EC |
3.4.22.63 |
Accepted name: |
caspase-10 |
Reaction: |
Strict requirement for Asp at position P1 and has a preferred cleavage sequence of Leu-Gln-Thr-Asp┼Gly |
Other name(s): |
FLICE2; Mch4; CASP-10; ICE-like apoptotic protease 4; apoptotic protease Mch-4; FAS-associated death domain protein interleukin-1β-converting enzyme 2 |
Comments: |
Caspase-10 is an initiator caspase, as are caspase-2 (EC 3.4.22.55), caspase-8 (EC 3.4.22.61) and caspase-9 (EC 3.4.22.62) [1]. Like caspase-8, caspase-10 contains two tandem death effector domains (DEDs) in its N-terminal prodomain, and these play a role in procaspase activation [1]. The enzyme has many overlapping substrates in common with caspase-8, such as RIP (the cleavage of which impairs NF-κB survival signalling and starts the cell-death process) and PAK2 (associated with some of the morphological features of apoptosis, such as cell rounding and apoptotic body formation) [2]. Bid, a Bcl2 protein, can be cleaved by caspase-3 (EC 3.4.22.56), caspase-8 and caspase-10 at Lys-Gln-Thr-Asp┼ to yield the pro-apoptotic p15 fragment. The p15 fragment is N-myristoylated and enhances the release of cytochrome c from mitochondria (which, in turn, initiatiates the intrinsic apoptosis pathway). Bid can be further cleaved by caspase-10 and granzyme B but not by caspase-3 or caspase-8 at Ile-Glu-Thr-Asp┼ to yield a p13 fragment that is not N-myristoylated [2]. Belongs in peptidase family C14. |
Links to other databases: |
BRENDA, EXPASY, Gene, KEGG, MetaCyc, CAS registry number: 189088-85-5 |
References: |
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. |
Fischer, U., Stroh, C. and Schulze-Osthoff, K. Unique and overlapping substrate specificities of caspase-8 and caspase-10. Oncogene 25 (2006) 152–159. [DOI] [PMID: 16186808] |
3. |
Shikama, Y., Yamada, M. and Miyashita, T. Caspase-8 and caspase-10 activate NF-κB through RIP, NIK and IKKα kinases. Eur. J. Immunol. 33 (2003) 1998–2006. [DOI] [PMID: 12884866] |
4. |
Boatright, K.M., Deis, C., Denault, J.B., Sutherlin, D.P. and Salvesen, G.S. Activation of caspases-8 and -10 by FLIPL. Biochem. J. 382 (2004) 651–657. [DOI] [PMID: 15209560] |
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[EC 3.4.22.63 created 2007] |
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