分子組成或可以包含連接分子和至少一個間隔分子，旨在將連接分子與化合物分開特定距離。 神經調節蛋白變體之製備

本發明之多肽可以藉由化學合成或重組方法產生。化學合成多肽之方法係本領域熟知的。使用重組方法合成多肽亦為本領域熟知的並且在本文進一步描述。

用於基因工程化細胞和/或細胞系以表現例如多肽之方法和載體係熟悉該項技術者熟知的；例如，各種技術說明於：Current Protocols in Molecular Biology [分子生物學現代方法], Ausubel等人, 編輯（Wiley & Sons [約翰威立父子公司], 紐約, 1988, 和季度更新）；Sambrook等人, Molecular Cloning: A Laboratory Manual [分子選殖：實驗室手冊]（冷泉實驗室出版社, 1989）；Kaufman, R.J., Large Scale Mammalian Cell Culture [大規模哺乳動物細胞培養], 1990,第15-69頁。可以使用本領域已知的方法測試產生的多肽對受體的結合親和力和受體之激活。

載體可為適合用於將編碼資訊的蛋白轉移和/或轉運至宿主細胞和/或特定位置和/或宿主細胞內的區室的任何分子或實體（例如，核酸、質體、噬菌體、轉座子、黏接質體、染色體、病毒、病毒殼體、病毒體、裸DNA、複合DNA等）。載體可以包括病毒和非病毒載體、非附加型哺乳動物載體。載體通常被稱為表現載體，例如，重組表現載體和選殖載體。可以將載體引入宿主細胞以允許載體自身的複製，並從而擴增其中含有的多核苷酸的拷貝。選殖載體可含有序列組分，該等序列組分通常包括但不限於複製起點、啟動子序列、轉錄起始序列、強化子序列和選擇性標記。該等元件可以由熟悉該項技術者適當選擇。

載體可用於對宿主細胞進行轉化且含有指導和/或控制（連同宿主細胞一起）與其可操作地連接的一或多個異源編碼區之表現的核酸序列的載體。表現構建體可以包括但不限於影響或控制轉錄、翻譯且在存在內含子時影響與其可操作地連接的編碼區之RNA剪接的序列。「可操作地連接」意指該術語所適用的組分呈允許其執行其固有功能的關係。例如，在與蛋白編碼序列「可操作地連接」的載體中的控制序列（例如啟動子）的排列使得該控制序列的正常活性導致該蛋白編碼序列之轉錄，從而導致所編碼的蛋白的重組表現。

可選擇在所採用的特定宿主細胞中具有功能性的載體（即，該載體與宿主細胞機構相容，從而允許可發生基因的擴增和/或表現）。在一些實施方式中，所使用的載體採用使用諸如二氫葉酸還原酶的蛋白報導序列的蛋白片段互補測定（參見例如美國專利案號6,270,964）。合適的表現載體係本領域已知的，並且亦為可商購的。

典型地，用於宿主細胞中的載體均將含有用於質體維持及用於選殖及表現外源核苷酸序列的序列。此類序列典型地將包含以下核苷酸序列中的一或多個：啟動子、一或多個強化子序列、複製起點、轉錄和翻譯控制序列、轉錄終止序列、含有供體和受體剪接位點的完整內含子序列、各種改善糖基化或產量的前序列（pre-sequence/pro-sequence）、用於多肽分泌的天然或異源訊息序列（前導序列或訊息肽）、核糖體結合位點、聚腺苷酸序列、內部核糖體進入位點（IRES）序列、表現增強序列元件（EASE）、來自腺病毒2的三聯體前導序列（TPA）和VA基因RNA、用於插入編碼待表現多肽的多核苷酸的多連接子區域以及選擇性標記元件。可以從起始載體（諸如可商購的載體）構建載體，可以單獨獲得其他元件並將其連接到載體中。用於獲得各組分的方法係熟悉該項技術者熟知的。

載體組分可為同源的（即，來自於與宿主細胞相同的物種和/或品系）、異源的（例如，來自於除宿主細胞物種或品系以外的物種）、雜合的（即，來自於多於一個來源的側接序列的組合）、合成的或天然的。可藉由本領域熟知的方法獲得該等載體中有用的組分的序列，諸如先前藉由作圖和/或藉由限制性核酸內切酶鑒定的那些。另外，它們可以藉由聚合酶鏈反應（PCR）和/或藉由用合適的探針篩選基因組文庫來獲得。

核糖體結合位點對於mRNA翻譯起始而言通常為必需的且以Shine-Dalgarno序列（原核生物）或Kozak序列（真核生物）為特徵。該元件典型地位於啟動子的3'且在待表現的多肽的編碼序列的5'。

複製的起點有助於宿主細胞中載體的擴增。它們可以作為可商購的原核載體的一部分包括在內，也可以基於已知序列化學合成並連接到載體中。各種病毒來源（例如，SV40、多瘤病毒、腺病毒、水泡性口炎病毒（VSV）或乳頭瘤病毒（諸如HPV或BPV））可用於在哺乳動物細胞中選殖載體。

哺乳動物宿主細胞表現載體的轉錄和翻譯控制序列可以從病毒基因組中切除。常用的啟動子和強化子序列源自多瘤病毒、腺病毒2、猿猴病毒40（SV40）和人巨細胞病毒（CMV）。例如，可以使用即時早期基因1的人CMV啟動子/強化子。參見例如，Patterson等人, 1994, Applied Microbiol. Biotechnol.[應用微生物學與生物技術] 40:691-98。源自SV40病毒基因組的DNA序列，例如，SV40來源、早期和晚期啟動子、強化子、剪接序列和聚腺苷酸位點可用於提供其他遺傳元件，用於在哺乳動物宿主細胞中表現結構基因序列。病毒早期和晚期啟動子係特別有用的，因為它們都容易從病毒基因組中作為片段獲得，也可以包含病毒複製起點（Fiers等人, 1978, Nature [自然] 273:113；Kaufman 1990, Meth. in Enzymol.[酶方法學] 185:487-511）。也可以使用更小或更大的SV40片段，前提係包括了從Hind III位點向位於SV40病毒複製起點的BglI位點延伸的約250 bp序列。

轉錄終止序列典型地位於多肽編碼區的3′端且用於終止轉錄。通常，原核細胞中的轉錄終止序列係富含G-C的片段，後接聚T序列。雖然序列可自文庫中容易地選殖或甚至作為載體的一部分而商購得到，但其還可使用熟悉該項技術者已知的那些核酸合成方法容易地合成。

選擇性標記基因編碼在選擇性培養基中生長的宿主細胞的存活及生長所必需的蛋白。典型的選擇標記物基因編碼如下蛋白質：(a) 賦予針對抗生素或其他毒素（例如，對於原核宿主細胞，胺苄青黴素、四環素或康黴素）的抗性；(b) 補充細胞的營養缺陷；或 (c) 提供不可得自複雜培養基或限定培養基的重要營養物。特定的可選擇標記物為康黴素抗性基因、胺苄青黴素抗性基因及四環素抗性基因。有利地，新黴素抗性基因還可用於在原核及真核宿主細胞二者中進行選擇。

其他可選擇基因可用於擴增將表現的基因。擴增為如下的過程：其中使產生對生長或細胞存活非常重要的蛋白質所需的基因在重組細胞連續世代的染色體內串聯重複。哺乳動物細胞的合適的選擇性標記之實例包括麩醯胺酸合成酶（GS）/甲硫胺酸亞碸亞胺（MSX）系統、二氫葉酸還原酶（DHFR）和無啟動子的胸苷激酶基因。使哺乳動物細胞轉化株處於選擇壓力下，其中由於載體中存在可選擇基因，故僅轉化株唯一適於存活。藉由在連續增加培養基中選擇劑的濃度的條件下培養經轉化細胞，由此使可選擇基因和編碼目的蛋白的DNA擴增來施加選擇壓力。因此，由經擴增的DNA合成增加量的目的多肽。

在一些情況下，例如在真核宿主細胞表現系統中需要糖基化時，可操縱各種前序列以改善糖基化或產率。例如，可以改變特定訊息肽的肽酶切割位點，或添加前序列，該等序列還可影響糖基化。最終蛋白質產物可以在-1位（相對於成熟蛋白質的第一個胺基酸）具有一或多個易於表現的另外的胺基酸，該等胺基酸可能未完全移除。例如，最終蛋白質產物可能具有一個或兩個在肽酶切割位點中發現的胺基酸殘基附接至胺基末端。可替代地，當酶在成熟多肽內的此類區域切割時，使用一些酶切割位點可能產生期望的多肽的略微截短的形式。

表現和選殖典型地將含有被宿主生物體識別且可操作地連接至編碼目的蛋白的分子的啟動子。啟動子為位於控制結構基因轉錄的結構基因起始密碼子（一般在約100至1000 bp內）上游（即，5'）的非轉錄序列。啟動子通常分組為兩種類別中的一個：誘導型啟動子及組成型啟動子。誘導型啟動子起始處於其控制下的DNA響應於培養條件的某種變化（諸如營養素的存在或不存在，或者溫度變化）以提高的水平轉錄。另一方面，組成型啟動子一致地轉錄其可操作地連接的基因，即，對基因表現具有極小控制或無控制。許多由多種潛在宿主細胞識別的啟動子係熟知的。

用於哺乳動物宿主細胞的適合啟動子係熟知的，且包括但不限於獲自病毒基因組的那些啟動子，該等病毒為諸如多瘤病毒、傳染性上皮瘤病毒、腺病毒（諸如腺病毒2）、牛乳頭狀瘤病毒、禽肉瘤病毒、巨細胞病毒、反轉錄病毒、B型肝炎病毒及猿猴病毒40（SV40）。其他適合哺乳動物啟動子包括異源哺乳動物啟動子，例如熱休克啟動子及肌動蛋白啟動子。

可能有意義的其他啟動子包括但不限於：SV40早期啟動子（Benoist和Chambon, 1981, Nature [自然] 290:304-310）；CMV啟動子（Thornsen等人, 1984, Proc.Natl.Acad.U.S.A. [美國國家科學院院刊] 81:659-663）；勞斯氏肉瘤病毒3'長末端重複序列中包含的啟動子（Yamamoto等人, 1980, Cell [細胞] 22:787-797）；皰疹病毒胸苷激酶啟動子（Wagner等人, 1981, Proc. Natl. Acad. Sci. U.S.A. [美國國家科學院院刊] 78:1444-1445）；甘油醛-3-磷酸脫氫酶（GAPDH）；來自金屬硫蛋白基因的啟動子和調控序列（Prinster等人, 1982, Nature [自然] 296:39-42）；以及原核啟動子，諸如β-內醯胺酶啟動子（Villa-Kamaroff等人, 1978, Proc. Natl. Acad. Sci. U.S.A. [美國國家科學院院刊] 75:3727-3731）；或tac啟動子（DeBoer等人, 1983, Proc. Natl. Acad. Sci. U.S.A. [美國國家科學院院刊] 80:21-25）。有意義的還有以下動物轉錄控制區，它們表現出組織特異性並已用於轉基因動物中：在胰臟腺泡細胞中有活性的彈性蛋白酶I基因控制區（Swift等人, 1984, Cell [細胞] 38:639-646；Ornitz等人, 1986, Cold Spring Harbor Symp. Quant. Biol.[冷泉港定量生物學研討會] 50:399-409；MacDonald, 1987, Hepatology [肝臟病學] 7:425-515）；在胰臟β細胞中具有活性的胰島素基因控制區（Hanahan, 1985, Nature [自然] 315:115-122）；在淋巴樣細胞中具有活性的免疫球蛋白基因控制區（Grosschedl等人, 1984, Cell [細胞] 38:647-658；Adames等人, 1985, Nature [自然] 318:533-538；Alexander等人, 1987, Mol. Cell. Biol.[分子細胞生物學] 7:1436-1444）；在睪丸、乳房、淋巴和肥大細胞中具有活性的小鼠乳房腫瘤病毒控制區（Leder等人, 1986, Cell [細胞] 45:485-495）；在肝中具有活性的白蛋白基因控制區（Pinkert等人, 1987, Genes and Devel. [基因與發育] 1:268-276）；在肝中具有活性的α-胎蛋白基因控制區（Krumlauf等人, 1985, Mol. Cell. Biol. [分子細胞生物學] 5:1639-1648；Hammer等人, 1987, Science [科學] 253:53-58）；在肝中具有活性的α1-抗胰蛋白酶基因控制區（Kelsey等人, 1987, Genes and Devel.[基因與發育]1:161-171）；在骨髓細胞中具有活性的β球蛋白基因控制區（Grosschedl等人, 1985, Cell [細胞] 315:338-340；Kollias等人, 1986, Cell [細胞] 46:89-94）；在腦中的寡樹突細胞中具有活性的髓磷脂鹼性蛋白基因控制區（Readhead等人, 1987, Cell [細胞] 48:703-712）；在骨骼肌中具有活性的肌球蛋白輕鏈-2基因控制區（Sani, 1985, Nature [自然] 314:283-286）；和在下視丘中具有活性的促性腺激素釋放激素基因控制區（Mason等人, 1986, Science [科學] 234:1372-1378）。

可將強化子序列插入該載體中以增加高等真核生物的轉錄。強化子為DNA的順式作用元件，長度通常為約10-300 bp，作用於啟動子以增加轉錄。強化子在方向及位置方面為相對獨立的，已見於轉錄單元的5'及3'位置。已知可得自哺乳動物基因（例如球蛋白、彈性蛋白酶、白蛋白、α-胎蛋白和胰島素）的若干強化子序列。然而，典型地使用來自於病毒的強化子。本領域中已知的SV40強化子、巨細胞病毒早期啟動子強化子、多瘤病毒強化子和腺病毒強化子係用於活化真核啟動子的示例性強化元件。儘管強化子可以定位於載體中編碼序列的5'或3'，但其典型地位於啟動子5'的位點處。

可將編碼適當天然或異源訊息序列（前導序列或訊息肽）的序列併入表現載體中，以促進目的蛋白的細胞外分泌。訊息肽或前導序列的選擇取決於待產生目的蛋白的宿主細胞的類型，且異源訊息序列可替換天然訊息序列。在哺乳動物宿主細胞中具有功能性的訊息肽之實例包括以下：美國專利案號4,965,195中所描述的介白素-7的訊息序列；Cosman等人,1984, Nature [自然] 312:768中所描述的介白素-2受體的訊息序列；歐洲專利案號0367 566中所描述的介白素-4受體訊息肽；美國專利案號4,968,607中所描述的I型介白素-1受體訊息肽；歐洲專利案號0 460 846中所描述的II型介白素-1受體訊息肽。

經證實會改善來自哺乳動物表現載體的異源基因表現的另外的控制序列包括諸如源自CHO細胞的表現增加序列元件（EASE）的元件（Morris等人, 在Animal Cell Technology [動物細胞技術]，第529-534頁(1997)中；美國專利案號6,312,951 B1、6,027,915和6,309,841 B1）和來自腺病毒2的三聯體前導序列（TPL）和VA基因RNA（Gingeras等人, 1982, J. Biol. Chem. [生物化學雜誌] 257:13475-13491）。病毒來源的內部核糖體進入位點（IRES）序列使雙順反子mRNA得以有效翻譯（Oh和Sarnow, 1993, Current Opinion in Genetics and Development [遺傳學與發育新見] 3:295-300；Ramesh等人, 1996, Nucleic Acids Research [核酸研究] 24:2697-2700）。

構建後，可將一或多種載體插入合適的細胞中以進行擴增和/或多肽表現。表現載體向所選細胞的轉化可以藉由熟知的方法完成，包括轉染、感染、磷酸鈣共沈澱、電穿孔、核轉染、顯微注射、DEAE-右旋糖酐介導的轉染、陽離子脂質介導的遞送、脂質體介導的轉染、微彈轟擊、受體介導的基因遞送，聚離胺酸、組蛋白、殼聚糖和肽介導的遞送。所選方法將部分隨待使用的宿主細胞類型而變化。該等方法及其他適合方法係熟練技術者熟知的，並且闡述於手冊和其他技術出版物中，例如，Sambrook等人, Molecular Cloning: A Laboratory Manual [分子選殖：實驗室手冊], 第3版, Cold Spring Harbor Laboratory Press [冷泉港實驗室出版社], 冷泉港, 紐約(2001)。

術語「轉化」係指細胞遺傳特性的改變，當細胞被修飾以含有新的DNA或RNA時，則該細胞就被轉化了。例如，細胞經由轉染、轉導或其他技術引入新的遺傳材料，由其原始狀態進行基因修飾，則該細胞就被轉化了。轉染或轉導後，轉化DNA可以藉由物理整合進入細胞染色體與細胞的DNA重組，或者可以作為一個不被複製的游離元件被暫時維持，或者可以作為質體獨立複製。當轉化DNA隨著細胞的分裂而複製時，細胞被認為已經「穩定地轉化」了。

術語「轉染」係指藉由細胞吸收外來或外源性DNA。許多轉染技術在本領域中係熟知的，並在本文中揭露。參見例如Graham等人, 1973, Virology [病毒學] 52:456；Sambrook等人, 2001, Molecular Cloning: A Laboratory Manual [分子選殖：實驗室手冊]，同上；Davis等人, 1986, Basic Methods in Molecular Biology [分子生物學基本方法], 愛思唯爾；Chu等人, 1981, Gene [基因] 13:197。

術語「轉導」係指外來DNA經由病毒載體被引入細胞的過程。參見Jones等人, (1998). Genetics: principles and analysis. [遺傳學：原理和分析] Boston: Jones & Bartlett Publ. [波士頓：鐘斯和巴特利特出版社]。

