Reaction: Strict requirement for an Asp residue at position P1 and has a preferred cleavage sequence of Tyr-Val-Ala-Asp
Other name(s): interleukin 1β-converting enzyme; protease VII; protease A; interleukin 1β precursor proteinase; interleukin 1 converting enzyme; interleukin 1β-converting endopeptidase; interleukin-1β convertase; interleukin-1β converting enzyme; interleukin-1β precursor proteinase; prointerleukin 1β protease; precursor interleukin-1β converting enzyme; pro-interleukin 1β proteinase; ICE
Comments: From mammalian monocytes. This enzyme is part of the family of inflammatory caspases, which also includes caspase-4 (EC 3.4.22.57) and caspase-5 (EC 3.4.22.58) 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 [6,7]. Cleaves pro-interleukin-1β (pro-IL-1β) to form mature IL-1β, a potent mediator of inflammation. Also activates the proinflammatory cytokine, IL-18, which is also known as interferon-γ-inducing factor [6]. Inhibited by Ac-Tyr-Val-Ala-Asp-CHO. Caspase-11 plays a critical role in the activation of caspase-1 in mice, whereas caspase-4 enhances its activation in humans [7]. Belongs in peptidase family C14.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 122191-40-6
References:
1. Howard, A., Kostura, M.J., Thornberry, N., Ding, G.J.., Limjuco, G., Weidner, J., Salley, J.P., Hogquist, K.A., Chaplin, D.D., Mumford, R.A., Schmidt, J.A. and Tocci, M.J. IL-1 converting enzyme requires aspartic acid residues for processing of the IL-1β precursor at two distinct sites and does not cleave 31-kDa IL-1α. J. Immunol. 147 (1991) 2964-2969. [PMID: 1919001]
2. Thornberry, N.A., Bull, H.G., Calaycay, J.R., Chapman, K.T., Howard, A.D., Kostura, M.J., Miller, D.K., Molineaux, S.M., Weidner, J.R., Aunins, J., Elliston, K.O., Ayala, J.M., Casano, F J., Chin, J., Ding, G.J.-F., Egger, L.A., Gaffney, E.P., Limjuco, G., Palyha, O.C., Raju, S.M., Rolando, A.M., Salley, J.P., Yamin, T.-T. and Tocci, M.J. A novel heterodimeric cysteine protease is required for interleukin-1β processing in monocytes. Nature 356 (1992) 768-774. [PMID: 1574116]
3. Thornberry, N.A. Interleukin-1β converting enzyme. Methods Enzymol. 244 (1994) 615-631. [PMID: 7845238]
4. Alnemri, E.S., Livingston, D.J., Nicholson, D.W., Salvesen, G., Thornberry, N.A., Wong, W.W. and Yuan, J.Y. Human ICE/CED-3 protease nomenclature. Cell 87 (1996) 171 only. [PMID: 8861900]
5. Margolin, N., Raybuck, S.A., Wilson, K.P., Chen, W.Y., Fox, T., Gu, Y. and Livingston, D.J. Substrate and inhibitor specificity of interleukin-1β-converting enzyme and related caspases. J. Biol. Chem. 272 (1997) 7223-7228. [PMID: 9054418]
6. Martinon, F. and Tschopp, J. Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases. Cell 117 (2004) 561-574. [PMID: 15163405]
7. 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]