but also cleaves at Asp-Glu-Val-Asp
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): ICErelII; ICErel-II; Ich-2; transcript X; TX; TX protease; caspase 4; CASP-4
Comments: This enzyme is part of the family of inflammatory caspases, which also includes caspase-1 (EC 3.4.22.36) 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 [3,5,6]. The enzyme is able to cleave itself and the p30 caspase-1 precursor, but, unlike caspase-1, it is very inefficient at generating mature interleukin-1β (IL-1β) from pro-IL-1β [1,4]. Both this enzyme and caspase-5 can cleave pro-caspase-3 to release the small subunit (p12) but not the large subunit (p17) [3]. The caspase-1 inhibitor Ac-Tyr-Val-Ala-Asp-CHO can also inhibit this enzyme, but more slowly [4]. Belongs in C14 Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 182762-08-9
References:
1. Faucheu, C., Diu, A., Chan, A.W., Blanchet, A.M., Miossec, C., Hervé, F., Collard-Dutilleul, V., Gu, Y., Aldape, R.A., Lippke, J.A., Rocher, C., Su, M.S.-S., Livingston, D.J., Hercend, T. and Lalanne, J.-L. A novel human protease similar to the interleukin-1β converting enzyme induces apoptosis in transfected cells. EMBO J. 14 (1995) 1914-1922. [PMID: 7743998]
2. Kamens, J., Paskind, M., Hugunin, M., Talanian, R.V., Allen, H., Banach, D., Bump, N., Hackett, M., Johnston, C.G., Li, P., Mankovich, J.A., Terranova, M. and Ghayur, T. Identification and characterization of ICH-2, a novel member of the interleukin-1β-converting enzyme family of cysteine proteases. J. Biol. Chem. 270 (1995) 15250-15256. [PMID: 7797510]
3. 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]
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]