A NOVEL TRYPSIN-LIKE SERINE PROTEASE (HEPSIN) WITH A PUTATIVE TRANSMEMBRANE DOMAIN EXPRESSED BY HUMAN-LIVER AND HEPATOMA-CELLS
A NOVEL TRYPSIN-LIKE SERINE PROTEASE (HEPSIN) WITH A PUTATIVE TRANSMEMBRANE DOMAIN EXPRESSED BY HUMAN-LIVER AND HEPATOMA-CELLS
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DOI：
10.1021/bi00403a032
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发表时间：
1988-02-09
期刊：
影响因子：
2.9
通讯作者：
DAVIE, EW
中科院分区：
文献类型：
--
作者：
LEYTUS, SP;LOEB, KR;DAVIE, EW
已从由人肝脏和肝癌细胞系 mRNA 制备的 cDNA 文库中分离出带有编码新丝氨酸蛋白酶（hepsin）的 cDNA 插入片段的重组克隆。 cDNA的总长度约为1.8kb，包括5''非翻译区、编码417个氨基酸的蛋白质的1251个核苷酸、3''非翻译区和poly(A)尾。 Hepsin cDNA 编码的氨基酸序列与血浆中存在的胰蛋白酶和其他丝氨酸蛋白酶具有高度的同一性。它还表现出丝氨酸蛋白酶的酶原特征，因为它包含用于蛋白酶激活的切割位点以及参与酶催化的 His、Asp 和 Ser 残基周围的高度保守区域。此外，hepsin 缺乏典型的氨基末端信号肽。然而，蛋白质序列的水疗分析揭示了一个由 27 个氨基酸组成的非常疏水的区域，从表观引发剂 Met 下游的 18 个残基开始。该区域可以充当内部信号序列和跨膜结构域。这种推定的跨膜结构域可能参与将hepsin锚定到细胞膜上，并以其含有催化结构域的羧基末端位于细胞外的方式对其进行定向。
Recombinant clones with cDNA inserts coding for a new serine protease (hepsin) have been isolated from cDNA libraries prepared from human liver and hepatoma cell line mRNA. The total length of the cDNA is approximately 1.8 kilobases and includes a 5'' untranslated region, 1251 nucleotides coding for a protein of 417 amino acids, a 3'' untranslated region, and poly(A) tail. The amino acid sequence coded by the cDNA for hepsin shows a high degree of identity to pancreatic trypsin and other serine proteases present in plasma. It also exhibits features characteristic of zymogens to serine proteases in that it contains a cleavage site for protease activation and the highly conserved regions surrounding the His, Asp, and Ser residues that participate in enzyme catalysis. In addition, hepsin lacks a typical amino-terminal signal peptide. Hydropathy analysis of the protein sequence, however, revealed a very hydrophobic region of 27 amino acids starting 18 residues downstream from the apparent initiator Met. This region may serve as an internal signal sequence and a transmembrane domain. This putative transmembrane domain could be involved in anchoring hepsin to the cell membrane and orienting it in such a manner that its carboxyl terminus, containing the catalytic domain, is extracellular.