title: Evolutionary and physical linkage between calpains and penta-EF-hand Ca2+-binding proteins.
abstract: 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.
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa-ku, Nagoya, Japan. mmaki@agr.nagoya-u.ac.jp
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Maki
authors.forename: Yuki
authors.initials: Y
authors.lastname: Maemoto
authors.forename: Yohei
authors.initials: Y
authors.lastname: Osako
authors.forename: Hideki
authors.initials: H
authors.lastname: Shibata
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism*; D020832:EF Hand Motifs; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D006801:Humans; D060066:Protein Interaction Maps
chemical_list: D002135:Calcium-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D002154:Calpain