適用於在培養中生長的多種哺乳動物細胞系可從美國典型培養物保藏中心（American Type Culture Collection）（維吉尼亞州馬納薩斯）和商業供應商處獲得。行業中通常使用的細胞系之實例包括由SV40（COS-7、ATCC CRL 1651）轉化的猴腎CVl系；人胚胎腎系（293細胞或亞選殖用於在懸浮培養中生長的293細胞（Graham等人, 1977, J. Gen Virol.[普通病毒學雜誌] 36:59）；幼倉鼠腎細胞（BHK，ATCC CCL 10）；小鼠塞托利細胞（TM4, Mather,1980, Biol. Reprod.[生殖生物學]23:243-251）；猴腎細胞（CVl ATCC CCL 70）；非洲綠猴腎細胞（VERO-76，ATCC CRL-1587）；人子宮頸癌細胞（HELA，ATCC CCL 2）；犬腎細胞（MDCK，ATCC CCL 34）；布法羅大鼠肝細胞（BRL 3A，ATCC CRL 1442）；人肺細胞（W138，ATCC CCL 75）；人肝癌細胞（Hep G2，HB 8065）；小鼠乳腺腫瘤（MMT 060562，ATCC CCL51）；TRI細胞（Mather等人, 1982, Annals N.Y Acad. Sci. [紐約科學院年報] 383:44-68）；MRC 5細胞或FS4細胞；哺乳動物骨髓瘤細胞，以及許多其他細胞系和中國倉鼠卵巢（CHO）細胞。

用於商業應用的蛋白的大規模生產通常在懸浮培養中進行。因此，用於生成本文描述的重組哺乳動物細胞的哺乳動物宿主細胞可以但不必適於在懸浮培養中生長。已知多種適應於在懸浮培養中生長的宿主細胞，包括來自CHO-S、DG44和DXB11細胞系的小鼠骨髓瘤NS0細胞和CHO細胞。其他合適的細胞系包括小鼠骨髓瘤SP2/0細胞、幼倉鼠BF1K-21細胞、人PER.C6 ^®細胞、人胚腎F1EK-293細胞和源自或工程化自本文揭露的任何細胞系的細胞系。

CHO細胞廣泛用於生產複合重組蛋白，包括CHOK1細胞（ATCC CCL61）。二氫葉酸還原酶（DHFR）缺陷突變體細胞系（Urlaub等人, 1980, Proc Natl Acad Sci USA[美國國家科學院院刊] 77: 4216-4220）DXB11和DG-44係理想的CHO宿主細胞系，因為有效的DHFR可選擇和可擴增基因表現系統允許在該等細胞中高水平表現重組蛋白（Kaufman R. J., 1990, Meth Enzymol[酶方法學] 185:537-566）。還包括利用基於麩醯胺酸合成酶（GS）的甲硫胺酸亞碸亞胺（MSX）選擇的麩醯胺酸合成酶（GS）-敲除CHOK1SV細胞系。其他合適的CHO宿主細胞可以包括但不限於以下（括號中的係ECACC登錄號）：CHO（85050302）、CHO（無蛋白）（00102307）、CHO-K1（85051005）、CHO-K1/SF（93061607）、CHO/dhfr-（94060607）、CHO/dhfr-無AC（05011002）、RR-CHOKI（92052129）。

重組蛋白的生產始於在培養板、燒瓶、管、生物反應器或其他合適的容器中建立表現該蛋白的細胞的哺乳動物細胞生產培養物。典型地使用較小的生產生物反應器，在一個實施方式中，生物反應器為500 L至2000 L。在另一個實施方式中，使用1000 L-2000 L的生物反應器。用於接種生物反應器的種子細胞密度可對生產的重組蛋白的水平具有積極影響。在一個實施方式中，生物反應器用在無血清培養基中至少0.5 x10 ⁶至超過3.0 x 10 ⁶個活細胞/mL接種。在另一個實施方式中，接種量為1.0 x 10 ⁶個活細胞/mL。

然後哺乳動物細胞經歷指數生長階段。可以在沒有補充補料的情況下維持細胞培養物，直至達到期望的細胞密度。在一個實施方式中，細胞培養在有或無補充補料的情況下維持長達三天。在另一個實施方式中，可以以期望的細胞密度接種培養物以開始生產階段而沒有短暫的生長階段。在本文的任何實施方式中，從生長階段到生產階段的轉換也可以藉由任何前述方法引發。

在介於生長階段與生產階段之間的過渡階段，以及在生產階段期間，細胞壓積百分比（%PCV）等於或小於35%。在生產階段維持的期望的細胞壓積等於或小於35%。在一個實施方式中，細胞壓積等於或小於30%。在另一個實施方式中，細胞壓積等於或小於20%。在又另一個實施方式中，細胞壓積等於或小於15%。在另外的實施方式中，細胞壓積等於或小於10%。

在藉由哺乳動物細胞培養生產重組蛋白的商業方法中典型地使用三種方法：分批培養、補料分批培養和灌注培養。分批培養係一種不連續的方法，其中細胞在固定體積的培養基中生長很短的一段時間，接著完全收穫。使用分批方法生長的培養物經歷細胞密度的增加直至達到最大細胞密度，接著隨著培養基組分的消耗和代謝副產物（諸如乳酸鹽和胺）水平的積聚，活細胞密度下降。收穫通常發生在達到最大細胞密度時（例如，5 x 10 ⁶個細胞/mL或更高，取決於培養基配方、細胞系等）。分批過程係最簡單的培養方法，然而活細胞密度受到營養物可用性的限制，並且一旦細胞處於最大密度，則培養物衰退並且產量降低。不能夠延長生產階段，這係因為廢棄產物的積聚和營養物的消耗迅速導致培養物衰退（通常約3-7天）。

補料分批培養藉由提供團式或連續培養基補料以補充已經消耗的那些培養基組分而改進了分批過程。由於補料分批培養在整個運行中接受額外的營養物，所以與分批方法相比，它們具有獲得更高的細胞密度（＞ 10至30 x 10 ⁶個細胞/ml，取決於培養基配方、細胞系等）和增加的產物滴度的潛力。與分批過程不同，可以藉由操縱補料策略和培養基配方來產生和維持雙相培養物，以區分實現期望的細胞密度的細胞增殖期（生長階段）與懸浮或緩慢細胞生長階段（生產階段）。因此，與分批培養相比，補料分批培養具有獲得更高產物滴度的潛力。典型地，在生長階段使用分批方法，在生產階段使用補料分批方法，但是在整個過程中可以使用補料分批補料策略。然而，與分批過程不同，生物反應器體積係限制補料量的限制因素。此外，與分批方法一樣，代謝副產物的積聚將導致培養物衰退，這限制了生產階段的持續時間，約10至21天。補料分批培養係不連續的，收穫典型地發生在代謝副產物水平或培養物活力達到預定水平時。與不進行補料的分批培養相比，補料分批培養可以產生更大量的重組蛋白。參見例如，美國專利案號5,672,502。

灌注方法藉由添加新鮮培養基並同時去除用過的培養基提供了對分批方法和補料分批方法的潛在改進。典型的大規模商業細胞培養策略致力於達到60 - 90(+) x 10 ⁶個細胞/mL的高細胞密度，其中反應器體積的幾乎三分之一到一半以上係生物質。利用灌注培養，已經實現了＞ 1 x 10 ⁸個細胞/mL的極端細胞密度，並且預測了甚至更高的密度。典型的灌注培養開始於持續一天或兩天的分批培養啟動，接著向培養物中連續、分步和/或間歇性添加新鮮補料培養基，並在培養的整個生長階段和生產階段同時去除用過的培養基並保留細胞和另外的高分子量化合物諸如蛋白（基於過濾分子量截斷值）。可以使用各種方法，諸如沈降、離心或過濾來去除用過的培養基，同時維持細胞密度。已經報導了每天一工作容積的一個分數至每天多個工作容積的灌注流速。

灌注方法的優點係生產培養物可以比分批培養或補料分批培養方法維持更長的時間。然而，需要增加培養基的製備、使用、儲存和處置以支持長期灌注培養，特別是具有高細胞密度的那些，還需要甚至更多的營養物，並且與分批和補料分批方法相比，所有該等驅使生產成本甚至更高。另外，較高的細胞密度可在生產過程中引起問題，諸如維持溶解氧水平和增加氣體處理的問題，包括供給更多的氧氣和去除更多的二氧化碳，這將導致更多的起泡和對改變消泡策略的需要；以及在收穫和下游加工期間，其中去除過量細胞材料所需的努力可導致產物損失，從而否定了由於細胞質量增加而增加滴度的益處。

還提供了一種大規模細胞培養策略，該策略結合了生長階段的補料分批補料和其後生產階段的連續灌注。該方法以細胞培養物維持在小於或等於35%的細胞壓積的生產階段為目標。

在一個實施方式中，使用具有團式補料的補料分批培養在生長階段期間維持細胞培養物。然後可以在生產階段期間使用灌注補料。在一個實施方式中，當細胞達到生產階段時開始灌注。在另一個實施方式中，在細胞培養的第3天或約第3天至第9天或約第9天開始灌注。在另一個實施方式中，在細胞培養的第5天或約第5天至第7天或約第7天開始灌注。

在生長階段期間使用團式補料允許細胞過渡到生產階段，導致對作為引發和控制生產階段的手段的溫度變換的依賴性較小，然而在生長階段與生產階段之間可發生約36°C至約31°C的溫度變換。在一個實施方式中，該變換為36°C至32°C。

如本文所描述，生物反應器可以用在無血清培養基中至少0.5 x 10 ⁶至超過3.0 x 10 ⁶個活細胞/mL接種，例如1.0 x 10 ⁶個活細胞/mL。

灌注培養係其中細胞培養物接收新鮮灌注供給培養基同時除去耗過培養基的培養。灌注可為連續的、分步的、間歇的、或任何該等中的任何一種或全部的組合。灌注率可以每天低於一工作容積至多個工作容積。細胞保留在培養物中，並且去除的用過的培養基基本上不含細胞或具有比培養物顯著更少的細胞。細胞培養物表現的重組蛋白也可以保留在培養物中。灌注可以藉由許多方式完成，包括離心、沈降或過濾，參見例如Voisard等人, 2003, Biotechnology and Bioengineering [生物技術和生物工程] 82:751-65。過濾方法之實例係交替切向流過濾。藉由中空纖維過濾器模組泵送培養基來維持交替切向流。參見例如，美國專利案號6,544,424；Furey, 2002, Gen. Eng. News. [基因工程新聞] 22 (7):62-63。

「灌注流速」係在給定時間內從生物反應器通過（添加和去除）的培養基的量，通常表示為工作容積的某一分數或多個工作容積。「工作容積」係指用於細胞培養的生物反應器容積的量。在一個實施方式中，灌注流速為每天一個工作容積或更少。可以配製灌注補料培養基以使灌注營養物濃度最大化，從而使灌注速率最小化。

細胞培養物可以補充含有在細胞培養物生產階段過程中被消耗的組分（諸如營養物和胺基酸）的濃縮補料培養基。

濃縮補料培養基可基於幾乎任何細胞培養基配方。這樣的濃縮補料培養基可以含有細胞培養基的大多數組分，例如它們正常量的約5X、6X、7X、8X、9X、10X、12X、14X、16X、20X、30X、50X、100x、200X、400X、600X、800X或甚至約1000X。濃縮補料培養基常常用於補料分批培養過程。

本文描述的方法可用於改善多階段培養過程中重組蛋白的生產。在多級過程中，在兩個或更多個不同階段培養細胞。例如，細胞可以首先在一或多個生長階段，在使細胞增殖和活力最大化的環境條件下培養，然後轉移到生產階段，在使蛋白生產最大化的條件下培養。在藉由哺乳動物細胞生產蛋白的商業過程中，通常存在多個，例如至少約2、3、4、5、6、7、8、9或10個生長階段，該等生長階段在最終生產培養之前在不同培養容器中發生。

生長階段和生產階段可以在一或多個過渡階段之前，或由一或多個過渡階段隔開。在多階段過程中，根據本發明之方法可以至少在商業細胞培養的最終生產階段的生長和生產階段中採用，但是它也可以在先前的生長階段中採用。生產階段可以大規模進行。大規模過程可以在至少約100、500、1000、2000、3000、5000、7000、8000、10,000、15,000、20,000升的體積中進行。在一個實施方式中，生產在500 L、1000 L和/或2000 L生物反應器中進行。

生長階段可以在比生產階段更高的溫度下進行。例如，生長階段可以在約35°C至約38°C的第一溫度下進行，並且生產階段可以在約29°C至約37°C，視需要約30°C至約36°C或約30°C至約34°C的第二溫度下進行。此外，可以在溫度變化之前和/或之後的同時添加蛋白質產生的化學誘導劑，如像咖啡因、丁酸酯和六亞甲基雙乙醯胺（HMBA）。如果在溫度變化後添加誘導劑，則可以在溫度變化後1小時至5天，視需要在溫度變化後1至2天添加誘導劑。細胞培養可維持數天或甚至數週，同時細胞產生期望的一或多種蛋白質。

可以使用本領域已知的任何分析技術監測和評價來自細胞培養物的樣本。可以在培養持續期間監測包括重組蛋白及培養基品質和特徵在內的多種參數。可以間歇性地以期望的頻率，包括連續監測，即時或接近即時採集和監測樣本。

典型地，在最終生產培養物之前的細胞培養物（N-x至N-1）用於生成種子細胞，該等種子細胞將用於接種生產生物反應器，N-1培養物。種子細胞密度可對生產的重組蛋白的水平具有積極影響。產物水平傾向於隨著種子密度的增加而增加。滴度的提高不僅與更高的種子密度有關，而且可能受進入生產的細胞的代謝和細胞周期狀態的影響。

種子細胞可藉由任何培養方法產生。一種這樣的方法係使用交替切向流過濾的灌注培養。N-1生物反應器可以使用交替切向流過濾來運行以提供高密度的細胞來接種生產生物反應器。N-1階段可用於使細胞生長至密度＞ 90 x 10 ⁶個細胞/mL。N-1生物反應器可用於生成團式種子培養物或者可用作滾動種子儲備培養物，其可維持在高種子細胞密度下接種多個生產生物反應器。生產的生長時期的持續時間範圍可為7至14天，並且可以設計成在接種生產生物反應器之前維持細胞處於指數生長。優化灌注速率、培養基配方和時間以使細胞生長並將它們以最有利於優化其生產的狀態遞送至生產生物反應器。對於接種生產生物反應器，可以實現＞ 15 x 10 ⁶個細胞/mL的種子細胞密度。接種時更高的種子細胞密度可減少或甚至消除達到期望的生產密度所需的時間。

本發明還提供了藥物組成物，該等藥物組成物包含神經調節蛋白的多肽變體或編碼本文描述的多肽變體的多核苷酸中之任一個和藥學上可接受的賦形劑或載劑。如本文所用，「藥學上可接受的賦形劑或載劑」包括當與活性成分組合時，允許該成分保留生物活性並且與受試者的免疫系統不反應的任何材料。實例包括但不限於任何標準藥物載劑，例如磷酸鹽緩衝鹽水溶液、水、乳劑（例如油/水乳劑）和各種類型的潤濕劑。用於氣溶膠或腸胃外投與的較佳的稀釋劑係磷酸鹽緩衝鹽水或生理（0.9%）鹽水。包含此類載劑的組成物藉由熟知的常規方法配製（參見例如，Remington's Pharmaceutical Sciences [雷明頓藥物科學], 第18版, A. Gennaro,編輯, Mack Publishing Co. [馬克出版公司], 伊斯頓, 賓夕法尼亞州, 1990；和Remington, The Science and Practice of Pharmacy [雷明頓：藥劑科學與實踐] 第20版 Mack Publishing [馬克出版公司], 2000）。典型地，在配製物中使用適當量的藥學上可接受的鹽以使該配製物等滲。載劑之實例包括鹽水、林格氏溶液和右旋糖溶液。溶液的pH較佳的是從約5至約8、以及更較佳的是從約7至約7.5。另外的載劑包括緩釋製劑，例如含有抗體的固體疏水聚合物的半透性基質，該等基質係成形物品（例如，薄膜、脂質體或微粒）的形式。對於熟悉該項技術者顯而易見的是，取決於例如投與途徑和所投與多肽和多核苷酸的濃度，某些載劑可為更較佳的。 使用神經調節蛋白變體之方法

本發明還提供了用於在個體中預防、治療或延遲疾病發展之方法，該方法包括經由激活ErbB2/ErbB4受體向個體投與包含本文描述的神經調節蛋白的多肽變體的藥物組成物。

根據本發明之神經調節蛋白變體還可以用於治療肌細胞以及影響肌細胞的醫學病症。特別地，這種神經調節蛋白變體可用於治療肌肉損傷、減少肌細胞萎縮以及增加肌細胞存活、增殖和/或再生。適合用神經調節蛋白變體治療的肌肉系統的病理生理學病症之實例包括骨骼肌疾病（例如，肌病或營養不良）、心肌障礙（包括心房心律不整、心肌病、缺血性損傷、先天性疾病和心臟創傷）、和平滑肌障礙（例如動脈硬化、血管病變或先天性血管疾病）。神經調節蛋白變體還可以用於降低高血壓和增加肌細胞（例如，在患有重症肌無力或心動過速的個體中）的功能性乙醯膽鹼受體。

除非另外說明，否則如本文所用的術語「治療心血管疾病」意指部分地或完全地抑制、壓制、延遲、逆轉或減輕受試者的心血管疾病或病症的發作，或受試者已存在的心血管疾病或病症或其症狀的進展。可以藉由本揭露的方法治療的心血管疾病之非限制性實例包括慢性心臟衰竭、鬱血性心臟衰竭（CHF）、急性心臟衰竭、心肌梗塞（MI）、左心室收縮功能障礙、與MI相關的再灌注損傷、化療誘導的心臟毒性（成人或小兒）、輻射誘導的心臟毒性、小兒先天性心臟病的輔助手術干預。心血管疾病症狀的非限制性實例包括氣短，咳嗽，快速的體重增加，腿、腳踝和腹部腫脹，暈眩，疲勞，虛弱，暈眩，胸痛，昏厥（暈厥），心動過速和心動過緩。確定心血管疾病進展和治療有效性的方法對熟悉該項技術者而言將是顯而易見的。例如，各種心血管疾病的進展可以藉由射出分率/心電圖（ECG）、ECG/動態心電圖、應力測試、心導管檢查、心臟的電腦斷層成像（CT）掃描和心臟的磁共振成像（MRI）確定。

在某些實施方式中，可以經由優先地激活ErbB2/ErbB4受體來預防、治療或延遲其發展的心血管疾病包括但不限於心臟衰竭、心肌梗塞、擴張型或肥厚型心肌病、和心肌炎（例如，病毒性心肌炎）、心臟毒性。

