| Primary Identifier | IPR036213 | Type | Homologous_superfamily |
| Short Name | Calpain_III_sf |
| description | This group of cysteine peptidases belong to the MEROPS peptidase family C2 (calpain family, clan CA). A type example is calpain, which is an intracellular protease involved in many important cellular functions that are regulated by calcium [, ]. The protein is a complex of 2 polypeptide chains (light and heavy), with eleven known active peptidases in humans and two non-peptidase homologues known as calpamodulin and androglobin []. These include a highly calcium-sensitive (i.e., micro-molar range) form known as mu-calpain, mu-CANP or calpain I; a form sensitive to calcium in the milli-molar range, known as m-calpain, m-CANP or calpain II; and a third form, known as p94, which is found in skeletal muscle only [].All forms have identical light but different heavy chains. Both mu- and m-calpain are heterodimers containing an identical 28kDa subunit and an 80kDa subunit that shares 55-65% sequence homology between the two proteases [, ]. The crystallographic structure of m-calpain reveals six "domains"in the 80kDa subunit [, ]: A 19-amino acid NH2-terminal sequence;Active site domain IIa;Active site domain IIb. Domain 2 showslow levels of sequence similarity to papain; although the catalytic His hasnot been located by biochemical means, it is likely that calpain and papainare related [].Domain III;An 18-amino acid extended sequence linking domain III to domain IV;Domain IV, which resembles the penta EF-hand family of polypeptides, binds calcium and regulates activity []. Ca2+-binding causes a rearrangement of the protein backbone, the net effect of which is that a Trp side chain, which acts as a wedge between catalytic domains IIa and IIb in the apo state, moves away from the active sitecleft allowing for the proper formation of the catalytic triad []. This superfamily describes domain III. Calpains are activated via rearrangement of the catalytic domain II induced by cooperative binding of Ca2+ to several sites of the molecule. A cluster of acidic residues in domain III, the acidic loop, has been proposed to function as part of an electrostatic switch in the activation process []. |
