{PDOC00864} {PS01121; CASPASE_HIS} {PS01122; CASPASE_CYS} {PS50207; CASPASE_P10} {PS50208; CASPASE_P20} {BEGIN} ****************************************** * Caspase family signatures and profiles * ****************************************** Interleukin-1 beta converting enzyme (EC 3.4.22.36) (ICE) [1,2] is responsible for the cleavage of the IL-1 beta precursor at an Asp-Ala bond to generate the mature biologically active cytokine. ICE a thiol protease composed of two subunits of 10 (p10) and 20 Kd (p20), both derived by the autocleavage of a 45 Kd precursor (p45). Two residues are implicated in the catalytic mechanism: a cysteine and an histidine. They are located in the P20 subunit after cleavage of the precursor. ICE belongs to a family of peptidases [3] which is implicated in programmed cell death (apoptosis) and which has been termed 'caspase' for cysteine aspase. ICE is known as Caspase-1 and the other members of this family [4] are: - Caspase-2 (ICH-1, NEDD-2). - Caspase-3 (also known as apopain, CPP32, Yama), a protease which, at the onset of apoptosis, proteolytically cleaves poly(ADP-ribose) polymerase (see ) at an Asp-Gly bond. - Caspase-4 (ICH-2, TX, ICErel-II). - Caspase-5 (ICH-3, TY, ICErel-III). - Caspase-6 (MCH-2). - Caspase-7 (MCH-3, ICE-LAP3, CMH-1, SCA-2, LICE2). - Caspase-8 (MCH-5, MACH, FLICE). - Caspase-9 (MCH-6, ICE-LAP6). - Caspase-10 (MCH-4, FLICE2). - Caspase-11. - Caspase-12. - Caspase-13 (ERICE). - Caspase-14. - Caenorhabditis elegans ced-3 involved in the initiation of apoptosis. - Drosophila Ice. We have developed signature patterns for both active site residues. We also developed two profiles, one specific for the caspase P10 subunit and one for the caspase P20 subunit. -Consensus pattern: H-x(2,4)-[SC]-x(2)-{A}-x-[LIVMF](2)-[ST]-H-G [The second H is an active site residue] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: 5. -Consensus pattern: K-P-K-[LIVMF]-[LIVMFY]-[LIVMF](2)-[QP]-[AF]-C-[RQG]-[GE] [C is the active site residue] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Note: These proteins belong to family C14 in the classification of peptidases [5,E1]. -Last update: December 2004 / Patterns and text revised. [ 1] Thornberry N.A., Molineaux S.M. "Interleukin-1 beta converting enzyme: a novel cysteine protease required for IL-1 beta production and implicated in programmed cell death." Protein Sci. 4:3-12(1995). PubMed=7773174 [ 2] Kumar S. "ICE-like proteases in apoptosis." Trends Biochem. Sci. 20:198-202(1995). PubMed=7610484 [ 3] Nicholson D.W., Thornberry N.A. "Caspases: killer proteases." Trends Biochem. Sci. 22:299-306(1997). PubMed=9270303 [ 4] Alnemri E.S., Livingston D.J., Nicholson D.W., Salvesen G., Thornberry N.A., Wong W.W., Yuan J. "Human ICE/CED-3 protease nomenclature." Cell 87:171-171(1996). PubMed=8861900 [ 5] Rawlings N.D., Barrett A.J. "Evolutionary families of peptidases." Biochem. J. 290:205-218(1993). PubMed=8439290 [E1] https://www.uniprot.org/docs/peptidas -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}