Calpain

Function Calpains (CAP) are calcium-dependent cysteine proteases. CAPs are regulated by Ca+2 concentration, phosphorylation and calpastatin. The CAP family contains 14 members. CAP1 (or mu-CAP) and CAP2 (or M-CAP) T are the best characterized CAPs. 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. Disease CAP3 defects lead to a certain muscular dystrophy. Defective CAPs have a role in neurodegeneration. Structural highlights CAP is a heterodimer containing a small 28kDa regulatory subunit which is identical for all CAPs and a large 80kDa catalytic subunit. CAP undergoes conformational change upon binding of Ca+2 ions resulting in closing of its active site cleft and activation as a cysteine protease.

spinqualitylabelsall models Human calpain1 large subunit complex with inhibitor and Ca+2 ions (green) (PDB entry 1zcm) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

3D structures of calpain3D structures of calpain

Updated on 18-November-2015

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• 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
    
  • 4phj – hCAP EF-hand subunit + Ca - human
    
  • 4phk, 4phm, 4phn – hCAP EF-hand subunit + Ca + inhibitor
    
• 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
    
  • 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
• CAP3
  • 4okh - hCAP EF-hand domain
    
• 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