Protein Domain : IPR022684

Type:  Family Name:  Peptidase C2, calpain family
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 2polypeptide chains (light and heavy), with three known forms in mammals[, ]: a highly calcium-sensitive (i.e., micro-molar range) form known as mu-calpain, mu-CANP or calpain I; a form sensitive to calcium inthe 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 site cleft allowing for the proper formation of the catalytic triad []. Calpain-like mRNAs have been identified in other organisms including bacteria, but the molecules encoded by these mRNAs have not been isolated, so little is knownabout their properties. How calpain activity is regulated in these organisms cells is still unclear In metazoans, the activity of calpain is controlled by a single proteinase inhibitor, calpastatin (). The calpastatin gene can produce eight or more calpastatin polypeptides ranging from 17 to 85 kDa by use of different promoters and alternative splicing events. The physiological significance of these different calpastatins is unclear, although all bind to three different places on the calpain molecule; binding to at least two of the sites is Ca2+ dependent. The calpains ostensibly participate in a variety of cellular processes including remodelling of cytoskeletal/membrane attachments, different signal transduction pathways, and apoptosis. Deregulated calpain activity following loss of Ca2+ homeostasis results in tissue damage in response to events such as myocardial infarcts, stroke, and brain trauma []. Short Name:  Calpain_cysteine_protease

9 Child Features

DB identifier Type Name
IPR029542 Family Calpain-9
IPR029540 Family Calpain-6
IPR029545 Family Calpain-12
IPR029544 Family Calpain-13
IPR029543 Family Calpain-8
IPR029531 Family Calpain-3
IPR029539 Family Calpain-2
IPR029643 Family Calpain-1
IPR028791 Family Calpain-10

5 Contains

DB identifier Type Name
IPR022682 Domain Peptidase C2, calpain, large subunit, domain III
IPR022683 Domain Peptidase C2, calpain, domain III
IPR001300 Domain Peptidase C2, calpain, catalytic domain
IPR015232 Domain Domain of unknown function DUF1935
IPR000169 Active_site Cysteine peptidase, cysteine active site

1 Cross References


0 Found In

3 GO Annotations

GO Term Gene Name Organism
GO:0004198 IPR022684
GO:0006508 IPR022684
GO:0005622 IPR022684

0 Parent Features

198 Proteins

DB identifier UniProt Accession Secondary Identifier Organism Name Length
235391 D8SWW6 PAC:15405421 Selaginella moellendorffii 2070  
236021 D8T469 PAC:15405894 Selaginella moellendorffii 2086  
evm.model.supercontig_119.40 PAC:16406557 Carica papaya 2117  
28842.m000951 B9SBQ0 PAC:16801839 Ricinus communis 2158  
Cucsa.142290.1 PAC:16963623 Cucumis sativus 2044  
GSVIVT01025470001 D7SLL2 PAC:17833457 Vitis vinifera 2159  
orange1.1g000112m A0A067EH92 PAC:18110041 Citrus sinensis 2161  
orange1.1g000111m A0A067EH92 PAC:18110042 Citrus sinensis 2161  
orange1.1g000135m A0A067EGZ4 PAC:18110043 Citrus sinensis 2087  
AT1G55350.3 Q8RVL2 PAC:19654953 Arabidopsis thaliana 2151  
AT1G55350.1 Q8RVL2 PAC:19654951 Arabidopsis thaliana 2151  
AT1G55350.4 Q8RVL2 PAC:19654954 Arabidopsis thaliana 2151  
AT1G55350.5 F4I0A4 PAC:19654950 Arabidopsis thaliana 2179  
AT1G55350.2 Q8RVL2 PAC:19654952 Arabidopsis thaliana 2151  
Thhalv10011175m V4MF78 PAC:20184556 Eutrema salsugineum 2152  
Ciclev10014012m V4TYY8 PAC:20817911 Citrus clementina 2091  
Carubv10008068m R0I1G2 PAC:20890720 Capsella rubella 2152  
MDP0000094595 PAC:22644345 Malus domestica 2174  
MDP0000077683 PAC:22621899 Malus domestica 2161  
MDP0000245785 PAC:22628770 Malus domestica 1797  
Lus10013411 PAC:23155070 Linum usitatissimum 1982  
Lus10010313 PAC:23169474 Linum usitatissimum 1613  
Potri.001G003900.1 B9GMB8 PAC:27046598 Populus trichocarpa 2123  
Potri.001G003900.2 PAC:27046599 Populus trichocarpa 1994  
Potri.003G221100.1 PAC:26997928 Populus trichocarpa 2157  
Potri.003G221100.2 PAC:26997927 Populus trichocarpa 2157  
Potri.003G221100.3 PAC:26997929 Populus trichocarpa 1945  
Gorai.003G153800.2 A0A0D2QCX5 PAC:26798951 Gossypium raimondii 2150  
Gorai.003G153800.3 A0A0D2QCX5 PAC:26798952 Gossypium raimondii 2150  
Gorai.003G153800.1 A0A0D2QCX5 PAC:26798950 Gossypium raimondii 2150  

5 Publications

First Author Title Year Journal Volume Pages PubMed ID