KEGG   ENZYME: 3.4.21.112Help
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)
NLE: 100590889(MBTPS1)
MCC: 714706(MBTPS1)
MCF: 101865233(MBTPS1)
CSAB: 103233385(MBTPS1)
RRO: 104656040(MBTPS1)
RBB: 108521220(MBTPS1)
CJC: 100402317(MBTPS1)
SBQ: 101033437(MBTPS1)
MMU: 56453(Mbtps1)
RNO: 89842(Mbtps1)
CGE: 100689417(Mbtps1)
NGI: 103729839(Mbtps1)
HGL: 101713902(Mbtps1)
CCAN: 109689505(Mbtps1)
OCU: 100344035(MBTPS1)
TUP: 102475098(MBTPS1)
CFA: 489684(MBTPS1)
AML: 100475586(MBTPS1)
UMR: 103662102(MBTPS1)
ORO: 101375212(MBTPS1)
FCA: 101081852(MBTPS1)
PTG: 102956847(MBTPS1)
AJU: 106985623(MBTPS1)
BTA: 511682(MBTPS1)
BOM: 102286126(MBTPS1)
BIU: 109572546(MBTPS1)
PHD: 102326022(MBTPS1)
CHX: 102183994(MBTPS1)
OAS: 101101912(MBTPS1)
SSC: 100516674(MBTPS1)
CFR: 102516706(MBTPS1)
CDK: 105089450(MBTPS1)
BACU: 103010202(MBTPS1)
LVE: 103091271(MBTPS1)
OOR: 101282350(MBTPS1)
ECB: 100055849(MBTPS1)
EPZ: 103557970(MBTPS1)
EAI: 106831751(MBTPS1)
MYB: 102256869(MBTPS1)
MYD: 102773346(MBTPS1)
HAI: 109378384(MBTPS1)
RSS: 109453717(MBTPS1)
PALE: 102897410(MBTPS1)
LAV: 100657282(MBTPS1)
TMU: 101348770
MDO: 100617183(MBTPS1)
SHR: 100918690(MBTPS1)
OAA: 100092098(MBTPS1)
GGA: 415704(MBTPS1)
MGP: 100541007(MBTPS1)
CJO: 107319051(MBTPS1)
APLA: 101798578(MBTPS1)
ACYG: 106043118(MBTPS1)
TGU: 100232413(MBTPS1)
GFR: 102042134(MBTPS1)
FAB: 101810063(MBTPS1)
PHI: 102103379(MBTPS1)
PMAJ: 107209834(MBTPS1)
CCAE: 111934551(MBTPS1)
CCW: 104687491(MBTPS1)
FPG: 101922174(MBTPS1)
FCH: 102053830(MBTPS1)
CLV: 102088320(MBTPS1)
EGZ: 104130222(MBTPS1)
AAM: 106483180(MBTPS1)
ASN: 102387504(MBTPS1)
AMJ: 102575073(MBTPS1)
PSS: 102450666(MBTPS1)
CMY: 102940720(MBTPS1)
CPIC: 101944235(MBTPS1)
ACS: 100556053(mbtps1)
PVT: 110085711(MBTPS1)
GJA: 107106027(MBTPS1)
XLA: 447205(mbtps1.L)
XTR: 780252(mbtps1)
NPR: 108796565(MBTPS1)
DRE: 326710(mbtps1)
SRX: 107726427 107733569(mbtps1)
IPU: 108264661(mbtps1)
AMEX: 103032608(mbtps1)
LCO: 104928249(mbtps1) 109140734
NCC: 104942697(mbtps1) 104967680
MZE: 101483615(mbtps1)
OLA: 101164978(mbtps1)
XMA: 102226028(mbtps1)
PRET: 103466358(mbtps1)
NFU: 107388539(mbtps1) 107395794
KMR: 108246903(mbtps1)
CSEM: 103379480(mbtps1) 103399614
LCF: 108901908(mbtps1)
SDU: 111225253(mbtps1)
HCQ: 109530407(mbtps1)
BPEC: 110169296(mbtps1)
MALB: 109962518(mbtps1)
OTW: 112252364(mbtps1)
ELS: 105018457(mbtps1)
SFM: 108918985(mbtps1)
LCM: 102363551(MBTPS1)
CMK: 103185935(mbtps1)
CIN: 100177229(mbtps1)
APLC: 110984753
SKO: 100375372(MBTPS1)
DME: Dmel_CG7169(S1P)
DSI: Dsimw501_GD12102(Dsim_GD12102)
MDE: 105261606
AAG: 5578190
AME: 412293
