title: An eccentric calpain, CAPN3/p94/calpain-3.
abstract: Calpains are Ca(2+)-regulated proteolytic enzymes that are involved in a variety of biological phenomena. Calpains process substrates by limited proteolysis to modulate various protein functions in the cell, and are thus called "modulator proteases." CAPN3, previously called p94 or calpain-3, has unique features that are not found in any of the other 14 human calpains, or even in other proteases. For instance, CAPN3 undergoes extremely rapid and exhaustive autodegradation. CAPN3 is also the first (and so far, the only) intracellular enzyme found to depend on Na(+) for its activation. CAPN3 has both proteolytic and non-proteolytic functions. It has the interesting distinction of being the only protease, other than a few virus proteases, with the ability to regain protease function after its autolytic dissociation; this occurs through a process known as intermolecular complementation (iMOC). Gene mutations causing CAPN3 defects are responsible for limb-girdle muscular dystrophy type 2A (LGMD2A). Unusual characteristics of CAPN3 have fascinated researchers, but have also hampered conventional biochemical analysis. In this review, we describe significant findings about CAPN3 from its discovery to the present, and suggest promising avenues for future CAPN3 research.
authors.affiliation: Calpain Project, Department of Advanced Science for Biomolecules, Tokyo Metropolitan Institute of Medical Science (IGAKUKEN), 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Ono
authors.affiliation: Calpain Project, Department of Advanced Science for Biomolecules, Tokyo Metropolitan Institute of Medical Science (IGAKUKEN), 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan; Animal Products Research Division, NARO Institute of Livestock and Grassland Science, Ikenodai 2, Tsukuba, Ibaraki 305-0901, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ojima
authors.affiliation: Calpain Project, Department of Advanced Science for Biomolecules, Tokyo Metropolitan Institute of Medical Science (IGAKUKEN), 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Shinkai-Ouchi
authors.affiliation: Calpain Project, Department of Advanced Science for Biomolecules, Tokyo Metropolitan Institute of Medical Science (IGAKUKEN), 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Hata
authors.affiliation: Calpain Project, Department of Advanced Science for Biomolecules, Tokyo Metropolitan Institute of Medical Science (IGAKUKEN), 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan. Electronic address: sorimachi-hr@igakuken.or.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sorimachi
mesh_terms: D002154:Calpain / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D049288:Muscular Dystrophies, Limb-Girdle / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D059748:Proteolysis; D012964:Sodium / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D009124:Muscle Proteins; D012964:Sodium; C105884:CAPN3 protein, human; D002154:Calpain
keywords: Autolysis; Calpain; Molecular evolution; Muscular dystrophy; Structure–activity relationship; Substrate