Molecular Biology of Mysterin/RNF213
Molecular Biology of Mysterin/RNF213
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DOI：
10.1007/978-981-10-2711-6_4
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Daisuke Morito;K. Nagata
中科院分区：
文献类型：
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作者：
Daisuke Morito;K. Nagata
Mysterin，也称为RNF213，是一个大的胞内蛋白(591 KDa)，含有两个串联的AAA+ATPase模块和一个环指泛素连接酶基序。尽管其生理作用尚不清楚，但神秘蛋白被认为是烟雾病最显著的易感因素，烟雾病是人类的一种特发性脑血管疾病。神秘蛋白的C端R4810K突变显著增加了烟雾病的风险，但其对神秘蛋白的分子作用在很大程度上仍不清楚。自其鉴定和分子克隆以来，已有多项研究在分子、细胞和组织/个体水平上探讨了其生理和病理作用，到目前为止的研究结果表明，它参与了血管生成和/或内皮细胞的行为；然而，目前还没有统一和准确的认识。在这一章中，我们概述了神秘蛋白的基因组组成、酶活性、结构和体内外的突变表型，并从分子生物学的角度讨论了其潜在的生理和病理作用。
Mysterin, also called RNF213, is a large intracellular protein (591 kDa) that contains two tandem AAA+ ATPase modules and a RING finger ubiquitin ligase motif. Although its physiological role remains unclear, mysterin is considered to be the most prominent susceptibility factor for moyamoya disease, an idiopathic cerebrovascular disorder in humans. The C-terminal R4810K mutation of mysterin significantly increases the risk of moyamoya disease, but its molecular effect on the mysterin protein remains largely unclear. Multiple studies have explored the physiological and pathological roles of mysterin at the molecular, cellular, and tissue/individual levels since its identification and molecular cloning, and the results obtained to date suggest that mysterin is involved in angiogenesis and/or endothelial cell behavior; however, no unified and precise understanding has yet been established. In this chapter, we provide an overview of mysterin’s genomic composition, enzymatic activities, structure, and mutant phenotypes in vitro and in vivo and discuss its potential physiological and pathological roles from the standpoint of molecular biology.