BIM: 100743550
BTER: 100643281
SOC: 105204443
AEC: 105153826
ACEP: 105624409
PBAR: 105423249
HST: 105190108
DQU: 106752164
CFO: 105258722
LHU: 105673703
PGC: 109856230
PCF: 106789824
NVI: 100123523
MDL: 103570637
TCA: 100142346
DPA: 109542269
NVL: 108566486
BMOR: 101735340
PMAC: 106719754
PRAP: 110999936
HAW: 110373879
API: 100167456
DNX: 107165716
CLEC: 106666878
ZNE: 110835787
TUT: 107371259
BMY: Bm1_08700
CRG: 105329246
MYI: 110453394
OBI: 106870664
SHX: MS3_09481
EPA: 110232444
HMG: 100215239
AQU: 100638666
ATH: AT5G19660(S1P)
CRB: 17883247
BRP: 103856389
BOE: 106335448
THJ: 104804980
CPAP: 110818536
CIT: 102618142
TCC: 18588592
EGR: 104438271
VAR: 108345744
CCAJ: 109800131
CAM: 101499133(MBTPS1)
LJA: Lj2g3v0794730.1(Lj2g3v0794730.1)
ADU: 107478620
AIP: 107630293
LANG: 109331606
FVE: 101310645
PPER: 18771256
PMUM: 103340965
PAVI: 110770930
PXB: 103962970
ZJU: 107431787
CSV: 101222509(MBTPS1)
CMO: 103501563
MCHA: 111014445
CMAX: 111485106
CMOS: 111461434
CPEP: 111780254
RCU: 8268362
JCU: 105637725
HBR: 110671793
POP: 7458767
JRE: 108979365
VVI: 100264570(MBTPS1)
SLY: 101247955
SOT: 102580686
NSY: 104219033
SIND: 105173516
OEU: 111411249
HAN: 110886911
DCR: 108196558
BVG: 104902212
SOE: 110775696
OSA: 4340224
DOSA: Os06t0163500-01(Os06g0163500)
OBR: 102708067
BDI: 100822086
ATS: 109739065(LOC109739065)
SBI: 8070876
ZMA: 103638020
SITA: 101786320
PDA: 103710901
EGU: 105040812
MUS: 103987062
DCT: 110095889
PEQ: 110020972
AOF: 109823710
ATR: 18426576
PPP: 112280075
APRO: F751_4604
DDI: DDB_G0282397(mbtps1)
DFA: DFA_02038(mbtps1) DFA_02083
 » 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 274:22795-804 (1999)
DOI:10.1074/jbc.274.32.22795
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 274:22805-12 (1999)
DOI:10.1074/jbc.274.32.22805
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 275:2349-58 (2000)
DOI:10.1074/jbc.275.4.2349
  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 6:1355-64 (2000)
DOI:10.1016/S1097-2765(00)00133-7
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 98:12701-5 (2001)
DOI:10.1073/pnas.221447598
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 514:333-9 (2002)
DOI:10.1016/S0014-5793(02)02394-3
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 77:8640-9 (2003)
DOI:10.1128/JVI.77.16.8640-8649.2003
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: 3.4.21.112
IUBMB Enzyme Nomenclature: 3.4.21.112
ExPASy - ENZYME nomenclature database: 3.4.21.112
BRENDA, the Enzyme Database: 3.4.21.112
CAS: 167140-48-9

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