Calpain

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Calpains (CAP) are calcium-dependent cysteine proteases. The CAP family contains 14 members. CAP is a heterodimer containing a small28kDa regulatory subunit which is identical for all CAPs and a large 80kDa catalytic subunit. The best characterized CAPs are CAP1 (or mu-CAP) and CAP2 (or M-CAP). CAP7 is atypical CAP that lacks a penta-EF-hand domain. CAP8 and CAP9 are involved in the mucosal defense against stress-induced gastropathies. CAP9 has been identified as the tumor suppressor for gastric cancer. CAP13 is expressed in testis and lungs. CAPs are regulated by Ca+2 concentration, phosphorylation and calpastatin.

3D structures of calpain

Updated on 31-May-2025

CAP small subunit

1aj5 – rCAP domain VI – rat

1dvi - rCAP domain VI + Ca
1np8 – rCAP residues 87-245 - Cd
1alv, 1nx2 - pCAP domain VI + Ca – pig
1alw, 1nx3 - pCAP domain VI + Ca+ inhibitor
1nx0 - pCAP domain VI + Ca+ Calpastatin peptide + small molecule inhibitor peptide
1nx1 - pCAP domain VI + Ca+ Calpastatin peptide

CAP1

1kxr, 1tlo, 1qxp - rCAP protease domain + Ca

1tl9 - rCAP protease domain + Ca+ leupeptin inhibitor
2g8e, 2g8j, 2nqg, 2nqi, 2r9c, 2r9f - rCAP protease domain + Ca+ inhibitor
2ary - hCAP protease domain + Ca – human
1zcm - hCAP protease domain (mutant) + Ca+ inhibitor

CAP2

1mdw – rCAP2 protease core domain I and II (mutant) + Ca

1df0, 1u5i – rCAP small subunit domain VI + rCAP2 large subunit
3df0 - hCAP small subunit + hCAP2 large subunit + Calpastatin + Ca
3bow - rCAP small subunit + rCAP2 large subunit + Calpastatin + Ca
1kfu, 1kfx – hCAP small subunit + hCAP2 large subunit

CAP7

2qfe - hCAP C2-like domain

CAP8

2nqa - hCAP protease domain + Ca+ leupeptin inhibitor

CAP9

1ziv – hCAP catalytic domain

2p0r - hCAP protease domain + Ca+ leupeptin inhibitor

CAP13

2i7a – hCAP domain IV + Ca


Human calpain1 large subunit complex with inhibitor and Ca+2 ions (green) (PDB entry 1zcm)

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Michal Harel, Alexander Berchansky