如本文所用，「個體」或「受試者」係哺乳動物，更較佳的是人。哺乳動物包括但不限於農場動物（例如牛、豬、綿羊、山羊）、競技動物、寵物（例如貓、狗、馬）、靈長類動物、小鼠和大鼠。

根據本發明，本文描述的神經調節蛋白-1的多肽變體、或編碼多肽變體的核酸，單獨或與其他藥劑、載劑或賦形劑組合，可以配製用於任何合適的投與途徑，例如皮下注射、靜脈內注射、肌內注射、皮內注射、口服或局部投與。該方法可採用以單位劑型在安瓿中或在多劑量容器中可注射投與的配製物，並添加了防腐劑。配製物可以採取此類形式，如油性或水性媒介物中的混懸劑、溶液或乳劑，並且可以含有配製劑，如懸浮劑、穩定劑和/或分散劑。可替代地，活性成分可以呈粉末形式以供在使用前用合適的媒介物、無菌無熱原質水或其他溶劑構造。本發明之局部投與可以採用使用泡沫、凝膠、乳膏、軟膏、透皮貼劑或糊劑。

在治療或預防中，治療劑量的大小將隨所需治療病症的類型和嚴重程度和投與途徑而變化。劑量和可能的劑量頻率也將根據個體患者的年齡、體重、病症和響應而變化。應當指出，由於毒性或不良反應，主治醫師會知道如何以及何時終止、中斷或調整療法以減少劑量。相反，如果臨床響應不充分（排除毒性副作用），醫師也將知道如何以及何時將治療調整到更高的水平。

要在治療上採用的神經調節蛋白變體組成物的劑量取決於例如治療目標、投與途徑、和患者的狀況。因此，臨床醫生有必要滴定劑量並且根據需要修改投與途徑以獲得最佳治療效果。典型的每日劑量可以在每天約1 μg/kg體重至高達100 mg/kg體重或更多的範圍內，但是典型地在約10 μg/kg/天至10 mg/kg/天之間。通常，臨床醫生以低劑量的藥物神經調節蛋白變體組成物開始，然後增加劑量直到達到期望的治療效果。

在實際使用中，根據常規的藥物化合物技術，神經調節蛋白的多肽變體、包含神經調節蛋白的多肽變體的融合蛋白、或編碼前述兩者之一的核酸，單獨或與其他藥劑組合可以作為活性藥劑與藥物載劑或賦形劑（例如β-環糊精和2-羥基-丙基-β-環糊精）在緊密混合物中組合。載劑可以採用投與（局部或腸胃外投與）所期望的多種形式的製劑。在製備用於腸胃外劑型（例如靜脈內注射或輸注）的組成物時，可以採用熟悉該項技術者已知的類似的藥物介質、水、乙二醇、油、緩衝液、糖、防腐劑、脂質體等。此類腸胃外組成物之實例包括但不限於右旋糖5% w/v、生理鹽水或其他溶液。神經調節蛋白-1的多肽變體或編碼該多肽變體的核酸的總劑量，單獨或與待投與的其他藥劑組合可以靜脈內液體的小瓶投與，範圍從約1 ml至2000 ml。稀釋液體的體積將根據投與的總劑量而變化。

此外，神經調節蛋白變體能增強具有合適的ErbB受體的細胞的存活、增殖、和/或分化。短語「增強細胞的存活」係指相對於沒有暴露於神經調節蛋白變體的細胞（「未治療的細胞」）的存在期，增加細胞在體外或在體內的存在期。

表現「增強細胞的增殖」意指相對於未治療的細胞，在體外或體內增加有絲分裂的速率或數量。細胞培養物中細胞增殖的增加可以藉由計算暴露於神經調節蛋白變體之前和之後的細胞數量或藉由顯微鏡檢查匯合程度來檢測。細胞增殖還可以藉由測量由細胞攝取的 ³H胸苷來定量。

短語「增強細胞的分化」係指增加細胞特化的程度。細胞特化的特徵在於獲得與原始細胞的特徵不同的一或多個特徵。因此，細胞特化的程度典型地藉由篩選細胞表型的改變（例如，識別細胞形態學中的改變）確定。

本發明在範圍上不受本文描述的特定實施方式的限制，該等特定實施方式旨在作為本發明各個方面的單個說明，並且功能上等效的方法和組分也在本發明之範圍內。實際上，除了本文中顯示和描述的那些之外，根據前述描述和附圖，本發明之各種修改對於熟悉該項技術者將變得顯而易見。這類改變旨在落入所附申請專利範圍之範圍內。實例實例1：酵母展示工程化和NRG變體之生成

神經調節蛋白變體序列通過與α凝集素的融合展示在酵母表面。通過使用NNK密碼子在結構確定的位置引入簡並密碼子以在NRG1與NRG4序列或全部20個胺基酸隨機化之間交替。使用三個視覺化標記選擇結合完整的/選擇性序列。第一種係與Brilliant Violet 421軛合的抗HA抗體以測量神經調節蛋白變體的表面展示水平。第二種係用於陰性選擇的與Alexafluor 488軛合的可溶性重組ErbB3受體ECD。第三種係用於陽性選擇的與Alexafluor 647軛合的可溶性重組ErbB4受體ECD。具有恒定的ErbB4濃度（2.5 nM）的多輪陽性分選和針對增加的ErbB3濃度（250、500、750 nM）的陰性分選導致獲得選擇性神經調節蛋白變體。使用標準金門選殖（golden gate cloning）方法將選擇的神經調節蛋白變體從gblock DNA選殖到哺乳動物表現載體中。如表1所示，最終構建體併入各種NRG結構域截斷點、各種連接子和不同的融合結構域和標籤（Fc、scFc、6xhis）。在嘌呤黴素選擇下，使用標準脂質體方法在懸浮液適應的CHO K1細胞系中完成穩定表現。在7天生產後，來自過濾的條件培養基的蛋白質通過三重串聯LFAS系統（ProA，線上稀釋，SEC）或ProA（或6xhis標記的蛋白質的NiNTA）、緩衝液交換、CIEX、和/或HIC的連續單獨柱方法純化，隨後將配製物放入10 mM乙酸鹽9%蔗糖（pH 5.2）的緩衝液中。藉由A280確定蛋白質濃度。神經調節蛋白變體對新生大鼠心肌細胞和大鼠施旺氏細胞中Akt的體外磷酸化。

神經調節蛋白變體對心肌細胞（ErbB4）對比施旺氏細胞（ErbB3）的特異性藉由測量由ErbB2/ErbB4和ErbB2/ErbB3複合物形成產生的Akt活性進行測試。在藉由神經調節蛋白激活後，ErbB4和ErbB3受體優先地與ErbB2共受體二聚化，從而在心肌細胞中形成ErbB2/ErbB4複合物並在施旺氏細胞中形成ErbB2/ErbB3複合物，兩者都通過Akt通路發出信號。根據製造商的方案，使用Neomyt套組（kit）從0至4天齡的Sprague Dawley大鼠幼鼠的心臟分離新生大鼠心肌細胞，並且在含有血清的NS培養基（所有來自Cellultron生命技術公司（Cellultron Life Technologies），巴爾的摩，馬里蘭州）中的Surecoat板上鋪板。將大鼠施旺氏細胞在塗有補充了胎牛血清（賽默飛世爾公司（Thermo Fisher））和毛喉素（密理博西格瑪公司（Millipore Sigma））的達爾伯克改良伊格爾培養基（Dulbecco’s modified Eagle’s media，DMEM）的聚-D-離胺酸板上鋪板。在維持在37°C和5% CO ₂的加濕孵育箱中孵育24小時後，使用無血清孵育基洗滌心肌細胞和施旺氏細胞，並且在補充有牛血清白蛋白（西格瑪公司（Sigma））的DMEM中再孵育16小時。然後，使用神經調節蛋白變體分子的滴定來處理兩種細胞系15分鐘，這之後在裂解緩衝液（中尺度發現公司（Meso Scale Discovery，MSD））中裂解細胞。對於Akt磷酸化的檢測，將裂解物添加到多點96孔4點磷酸（絲胺酸473）/總Akt板（MSD）中，根據製造商的方案孵育並在SECTOR成像器6000（MSD）上讀數。對於兩種細胞測定，Akt的磷酸化百分比藉由將磷酸Akt信號乘以2，然後除以添加到總Akt信號中的磷酸Akt信號，然後乘以100進行計算。Akt的磷酸化數據點使用對數（促效劑）對比響應、GraphPad Prism中的可變斜率（4個參數）分析進行擬合以生成EC ₅₀曲線。CM%激動反映數據點的最高值。

結果顯示在下表3中。 [表3]

	心肌細胞（CM）（ErbB4）	施旺氏細胞（SC）（ErbB3）	選擇性	CM%激動	SEQ ID NO:
	Avg EC ₅₀(M)	Avg EC ₅₀(M)	SC/CM	AVG
huNRG1(S177-F229)(NRGE1C)::3x(G4Q)::huFcSEFL2 (Pb)	3.30E-10	＞1E-5	＞10000	77.3	1
huNRG1(S177-F229)(NRGE1C)::1KmodT482V,M493L)::huFcSEFL2 (Pb)	4.00E-10	＞1E-5	＞10000	75.8	2
huNRG1(S177-F229)(NRGE1C)::(G4A)2:G4::huFcSEFL2 (Pb)	4.90E-10	＞1E-5	＞10000	82.7	3
huNRG1(S177-F229)(NRGE1C)((G4E)2)::G4::huFcSEFL2 (Pb)	3.60E-10	＞1E-5	＞10000	81.9	4
huNRG1(S177-F229)(NRGE1C)::(G4S)2::G4::huFcSEFL2 (Pb)	6.20E-10	＞1E-5	＞10000	79.4	5
huNRG1(S177-F229)(NRGE1C)(G4E)::G4S::G4::huFcSEFL2 (Pb)	4.20E-10	＞1E-5	＞10000	82.2	6
huNRG1(S177-F229)(NRGE1C)(NRGmod)::G4::huFcSEFL2 (Pb)	8.70E-10	＞1E-5	＞10000	75.5	7
huNRG1(S177-F229)(NRGE1D)::3x(G4Q)::huFcSEFL2 (Pb)	2.90E-10	4.10E-07	1401	74.4	8
huNRG1(S177-F229)(NRGE1D)::1KmodT482V,M493L)::huFcSEFL2 (Pb)	3.40E-10	＞1E-5	＞10000	83.4	9
huNRG1(S177-F229)(NRGE1D)::(G4A)2:G4::huFcSEFL2 (Pb)	3.20E-10	＞1E-5	＞10000	78.8	10
huNRG1(S177-F229)(NRGE1D)((G4E)2)::G4::huFcSEFL2 (Pb)	2.80E-10	＞1E-5	＞10000	84.6	11
huNRG1(S177-F229)(NRGE1D)::(G4S)2::G4::huFcSEFL2 (Pb)	4.60E-10	＞1E-5	＞10000	80.5	12
huNRG1(S177-F229)(NRGE1D)(G4E)::G4S::G4::huFcSEFL2 (Pb)	3.50E-10	＞1E-5	＞10000	85	13
huNRG1(S177-F229)(NRGE1D)(NRGmod)::G4::huFcSEFL2 (Pb)	5.40E-10	＞1E-5	＞10000	74.9	14
野生型作為對照	2.80E-10	2.70E-10	1	100
huNRG1(S177-Q237)(3H8)::3xG4S::huFcSEFL2 (Pb)	2E-10	＞1E-5	＞10000		15
huNRG1(S177-F229)(3H8)::3x(G4Q)::huFcSEFL2 (Pb)	2.8E-10	1.49E-7	527		16
huNRG1(S177-Q237)(3H8)::3x(G4Q)::huFcSEFL2 (Pb)	2.4E-10	1E-7	414		17
huNRG1(S177-S228)(3H8)::3x(G4Q)::huFcSEFL2 (Pb)	4.35E-08	2.77E-8	0.6		18
huNRG1(S177-Q237)(NRGE1C)::GG::huFcSEFL2 (Pb)	4.1E-10	＞1E-5	＞10000		19
huNRG1(S177-F229)(NRGE1C)::3x(G4Q)::huFcSEFL2 (Pb)	2.4E-10	＞1E-5	＞10000		1
huNRG1(S177-Q237)(NRGE1C)::3x(G4Q)::huFcSEFL2 (Pb)	2.2E-10	＞1E-5	＞10000		20
huNRG1(S177-S228)(NRGE1C)::3x(G4Q)::huFcSEFL2 (Pb)	1.48E-08	7.83E-7	53		21
huNRG1(S177-Q237)(NRGE1D)::GG::huFcSEFL2 (Pb)	3.3E-10	＞1E-5	＞10000		22
huNRG1(S177-F229)(NRGE1D)::3x(G4Q)::huFcSEFL2 (Pb)	3E-10	4.46E-7	1491		8
huNRG1(S177-Q237)(NRGE1D)::3x(G4Q)::huFcSEFL2 (Pb)	2.1E-10	＞1E-5	＞10000		23
huNRG1(S177-S228)(NRGE1D)::3x(G4Q)::huFcSEFL2 (Pb)	2.29E-07	＞1E-5	＞100		24
huNRG1(S177-Q237)(wt)::GG::huFcSEFL2 (Pb)	6E-10	1.5E-10	0.3		25
huNRG1(S177-F229)(wt)::3x(G4Q)::huFcSEFL2 (Pb)	3.4E-10	1E10	0.3		26
huNRG1(S177-Q237)(wt)::3x(G4Q)::huFcSEFL2 (Pb)	2.1E-10	7E-11	0.3		27
huNRG1(S177-S228)(wt)::3x(G4Q)::huFcSEFL2 (Pb)	2.6E-9	7E-11	0.03		28
huNRG1(S177-Q237)(NRGE1A)::GG::huFcSEFL2 (Pb)	1.84E-09	＞1E-05	＞5500	72	29
huNRG1(S177-Q237)(NRGE1B)::GG::huFcSEFL2 (Pb)	1.48E-09	＞1E-05	＞6700	76	30
huNRG1(S177-Q237)(NRGE1C)::GG::huFcSEFL2 (Pb)	4.76E-10	＞1E-05	＞10000	82	19
huNRG1(S177-Q237)(NRGE1D)::GG::huFcSEFL2 (Pb)	3.03E-10	＞1E-05	＞10000	83	22
huNRG1(S177-Q237)(NRGE1E)::GG::huFcSEFL2 (Pb)	9.95E-10	＞1E-05	＞10000	83	31
huNRG1(S177-Q237)(NRGE1F)::GG::huFcSEFL2 (Pb)	6.50E-10	＞1E-05	＞10000	90	32
huNRG1(S177-Q237)(NRGE1G)::GG::huFcSEFL2 (Pb)	2.18E-10	＞1E-05	＞10000	84	33
huNRG1(S177-Q237)(NRGE1H)::GG::huFcSEFL2 (Pb)	2.86E-10	＞1E-05	＞10000	88	34
huNRG1(S177-Q237)(NRGE1I)::GG::huFcSEFL2 (Pb)	2.29E-08	＞1E-05	437	67	35
huNRG1(S177-Q237)(NRGE1J)::GG::huFcSEFL2 (Pb)	1.41E-08	＞1E-05	710	68	36
huNRG1(S177-Q237)(NRGE1K)::GG::huFcSEFL2 (Pb)	7.54E-09	＞1E-05	1320	66	37
huNRG1(S177-Q237)(NRGE1L)::GG::huFcSEFL2 (Pb)	2.29E-09	＞1E-05	＞4370	74	38
huNRG1(S177-Q237)(NRGE1M)::GG::huFcSEFL2 (Pb)	2.56E-08	1.01E-06	39	30	39
huNRG1(S177-Q237)(NRGE1N)::GG::huFcSEFL2 (Pb)	1.73E-09	7.51E-07	435	26	40
huNRG1(S177-Q237)(NRGE1O)::GG::huFcSEFL2 (Pb)	1.04E-09	5.46E-07	526	27	41
huNRG1(S177-Q237)(NRGE1P)::GG::huFcSEFL2 (Pb)	2.22E-09	5.10E-07	229	28	42
野生型作為對照	2.53E-10	6.52E-10	2.6	100
huNRG1(S177-Q237)(1D3)::GG::huFcSEFL2 (Pb)	1.62E-09	＞1E-5	＞6170	78	43
huNRG1(S177-F229)(NRGE1C) (D48T_F49Q_M50I) huIgG1z SELF2 Fc	2.4E-10	1E-5	＞10000	83.6	44
huNRG1(S177-F229)(NRGE1C) (E47A_D48P_F49H_M50I) huIgG1z SELF2 Fc	2.3E-10	1E-5	＞10000	85.8	45
huNRG1(S177-F229)(NRGE1C) (E47K_D48T_F49S_M50L) huIgG1z SELF2 Fc	2.5E-10	1E-5	＞10000	92.9	46
huNRG1(S177-F229)(NRGE1C) (E47Q_D48S_M50P) huIgG1z SELF2 Fc	3E-10	1E-5	＞10000	83.2	47
huNRG1(S177-F229)(NRGE1C) (E47S_D48A_F49L_M50T) huIgG1z SELF2 Fc	4.8E-10	1E-5	＞10000	87.8	48
huNRG1(S177-F229)(NRGE1C) (E47S_D48T_F49R_M50V) huIgG1z SELF2 Fc	1.9E-10	1E-5	＞10000	76	49
huNRG1(S177-F229)(NRGE1C) huIgG1z SELF2 Fc	2.8E-10	1E-5	＞10000	77.2	50
huNRG1(S177-F229)(NRGE1D) (E47K_D48L_F49D_M50I) huIgG1z SELF2 Fc	1.5E-10	9.33E-09	62.2	88.5	51
huNRG1(S177-F229)(NRGE1D) (E47S_D48S_F49E_M50L) huIgG1z SELF2 Fc	3.7E-10	1E-5	＞10000	86.3	52
huNRG1(S177-F229)(NRGE1D) (E47T_D48S_F49L_M50L) huIgG1z SELF2 Fc	3.9E-10	1E-5	＞10000	79.5	53
huNRG1(S177-F229)(NRGE1D) huIgG1z SELF2 Fc	4.8E-10	1E-5	＞10000	82.2	54
huNRG1(S177-F229) huIgG1z SELF2 Fc	3.1E-10	1.4E-10	0.45161	91.4	55
huNRG1(S177-F229)(NRGE1C) 6xHis	1.444E-09	1E-5	＞10000	106	56
huNRG1(S177-F229)(NRGE1C) (D48T_F49Q_M50I) 6xHis	7.123E-10	1E-5	＞10000	105.7	57
huNRG1(S177-F229)(NRGE1C) (E47A_D48P_F49H_M50I) 6xHis	1.104E-09	1E-5	＞10000	96.47	58
huNRG1(S177-F229)(NRGE1C) (E47K_D48T_F49S_M50L) 6xHis	8.251E-10	1E-5	＞10000	91.82	59
huNRG1(S177-F229)(NRGE1C) (E47Q_D48S_M50P) 6xHis	#N/A	#N/A	#N/A	#N/A	60
huNRG1(S177-F229)(NRGE1C) (E47S_D48A_F49L_M50T) 6xHis	6.948E-10	1E-5	＞10000	85.89	61
huNRG1(S177-F229)(NRGE1C) (E47S_D48T_F49R_M50V) 6xHis	5.795E-10	1E-5	＞10000	87.47	62
huNRG1(S177-F229)(NRGE1D) 6xHis	3.896E-10	1E-5	＞10000	90.65	63
huNRG1(S177-F229)(NRGE1D) (E47K_D48L_F49D_M50I) 6xHis	3.11E-10	1.723E-08	55.4019	91.65	64
huNRG1(S177-F229)(NRGE1D) (E47S_D48S_F49E_M50L) 6xHis	5.572E-10	1E-5	＞10000	96.05	65
huNRG1(S177-F229)(NRGE1D) (E47T_D48S_F49L_M50L) 6xHis	3.295E-10	1E-5	＞10000	99.83	66
huNRG1(S177-F229)(NRGE1D) (E47V_D48T_F49R_M50L) 6xHis	2.24E-10	1E-5	＞10000	97.95	67
huNRG1(S177-F229) 6xHis	5.865E-10	3.616E-9	6.16539	97.51	68
:huFcSEFL2(desK):G4SG4:huNRG1(S177-F229)(NRGE1C)	2.90E-10	無活性	＞10000	71.8	69
:huFcSEFL2(desK):G4SG4:huNRG1(S177-F229)(NRGE1D)	2.30E-10	無活性	＞10000	76.2	70
:huFcSEFL2(desK):G4SG4:huNRG1(S177-Q237)(NRGE1C)	1.10E-10	無活性	＞10000	84.9	71
:huFcSEFL2(desK):G4SG4:huNRG1(S177-Q237)(NRGE1D)	1.00E-10	無活性	＞10000	90.5	72
:huFcSEFL2(desK)v131(+):G4SG4:huNRG1(S177-F229)(NRGE1C)	6.40E-09	無活性	＞10000	62.7	73
:huFcSEFL2(desK)v131(+):G4SG4:huNRG1(S177-F229)(NRGE1D)	4.30E-09	無活性	＞10000	72.3	74
:huFcSEFL2(desK)v131(+):G4SG4:huNRG1(S177-Q237)(NRGE1C)	3.00E-10	無活性	＞10000	85.4	75
:huFcSEFL2(desK)v131(+):G4SG4:huNRG1(S177-Q237)(NRGE1D)	2.30E-10	無活性	＞10000	88.7	76
:huNRG1(S177-F229)(NRGE1C) ::2X(G4A)G4::huFcSEFL2v131(+)	3.40E-09	無活性	＞10000	91.6	77
:huNRG1(S177-F229)(NRGE1C) ::2X(G4E)G4::huFcSEFL2v131(+)	2.90E-09	無活性	＞10000	94	78
:huNRG1(S177-F229)(NRGE1D) ::2X(G4A)G4::huFcSEFL2v131(+)	2.00E-09	無活性	＞10000	87.1	79
:huNRG1(S177-F229)(NRGE1D) ::2X(G4E)G4::huFcSEFL2v131(+)	1.90E-09	無活性	＞10000	91.9	80
野生型作為對照	1.50E-10	3.18E-10	2.12	100
huNRG1(S177-S228)(wt)((G4E)2:G4)::huFcSEFL2 (Pb)	8.40E-11	2.22E-11	0.26429	92.6	81
huNRG1(S177-F229)(NRGE1C)((G4E)2，GGT-＞GGC 末端離胺酸前緘默突變)::G4::huFcSEFL2	7.30E-11	無活性	＞10000	88.7	4
huNRG1(S177-F229)(NRGE1D)((G4E)2:G4)::huFcSEFL2 (Pb)	7.90E-11	無活性	＞10000	88.2	11
huNRG1(S177-Q237)(1A1)::GG::huFcSEFL2 (Pb)	1.33E-10	9.11E-09	69	全部	82
huNRG1(S177-Q237)(1A12)::GG::huFcSEFL2 (Pb)	7.22E-10	4.79E-08	66	全部	83
huNRG1(S177-Q237)(1A7)::GG::huFcSEFL2 (Pb)	6.19E-10	1.00E-06	1616	全部	84
huNRG1(S177-Q237)(1B4)::GG::huFcSEFL2 (Pb)	9.96E-10	1.00E-05	＞10000	全部	85
huNRG1(S177-Q237)(1B9)::GG::huFcSEFL2 (Pb)	1.92E-09	1.00E-06	520	部分(＜50%)	86
huNRG1(S177-Q237)(1C11)::GG::huFcSEFL2 (Pb)	1.10E-09	8.70E-08	79	全部	87
huNRG1(S177-Q237)(1D10)::GG::huFcSEFL2 (Pb)	7.41E-10	＞3E-6	＞4000	全部	88
huNRG1(S177-Q237)(1D3)::GG::huFcSEFL2 (Pb)	7.72E-10	1.00E-05	＞10000	全部	43
huNRG1(S177-Q237)(1D4)::GG::huFcSEFL2 (Pb)	9.24E-10	2.26E-07	245	全部	89
huNRG1(S177-Q237)(1D4)::GG::huFcSEFL2 (Pb)	5.76E-10	3.23E-08	56	全部	89
huNRG1(S177-Q237)(2E3)::GG::huFcSEFL2 (Pb)	6.58E-10	1.00E-06	1521	部分(＜50%)	90
huNRG1(S177-Q237)(2E4)::GG::huFcSEFL2 (Pb)	4.29E-10	6.15E-08	143	全部	91
huNRG1(S177-Q237)(2F2)::GG::huFcSEFL2 (Pb)	2.44E-10	2.02E-07	826	全部	92
huNRG1(S177-Q237)(2G3)::GG::huFcSEFL2 (Pb)	2.08E-10	6.08E-08	292	全部	93
huNRG1(S177-Q237)(2G4)::GG::huFcSEFL2 (Pb)	2.42E-09	1.00E-06	414	部分(＜50%)	94
huNRG1(S177-Q237)(2H7)::GG::huFcSEFL2 (Pb)	3.00E-10	1.10E-07	368	部分(＜50%)	95
huNRG1(S177-Q237)(3A7)::GG::huFcSEFL2 (Pb)	3.66E-10	4.65E-08	127	部分(＜50%)	96
huNRG1(S177-Q237)(3B8)::GG::huFcSEFL2 (Pb)	1.40E-09	3.00E-06	2147	部分(＜50%)	97
huNRG1(S177-Q237)(3D6)::GG::huFcSEFL2 (Pb)	2.60E-09	＞1E-5	＞3800	部分(＜50%)	98
huNRG1(S177-Q237)(3D8)::GG::huFcSEFL2 (Pb)	5.10E-10	＞3E-6	＞5800	部分(＜50%)	99
huNRG1(S177-Q237)(3E6)::GG::huFcSEFL2 (Pb)	3.50E-10	＞1E-5	＞10000	全部	100
huNRG1(S177-Q237)(3E9)::GG::huFcSEFL2 (Pb)	2.68E-09	＞3E-6	＞8500	部分(70%)	101
huNRG1(S177-Q237)(3F2)::GG::huFcSEFL2 (Pb)	7.38E-10	＞1E-5	＞10000	部分(70%)	102
huNRG1(S177-Q237)(3G3)::GG::huFcSEFL2 (Pb)	1.84E-09	＞1E-5	＞5400	部分(70%)	103
huNRG1(S177-Q237)(3G9)::GG::huFcSEFL2 (Pb)	5.81E-10	＞1E-5	＞10000	全部	104
huNRG1(S177-Q237)(3H5)::GG::huFcSEFL2 (Pb)	1.27E-09	＞1E-5	＞7800	全部	105
huNRG1(S177-Q237)(3H8)::GG::huFcSEFL2 (Pb)	2.76E-10	＞1E-5	＞10000	全部	106
huNRG1(S177-Q237)(_200E)::GG::huFcSEFL2 (Pb)	4.52E-10	4.82E-09	11	全部	107
huNRG1(S177-Q237)(_200E_KDF)::GG::huFcSEFL2 (Pb)	2.00E-09	1.21E-07	60	全部	108
huNRG1(S177-Q237)(_FVIEDPSI)::GG::huFcSEFL2 (Pb)	1.77E-10	4.27E-09	24	全部	109
huNRG1(S177-Q237)(wt)::GG::huFcSEFL2 (Pb)	2.75E-10	1.12E-10	0.4	全部	25
huNRG1(S177-Q237)(v80)::GG::huFcSEFL2 (Pb)	9.98E-10	6.65E-09	7	全部	110
huNRG1(S177-Q237)(v80.3)::GG::huFcSEFL2 (Pb)	3.36E-08	3.00E-06	89	全部	111
野生型作為對照	1.54E-10	3.28E-10	2	全部

