Reaction: Cleavage of non-polar aliphatic amino-acids at the P1 position, with a preference for Val, Ile and Met. At the P2 and P3 positions, Arg is selected most strongly with a secondary preference for other hydrophilic residues
Other name(s): high temperature requirement protein A2; HtrA2; Omi stress-regulated endoprotease; serine proteinase OMI; HtrA2 protease; OMI/HtrA2 protease; HtrA2/Omi; Omi/HtrA2
Comments: This enzyme is upregulated in mammalian cells in response to stress induced by both heat shock and tunicamycin treatment [4]. It can induce apoptosis in a caspase-independent manner through its peptidase activity and in a caspase-dependent manner by disrupting the interaction between caspase and the inhibitor of apoptosis (IAP) [3]. Belongs in peptidase family S1C.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number:
References:
1. Srinivasula, S.M., Gupta, S., Datta, P., Zhang, Z., Hegde, R., Cheong, N., Fernandes-Alnemri, T. and Alnemri, E.S. Inhibitor of apoptosis proteins are substrates for the mitochondrial serine protease Omi/HtrA2. J. Biol. Chem. 278 (2003) 31469-31472. [PMID: 12835328]
2. Savopoulos, J.W., Carter, P.S., Turconi, S., Pettman, G.R., Karran, E.H., Gray, C.W., Ward, R.V., Jenkins, O. and Creasy, C.L. Expression, purification, and functional analysis of the human serine protease HtrA2. Protein. Expr. Purif. 19 (2000) 227-234. [PMID: 10873535]
3. Martins, L.M., Turk, B.E., Cowling, V., Borg, A., Jarrell, E.T., Cantley, L.C. and Downward, J. Binding specificity and regulation of the serine protease and PDZ domains of HtrA2/Omi. J. Biol. Chem. 278 (2003) 49417-49427. [PMID: 14512424]
4. Gray, C.W., Ward, R.V., Karran, E., Turconi, S., Rowles, A., Viglienghi, D., Southan, C., Barton, A., Fantom, K.G., West, A., Savopoulos, J., Hassan, N.J., Clinkenbeard, H., Hanning, C., Amegadzie, B., Davis, J.B., Dingwall, C., Livi, G.P. and Creasy, C.L. Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response. Eur. J. Biochem. 267 (2000) 5699-5710. [PMID: 10971580]
5. Li, W., Srinivasula, S.M., Chai, J., Li, P., Wu, J.W., Zhang, Z., Alnemri, E.S. and Shi, Y. Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi. Nat. Struct. Biol. 9 (2002) 436-441. [PMID: 11967569]