Calpain large subunit, domain III superfamily
IPR036213
Definition
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 [[cite:PMID:2539381], [cite:PMID:11517928]]. 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 PMID:21864727. 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 PMID:2555341. 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 [[cite:PMID:7845226], [cite:PMID:2539381]]. The crystallographic structure of m-calpain reveals six "domains" in the 80kDa subunit [[cite:PMID:9396712], [cite:PMID:11328585]]: A 19-amino acid NH2-terminal sequence; Active site domain IIa; Active site domain IIb. Domain 2 shows low levels of sequence similarity to papain; although the catalytic His has not been located by biochemical means, it is likely that calpain and papain are related PMID:7845226. 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 PMID:7845226. 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 site cleft allowing for the proper formation of the catalytic triad PMID:11914728. 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 PMID:15180595.
13 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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