ExplorEnz: EC 3.4.21.112

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3.4.21.112

Accepted name:

site-1 protease

Reaction:

Processes precursors containing basic and hydrophobic/aliphatic residues at P4 and P2, respectively, with a relatively relaxed acceptance of amino acids at P1 and P3

Other name(s):

mammalian subtilisin/kexin isozyme 1; membrane-bound transcription factor site-1 protease; proprotein convertase SKI-1; proprotein convertase SKI-1/S1PPS1; S1P endopeptidase; S1P protease; site-1 peptidase; site-1 protease; SKI-1; SREBP proteinase; SREBP S1 protease; SREBP-1 proteinase; SREBP-2 proteinase; sterol regulatory element-binding protein proteinase; sterol regulatory element-binding protein site 1 protease; sterol-regulated luminal protease; subtilase SKI-1; subtilase SKI-1/S1P; subtilisin/kexin-isozyme 1

Comments:

Cleaves sterol regulatory element-binding proteins (SREBPs) and thereby initiates a process by which the active fragments of the SREBPs translocate to the nucleus and activate genes controlling the synthesis and uptake of cholesterol and unsaturated fatty acids into the bloodstream [1]. The enzyme also processes pro-brain-derived neurotrophic factor and undergoes autocatalytic activation in the endoplasmic reticulum through sequential cleavages [5]. The enzyme can also process the unfolded protein response stress factor ATF6 at an Arg-His-Lys-Lys┼ site [4,8], and the envelope glycoprotein of the highly infectious Lassa virus [5,8] and Crimean Congo hemorrhagic fever virus at Arg-Arg-Lys-Lys┼ [7,8]. Belongs in peptidase family S8A.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, MetaCyc, CAS registry number: 167140-48-9

References:

1.	Espenshade, P.J., Cheng, D., Goldstein, J.L. and Brown, M.S. Autocatalytic processing of site-1 protease removes propeptide and permits cleavage of sterol regulatory element-binding proteins. J. Biol. Chem. 274 (1999) 22795–22804. [DOI] [PMID: 10428864]
2.	Cheng, D., Espenshade, P.J., Slaughter, C.A., Jaen, J.C., Brown, M.S. and Goldstein, J.L. Secreted site-1 protease cleaves peptides corresponding to luminal loop of sterol regulatory element-binding proteins. J. Biol. Chem. 274 (1999) 22805–22812. [DOI] [PMID: 10428865]
3.	Touré, B.B., Munzer, J.S., Basak, A., Benjannet, S., Rochemont, J., Lazure, C., Chrétien, M. and Seidah, N.G. Biosynthesis and enzymatic characterization of human SKI-1/S1P and the processing of its inhibitory prosegment. J. Biol. Chem. 275 (2000) 2349–2358. [DOI] [PMID: 10644685]
4.	Ye, J., Rawson, R.B., Komuro, R., Chen, X., Dave, U.P., Prywes, R., Brown, M.S. and Goldstein, J.L. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol. Cell 6 (2000) 1355–1364. [DOI] [PMID: 11163209]
5.	Lenz, O., ter Meulen, J., Klenk, H.D., Seidah, N.G. and Garten, W. The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P. Proc. Natl. Acad. Sci. USA 98 (2001) 12701–12705. [DOI] [PMID: 11606739]
6.	Basak, A., Chrétien, M. and Seidah, N.G. A rapid fluorometric assay for the proteolytic activity of SKI-1/S1P based on the surface glycoprotein of the hemorrhagic fever Lassa virus. FEBS Lett. 514 (2002) 333–339. [DOI] [PMID: 11943176]
7.	Vincent, M.J., Sanchez, A.J., Erickson, B.R., Basak, A., Chretien, M., Seidah, N.G. and Nichol, S.T. Crimean-Congo hemorrhagic fever virus glycoprotein proteolytic processing by subtilase SKI-1. J. Virol. 77 (2003) 8640–8649. [DOI] [PMID: 12885882]
8.	Seidah, N.G. and Chrétien, M. Proprotein convertase SKI-1/S1P. In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Ed.), Handbook of Proteolytic Enzymes, 2nd edn, vol. 2, Elsevier, London, 2004, pp. 1845–1847.

[EC 3.4.21.112 created 2006]