Reaction: Strict requirement for an Asp residue at positions P1 and P4. It has a preferred cleavage sequence of Asp-Xaa-Xaa-Asp with a hydrophobic amino-acid residue at P2 and a hydrophilic amino-acid residue at P3, although Val or Ala are also accepted at this position
Other name(s): CPP32; apopain; yama protein
Comments: Caspase-3 is an effector/executioner caspase, as are caspase-6 (EC 188.8.131.52) and caspase-7 (EC 184.108.40.206) . These caspases are responsible for the proteolysis of the majority of cellular polypeptides [e.g. poly(ADP-ribose) polymerase (PARP)], which leads to the apoptotic phenotype [3,5]. Procaspase-3 can be activated by caspase-1 (EC 220.127.116.11), caspase-8 (EC 18.104.22.168), caspase-9 (EC 22.214.171.124) and caspase-10 (EC 126.96.36.199) as well as by the serine protease granzyme B . Caspase-3 can activate procaspase-2 (EC 188.8.131.52) . Activation occurs by inter-domain cleavage followed by removal of the N-terminal prodomain . Although Asp-Glu-(Val/Ile)-Asp is thought to be the preferred cleavage sequence, the enzyme can accommodate different residues at P2 and P3 of the substrate . Like caspase-2, a hydrophobic residue at P5 of caspase-3 leads to more efficient hydrolysis, e.g. (Val/Leu)-Asp-Val-Ala-Asp is a better substrate than Asp-Val-Ala-Asp . This is not the case for caspase-7 . Belongs in peptidase family C14.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 169592-56-7
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