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.