Reaction: Strict requirement for an Asp residue at position P1 and with a marked preference for His at position P2. It has a preferred cleavage sequence of Leu-Gly-His-AspXaa
Other name(s): CASP-9; ICE-like apoptotic protease 6; ICE-LAP6; apoptotic protease Mch-6; apoptotic protease-activating factor 3; APAF-3
Comments: Caspase-9 is an initiator caspase, as are caspase -2 (EC 126.96.36.199), caspase-8 (EC 188.8.131.52) and caspase-10 (EC 184.108.40.206) . Caspase-9 contains a caspase-recruitment domain (CARD) in its N-terminal prodomain, which plays a role in procaspase activation . An alternatively spliced version of caspase-9 also exists, caspase-9S, that inhibits apoptosis, similar to the situation found with caspase-2 . Phosphorylation of caspase-9 from some species by Akt, a serine-threonine protein kinase, inhibits caspase activity in vitro and caspase activation in vivo . The activity of caspase-9 is increased dramatically upon association with the apoptosome but the enzyme can be activated without proteolytic cleavage [2,3]. Procaspase-3 is the enzyme's physiological substrate . Belongs in peptidase family C14.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 180189-96-2
1. Chang, H.Y. and Yang, X. Proteases for cell suicide: functions and regulation of caspases. Microbiol. Mol. Biol. Rev. 64 (2000) 821-846. [PMID: 11104820]
2. Yin, Q., Park, H.H., Chung, J.Y., Lin, S.C., Lo, Y.C., da Graca, L.S., Jiang, X. and Wu, H. Caspase-9 holoenzyme is a specific and optimal procaspase-3 processing machine. Mol. Cell. 22 (2006) 259-268. [PMID: 16630893]
3. Boatright, K.M., Renatus, M., Scott, F.L., Sperandio, S., Shin, H., Pedersen, I.M., Ricci, J.E., Edris, W.A., Sutherlin, D.P., Green, D.R. and Salvesen, G.S. A unified model for apical caspase activation. Mol. Cell. 11 (2003) 529-541. [PMID: 12620239]
4. Salvesen, G.S. and Boatright, K.M. Caspase-9. In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Eds), Handbook of Proteolytic Enzymes, 2nd edn, Elsevier, London, 2004, pp. 1296-1298.