測試的神經調節蛋白變體通常顯示對Erbb4具有改善的選擇性，以SM/CM的比率表示，許多具有大於1000並且甚至10000的選擇性。與野生型序列相比，許多神經調節蛋白變體還顯示對心肌細胞至少80%的激動作用。

該等結果證明可以將神經調節蛋白變體設計為對心臟細胞具有選擇性。這表明該等神經調節蛋白變體係用於治療心臟病的候選物，並且可以顯示對神經細胞具有較低的副作用。實例2：在大鼠心肌梗塞（MI）模型中的ErbB4選擇性促效劑功效。

在大鼠MI模型中測試ErbB4選擇性促效劑（huNRG1(S177-F229)(NRGE1C)((G4E)2)::G4::huFcSEFL2（Pb））以確定是否可以在改善心臟功能方面看到益處。

手術誘導的心肌梗塞（MI）Sprague Dawley（SD）大鼠（體重180-200 g）購自ENVIGO（印弟安納波里斯，印第安那州，美國）。MI手術前14天，對大鼠進行超音波心動圖顯像以藉由射出分率（EF%）評估心臟功能。使用Vevo 2100系統（VisualSonics公司，多倫多，加拿大）獲得非侵入性胸骨旁長軸B模式電影重播（cine loop）。使用製造商推薦的方法計算EF。根據基線射出分率量將大鼠隨機分為三組：1. 媒介物；2. ErbB4促效劑10 μg/kg；3. ErbB4促效劑20 μg/kg。在第2週隨機分組後，使用媒介物或10 μg/kg或20 μg/kg ErbB4促效劑經皮下（SC）給藥至16隻大鼠。

麻醉暴露影響心臟功能係已知的，因此在超音波心動圖顯像期間將異氟醚維持在2.5%，以最小化其對心臟功能的影響。在超音波心動圖顯像期間，每隻動物的異氟醚暴露持續時間＜ 10 min。在研究期間密切監測動物。在整個研究期間，沒有發現不良事件（死亡/發病）。

在第2週隨機分組後，所有組的基線心臟功能和心率係相似的。所有登記入組的大鼠均表現心臟衰竭病症。與媒介物組相比，ErbB4治療組中的終末期血清暴露顯著更高（圖1A）。20 μg/kg組的ErbB4血漿暴露水平明顯高於10 μg/kg組（圖2A）。皮下（SC）給藥一週後，與媒介物組相比，ErbB4選擇性促效劑改善了ErbB4選擇性促效劑治療組的心臟功能（圖1B）。沒有發現ErbB4選擇性促效劑對心率的統計學顯著性的影響（圖1C），這表明ErbB4選擇性促效劑介導的心臟功能改善不是組間心率可變性造成的。雖然20 μg/kg組的血漿暴露高於10 μg/kg組，但是兩個治療組都顯示相似的心臟功能改善。這表明可能需要更高的血漿ErbB4選擇性促效劑暴露（＞ 1.9 ng/mL）才能誘導比10 μg/kg觀察到的顯著更高的心臟功能。在ErbB4選擇性促效劑治療後，沒有發現不良事件（死亡/發病）。

ErbB4選擇性促效劑治療顯著改善大鼠心肌梗塞模型中的心臟功能。在ErbB4選擇性促效劑治療後，沒有發現對心率的顯著影響。在心肌梗塞模型中，ErbB4治療與死亡率和發病率無關。實例3：無Fc的ErbB4選擇性促效劑在大鼠心肌梗塞（MI）模型中功效。

在大鼠MI模型中測試ErbB4選擇性促效劑（huNRG1(S177-F229)(NRGE1C) (E47S_D48A_F49L_M50T) 6xHis: SEQ ID NO: 61）以確定是否可以觀察到治療的響應對心臟功能的益處。

對Sprague Dawley（Envigo公司，印第安那州）大鼠（體重142-280 g）進行手術以誘導MI。MI手術後7天，對大鼠進行超音波心動圖顯像以藉由射出分率（EF%）評估心臟功能。使用Vevo 3100系統（VisualSonics公司，多倫多，加拿大）獲得非侵入性胸骨旁長軸B模式電影重播。使用製造商推薦的方法計算EF%。根據基線EF%將大鼠隨機分組：[1. 媒介物]；[2. ErbB4促效劑50 μg/kg]；[3.ErbB4促效劑150 μg/kg]；[4.ErbB4促效劑500 μg/kg]。在MI手術後8天隨機分組後，所有登記入組的大鼠均表現出心臟功能障礙，並且接受了頸靜脈插管手術以進行IV劑量投與，並且按照治療組標籤開始給藥：媒介物或50 μg/kg/天或150 μg/kg/天或500 μg/kg/天的ErbB4促效劑，藉由頸靜脈插管，每日一次，持續10天。

對治療後第10天10分鐘收集的血液樣本進行血清暴露測定，並且分析來自在開始給藥後第11天和約4週進行的超音波心動圖顯像的數據以評估對心臟功能的影響（EF%）。

無

[圖1A-1C]示出了ErbB4促效劑給藥後1週的心臟功能評估。使用GraphPad單因素方差分析評估組間統計學顯著性。A) 終末期血清暴露。B) 按射出分率（EF）計算的心臟功能。C) 在超音波心動圖顯像期間的心率（HR）。

