Calpain Project, Department of Advanced Science for Biomolecules, Tokyo Metropolitan Institute of Medical Science, Tokyo156-8506, Japan.
J Biochem. 2011 Jul;150(1):23-37. doi: 10.1093/jb/mvr070. Epub 2011 May 24.
Calpain has long been an enigmatic enzyme, although it is involved in a variety of biological phenomena. Recent progress in calpain genetics has highlighted numerous physiological contexts in which the functions of calpain are of great significance. This review focuses on recent findings in the field of calpain genetics and the importance of calpain function. Calpain is an intracellular Ca(2+)-dependent cysteine protease (EC 3.4.22.17; Clan CA, family C02) found in almost all eukaryotes. It is also present in a few bacteria, but not in archaebacteria. Calpain has limited proteolytic activity; rather, it transforms or modulates the structure and/or activity of its substrates. It is, therefore, referred to as a 'modulator protease'. Within the human genome, 15 genes (CAPN1-3, CAPN5-16) encode a calpain-like protease (CysPc) domain along with several different functional domains. Thus, calpains can be regarded as a distinct family of versatile enzymes that fulfil numerous tasks in vivo. Genetic studies show that a variety of defects in many different organisms, including lethality, muscular dystrophies and gastropathy, actually stem from calpain deficiencies. The cause-effect relationships identified by these studies form the basis for ongoing and future studies regarding the physiological role of calpains.
钙蛋白酶长期以来一直是一种神秘的酶，尽管它参与了多种生物现象。钙蛋白酶遗传学的最新进展突出了许多生理环境，其中钙蛋白酶的功能具有重要意义。本综述重点介绍了钙蛋白酶遗传学领域的最新发现以及钙蛋白酶功能的重要性。钙蛋白酶是一种存在于几乎所有真核生物中的细胞内 Ca(2+)-依赖性半胱氨酸蛋白酶（EC 3.4.22.17；Clan CA，家族 C02）。它也存在于少数细菌中，但不存在于古细菌中。钙蛋白酶的蛋白水解活性有限；相反，它会改变或调节其底物的结构和/或活性。因此，它被称为“调节剂蛋白酶”。在人类基因组中，有 15 个基因（CAPN1-3、CAPN5-16）编码一种钙蛋白酶样蛋白酶（CysPc）结构域以及几个不同的功能结构域。因此，钙蛋白酶可以被视为一类独特的多功能酶，在体内完成许多任务。遗传研究表明，许多不同生物体中的多种缺陷，包括致死性、肌肉营养不良和胃病，实际上都源于钙蛋白酶的缺乏。这些研究确定的因果关系为钙蛋白酶的生理作用的正在进行和未来的研究奠定了基础。
