Reaction: Strict requirement for Asp at the P1 position. It has a preferred cleavage sequence of Tyr-Val-Ala-Asp but also cleaves at Asp-Glu-Val-Asp
Other name(s): ICErel-III; Ich-3; ICH-3 protease; transcript Y; TY; CASP-5
Comments: This enzyme is part of the family of inflammatory caspases, which also includes caspase-1 (EC 3.4.22.36) and caspase-4 (EC 3.4.22.57) in humans and caspase-11 (EC 3.4.22.64), caspase-12, caspase-13 and caspase-14 in mice. Contains a caspase-recruitment domain (CARD) in its N-terminal prodomain, which plays a role in procaspase activation [3,5,6]. The enzyme is able to cleave itself and the p30 caspase-1 precursor, but is very inefficient at generating mature interleukin-1β (IL-1β) from pro-IL-1β [1,4]. Both this enzyme and caspase-4 can cleave pro-caspase-3 to release the small subunit (p12) but not the large subunit (p17) [3]. Unlike caspase-4, this enzyme can be induced by lipopolysaccharide [3]. Belongs in peptidase family C14.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 192465-11-5
References:
1. Faucheu, C., Blanchet, A.M., Collard-Dutilleul, V., Lalanne, J.L. and Diu-Hercend, A. Identification of a cysteine protease closely related to interleukin-1 β-converting enzyme. Eur. J. Biochem. 236 (1996) 207-213. [PMID: 8617266]
2. Kamada, S., Funahashi, Y. and Tsujimoto, Y. Caspase-4 and caspase-5, members of the ICE/CED-3 family of cysteine proteases, are CrmA-inhibitable proteases. Cell Death Differ. 4 (1997) 473-478. [PMID: 16465268]
3. Lin, X.Y., Choi, M.S. and Porter, A.G. Expression analysis of the human caspase-1 subfamily reveals specific regulation of the CASP5 gene by lipopolysaccharide and interferon-γ. J. Biol. Chem. 275 (2000) 39920-39926. [PMID: 10986288]
4. Fassy, F., Krebs, O., Rey, H., Komara, B., Gillard, C., Capdevila, C., Yea, C., Faucheu, C., Blanchet, A.M., Miossec, C. and Diu-Hercend, A. Enzymatic activity of two caspases related to interleukin-1β-converting enzyme. Eur. J. Biochem. 253 (1998) 76-83. [PMID: 9578463]
5. Martinon, F. and Tschopp, J. Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases. Cell 117 (2004) 561-574. [PMID: 15163405]
6. 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]