無


          <![CDATA[<110>  美商安進公司（AMGEN INC.）]]>
                 BATES, Darren L.
                 LIU, Zhi
                 LEE, TaeWeon
                 MICHAELS, Mark Leo
                 WANG, Zhulun
          <![CDATA[<120>  對ErbB4而非ErbB3具有改善的選擇性的工程化NRG-1變體]]>
          <![CDATA[<130>  A-2828-WO-PCT]]>
          <![CDATA[<160>  229   ]]>
          <![CDATA[<170>  PatentIn  3.5版]]>
          <![CDATA[<210>  1]]>
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          <![CDATA[<212>  PRT]]>
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          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRG]]>E1C)::3x(G4Q)::huFcSEFL2 (Pb)
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          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly 
              50                  55                  60                  
          Gly Gly Gly Gln Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
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          Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
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          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
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          <![CDATA[<210>  2]]>
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          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C)::1KmodT482V,M493L)::huFcSEFL2 (Pb)]]>
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          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
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          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Ser Gly Ser Ala Thr Gly Gly Ser Gly Ser 
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          Val Ala Ser Ser Gly Ser Gly Ser Ala Thr His Leu Asp Lys Thr His 
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          Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 
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          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
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          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
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          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
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          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
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          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
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          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala Gly 
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          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
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          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
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          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
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          <![CDATA[<211>  294]]>
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          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C)((G4E)2)::G4::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  4]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Glu Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  5]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C)::(G4S)2::G4::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  5]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  6]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C)(G4E)::G4S::G4::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  6]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ser Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  7]]>
          <![CDATA[<211>  292]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C)(NRGmod)::G4::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  7]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Ala Ala Ala Glu Glu Leu Tyr Gln Gly Gly Gly 
              50                  55                  60                  
          Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
          65                  70                  75                  80  
          Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                          85                  90                  95      
          Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                      100                 105                 110         
          His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
                  115                 120                 125             
          Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr 
              130                 135                 140                 
          Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
          145                 150                 155                 160 
          Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
                          165                 170                 175     
          Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                      180                 185                 190         
          Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
                  195                 200                 205             
          Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
              210                 215                 220                 
          Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
          225                 230                 235                 240 
          Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
                          245                 250                 255     
          Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                      260                 265                 270         
          Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
                  275                 280                 285             
          Ser Pro Gly Lys 
              290         
          <![CDATA[<210>  8]]>
          <![CDATA[<211>  295]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1D)::1KmodT482V,M493L)::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  8]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly 
              50                  55                  60                  
          Gly Gly Gly Gln Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
          65                  70                  75                  80  
          Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                          85                  90                  95      
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                      100                 105                 110         
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
                  115                 120                 125             
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr 
              130                 135                 140                 
          Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp 
          145                 150                 155                 160 
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                          165                 170                 175     
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                      180                 185                 190         
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
                  195                 200                 205             
          Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
              210                 215                 220                 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
          225                 230                 235                 240 
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                          245                 250                 255     
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                      260                 265                 270         
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
                  275                 280                 285             
          Leu Ser Leu Ser Pro Gly Lys 
              290                 295 
          <![CDATA[<210>  9]]>
          <![CDATA[<211>  303]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1D)::1KmodT482V,M493L)::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  9]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Ser Gly Ser Ala Thr Gly Gly Ser Gly Ser 
              50                  55                  60                  
          Val Ala Ser Ser Gly Ser Gly Ser Ala Thr His Leu Asp Lys Thr His 
          65                  70                  75                  80  
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 
                          85                  90                  95      
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                      100                 105                 110         
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                  115                 120                 125             
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
              130                 135                 140                 
          Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys Val Ser 
          145                 150                 155                 160 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                          165                 170                 175     
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                      180                 185                 190         
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                  195                 200                 205             
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
              210                 215                 220                 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
          225                 230                 235                 240 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                          245                 250                 255     
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                      260                 265                 270         
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                  275                 280                 285             
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              290                 295                 300             
          <![CDATA[<210>  10]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1D)::(G4A)2:G4::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  10]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  11]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1D)::(G4S)2::G4::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  11]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Glu Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  12]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1D)(G4E)::G4S::G4::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  12]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  13]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1D)(NRGmod)::G4::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  13]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ser Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  14]]>
          <![CDATA[<211>  292]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1D)(NRGmod)::G4::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  14]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Ala Ala Ala Glu Glu Leu Tyr Gln Gly Gly Gly 
              50                  55                  60                  
          Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
          65                  70                  75                  80  
          Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                          85                  90                  95      
          Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                      100                 105                 110         
          His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
                  115                 120                 125             
          Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr 
              130                 135                 140                 
          Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
          145                 150                 155                 160 
          Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
                          165                 170                 175     
          Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                      180                 185                 190         
          Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
                  195                 200                 205             
          Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
              210                 215                 220                 
          Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
          225                 230                 235                 240 
          Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
                          245                 250                 255     
          Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                      260                 265                 270         
          Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
                  275                 280                 285             
          Ser Pro Gly Lys 
              290         
          <![CDATA[<210>  15]]>
          <![CDATA[<211>  303]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(3H8)::3xG4S::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  15]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Gly 
              50                  55                  60                  
          Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His 
          65                  70                  75                  80  
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 
                          85                  90                  95      
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                      100                 105                 110         
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                  115                 120                 125             
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
              130                 135                 140                 
          Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys Val Ser 
          145                 150                 155                 160 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                          165                 170                 175     
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                      180                 185                 190         
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                  195                 200                 205             
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
              210                 215                 220                 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
          225                 230                 235                 240 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                          245                 250                 255     
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                      260                 265                 270         
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                  275                 280                 285             
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              290                 295                 300             
          <![CDATA[<210>  16]]>
          <![CDATA[<211>  295]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(3H8)::3x(G4Q)::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  16]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly 
              50                  55                  60                  
          Gly Gly Gly Gln Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
          65                  70                  75                  80  
          Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                          85                  90                  95      
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                      100                 105                 110         
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
                  115                 120                 125             
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr 
              130                 135                 140                 
          Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp 
          145                 150                 155                 160 
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                          165                 170                 175     
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                      180                 185                 190         
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
                  195                 200                 205             
          Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
              210                 215                 220                 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
          225                 230                 235                 240 
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                          245                 250                 255     
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                      260                 265                 270         
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
                  275                 280                 285             
          Leu Ser Leu Ser Pro Gly Lys 
              290                 295 
          <![CDATA[<210>  17]]>
          <![CDATA[<211>  303]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(3H8)::3x(G4Q)::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  17]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Gly 
              50                  55                  60                  
          Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Asp Lys Thr His 
          65                  70                  75                  80  
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 
                          85                  90                  95      
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                      100                 105                 110         
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                  115                 120                 125             
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
              130                 135                 140                 
          Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys Val Ser 
          145                 150                 155                 160 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                          165                 170                 175     
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                      180                 185                 190         
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                  195                 200                 205             
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
              210                 215                 220                 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
          225                 230                 235                 240 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                          245                 250                 255     
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                      260                 265                 270         
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                  275                 280                 285             
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              290                 295                 300             
          <![CDATA[<210>  18]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-S228)(3H8)::3x(G4Q)::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  18]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly 
              50                  55                  60                  
          Gly Gly Gln Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  19]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(NRGE1C)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  19]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  20]]>
          <![CDATA[<211>  231]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-S228)(NRGE1C)::3x(G4Q)::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  20]]>
          Gly Gly Gly Gln Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
          1               5                   10                  15      
          Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      20                  25                  30          
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  35                  40                  45              
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              50                  55                  60                  
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr 
          65                  70                  75                  80  
          Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp 
                          85                  90                  95      
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      100                 105                 110         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  115                 120                 125             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              130                 135                 140                 
          Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
          145                 150                 155                 160 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          165                 170                 175     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                      180                 185                 190         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  195                 200                 205             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              210                 215                 220                 
          Leu Ser Leu Ser Pro Gly Lys 
          225                 230     
          <![CDATA[<210>  21]]>
          <![CDATA[<211>  150]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-S228)(NRGE1C)::3x(G4Q)::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  21]]>
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          1               5                   10                  15      
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                      20                  25                  30          
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                  35                  40                  45              
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
              50                  55                  60                  
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
          65                  70                  75                  80  
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
                          85                  90                  95      
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                      100                 105                 110         
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                  115                 120                 125             
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
              130                 135                 140                 
          Ser Leu Ser Pro Gly Lys 
          145                 150 
          <![CDATA[<210>  22]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(NRGE1D)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  22]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  23]]>
          <![CDATA[<211>  303]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(NRGE1D)::3x(G4Q)::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  23]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Gly 
              50                  55                  60                  
          Gly Gln Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Asp Lys Thr His 
          65                  70                  75                  80  
          Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 
                          85                  90                  95      
          Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                      100                 105                 110         
          Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                  115                 120                 125             
          Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
              130                 135                 140                 
          Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys Val Ser 
          145                 150                 155                 160 
          Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                          165                 170                 175     
          Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
                      180                 185                 190         
          Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                  195                 200                 205             
          Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
              210                 215                 220                 
          Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
          225                 230                 235                 240 
          Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                          245                 250                 255     
          Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                      260                 265                 270         
          Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                  275                 280                 285             
          His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
              290                 295                 300             
          <![CDATA[<210>  24]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-S228)(NRGE1D)::3x(G4Q)::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  24]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly Gly 
              50                  55                  60                  
          Gly Gly Gln Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  25]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(wt)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  25]]>
          Ser His Leu Val Lys Cys Ala Glu Lys Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Lys Asp Leu Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Tyr 
                  35                  40                  45              
          Val Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  26]]>
          <![CDATA[<211>  295]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(wt)::3x(G4Q)::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  26]]>
          Ser His Leu Val Lys Cys Ala Glu Lys Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Lys Asp Leu Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Tyr 
                  35                  40                  45              
          Val Met Ala Ser Phe Gly Gly Gly Gly Gln Gly Gly Gly Gly Gln Gly 
              50                  55                  60                  
          Gly Gly Gly Gln Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
          65                  70                  75                  80  
          Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                          85                  90                  95      
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                      100                 105                 110         
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
                  115                 120                 125             
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr 
              130                 135                 140                 
          Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp 
          145                 150                 155                 160 
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                          165                 170                 175     
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                      180                 185                 190         
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
                  195                 200                 205             
          Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
              210                 215                 220                 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
          225                 230                 235                 240 
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                          245                 250                 255     
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                      260                 265                 270         
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
                  275                 280                 285             
          Leu Ser Leu Ser Pro Gly Lys 
              290                 295 
          <![CDATA[<210>  27]]>
          <![CDATA[<211>  231]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(wt)::3x(G4Q)::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  27]]>
          Gly Gly Gly Gln Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
          1               5                   10                  15      
          Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
                      20                  25                  30          
          Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
                  35                  40                  45              
          Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
              50                  55                  60                  
          Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr 
          65                  70                  75                  80  
          Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp 
                          85                  90                  95      
          Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
                      100                 105                 110         
          Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
                  115                 120                 125             
          Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys 
              130                 135                 140                 
          Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
          145                 150                 155                 160 
          Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                          165                 170                 175     
          Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
                      180                 185                 190         
          Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
                  195                 200                 205             
          Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
              210                 215                 220                 
          Leu Ser Leu Ser Pro Gly Lys 
          225                 230     
          <![CDATA[<210>  28]]>
          <![CDATA[<211>  150]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-S228)(wt)::3x(G4Q)::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  28]]>
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          1               5                   10                  15      
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                      20                  25                  30          
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                  35                  40                  45              
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
              50                  55                  60                  
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
          65                  70                  75                  80  
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
                          85                  90                  95      
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                      100                 105                 110         
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                  115                 120                 125             
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
              130                 135                 140                 
          Ser Leu Ser Pro Gly Lys 
          145                 150 
          <![CDATA[<210>  29]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(NRGE1A)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  29]]>
          Ser His Leu Val Lys Cys Ala Glu Asn Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  30]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(NRGE1B)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  30]]>
          Ser His Leu Val Lys Cys Gly Glu Asn Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  31]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(NRGE1E)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  31]]>
          Ser His Leu Val Lys Cys Gly Glu Asn Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  32]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(NRGE1F)::GG::huFcSEFL]]>2 (Pb)
          <![CDATA[<400>  32]]>
          Ser His Leu Val Lys Cys Ala Glu Asn Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  33]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(NRGE1G)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  33]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  34]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(NRGE1H)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  34]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  35]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(NRGE1J)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  35]]>
          Ser His Leu Val Lys Cys Gly Glu Asn Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  36]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(NRGE1J)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  36]]>
          Ser His Leu Val Lys Cys Gly Glu Asn Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  37]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(NRGE1K)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  37]]>
          Ser His Leu Val Lys Cys Ala Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  38]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(NRGE1L)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  38]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  39]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(NRGE1M)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  39]]>
          Ser His Leu Val Lys Cys Gly Glu Asn Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Phe 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  40]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(NRGE1N)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  40]]>
          Ser His Leu Val Lys Cys Gly Glu Asn Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Phe 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  41]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220]]>>]]&gt;
          <br/>&lt;![CDATA[&lt;223&gt;  huNRG1(S177-Q237)(NRGE1O)::GG::huFcSEFL2 (Pb)]]&gt;
          <br/>
          <br/>&lt;![CDATA[&lt;400&gt;  41]]&gt;
          <br/>
          <br/><![CDATA[Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Phe 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  42]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(1D3)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  42]]>
          Ser His Leu Val Lys Cys Ala Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Phe 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  43]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(1D3)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  43]]>
          Ser His Leu Val Lys Cys Gly Glu Asn Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Val Ile Glu Asp Pro Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Asp 
                  35                  40                  45              
          Phe Leu Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  44]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C) (E47A_D48P_F49H_M50I) huIgG1z SELF2 Fc]]>
          <![CDATA[<400>  44]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Ala Pro 
                  35                  40                  45              
          His Ile Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  45]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C) (E47A_D48P_F49H_M50I) huIgG1z SELF2 Fc]]>
          <![CDATA[<400>  45]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Ala Pro 
                  35                  40                  45              
          His Ile Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  46]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C) (E47K_D48T_F49S_M50L) huIgG1z SELF2 Fc]]>
          <![CDATA[<400>  46]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Thr 
                  35                  40                  45              
          Ser Leu Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  47]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C) (E47Q_D48S_M50P) huIgG1z SELF2 Fc]]>
          <![CDATA[<400>  47]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Gln Ser 
                  35                  40                  45              
          Phe Pro Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  48]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C) (E47S_D48A_F49L_M50T) huIgG1z SELF2 Fc]]>
          <![CDATA[<400>  48]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Ser Ala 
                  35                  40                  45              
          Leu Thr Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  49]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C) (E47S_D48T_F49R_M50V) huIgG1z SELF2 Fc]]>
          <![CDATA[<400>  49]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Ser Thr 
                  35                  40                  45              
          Arg Val Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  50]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C) huIgG1z SELF2 Fc]]>
          <![CDATA[<400>  50]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  51]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1D) (E47K_D48L_F49D_M50I) huIgG1z SELF2 Fc]]>
          <![CDATA[<400>  51]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Leu 
                  35                  40                  45              
          Asp Ile Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  52]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1D) (E47S_D48S_F49E_M50L) huIgG1z SELF2 Fc]]>
          <![CDATA[<400>  52]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Ser Ser 
                  35                  40                  45              
          Glu Leu Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  53]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1D) (E47T_D48S_F49L_M50L) huIgG1z SELF2 Fc]]>
          <![CDATA[<400>  53]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Thr Ser 
                  35                  40                  45              
          Leu Leu Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  54]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229) huIgG1z SELF2 Fc]]>
          <![CDATA[<400>  54]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  55]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229) huIgG1z SELF2 Fc]]>
          <![CDATA[<400>  55]]>
          Ser His Leu Val Lys Cys Ala Glu Lys Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Lys Asp Leu Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Tyr 
                  35                  40                  45              
          Val Met Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  56]]>
          <![CDATA[<211>  73]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C) 6xHis]]>
          <![CDATA[<400>  56]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly His His His His His His 
          65                  70              
          <![CDATA[<210>  57]]>
          <![CDATA[<211>  73]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C) (D48T_F49Q_M50I) 6xHis]]>
          <![CDATA[<400>  57]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Thr 
                  35                  40                  45              
          Gln Ile Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly His His His His His His 
          65                  70              
          <![CDATA[<210>  58]]>
          <![CDATA[<211>  73]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C) (E47A_D48P_F49H_M50I) 6xHis]]>
          <![CDATA[<400>  58]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Ala Pro 
                  35                  40                  45              
          His Ile Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly His His His His His His 
          65                  70              
          <![CDATA[<210>  59]]>
          <![CDATA[<211>  73]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C) (E47K_D48T_F49S_M50L) 6xHis]]>
          <![CDATA[<400>  59]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Thr 
                  35                  40                  45              
          Ser Leu Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly His His His His His His 
          65                  70              
          <![CDATA[<210>  60]]>
          <![CDATA[<211>  73]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C) (E47Q_D48S_M50P) 6xHis]]>
          <![CDATA[<400>  60]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Gln Ser 
                  35                  40                  45              
          Phe Pro Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly His His His His His His 
          65                  70              
          <![CDATA[<210>  61]]>
          <![CDATA[<211>  73]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C) (E47S_D48A_F49L_M50T) 6xHis]]>
          <![CDATA[<400>  61]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Ser Ala 
                  35                  40                  45              
          Leu Thr Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly His His His His His His 
