CHARACTERIZATION OF A CDNA CODING FOR HUMAN FACTOR-VII
CHARACTERIZATION OF A CDNA CODING FOR HUMAN FACTOR-VII
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DOI：
10.1073/pnas.83.8.2412
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发表时间：
1986-04-01
影响因子：
11.1
通讯作者：
DAVIE, EW
中科院分区：
文献类型：
--
作者：
HAGEN, FS;GRAY, CL;DAVIE, EW
因子VII是存在于哺乳动物血浆中的丝氨酸蛋白酶的前体。在其活化形式中，其通过在组织因子和钙存在下活化因子X和/或因子IX参与血液凝固。从人肝和Hep G2细胞的poly（A）RNA制备的两个cDNA文库中获得编码因子VII的克隆。从cDNA推导的氨基酸序列表明，因子VII是用60或38个氨基酸的前原前导序列合成的。在血浆中循环的成熟蛋白质是由406个氨基酸组成的单链多肽。蛋白质的氨基酸序列分析和从cDNA推导的氨基酸序列表明，因子VII通过精氨酸和异亮氨酸之间的单个内部键的断裂转化为因子VIIa。这导致形成通过二硫键连接在一起的轻链（152个氨基酸）和重链（254个氨基酸）。轻链含有γ-该分子的重链包含羧基谷氨酸（Gla）结构域和两个潜在的表皮生长因子结构域，而重链包含该分子的丝氨酸蛋白酶部分。因子VII显示出与其他维生素K依赖性血浆蛋白高度的氨基酸序列同源性。
Factor VII is a precursor to a serine protease that is present in mammalian plasma. In its activated form, it participates in blood coagulation by activating factor X and/or factor IX in the presence of tissue factor and calcium. Clones coding for factor VII were obtained from two cDNA libraries prepared from poly(A) RNA from human liver and Hep G2 cells. The amino acid sequence deduced from the cDNAs indicates that factor VII is synthesized with a prepro-leader sequence of 60 or 38 amino acids. The mature protein that circulates in plasma is a single-chain polypeptide composed of 406 amino acids. The amino acid sequence analysis of the protein and the amino acid sequence deduced from the cDNAs indicate that factor VII is converted to factor VIIa by the cleavage of a single internal bond between arginine and isoleucine. This results in the formation of a light chain (152 amino acids) and a heavy chain (254 amino acids) that are held together by a disulfide bond. The light chain contains a .gamma.-carboxyglutamic acid (Gla) domain and the two potential epidermal growth factor domains, while the heavy chain contains the serine protease portion of the molecule. Factor VII shows a high degree of amino acid sequence homology with the other vitamin K-dependent plasma proteins.