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Entry
EC 3.4.21.112               Enzyme                                 

Name
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
Class
Hydrolases;
Acting on peptide bonds (peptidases);
Serine endopeptidases
BRITE hierarchy
Reaction(IUBMB)
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
Comment
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.
History
EC 3.4.21.112 created 2006
Orthology
K08653  
membrane-bound transcription factor site-1 protease
Genes
HSA: 
8720(MBTPS1)
PTR: 
468050(MBTPS1)
PPS: 
100979845(MBTPS1)
GGO: 
101137346(MBTPS1)
PON: 
100173978(MBTPS1)
MCC: 
714706(MBTPS1)
MCF: 
MMU: 
56453(Mbtps1)
RNO: 
89842(Mbtps1)
CGE: 
100689417(Mbtps1)
HGL: 
101713902(Mbtps1)
TUP: 
102475098(MBTPS1)
CFA: 
489684(MBTPS1)
AML: 
100475586(MBTPS1)
FCA: 
101081852(MBTPS1)
PTG: 
102956847(MBTPS1)
BTA: 
511682(MBTPS1)
BOM: 
102286126(MBTPS1)
PHD: 
102326022(MBTPS1)
CHX: 
102183994(MBTPS1)
SSC: 
100516674(MBTPS1)
CFR: 
102516706(MBTPS1)
BACU: 
103010202(MBTPS1)
LVE: 
103091271(MBTPS1)
ECB: 
100055849(MBTPS1)
MYB: 
102256869(MBTPS1)
MYD: 
102773346(MBTPS1)
PALE: 
102897410(MBTPS1)
MDO: 
100617183(MBTPS1)
SHR: 
100918690(MBTPS1)
OAA: 
100092098(MBTPS1)
GGA: 
415704(MBTPS1)
MGP: 
100541007(MBTPS1)
TGU: 
100232413(MBTPS1)
FAB: 
101810063(MBTPS1)
PHI: 
102103379(MBTPS1)
APLA: 
101798578(MBTPS1)
FPG: 
101922174(MBTPS1)
FCH: 
102053830(MBTPS1)
CLV: 
102088320(MBTPS1)
ASN: 
102387504(MBTPS1)
AMJ: 
102575073(MBTPS1)
PSS: 
102450666(MBTPS1)
CMY: 
102940720(MBTPS1)
ACS: 
100556053(mbtps1)
PBI: 
XLA: 
447205(mbtps1)
XTR: 
780252(mbtps1)
DRE: 
326710(mbtps1)
TRU: 
MZE: 
OLA: 
XMA: 
LCM: 
102363551(MBTPS1)
CMK: 
103185935(mbtps1)
BFO: 
CIN: 
100177229(mbtps1)
SPU: 
DME: 
DAN: 
DER: 
DPE: 
DSE: 
DSI: 
DWI: 
DYA: 
DGR: 
DMO: 
DVI: 
AGA: 
AAG: 
CQU: 
AME: 
412293(GB12105)
NVI: 
TCA: 
BMOR: 
API: 
PHU: 
BMY: 
LOA: 
SMM: 
HMG: 
TAD: 
AQU: 
ATH: 
ALY: 
CRB: 
EUS: 
CIT: 
CIC: 
TCC: 
GMX: 
PVU: 
MTR: 
CAM: 
101499133(MBTPS1)
FVE: 
PPER: 
CSV: 
101222509(MBTPS1)
RCU: 
POP: 
POPTR_0018s08810g(POPTRDRAFT_779308)
VVI: 
100264570(MBTPS1)
SLY: 
SOT: 
OSA: 
DOSA: 
Os06t0163500-01(Os06g0163500)
OBR: 
BDI: 
100822086(MBTPS1)
SBI: 
SORBI_10g004450(SORBIDRAFT_10g004450)
SITA: 
ATR: 
s00109p00040520(AMTR_s00109p00040520)
SMO: 
PPP: 
CRE: 
VCN: 
OLU: 
OTA: 
MIS: 
MPP: 
BPG: 
CSL: 
CVR: 
GSL: 
CCP: 
MBR: 
DDI: 
DDB_G0282397(mbtps1)
DPP: 
DFA: 
ACAN: 
PIF: 
EHX: 
NGR: 
 » show all
Taxonomy
Reference
1  [PMID:10428864]
  Authors
Espenshade PJ, Cheng D, Goldstein JL, Brown MS.
  Title
Autocatalytic processing of site-1 protease removes propeptide and permits cleavage of sterol regulatory element-binding proteins.
  Journal
J. Biol. Chem. 274 (1999) 22795-804.
  Organism
Homo sapiens, Cricetulus griseus
Reference
2  [PMID:10428865]
  Authors
Cheng D, Espenshade PJ, Slaughter CA, Jaen JC, Brown MS, Goldstein JL.
  Title
Secreted site-1 protease cleaves peptides corresponding to luminal loop of sterol regulatory element-binding proteins.
  Journal
J. Biol. Chem. 274 (1999) 22805-12.
  Organism
Cricetulus griseus
Reference
3  [PMID:10644685]
  Authors
Toure BB, Munzer JS, Basak A, Benjannet S, Rochemont J, Lazure C, Chretien M, Seidah NG.
  Title
Biosynthesis and enzymatic characterization of human SKI-1/S1P and the processing of its inhibitory prosegment.
  Journal
J. Biol. Chem. 275 (2000) 2349-58.
  Organism
Homo sapiens
  Sequence
[hsa:8720]
Reference
4  [PMID:11163209]
  Authors
Ye J, Rawson RB, Komuro R, Chen X, Dave UP, Prywes R, Brown MS, Goldstein JL.
  Title
ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs.
  Journal
Mol. Cell. 6 (2000) 1355-64.
  Organism
Homo sapiens
  Sequence
[hsa:22926]
Reference
5  [PMID:11606739]
  Authors
Lenz O, ter Meulen J, Klenk HD, Seidah NG, Garten W.
  Title
The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P.
  Journal
Proc. Natl. Acad. Sci. U. S. A. 98 (2001) 12701-5.
  Organism
Homo sapiens, Mus musculus, Rattus norvegicus, Cricetulus griseus
  Sequence
[up:P08669]
Reference
6  [PMID:11943176]
  Authors
Basak A, Chretien M, Seidah NG.
  Title
A rapid fluorometric assay for the proteolytic activity of SKI-1/S1P based on the surface glycoprotein of the hemorrhagic fever Lassa virus.
  Journal
FEBS. Lett. 514 (2002) 333-9.
Reference
7  [PMID:12885882]
  Authors
Vincent MJ, Sanchez AJ, Erickson BR, Basak A, Chretien M, Seidah NG, Nichol ST.
  Title
Crimean-Congo hemorrhagic fever virus glycoprotein proteolytic processing by subtilase SKI-1.
  Journal
J. Virol. 77 (2003) 8640-9.
  Organism
Homo sapiens
Reference
8
  Authors
Seidah, N.G. and Chretien, M.
  Title
Proprotein convertase SKI-1/S1P.
  Journal
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.
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 
CAS: 
167140-48-9

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