Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa-ku, Nagoya, Japan.
FEBS J. 2012 Apr;279(8):1414-21. doi: 10.1111/j.1742-4658.2012.08560.x. Epub 2012 Mar 23.
The name calpain was historically given to a protease that is activated by Ca(2+) and whose primary structure contains a Ca(2+)-binding penta-EF-hand (PEF) as well as a calpain cysteine protease (CysPc) domain and a C2-domain-like (C2L) domain. In the human genome, CysPc domains are found in 15 genes, but only nine of them encode PEF domains. Fungi and budding yeasts have calpain-like sequences that lack the PEF domain, and each protein (designated PalB and Rim13, respectively) is orthologous to human calpain-7, indicating that the calpain-7 orthologs are evolutionarily more conserved than classical calpains possessing PEF domains. An N-terminal region of calpain-7 has a tandem repeat of microtubule-interacting and transport domains that interact with a subset of endosomal sorting complex required for transport (ESCRT) III proteins. In addition to calpains, PEF domains are found in other Ca(2+)-binding proteins including ALG-2 that associates with ALIX (an ESCRT-III accessory protein) and TSG101 (an ESCRT-I subunit). Phylogenetic comparison of dissected domain structures of calpains and experimentally confirmed protein-protein interaction networks imply that there is an evolutionary and physical linkage between mammalian calpains and PEF proteins involving the ESCRT system.
钙蛋白酶这个名称最初是指一种在钙离子（Ca(2+)）激活下具有活性的蛋白酶，其一级结构包含一个 Ca(2+)结合的五 EF 手（PEF）以及钙蛋白酶半胱氨酸蛋白酶（CysPc）结构域和一个类似 C2 结构域（C2L）结构域。在人类基因组中，CysPc 结构域存在于 15 个基因中，但只有其中的 9 个编码 PEF 结构域。真菌和芽殖酵母具有缺乏 PEF 结构域的钙蛋白酶样序列，并且每种蛋白（分别指定为 PalB 和 Rim13）与人类钙蛋白酶-7 是同源的，这表明钙蛋白酶-7 的同源物比具有 PEF 结构域的经典钙蛋白酶在进化上更为保守。钙蛋白酶-7 的 N 端区域具有微管相互作用和运输结构域的串联重复，这些结构域与内体分选复合物所需的运输（ESCRT）III 蛋白的一部分相互作用。除了钙蛋白酶之外，PEF 结构域还存在于其他 Ca(2+)结合蛋白中，包括与 ALIX（ESCRT-III 辅助蛋白）和 TSG101（ESCRT-I 亚基）结合的 ALG-2。对钙蛋白酶和经过实验验证的蛋白质-蛋白质相互作用网络的离散结构域结构进行的系统发育比较表明，哺乳动物钙蛋白酶和 PEF 蛋白之间存在与 ESCRT 系统有关的进化和物理联系。