          65                  70              
          <![CDATA[<210>  62]]>
          <![CDATA[<211>  73]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1C) (E47S_D48T_F49R_M50V) 6xHis]]>
          <![CDATA[<400>  62]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Ser Thr 
                  35                  40                  45              
          Arg Val Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly His His His His His His 
          65                  70              
          <![CDATA[<210>  63]]>
          <![CDATA[<211>  73]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1D) 6xHis]]>
          <![CDATA[<400>  63]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly His His His His His His 
          65                  70              
          <![CDATA[<210>  64]]>
          <![CDATA[<211>  73]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1D) (E47K_D48L_F49D_M50I) 6xHis]]>
          <![CDATA[<400>  64]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Leu 
                  35                  40                  45              
          Asp Ile Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly His His His His His His 
          65                  70              
          <![CDATA[<210>  65]]>
          <![CDATA[<211>  73]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1D) (E47S_D48S_F49E_M50L) 6xHis]]>
          <![CDATA[<400>  65]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Ser Ser 
                  35                  40                  45              
          Glu Leu Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly His His His His His His 
          65                  70              
          <![CDATA[<210>  66]]>
          <![CDATA[<211>  73]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1D) (E47T_D48S_F49L_M50L) 6xHis]]>
          <![CDATA[<400>  66]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Thr Ser 
                  35                  40                  45              
          Leu Leu Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly His His His His His His 
          65                  70              
          <![CDATA[<210>  67]]>
          <![CDATA[<211>  73]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229)(NRGE1D) (E47V_D48T_F49R_M50L) 6xHis]]>
          <![CDATA[<400>  67]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Val Thr 
                  35                  40                  45              
          Arg Leu Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly His His His His His His 
          65                  70              
          <![CDATA[<210>  68]]>
          <![CDATA[<211>  73]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-F229) 6xHis]]>
          <![CDATA[<400>  68]]>
          Ser His Leu Val Lys Cys Ala Glu Lys Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Lys Asp Leu Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Tyr 
                  35                  40                  45              
          Val Met Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly His His His His His His 
          65                  70              
          <![CDATA[<210>  69]]>
          <![CDATA[<211>  576]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  :huFcSEFL2(desK):G4SG4:huNRG1(S177-F229)(NRGE1C)]]>
          <![CDATA[<400>  69]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                      180                 185                 190         
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser His Leu Val Lys 
          225                 230                 235                 240 
          Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn Gly Gly Glu Cys Phe 
                          245                 250                 255     
          Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr Leu Cys Lys Cys Pro 
                      260                 265                 270         
          Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp Phe Met Ala Ser Phe 
                  275                 280                 285             
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
              290                 295                 300                 
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
          305                 310                 315                 320 
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                          325                 330                 335     
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
                      340                 345                 350         
          His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr 
                  355                 360                 365             
          Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
              370                 375                 380                 
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
          385                 390                 395                 400 
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                          405                 410                 415     
          Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
                      420                 425                 430         
          Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
                  435                 440                 445             
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
              450                 455                 460                 
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
          465                 470                 475                 480 
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                          485                 490                 495     
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
                      500                 505                 510         
          Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser His Leu Val Lys 
                  515                 520                 525             
          Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn Gly Gly Glu Cys Phe 
              530                 535                 540                 
          Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr Leu Cys Lys Cys Pro 
          545                 550                 555                 560 
          Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp Phe Met Ala Ser Phe 
                          565                 570                 575     
          <![CDATA[<210>  70]]>
          <![CDATA[<211>  576]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  :huFcSEFL2(desK):G4SG4:huNRG1(S177-F229)(NRGE1D)]]>
          <![CDATA[<400>  70]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                      180                 185                 190         
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser His Leu Val Lys 
          225                 230                 235                 240 
          Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn Gly Gly Glu Cys Tyr 
                          245                 250                 255     
          Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr Leu Cys Lys Cys Pro 
                      260                 265                 270         
          Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp Phe Met Ala Ser Phe 
                  275                 280                 285             
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
              290                 295                 300                 
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
          305                 310                 315                 320 
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                          325                 330                 335     
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
                      340                 345                 350         
          His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr 
                  355                 360                 365             
          Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
              370                 375                 380                 
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
          385                 390                 395                 400 
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                          405                 410                 415     
          Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
                      420                 425                 430         
          Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
                  435                 440                 445             
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
              450                 455                 460                 
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
          465                 470                 475                 480 
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                          485                 490                 495     
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
                      500                 505                 510         
          Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser His Leu Val Lys 
                  515                 520                 525             
          Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn Gly Gly Glu Cys Tyr 
              530                 535                 540                 
          Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr Leu Cys Lys Cys Pro 
          545                 550                 555                 560 
          Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp Phe Met Ala Ser Phe 
                          565                 570                 575     
          <![CDATA[<210>  71]]>
          <![CDATA[<211>  592]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  :huFcSEFL2(desK):G4SG4:huNRG1(S177-Q237)(NRGE1C)]]>
          <![CDATA[<400>  71]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                      180                 185                 190         
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser His Leu Val Lys 
          225                 230                 235                 240 
          Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn Gly Gly Glu Cys Phe 
                          245                 250                 255     
          Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr Leu Cys Lys Cys Pro 
                      260                 265                 270         
          Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp Phe Met Ala Ser Phe 
                  275                 280                 285             
          Tyr Lys Ala Glu Glu Leu Tyr Gln Asp Lys Thr His Thr Cys Pro Pro 
              290                 295                 300                 
          Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 
          305                 310                 315                 320 
          Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 
                          325                 330                 335     
          Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn 
                      340                 345                 350         
          Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys 
                  355                 360                 365             
          Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val 
              370                 375                 380                 
          Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 
          385                 390                 395                 400 
          Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 
                          405                 410                 415     
          Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu 
                      420                 425                 430         
          Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 
                  435                 440                 445             
          Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
              450                 455                 460                 
          Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
          465                 470                 475                 480 
          Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
                          485                 490                 495     
          Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
                      500                 505                 510         
          Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly 
                  515                 520                 525             
          Gly Gly Gly Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe 
              530                 535                 540                 
          Cys Val Asn Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro 
          545                 550                 555                 560 
          Ser Arg Tyr Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys 
                          565                 570                 575     
          Gln Glu Asp Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
                      580                 585                 590         
          <![CDATA[<210>  72]]>
          <![CDATA[<211>  592]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  :huFcSEFL2(desK):G4SG4:huNRG1(S177-Q237)(NRGE1D)]]>
          <![CDATA[<400>  72]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                      180                 185                 190         
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser His Leu Val Lys 
          225                 230                 235                 240 
          Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn Gly Gly Glu Cys Tyr 
                          245                 250                 255     
          Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr Leu Cys Lys Cys Pro 
                      260                 265                 270         
          Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp Phe Met Ala Ser Phe 
                  275                 280                 285             
          Tyr Lys Ala Glu Glu Leu Tyr Gln Asp Lys Thr His Thr Cys Pro Pro 
              290                 295                 300                 
          Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 
          305                 310                 315                 320 
          Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 
                          325                 330                 335     
          Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn 
                      340                 345                 350         
          Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys 
                  355                 360                 365             
          Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val 
              370                 375                 380                 
          Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 
          385                 390                 395                 400 
          Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 
                          405                 410                 415     
          Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu 
                      420                 425                 430         
          Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 
                  435                 440                 445             
          Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
              450                 455                 460                 
          Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
          465                 470                 475                 480 
          Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
                          485                 490                 495     
          Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
                      500                 505                 510         
          Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly 
                  515                 520                 525             
          Gly Gly Gly Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe 
              530                 535                 540                 
          Cys Val Asn Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro 
          545                 550                 555                 560 
          Ser Arg Tyr Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys 
                          565                 570                 575     
          Gln Glu Asp Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
                      580                 585                 590         
          <![CDATA[<210>  73]]>
          <![CDATA[<211>  515]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  :huFcSEFL2(desK)v131(+):G4SG4:huNRG1(S177-F229)(NRGE1C)]]>
          <![CDATA[<400>  73]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Glu Lys Met Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Lys Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                      180                 185                 190         
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser His Leu Val Lys 
          225                 230                 235                 240 
          Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn Gly Gly Glu Cys Phe 
                          245                 250                 255     
          Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr Leu Cys Lys Cys Pro 
                      260                 265                 270         
          Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp Phe Met Ala Ser Phe 
                  275                 280                 285             
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
              290                 295                 300                 
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
          305                 310                 315                 320 
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                          325                 330                 335     
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
                      340                 345                 350         
          His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr 
                  355                 360                 365             
          Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
              370                 375                 380                 
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
          385                 390                 395                 400 
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                          405                 410                 415     
          Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Glu Asn Gln Val Ser 
                      420                 425                 430         
          Leu Thr Cys Leu Val Glu Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
                  435                 440                 445             
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Glu Thr Thr Pro Pro 
              450                 455                 460                 
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Asp Leu Thr Val 
          465                 470                 475                 480 
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                          485                 490                 495     
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
                      500                 505                 510         
          Pro Gly Lys 
                  515 
          <![CDATA[<210>  74]]>
          <![CDATA[<211>  515]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  :huFcSEFL2(desK)v131(+):G4SG4:huNRG1(S177-F229)(NRGE1D)]]>
          <![CDATA[<400>  74]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Glu Lys Met Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Lys Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                      180                 185                 190         
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser His Leu Val Lys 
          225                 230                 235                 240 
          Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn Gly Gly Glu Cys Tyr 
                          245                 250                 255     
          Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr Leu Cys Lys Cys Pro 
                      260                 265                 270         
          Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp Phe Met Ala Ser Phe 
                  275                 280                 285             
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
              290                 295                 300                 
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
          305                 310                 315                 320 
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                          325                 330                 335     
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
                      340                 345                 350         
          His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr 
                  355                 360                 365             
          Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
              370                 375                 380                 
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
          385                 390                 395                 400 
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                          405                 410                 415     
          Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Glu Asn Gln Val Ser 
                      420                 425                 430         
          Leu Thr Cys Leu Val Glu Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
                  435                 440                 445             
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Glu Thr Thr Pro Pro 
              450                 455                 460                 
          Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Asp Leu Thr Val 
          465                 470                 475                 480 
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                          485                 490                 495     
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
                      500                 505                 510         
          Pro Gly Lys 
                  515 
          <![CDATA[<210>  75]]>
          <![CDATA[<211>  523]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  :huFcSEFL2(desK)v131(+):G4SG4:huNRG1(S177-Q237)(NRGE1C)]]>
          <![CDATA[<400>  75]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Glu Lys Met Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Lys Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                      180                 185                 190         
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser His Leu Val Lys 
          225                 230                 235                 240 
          Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn Gly Gly Glu Cys Phe 
                          245                 250                 255     
          Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr Leu Cys Lys Cys Pro 
                      260                 265                 270         
          Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp Phe Met Ala Ser Phe 
                  275                 280                 285             
          Tyr Lys Ala Glu Glu Leu Tyr Gln Asp Lys Thr His Thr Cys Pro Pro 
              290                 295                 300                 
          Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 
          305                 310                 315                 320 
          Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 
                          325                 330                 335     
          Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn 
                      340                 345                 350         
          Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys 
                  355                 360                 365             
          Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val 
              370                 375                 380                 
          Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 
          385                 390                 395                 400 
          Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 
                          405                 410                 415     
          Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu 
                      420                 425                 430         
          Glu Met Thr Glu Asn Gln Val Ser Leu Thr Cys Leu Val Glu Gly Phe 
                  435                 440                 445             
          Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
              450                 455                 460                 
          Asn Asn Tyr Glu Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
          465                 470                 475                 480 
          Phe Leu Tyr Ser Asp Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
                          485                 490                 495     
          Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
                      500                 505                 510         
          Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                  515                 520             
          <![CDATA[<210>  76]]>
          <![CDATA[<211>  523]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  :huFcSEFL2(desK)v131(+):G4SG4:huNRG1(S177-Q237)(NRGE1D)]]>
          <![CDATA[<400>  76]]>
          Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
          1               5                   10                  15      
          Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
                      20                  25                  30          
          Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                  35                  40                  45              
          Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
              50                  55                  60                  
          His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr 
          65                  70                  75                  80  
          Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                          85                  90                  95      
          Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
                      100                 105                 110         
          Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                  115                 120                 125             
          Tyr Thr Leu Pro Pro Ser Arg Glu Lys Met Thr Lys Asn Gln Val Ser 
              130                 135                 140                 
          Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
          145                 150                 155                 160 
          Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                          165                 170                 175     
          Val Leu Lys Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
                      180                 185                 190         
          Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                  195                 200                 205             
          His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
              210                 215                 220                 
          Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser His Leu Val Lys 
          225                 230                 235                 240 
          Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn Gly Gly Glu Cys Tyr 
                          245                 250                 255     
          Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr Leu Cys Lys Cys Pro 
                      260                 265                 270         
          Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp Phe Met Ala Ser Phe 
                  275                 280                 285             
          Tyr Lys Ala Glu Glu Leu Tyr Gln Asp Lys Thr His Thr Cys Pro Pro 
              290                 295                 300                 
          Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 
          305                 310                 315                 320 
          Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 
                          325                 330                 335     
          Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn 
                      340                 345                 350         
          Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys 
                  355                 360                 365             
          Glu Glu Gln Tyr Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val 
              370                 375                 380                 
          Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 
          385                 390                 395                 400 
          Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 
                          405                 410                 415     
          Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu 
                      420                 425                 430         
          Glu Met Thr Glu Asn Gln Val Ser Leu Thr Cys Leu Val Glu Gly Phe 
                  435                 440                 445             
          Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
              450                 455                 460                 
          Asn Asn Tyr Glu Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
          465                 470                 475                 480 
          Phe Leu Tyr Ser Asp Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
                          485                 490                 495     
          Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
                      500                 505                 510         
          Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                  515                 520             
          <![CDATA[<210>  77]]>
          <![CDATA[<211>  521]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  :huNRG1(S177-F229)(NRGE1C) ::2X(G4A)G4::huFcSEFL2v131(+)]]>
          <![CDATA[<400>  77]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Lys Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Lys Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
              290                 295                 300                 
          Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          305                 310                 315                 320 
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                          325                 330                 335     
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                      340                 345                 350         
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu 
                  355                 360                 365             
          Gln Tyr Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His 
              370                 375                 380                 
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
          385                 390                 395                 400 
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                          405                 410                 415     
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
                      420                 425                 430         
          Thr Glu Asn Gln Val Ser Leu Thr Cys Leu Val Glu Gly Phe Tyr Pro 
                  435                 440                 445             
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
              450                 455                 460                 
          Tyr Glu Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
          465                 470                 475                 480 
          Tyr Ser Asp Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                          485                 490                 495     
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                      500                 505                 510         
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                  515                 520     
          <![CDATA[<210>  78]]>
          <![CDATA[<211>  521]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  :huNRG1(S177-F229)(NRGE1C) ::2X(G4E)G4::huFcSEFL2v131(+)]]>
          <![CDATA[<400>  78]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Glu Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Lys Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Lys Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
              290                 295                 300                 
          Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          305                 310                 315                 320 
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                          325                 330                 335     
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                      340                 345                 350         
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu 
                  355                 360                 365             
          Gln Tyr Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His 
              370                 375                 380                 
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
          385                 390                 395                 400 
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                          405                 410                 415     
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
                      420                 425                 430         
          Thr Glu Asn Gln Val Ser Leu Thr Cys Leu Val Glu Gly Phe Tyr Pro 
                  435                 440                 445             
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
              450                 455                 460                 
          Tyr Glu Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
          465                 470                 475                 480 
          Tyr Ser Asp Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                          485                 490                 495     
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                      500                 505                 510         
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                  515                 520     
          <![CDATA[<210>  79]]>
          <![CDATA[<211>  521]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  :huNRG1(S177-F229)(NRGE1D) ::2X(G4A)G4::huFcSEFL2v131(+)]]>
          <![CDATA[<400>  79]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Ala Gly Gly Gly Gly Ala Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Lys Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Lys Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
              290                 295                 300                 
          Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          305                 310                 315                 320 
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                          325                 330                 335     
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                      340                 345                 350         
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu 
                  355                 360                 365             
          Gln Tyr Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His 
              370                 375                 380                 
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
          385                 390                 395                 400 
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                          405                 410                 415     
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
                      420                 425                 430         
          Thr Glu Asn Gln Val Ser Leu Thr Cys Leu Val Glu Gly Phe Tyr Pro 
                  435                 440                 445             
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
              450                 455                 460                 
          Tyr Glu Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
          465                 470                 475                 480 
          Tyr Ser Asp Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                          485                 490                 495     
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                      500                 505                 510         
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                  515                 520     
          <![CDATA[<210>  80]]>
          <![CDATA[<211>  521]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213> ]]> 人工序列
          <![CDATA[<220>]]>
          <![CDATA[<223>  :huNRG1(S177-F229)(NRGE1D) ::2X(G4E)G4::huFcSEFL2v131(+)]]>
          <![CDATA[<400>  80]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Glu Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Lys Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Lys Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
              290                 295                 300                 
          Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
          305                 310                 315                 320 
          Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
                          325                 330                 335     
          Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
                      340                 345                 350         
          Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu 
                  355                 360                 365             
          Gln Tyr Gly Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His 
              370                 375                 380                 
          Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
          385                 390                 395                 400 
          Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
                          405                 410                 415     
          Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
                      420                 425                 430         
          Thr Glu Asn Gln Val Ser Leu Thr Cys Leu Val Glu Gly Phe Tyr Pro 
                  435                 440                 445             
          Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
              450                 455                 460                 
          Tyr Glu Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
          465                 470                 475                 480 
          Tyr Ser Asp Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
                          485                 490                 495     
          Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                      500                 505                 510         
          Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                  515                 520     
          <![CDATA[<210>  81]]>
          <![CDATA[<211>  294]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-S228)(wt)((G4E)2:G4)::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  81]]>
          Ser His Leu Val Lys Cys Ala Glu Lys Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Lys Asp Leu Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Tyr 
                  35                  40                  45              
          Val Met Ala Ser Phe Gly Gly Gly Gly Glu Gly Gly Gly Gly Glu Gly 
              50                  55                  60                  
          Gly Gly Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
          65                  70                  75                  80  
          Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                          85                  90                  95      
          Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                      100                 105                 110         
          Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
                  115                 120                 125             
          Val Glu Val His Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly 
              130                 135                 140                 
          Ser Thr Tyr Arg Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
          145                 150                 155                 160 
          Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                          165                 170                 175     
          Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
                      180                 185                 190         
          Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
                  195                 200                 205             
          Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
              210                 215                 220                 
          Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
          225                 230                 235                 240 
          Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                          245                 250                 255     
          Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
                      260                 265                 270         
          Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
                  275                 280                 285             
          Ser Leu Ser Pro Gly Lys 
              290                 
          <![CDATA[<210>  82]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(1A1)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  82]]>
          Ser His Leu Val Lys Cys Gly Glu Ser Glu Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Val Ile Glu Asp Ser Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Val 
