site-1 protease;
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

Hydrolases;
Acting on peptide bonds (peptidases);
Serine endopeptidases

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

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.

1  [PMID:10428864]

Espenshade PJ, Cheng D, Goldstein JL, Brown MS.

Autocatalytic processing of site-1 protease removes propeptide and permits cleavage of sterol regulatory element-binding proteins.

J. Biol. Chem. 274 (1999) 22795-804.

Homo sapiens [GN:hsa], Cricetulus griseus

2  [PMID:10428865]

Cheng D, Espenshade PJ, Slaughter CA, Jaen JC, Brown MS, Goldstein JL.

Secreted site-1 protease cleaves peptides corresponding to luminal loop of sterol regulatory element-binding proteins.

J. Biol. Chem. 274 (1999) 22805-12.

Cricetulus griseus

3  [PMID:10644685]

Toure BB, Munzer JS, Basak A, Benjannet S, Rochemont J, Lazure C, Chretien M, Seidah NG.

Biosynthesis and enzymatic characterization of human SKI-1/S1P and the processing of its inhibitory prosegment.

J. Biol. Chem. 275 (2000) 2349-58.

Homo sapiens [GN:hsa]

4  [PMID:11163209]

Ye J, Rawson RB, Komuro R, Chen X, Dave UP, Prywes R, Brown MS, Goldstein JL.

ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs.

Mol. Cell. 6 (2000) 1355-64.

Homo sapiens [GN:hsa]

5  [PMID:11606739]

Lenz O, ter Meulen J, Klenk HD, Seidah NG, Garten W.

The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P.

Proc. Natl. Acad. Sci. U. S. A. 98 (2001) 12701-5.

Homo sapiens [GN:hsa], Mus musculus [GN:mmu], Rattus norvegicus [GN:rno], Cricetulus griseus

6  [PMID:11943176]

Basak A, Chretien M, Seidah NG.

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) 333-9.

7  [PMID:12885882]

Vincent MJ, Sanchez AJ, Erickson BR, Basak A, Chretien M, Seidah NG, Nichol ST.

Crimean-Congo hemorrhagic fever virus glycoprotein proteolytic processing by subtilase SKI-1.

J. Virol. 77 (2003) 8640-9.

Homo sapiens [GN:hsa]

8

Seidah, N.G. and Chretien, M.

Proprotein convertase SKI-1/S1P.

In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Eds.), Handbook of Proteolytic Enzymes, 2nd ed., vol. 2, Elsevier, London, 2004, p. 1845-1847.