EC 3.4.21.112 - Site-1 protease

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IntEnz Enzyme Nomenclature
EC 3.4.21.112

Names

Accepted name:
site-1 protease
Other names:
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
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
subtilisin/kexin isozyme 1
Systematic name:
-

Reaction

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

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , MEROPS , UniPathway
Protein domains and families: PROSITE:PDOC00125
Structural data: CSA , EC2PDB
UniProtKB/Swiss-Prot:

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 : 22795-22804 (1999). [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 : 22805-22812 (1999). [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 : 2349-2358 (2000). [PMID: 10644685]
  4. Ye, J., Rawson, R.B., Komuro, R., Chen, X., Davé, 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 : 1355-1364 (2000). [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 : 12701-12705 (2001). [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 : 333-339 (2002). [PMID: 11943176]
  7. Vincent, M.J., Sanchez, A.J., Erickson, B.R., Basak, A., Chrétien, M., Seidah, N.G. and Nichol, S.T.
    Crimean-Congo hemorrhagic fever virus glycoprotein proteolytic processing by subtilase SKI-1.
    J. Virol. 77 : 8640-8649 (2003). [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 (Eds.) Handbook of proteolytic enyzmes , 2nd ed. vol. 2 , Elsevier , London , 2004 , 1845-1847

[EC 3.4.21.112 created 2006]