                  35                  40                  45              
          Phe Leu Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  83]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(1A12)::GG::huFcSEFL2]]> (Pb)
          <![CDATA[<400>  83]]>
          Ser His Leu Val Lys Cys Ala Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Val Val Glu Arg Pro Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Phe 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  84]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(1B4)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  84]]>
          Ser His Leu Val Lys Cys Ala Glu Arg Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Val Ile Glu His Leu Ser Asn Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  85]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(1B4)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  85]]>
          Ser His Leu Val Lys Cys Gly Glu Arg Asp Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Asp Ser Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  86]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(1B9)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  86]]>
          Ser His Leu Val Lys Cys Ala Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Glu Asp Leu Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Val 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  87]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(1C11)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  87]]>
          Ser His Leu Val Lys Cys Gly Glu Lys Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Arg Pro Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Phe 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  88]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(1D10)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  88]]>
          Ser His Leu Val Lys Cys Ala Glu Arg Asp Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Ile Glu Asp Leu Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  89]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(1D4)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  89]]>
          Ser His Leu Val Lys Cys Gly Glu Arg Asp Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Val Val Glu His Ser Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Phe 
                  35                  40                  45              
          Phe Leu Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  90]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(2E3)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  90]]>
          Ser His Leu Val Lys Cys Gly Glu Lys Glu Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Ile Glu Gly Leu Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Val 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  91]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(2E4)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  91]]>
          Ser His Leu Val Lys Cys Gly Glu Ser Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Lys Arg Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Val 
                  35                  40                  45              
          Phe Leu Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  92]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(2F2)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  92]]>
          Ser His Leu Val Lys Cys Ala Glu Ser Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Ile Glu His Pro Ser Asn Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Val 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  93]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(2G3)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  93]]>
          Ser His Leu Val Lys Cys Gly Glu Arg Gln Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Asp Leu Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Val 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  94]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(2G4)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  94]]>
          Ser His Leu Val Lys Cys Ala Glu Asn Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Val Val Glu Gly Leu Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Val 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  95]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(2H7)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  95]]>
          Ser His Leu Val Lys Cys Gly Glu Lys Glu Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Val Val Glu Asp Leu Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Val 
                  35                  40                  45              
          Val Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  96]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(3A7)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  96]]>
          Ser His Leu Val Lys Cys Ala Glu Lys Glu Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Val Ile Glu Gly Ser Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Val 
                  35                  40                  45              
          Val Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  97]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(3B8)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  97]]>
          Ser His Leu Val Lys Cys Gly Glu Arg Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Glu Arg Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Phe 
                  35                  40                  45              
          Phe Leu Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  98]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(3D6)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  98]]>
          Ser His Leu Val Lys Cys Gly Glu Ser Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Val Ile Glu Gly Ser Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Phe 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  99]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(3E6)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  99]]>
          Ser His Leu Val Lys Cys Gly Glu Lys Asp Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Glu Asp Leu Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Phe 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  100]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(3E6)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  100]]>
          Ser His Leu Val Lys Cys Ala Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Val Ile Glu Gly Ser Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  101]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(3F2)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  101]]>
          Ser His Leu Val Lys Cys Ala Glu Asn His Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Val Ile Glu Gly Ser Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Val 
                  35                  40                  45              
          Phe Leu Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  102]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(3F2)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  102]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  103]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(3G3)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  103]]>
          Ser His Leu Val Lys Cys Gly Glu Arg Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu His Leu Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  104]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人]]>工序列
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(3G9)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  104]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Glu Asp Leu Ser Asn Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  105]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(3H5)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  105]]>
          Ser His Leu Val Lys Cys Gly Glu Arg His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Val Val Glu Arg Pro Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Asp 
                  35                  40                  45              
          Phe Leu Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  106]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(3H8)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  106]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  107]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(_200E)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  107]]>
          Ser His Leu Val Lys Cys Ala Glu Lys Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Glu Asp Leu Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Tyr 
                  35                  40                  45              
          Val Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  108]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(_200E_KDF)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  108]]>
          Ser His Leu Val Lys Cys Ala Glu Lys Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Glu Asp Leu Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  109]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(_FVIEDPSI)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  109]]>
          Ser His Leu Val Lys Cys Ala Glu Lys Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Val Ile Glu Asp Pro Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Tyr 
                  35                  40                  45              
          Val Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  110]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(v80)::GG::huFcSEFL2]]> (Pb)
          <![CDATA[<400>  110]]>
          Ser His Leu Val Lys Cys Ala Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Val Ile Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Asp 
                  35                  40                  45              
          Val Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  111]]>
          <![CDATA[<211>  290]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  huNRG1(S177-Q237)(v80.3)::GG::huFcSEFL2 (Pb)]]>
          <![CDATA[<400>  111]]>
          Ser His Leu Val Lys Cys Ala Glu Arg His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Val Ile Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Glu Lys Asp 
                  35                  40                  45              
          Val Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln Gly Gly Asp 
              50                  55                  60                  
          Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
          65                  70                  75                  80  
          Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                          85                  90                  95      
          Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
                      100                 105                 110         
          Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
                  115                 120                 125             
          Asn Ala Lys Thr Lys Pro Cys Glu Glu Gln Tyr Gly Ser Thr Tyr Arg 
              130                 135                 140                 
          Cys Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
          145                 150                 155                 160 
          Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                          165                 170                 175     
          Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
                      180                 185                 190         
          Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
                  195                 200                 205             
          Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
              210                 215                 220                 
          Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
          225                 230                 235                 240 
          Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                          245                 250                 255     
          Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
                      260                 265                 270         
          Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
                  275                 280                 285             
          Gly Lys 
              290 
          <![CDATA[<210>  112]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PR]]>T
          <![CDATA[<213>  智人]]>
          <![CDATA[<400>  112]]>
          Ser His Leu Val Lys Cys Ala Glu Lys Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Lys Asp Leu Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Tyr 
                  35                  40                  45              
          Val Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  113]]>
          <![CDATA[<211>  10]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  G4S接頭]]>
          <![CDATA[<400>  113]]>
          Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
          1               5                   10  
          <![CDATA[<210>  114]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (NRGE1A)]]>
          <![CDATA[<400>  114]]>
          Ser His Leu Val Lys Cys Ala Glu Asn Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  115]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (NRGE1B)]]>
          <![CDATA[<400>  115]]>
          Ser His Leu Val Lys Cys Gly Glu Asn Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  116]]>
          <![CDATA[<211>  52]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-S228) (NRGE1C)]]>
          <![CDATA[<400>  116]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser 
              50          
          <![CDATA[<210>  117]]>
          <![CDATA[<211>  53]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-F229) (NRGE1C)]]>
          <![CDATA[<400>  117]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe 
              50              
          <![CDATA[<210>  118]]>
          <![CDATA[<211>  53]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-F229) (NRGE1C TQI)]]>
          <![CDATA[<400>  118]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Thr 
                  35                  40                  45              
          Gln Ile Ala Ser Phe 
              50              
          <![CDATA[<210>  119]]>
          <![CDATA[<211>  53]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-F229) (NRGE1C APHI)]]>
          <![CDATA[<400>  119]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Ala Pro 
                  35                  40                  45              
          His Ile Ala Ser Phe 
              50              
          <![CDATA[<210>  120]]>
          <![CDATA[<211>  53]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-F229) (NRGE1C KTSL)]]>
          <![CDATA[<400>  120]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Thr 
                  35                  40                  45              
          Ser Leu Ala Ser Phe 
              50              
          <![CDATA[<210>  121]]>
          <![CDATA[<211>  53]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-F229) (NRGE1C QSP)]]>
          <![CDATA[<400>  121]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Gln Ser 
                  35                  40                  45              
          Phe Pro Ala Ser Phe 
              50              
          <![CDATA[<210>  122]]>
          <![CDATA[<211>  53]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-F229) (NRGE1C SALT)]]>
          <![CDATA[<400>  122]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Ser Ala 
                  35                  40                  45              
          Leu Thr Ala Ser Phe 
              50              
          <![CDATA[<210>  123]]>
          <![CDATA[<211>  53]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-F229) (NRGE1C STRV)]]>
          <![CDATA[<400>  123]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Ser Thr 
                  35                  40                  45              
          Arg Val Ala Ser Phe 
              50              
          <![CDATA[<210>  124]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (NRGE1C)]]>
          <![CDATA[<400>  124]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  125]]>
          <![CDATA[<211>  52]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-S228) (NRGE1D)]]>
          <![CDATA[<400>  125]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser 
              50          
          <![CDATA[<210>  126]]>
          <![CDATA[<211>  53]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-F229) (NRGE1D)]]>
          <![CDATA[<400>  126]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe 
              50              
          <![CDATA[<210>  127]]>
          <![CDATA[<211>  53]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-F229) (NRGE1D KLDI)]]>
          <![CDATA[<400>  127]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Leu 
                  35                  40                  45              
          Asp Ile Ala Ser Phe 
              50              
          <![CDATA[<210>  128]]>
          <![CDATA[<211>  53]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-F229) (NRGE1D SSEL)]]>
          <![CDATA[<400>  128]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Ser Ser 
                  35                  40                  45              
          Glu Leu Ala Ser Phe 
              50              
          <![CDATA[<210>  129]]>
          <![CDATA[<211>  53]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-F229) (NRGE1D TSLL)]]>
          <![CDATA[<400>  129]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Thr Ser 
                  35                  40                  45              
          Leu Leu Ala Ser Phe 
              50              
          <![CDATA[<210>  130]]>
          <![CDATA[<211>  53]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-F229) (NRGE1D VTRL)]]>
          <![CDATA[<400>  130]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Val Thr 
                  35                  40                  45              
          Arg Leu Ala Ser Phe 
              50              
          <![CDATA[<210>  131]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (NRGE1D)]]>
          <![CDATA[<400>  131]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  132]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (NRGE1E)]]>
          <![CDATA[<400>  132]]>
          Ser His Leu Val Lys Cys Gly Glu Asn Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  133]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (NRGE1F)]]>
          <![CDATA[<400>  133]]>
          Ser His Leu Val Lys Cys Ala Glu Asn Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  134]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (NRGE1G)]]>
          <![CDATA[<400>  134]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  135]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (NRGE1H)]]>
          <![CDATA[<400>  135]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  136]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (NRGE1I)]]>
          <![CDATA[<400>  136]]>
          Ser His Leu Val Lys Cys Gly Glu Asn Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  137]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (NRGE1J)]]>
          <![CDATA[<400>  137]]>
          Ser His Leu Val Lys Cys Gly Glu Asn Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  138]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (NRGE1K)]]>
          <![CDATA[<400>  138]]>
          Ser His Leu Val Lys Cys Ala Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  139]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (NRGE1L)]]>
          <![CDATA[<400>  139]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  140]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (NRGE1M)]]>
          <![CDATA[<400>  140]]>
          Ser His Leu Val Lys Cys Gly Glu Asn Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Phe 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  141]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (NRGE1N)]]>
          <![CDATA[<400>  141]]>
          Ser His Leu Val Lys Cys Gly Glu Asn Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Phe 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  142]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (NRGE1O)]]>
          <![CDATA[<400>  142]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Phe 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  143]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237]]>) (NRGE1P)
          <![CDATA[<400>  143]]>
          Ser His Leu Val Lys Cys Ala Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Phe 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  144]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (1A1)]]>
          <![CDATA[<400>  144]]>
          Ser His Leu Val Lys Cys Gly Glu Ser Glu Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Val Ile Glu Asp Ser Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Val 
                  35                  40                  45              
          Phe Leu Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  145]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (1A12)]]>
          <![CDATA[<400>  145]]>
          Ser His Leu Val Lys Cys Ala Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Val Val Glu Arg Pro Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Phe 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  146]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237)  (1A7)]]>
          <![CDATA[<400>  146]]>
          Ser His Leu Val Lys Cys Ala Glu Arg Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Val Ile Glu His Leu Ser Asn Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  147]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (1B4)]]>
          <![CDATA[<400>  147]]>
          Ser His Leu Val Lys Cys Gly Glu Arg Asp Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Asp Ser Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  148]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (1B9)]]>
          <![CDATA[<400>  148]]>
          Ser His Leu Val Lys Cys Ala Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Glu Asp Leu Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Val 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  149]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (1C11)]]>
          <![CDATA[<400>  149]]>
          Ser His Leu Val Lys Cys Gly Glu Lys Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Arg Pro Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Phe 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  150]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S1]]>77-Q237)   (1D10)
          <![CDATA[<400>  150]]>
          Ser His Leu Val Lys Cys Ala Glu Arg Asp Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Ile Glu Asp Leu Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  151]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (1D3)]]>
          <![CDATA[<400>  151]]>
          Ser His Leu Val Lys Cys Gly Glu Asn Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Val Ile Glu Asp Pro Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Asp 
                  35                  40                  45              
          Phe Leu Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  152]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(]]>S177-Q237) (1D4)
          <![CDATA[<400>  152]]>
          Ser His Leu Val Lys Cys Gly Glu Arg Asp Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Val Val Glu His Ser Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Phe 
                  35                  40                  45              
          Phe Leu Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  153]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237)(2E3)]]>
          <![CDATA[<400>  153]]>
          Ser His Leu Val Lys Cys Gly Glu Lys Glu Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Ile Glu Gly Leu Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Val 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  154]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (2E4)]]>
          <![CDATA[<400>  154]]>
          Ser His Leu Val Lys Cys Gly Glu Ser Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Lys Arg Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Val 
                  35                  40                  45              
          Phe Leu Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  155]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (2F2)]]>
          <![CDATA[<400>  155]]>
          Ser His Leu Val Lys Cys Ala Glu Ser Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Ile Glu His Pro Ser Asn Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Val 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  156]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (2G3)]]>
          <![CDATA[<400>  156]]>
          Ser His Leu Val Lys Cys Gly Glu Arg Gln Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Asp Leu Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Val 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  157]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) ]]>(2G4)
          <![CDATA[<400>  157]]>
          Ser His Leu Val Lys Cys Ala Glu Asn Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Val Val Glu Gly Leu Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Val 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  158]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (2H7)]]>
          <![CDATA[<400>  158]]>
          Ser His Leu Val Lys Cys Gly Glu Lys Glu Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Val Val Glu Asp Leu Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Val 
                  35                  40                  45              
          Val Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  159]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (3A7)]]>
          <![CDATA[<400>  159]]>
          Ser His Leu Val Lys Cys Ala Glu Lys Glu Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Val Ile Glu Gly Ser Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Val 
                  35                  40                  45              
          Val Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  160]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (3B8)]]>
          <![CDATA[<400>  160]]>
          Ser His Leu Val Lys Cys Gly Glu Arg Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Glu Arg Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Phe 
                  35                  40                  45              
          Phe Leu Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  161]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-]]>Q237) (3D6)
          <![CDATA[<400>  161]]>
          Ser His Leu Val Lys Cys Gly Glu Ser Asp Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Val Ile Glu Gly Ser Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Phe 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  162]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (3D8)]]>
          <![CDATA[<400>  162]]>
          Ser His Leu Val Lys Cys Gly Glu Lys Asp Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Glu Asp Leu Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Phe 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  163]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237)(3E6)]]>
          <![CDATA[<400>  163]]>
          Ser His Leu Val Lys Cys Ala Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Val Ile Glu Gly Ser Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  164]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237)(]]>3E9)
          <![CDATA[<400>  164]]>
          Ser His Leu Val Lys Cys Ala Glu Asn His Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Val Ile Glu Gly Ser Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Val 
                  35                  40                  45              
          Phe Leu Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  165]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (3F2)]]>
          <![CDATA[<400>  165]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu Gly Pro Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asp Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  166]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (3G3)]]>
          <![CDATA[<400>  166]]>
          Ser His Leu Val Lys Cys Gly Glu Arg Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Ile Glu His Leu Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  167]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (3G9)]]>
          <![CDATA[<400>  167]]>
          Ser His Leu Val Lys Cys Gly Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Glu Asp Leu Ser Asn Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  168]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (3H5)]]>
          <![CDATA[<400>  168]]>
          Ser His Leu Val Lys Cys Gly Glu Arg His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Val Val Glu Arg Pro Ser Ile Pro Ser Arg Phe 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Asp 
                  35                  40                  45              
          Phe Leu Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  169]]>
          <![CDATA[<211>  52]]>
          <![CDATA[<212]]>>  PRT]]&gt;
          <br/>&lt;![CDATA[&lt;213&gt;  人工序列]]&gt;
          <br/>
          <br/>&lt;![CDATA[&lt;220&gt;]]&gt;
          <br/>&lt;![CDATA[&lt;223&gt;  NRG1(S177-S228) (3H8)]]&gt;
          <br/>
          <br/>&lt;![CDATA[&lt;400&gt;  169]]&gt;
          <br/>
          <br/><![CDATA[Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser 
              50          
          <![CDATA[<210>  170]]>
          <![CDATA[<211>  53]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-F229) (3H8)]]>
          <![CDATA[<400>  170]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe 
              50              
          <![CDATA[<210>  171]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (3H8)]]>
          <![CDATA[<400>  171]]>
          Ser His Leu Val Lys Cys Gly Glu Lys His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Tyr Met Val Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Glu Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  172]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (200E)]]>
          <![CDATA[<400>  172]]>
          Ser His Leu Val Lys Cys Ala Glu Lys Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Glu Asp Leu Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Tyr 
                  35                  40                  45              
          Val Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  173]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q]]>237) (200E_KDF)
          <![CDATA[<400>  173]]>
          Ser His Leu Val Lys Cys Ala Glu Lys Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Met Val Glu Asp Leu Ser Asn Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Asp 
                  35                  40                  45              
          Phe Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  174]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (FVIEDPSI)]]>
          <![CDATA[<400>  174]]>
          Ser His Leu Val Lys Cys Ala Glu Lys Glu Lys Thr Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Val Ile Glu Asp Pro Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Asn Tyr 
                  35                  40                  45              
          Val Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  175]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (v80)]]>
          <![CDATA[<400>  175]]>
          Ser His Leu Val Lys Cys Ala Glu Ser His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Val Ile Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Gln Lys Asp 
                  35                  40                  45              
          Val Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  176]]>
          <![CDATA[<211>  61]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  NRG1(S177-Q237) (v80.3)]]>
          <![CDATA[<400>  176]]>
          Ser His Leu Val Lys Cys Ala Glu Arg His Lys Ser Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Phe Val Ile Glu Gly Ser Ser Ile Pro Ser Arg Tyr 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Glu Lys Asp 
                  35                  40                  45              
          Val Met Ala Ser Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
              50                  55                  60      
          <![CDATA[<210>  177]]>
          <![CDATA[<211> ]]> 53
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  尚未歸類的特徵]]>
          <![CDATA[<222>  (7)..(7)]]>
          <![CDATA[<223>  Xaa可為任何天然存在的胺基酸]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  尚未歸類的特徵]]>
          <![CDATA[<222>  (9)..(10)]]>
          <![CDATA[<223>  Xaa可為任何天然存在的胺基酸]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  尚未歸類的特徵]]>
          <![CDATA[<222>  (12)..(12)]]>
          <![CDATA[<223>  Xaa可為任何天然存在的胺基酸]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  尚未歸類的特徵]]>
          <![CDATA[<222>  (21)..(26)]]>
          <![CDATA[<223>  Xaa可為任何天然存在的胺基酸]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  尚未歸類的特徵]]>
          <![CDATA[<222>  (28)..(28)]]>
          <![CDATA[<223>  Xaa可為任何天然存在的胺基酸]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  尚未歸類的特徵]]>
          <![CDATA[<222>  (32)..(32)]]>
          <![CDATA[<223>  Xaa可為任何天然存在的胺基酸]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  尚未歸類的特徵]]>
          <![CDATA[<222>  (46)..(50)]]>
          <![CDATA[<223>  Xaa可為任何天然存在的胺基酸]]>
          <![CDATA[<220>]]>
          <![CDATA[<221>  尚未歸類的特徵]]>
          <![CDATA[<222>  (5]]>3)..(53)
          <![CDATA[<223>  Xaa可為任何天然存在的胺基酸]]>
          <![CDATA[<400>  177]]>
          Ser His Leu Val Lys Cys Xaa Glu Xaa Xaa Lys Xaa Phe Cys Val Asn 
          1               5                   10                  15      
          Gly Gly Glu Cys Xaa Xaa Xaa Xaa Xaa Xaa Ser Xaa Pro Ser Arg Xaa 
                      20                  25                  30          
          Leu Cys Lys Cys Pro Asn Glu Phe Thr Gly Asp Arg Cys Xaa Xaa Xaa 
                  35                  40                  45              
          Xaa Xaa Ala Ser Xaa 
              50              
          <![CDATA[<210>  178]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體基序197-202]]>
          <![CDATA[<400>  178]]>
          Phe Met Ile Glu Asp Ser 
          1               5       
          <![CDATA[<210>  179]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體基序197-202]]>
          <![CDATA[<400>  179]]>
          Phe Met Ile Glu Gly Pro 
          1               5       
          <![CDATA[<210>  180]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體基序197-202]]>
          <![CDATA[<400>  180]]>
          Phe Met Ile Glu His Leu 
          1               5       
          <![CDATA[<210>  181]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體基序197-202]]>
          <![CDATA[<400>  181]]>
          Phe Met Val Glu Asp Leu 
          1               5       
          <![CDATA[<210>  182]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體基序197-202]]>
          <![CDATA[<400>  182]]>
          Phe Met Val Glu Arg Ser 
          1               5       
          <![CDATA[<210>  183]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體基序197-202]]>
          <![CDATA[<400>  183]]>
          Phe Met Val Lys Arg Pro 
          1               5       
          <![CDATA[<210>  184]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體基序197-202]]>
          <![CDATA[<400>  184]]>
          Phe Val Ile Glu Asp Pro 
          1               5       
          <![CDATA[<210>  185]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體基序197-202]]>
          <![CDATA[<400>  185]]>
          Phe Val Ile Glu Gly Ser 
          1               5       
          <![CDATA[<210>  186]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體基序197-202]]>
          <![CDATA[<400>  186]]>
          Phe Val Val Glu Gly Leu 
          1               5       
          <![CDATA[<210>  187]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體基序197-202]]>
          <![CDATA[<400>  187]]>
          Tyr Met Ile Glu Asp Leu 
          1               5       
          <![CDATA[<210>  188]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白]]>變體基序197-202
          <![CDATA[<400>  188]]>
          Tyr Met Ile Glu Gly Leu 
          1               5       
          <![CDATA[<210>  189]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體基序197-202]]>
          <![CDATA[<400>  189]]>
          Tyr Met Ile Glu His Pro 
          1               5       
          <![CDATA[<210>  190]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體基序197-202]]>
          <![CDATA[<400>  190]]>
          Tyr Met Val Glu Asp Leu 
          1               5       
          <![CDATA[<210>  191]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體基序197-202]]>
          <![CDATA[<400>  191]]>
          Tyr Met Val Glu Gly Ser 
          1               5       
          <![CDATA[<210>  192]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體基序197-202]]>
          <![CDATA[<400>  192]]>
          Tyr Met Val Glu Arg Pro 
          1               5       
          <![CDATA[<210>  193]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體基序197-202]]>
          <![CDATA[<400>  193]]>
          Tyr Val Ile Glu Asp Ser 
          1               5       
          <![CDATA[<210>  194]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體197-202]]>
          <![CDATA[<400>  194]]>
          Tyr Val Ile Glu Gly Ser 
          1               5       
          <![CDATA[<210>  195]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體197-202]]>
          <![CDATA[<400>  195]]>
          Tyr Val Ile Glu His Leu 
          1               5       
          <![CDATA[<210>  196]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體197-202]]>
          <![CDATA[<400>  196]]>
          Tyr Val Val Glu Asp Leu 
          1               5       
          <![CDATA[<210>  197]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體197-202]]>
          <![CDATA[<400>  197]]>
          Tyr Val Val Glu His Ser 
          1               5       
          <![CDATA[<210>  198]]>
          <![CDATA[<211>  6]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序]]>列
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體197-202]]>
          <![CDATA[<400>  198]]>
          Tyr Val Val Glu Arg Pro 
          1               5       
          <![CDATA[<210>  199]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  199]]>
          Glu Lys Asp Val Met 
          1               5   
          <![CDATA[<210>  200]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  200]]>
          Gln Ala Pro His Ile 
          1               5   
          <![CDATA[<210>  201]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  201]]>
          Gln Asp Asp Phe Met 
          1               5   
          <![CDATA[<210>  202]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  202]]>
          Gln Asp Phe Phe Leu 
          1               5   
          <![CDATA[<210>  203]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  203]]>
          Gln Asp Phe Phe Met 
          1               5   
          <![CDATA[<210>  204]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  204]]>
          Gln Asp Val Phe Leu 
          1               5   
          <![CDATA[<210>  205]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  205]]>
          Gln Asp Val Phe Met 
          1               5   
          <![CDATA[<210>  206]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  206]]>
          Gln Glu Asp Phe Met 
          1               5   
          <![CDATA[<210>  207]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  207]]>
          Gln Glu Thr Gln Ile 
          1               5   
          <![CDATA[<210>  208]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  208]]>
          Gln Lys Asp Phe Leu 
          1               5   
          <![CDATA[<210>  209]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  209]]>
          Gln Lys Asp Phe Met 
          1               5   
          <![CDATA[<210>  210]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  210]]>
          Gln Lys Asp Val Met 
          1               5   
          <![CDATA[<210>  211]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  211]]>
          Gln Lys Phe Phe Leu 
          1               5   
          <![CDATA[<210>  212]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  212]]>
          Gln Lys Phe Phe Met 
          1               5   
          <![CDATA[<210>  213]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  213]]>
          Gln Lys Leu Asp Ile 
          1               5   
          <![CDATA[<210>  214]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  214]]>
          Gln Lys Thr Ser Leu 
          1               5   
          <![CDATA[<210>  215]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  215]]>
          Gln Lys Val Phe Leu 
          1               5   
          <![CDATA[<210>  216]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223> ]]> 神經調節蛋白變體模體222-226
          <![CDATA[<400>  216]]>
          Gln Lys Val Phe Met 
          1               5   
          <![CDATA[<210>  217]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  217]]>
          Gln Lys Val Val Met 
          1               5   
          <![CDATA[<210>  218]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  218]]>
          Gln Asn Asp Phe Leu 
          1               5   
          <![CDATA[<210>  219]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  219]]>
          Gln Asn Asp Phe Met 
          1               5   
          <![CDATA[<210>  220]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  2]]>20
          Gln Asn Val Phe Leu 
          1               5   
          <![CDATA[<210>  221]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  221]]>
          Gln Asn Val Phe Met 
          1               5   
          <![CDATA[<210>  222]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  智人]]>
          <![CDATA[<400>  222]]>
          Gln Asn Tyr Val Met 
          1               5   
          <![CDATA[<210>  223]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  223]]>
          Gln Gln Ser Phe Pro 
          1               5   
          <![CDATA[<210>  224]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  224]]>
          Gln Ser Ala Leu Thr 
          1               5   
          <![CDATA[<210>  225]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  225]]>
          Gln Ser Ser Glu Leu 
          1               5   
          <![CDATA[<210>  226]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  226]]>
          Gln Ser Thr Arg Val 
          1               5   
          <![CDATA[<210>  227]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  227]]>
          Gln Thr Ser Leu Leu 
          1               5   
          <![CDATA[<210>  228]]>
          <![CDATA[<211>  5]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  人工序列]]>
          <![CDATA[<220>]]>
          <![CDATA[<223>  神經調節蛋白變體模體222-226]]>
          <![CDATA[<400>  228]]>
          Gln Val Thr Arg Leu 
          1               5   
          <![CDATA[<210>  229]]>
          <![CDATA[<211>  9]]>
          <![CDATA[<212>  PRT]]>
          <![CDATA[<213>  智人]]>
          <![CDATA[<400>  229]]>
          Phe Tyr Lys Ala Glu Glu Leu Tyr Gln 
          1               5

