TMX, a human transmembrane oxidoreductase of the thioredoxin family: the possible role in disulfide-linked protein folding in the endoplasmic reticulum
TMX, a human transmembrane oxidoreductase of the thioredoxin family: the possible role in disulfide-linked protein folding in the endoplasmic reticulum
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DOI：
10.1016/j.abb.2003.11.003
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发表时间：
2004-03-01
影响因子：
3.9
通讯作者：
Yodoi, J
中科院分区：
文献类型：
--
作者：
Matsuo, Y;Nishinaka, Y;Yodoi, J
硫氧还蛋白（Trx）活性位点序列（Cys-Xxx-Xxx-Cys）的多样性已被发现并被归类为超家族。其中，跨膜Trx相关蛋白（transmembrane Trx related protein，TMX）是最近发现的一种具有非典型活性位点序列Cys-Pro-Ala-Cys的新蛋白。在本研究中，我们描述了这种膜Trx相关分子的性质。内源性TMX被检测为具有可切割信号肽的约30 kDa的蛋白质。TMX富含膜组分，并表现出类似的亚细胞分布与钙连接蛋白定位在内质网（ER）。TMX的膜拓扑结构的检查表明，含有Trx样结构域的N-末端区域存在于ER腔中，其中蛋白质二硫键异构酶。(PDI)有助于蛋白质折叠。重组TMX表现出类似PDI的活性，以重折叠乱序RNA酶。这些结果表明，TMX可以修饰某些分子的氧化还原酶活性，并参与在ER的氧化还原调节的可能性。(C)2003年爱思唯尔公司All rights reserved.
Various proteins sharing thioredoxin (Trx)-like active site sequences (Cys-Xxx-Xxx-Cys) have been found and classified in the superfamily. Among them, transmembrane Trx-related protein (TMX) was recently identified as a novel protein possessing an atypical active site sequence, Cys-Pro-Ala-Cys. In the present study, we describe the properties of this membranous Trx-related molecule. Endogenous TMX was detected as a protein of approximately 30 kDa with a cleavable signal peptide. TMX was enriched in membrane fractions and exhibited a similar subcellular distribution with calnexin localized in the endoplasmic reticulum (ER). The examination of membrane topology of TMX suggested that the N-terminal region containing the Trx-like domain was present in the ER lumen, where protein disulfide isomerase.(PDI) was found to assist protein folding. Recombinant TMX showed PDI-Iike activity to refold scrambled RNase. These results indicate the possibility that TMX can modify certain molecules with its oxidoreductase activity and be involved in the redox regulation in the ER. (C) 2003 Elsevier Inc. All rights reserved.