Calpastatin (CAST)

Calpastatin is the endogenous, specific inhibitor of the calpain family of calcium-dependent cysteine proteases. The human calpastatin protein, encoded by the CAST gene, contains one N-terminal regulatory domain and four repetitive calpain-inhibition domains. It tightly controls calpain activity, which is critical for cellular functions including cytoskeletal remodeling, signal transduction, membrane fusion events, cell cycle progression, and apoptosis. Calpastatin acts by reversible, calcium-dependent binding and inhibition of calpain, uniquely blocking the protease without itself being cleaved, through a novel domain conformational mechanism. Dysregulation of calpastatin or calpain activity is implicated in diseases such as muscular dystrophy, skin disorders, cancer, and neurodegenerative diseases.

Other names

BS-17MIR583HGPLACKcalpastatinMIR583 hostcalpain inhibitorsperm BS-17 componentCAST

Competitive inhibition of calpain active site in a calcium-dependent manner. Occupies calpain active site cleft to block substrate access, escapes cleavage by a novel looping mechanism.