Claims

一種神經調節蛋白變體，其包含具有下式的胺基酸序列： SHLVKCX ₁₈₃EX ₁₈₅X ₁₈₆KX ₁₈₈FCVNGGECX ₁₉₇X ₁₉₈X ₁₉₉X ₂₀₀X ₂₀₁X ₂₀₂SX ₂₀₄PSRX ₂₀₈LCKCPNEFTGDRCX ₂₂₂X ₂₂₃X ₂₂₄X ₂₂₅X ₂₂₆ASX ₂₂₉（SEQ ID NO:177）其中 X ₁₈₃係A或G； X ₁₈₅X ₁₈₆係KD、KE、KH、ND、NE、NH、RD、RE、RH、RQ、SD、SE或SH； X ₁₈₈係S或T； X ₁₉₇X ₁₉₈X ₁₉₉X ₂₀₀X ₂₀₁X ₂₀₂係FMIEDS（SEQ ID NO:178）、FMIEGP（SEQ ID NO:179）、FMIEHL（SEQ ID NO:180）、FMVEDL（SEQ ID NO:181）、FMVERS（SEQ ID NO:182）、FMVKRP（SEQ ID NO:183）、FVIEDP（SEQ ID NO:184）、FVIEGS（SEQ ID NO:185）、FVVEGL（SEQ ID NO:186）、YMIEDL（SEQ ID NO:187）、YMIEGL（SEQ ID NO:188）、YMIEHP（SEQ ID NO:189）、YMVEDL（SEQ ID NO:190）、YMVEGS（SEQ ID NO:191）、YMVERP（SEQ ID NO:192）、YVIEDS（SEQ ID NO:193）、YVIEGS（SEQ ID NO:194）、YVIEHL（SEQ ID NO:195）、YVVEDL（SEQ ID NO:196）、YVVEHS（SEQ ID NO:197）或YVVERP（SEQ ID NO:198）； X ₂₀₄係I或N； X ₂₀₈係F或Y； X ₂₂₂X ₂₂₃X ₂₂₄X ₂₂₅X ₂₂₆係EKDVM（SEQ ID NO:199）、QAPHI（SEQ ID NO:200）、QDDFM（SEQ ID NO:201）、QDFFL（SEQ ID NO:202）、QDFFM（SEQ ID NO:203）、QDVFL（SEQ ID NO:204）、QDVFM（SEQ ID NO:205）、QEDFM（SEQ ID NO:206）、QETQI（SEQ ID NO:207）、QKDFL（SEQ ID NO:208）、QKDFM（SEQ ID NO:209）、QKDVM（SEQ ID NO:210）、QKFFL（SEQ ID NO:211）、QKFFM（SEQ ID NO:212）、QKLDI（SEQ ID NO:213）、QKTSL（SEQ ID NO:214）、QKVFL（SEQ ID NO:215）、QKVFM（SEQ ID NO:216）、QKVVM（SEQ ID NO:217）、QNDFL（SEQ ID NO:218）、QNDFM（SEQ ID NO:219）、QNVFL（SEQ ID NO:220）、QNVFM（SEQ ID NO:221）、QNYVM（SEQ ID NO:222）、QQSFP（SEQ ID NO:223）、QSALT（SEQ ID NO:224）、QSSEL（SEQ ID NO:225）、QSTRV（SEQ ID NO:226）、QTSLL（SEQ ID NO:227）或QVTRL（SEQ ID NO:228）；並且 X ₂₂₉不存在，係F或FYKAEELYQ（SEQ ID NO:229）。
如請求項1所述之神經調節蛋白變體，其包含SEQ ID No: 114至176中任一個的胺基酸序列。
如請求項1所述之神經調節蛋白變體，其中 X ₁₈₃係A或G； X ₁₈₅X ₁₈₆係KD、KE、KH、ND、NH、RD、RE、RH、RQ、SD、SE或SH； X ₁₈₈係S或T； X ₁₉₇X ₁₉₈X ₁₉₉X ₂₀₀X ₂₀₁X ₂₀₂係FMIEDS（SEQ ID NO:178）、FMIEGP（SEQ ID NO:179）、FMIEHL（SEQ ID NO:180）、FMVEDL（SEQ ID NO:181）、FMVERS（SEQ ID NO:182）、FMVKRP（SEQ ID NO:183）、FVIEDP（SEQ ID NO:184）、FVIEGS（SEQ ID NO:185）、YMIEDL（SEQ ID NO:187）、YMIEGL（SEQ ID NO:188）、YMIEHP（SEQ ID NO:189）、YMVEDL（SEQ ID NO:190）、YMVEGS（SEQ ID NO:191）、YMVERP（SEQ ID NO:192）、YVIEDS（SEQ ID NO:193）、YVIEGS（SEQ ID NO:194）、YVIEHL（SEQ ID NO:195）、YVVEHS（SEQ ID NO:197）或YVVERP（SEQ ID NO:198）； X ₂₀₄係I或N； X ₂₀₈係F或Y； X ₂₂₂X ₂₂₃X ₂₂₄X ₂₂₅X ₂₂₆係EKDVM（SEQ ID NO:199）、QAPHI（SEQ ID NO:200）、QDFFL（SEQ ID NO:202）、QDFFM（SEQ ID NO:203）、QDVFL（SEQ ID NO:204）、QEDFM（SEQ ID NO:206）、QETQI（SEQ ID NO:207）、QKDFL（SEQ ID NO:208）、QKDFM（SEQ ID NO:209）、QKDVM（SEQ ID NO:210）、QKFFL（SEQ ID NO:211）、QKFFM（SEQ ID NO:212）、QKLDI（SEQ ID NO:213）、QKTSL（SEQ ID NO:214）、QKVFL（SEQ ID NO:215）、QNDFL（SEQ ID NO:218）、QNDFM（SEQ ID NO:219）、QNVFL（SEQ ID NO:220）、QNVFM（SEQ ID NO:221）、QNYVM（SEQ ID NO:222）、QQSFP（SEQ ID NO:223）、QSALT（SEQ ID NO:224）、QSSEL（SEQ ID NO:225）、QSTRV（SEQ ID NO:226）、QTSLL（SEQ ID NO:227）或QVTRL（SEQ ID NO:228）；並且 X ₂₂₉係F或FYKAEELYQ（SEQ ID NO:229）。
如請求項3所述之神經調節蛋白變體，其包含SEQ ID No: 114、115、117至124、126至135、138、139、144至147、149至156、160至168、或171至176中任一個的胺基酸序列。
如請求項1所述之神經調節蛋白變體，其中 X ₁₈₃係A或G； X ₁₈₅係KE、KH、ND、RD、RH、RQ、SD、SE或SH； X ₁₈₈係S或T； X ₁₉₇X ₁₉₈X ₁₉₉X ₂₀₀X ₂₀₁X ₂₀₂係FMIEDS（SEQ ID NO:178）、FMIEGP（SEQ ID NO:179）、FMVEDL（SEQ ID NO:181）、FMVKRP（SEQ ID NO:183）、FVIEDP（SEQ ID NO:184）、FVIEGS（SEQ ID NO:185）、YMIEDL（SEQ ID NO:187）、YMIEHP（SEQ ID NO:189）、YMVEDL（SEQ ID NO:190）、YMVEGS（SEQ ID NO:191）、YMVERP（SEQ ID NO:192）、YVIEDS（SEQ ID NO:193）、YVIEGS（SEQ ID NO:194）、YVIEHL（SEQ ID NO:195）、YVVEHS（SEQ ID NO:197）或YVVERP（SEQ ID NO:198）； X ₂₀₄係I或N； X ₂₀₈係F或Y； X ₂₂₂X ₂₂₃X ₂₂₄X ₂₂₅X ₂₂₆係EKDVM（SEQ ID NO:199）、QAPHI（SEQ ID NO:200）、QEDFM（SEQ ID NO:206）、QETQI（SEQ ID NO:207）、QKDFL（SEQ ID NO:208）、QKDFM（SEQ ID NO:209）、QKDVM（SEQ ID NO:210）、QKFFL（SEQ ID NO:211）、QKFFM（SEQ ID NO:212）、QKLDI（SEQ ID NO:213）、QKTSL（SEQ ID NO:214）、QKVFL（SEQ ID NO:215）、QNDFL（SEQ ID NO:218）、QNDFM（SEQ ID NO:219）、QNVFL（SEQ ID NO:220）、QNVFM（SEQ ID NO:221）、QNYVM（SEQ ID NO:222）、QQSFP（SEQ ID NO:223）、QSALT（SEQ ID NO:224）、QSSEL（SEQ ID NO:225）、QSTRV（SEQ ID NO:226）、QTSLL（SEQ ID NO:227）或QVTRL（SEQ ID NO:228）；並且 X ₂₂₉係F或FYKAEELYQ（SEQ ID NO:229）。
如請求項5所述之神經調節蛋白變體，其包含SEQ ID No: 117至124、126至135、144至147、149至152、154至156、163、167、168、或171至176中任一個的胺基酸序列。
如請求項1所述之神經調節蛋白變體，其中其中 X ₁₈₃係A或G； X ₁₈₅X ₁₈₆係KH、ND、RD、RH或SH； X ₁₈₈係S或T； X ₁₉₇X ₁₉₈X ₁₉₉X ₂₀₀X ₂₀₁X ₂₀₂係FMIEDS（SEQ ID NO:178）、FMIEGP（SEQ ID NO:179）、FMVEDL（SEQ ID NO:181）、FVIEDP（SEQ ID NO:184）、YMIEDL（SEQ ID NO:187）、YMVEGS（SEQ ID NO:191）、YVIEGS（SEQ ID NO:194）、YVIEHL（SEQ ID NO:195）或YVVERP（SEQ ID NO:198）； X ₂₀₄係I或N； X ₂₀₈係F或Y； X ₂₂₂X ₂₂₃X ₂₂₄X ₂₂₅X ₂₂₆係QAPHI（SEQ ID NO:200）、QEDFM（SEQ ID NO:206）、QETQI（SEQ ID NO:207）、QKDFL（SEQ ID NO:208）、QKDFM（SEQ ID NO:209）、QKTSL（SEQ ID NO:214）、QNDFL（SEQ ID NO:218）、QNDFM（SEQ ID NO:219）、QQSFP（SEQ ID NO:223）、QSALT（SEQ ID NO:224）、QSSEL（SEQ ID NO:225）、QSTRV（SEQ ID NO:226）、QTSLL（SEQ ID NO:227）或QVTRL（SEQ ID NO:228）；並且 X ₂₂₉係F或FYKAEELYQ（SEQ ID NO:229）。
如請求項7所述之神經調節蛋白變體，其包含SEQ ID No: 117至124、126、128至135、146、147、150、151、163、167、168或171中任一個的胺基酸序列。
如請求項8所述之神經調節蛋白變體，其包含SEQ ID No: 117、118、119、120、122、123、124、126、128、129、130、131、133或135中任一個的胺基酸序列。
如請求項1至9中任一項所述之神經調節蛋白變體，其進一步包含第二胺基酸序列，該第二胺基酸序列包含訊息序列、半衰期延長部分或純化標籤。
如請求項9所述之神經調節蛋白變體，其中該第二胺基酸序列包括Fc區或His標籤。
如請求項11所述之神經調節蛋白變體，其包含SEQ ID No: 1至24、29至54、56至67、69至80、82至111中任一個的胺基酸序列。
如請求項11所述之神經調節蛋白變體，其包含SEQ ID No: 1至15、19、20、22、23、29至34、37、38、43至54、56至59、61至67、69至80、82至85、87至93、或97至111中任一個的胺基酸序列。
如請求項11所述之神經調節蛋白變體，其包含SEQ ID No: 3、4、6、9、11至13、19、22、31至34、43至48、52、54、56至59、61至63、65至67、71、72、75至80、84、85、88、100、或104至106中任一個的胺基酸序列。
如請求項11所述之神經調節蛋白變體，其包含SEQ ID No: 3、4、6、9、11至13、19、22、31至34、43至48、52、54、56至59、61至63、65至67、71、72、75至80、84、85、88、100、或104至106中任一個的胺基酸序列。
如請求項15所述之神經調節蛋白變體，其包含SEQ ID NO:4、11、13、32、34、45、46、48、52、72、75、76、77、78、79或80的胺基酸序列。
如請求項15所述之神經調節蛋白變體，其包含SEQ ID NO:56、57、58、59、61、62、63、65、66或67的胺基酸序列。
一種藥物組成物，其包含如請求項1至17中任一項所述之神經調節蛋白變體、和藥學上可接受的載劑。
一種在有需要的受試者中治療心血管疾病或病症之方法，該方法包括投與治療有效量的如請求項1至17中任一項所述之神經調節蛋白變體、或如請求項18所述之藥物組成物。
如請求項19所述之方法，其中該心血管疾病或病症係心臟衰竭、心肌梗塞、擴張型或肥厚型心肌病、心肌炎或心臟毒性。
如請求項19或20所述之方法，其中該受試者係人。