Entry
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
MFOT : 126502089 126515482
PCAD : 102993106 114483867(MBTPS1)
SRX : 107726427 107733569(mbtps1)
SANH : 107672278 107694940
CCAR : 109068651 109108692
CAUA : 113070216 113118429
CGIB : 127934276 127977671
MASI : 127417054 127455952
GAT : 120809525(mbtps1) 120812201
SASA : 106560820 106573750
CCLU : 121531878 121576639
PSPA : 121296512 121325594
ARUT : 117424734 117425854(mbtps1)
BBEL : 109472457 109483234
DSI : Dsimw501_GD12102(Dsim_GD12102)
DYA : Dyak_GE22309 Dyak_GE22979
AALB : 109431986 115254126
CFEL : 113385761 113385762
PPOI : 119107421 119107424
SHX : MS3_00009089(MBTPS1)
OVI : T265_10520 T265_15172
CSAT : 104706301 104738055 104770338
GHI : 107907212 107932897 107939494 107958761
HSYR : 120123243 120149767 120159316
QSA : O6P43_004028 O6P43_007922
MSYL : 126594356 126605305
CAVE : 132165671 132165803
CANN : 107843032 107843362
NTA : 107774733 107799117 107828026
SSPL : 121779821 121782145
SMIL : 131003031 131014087
CCAV : 112504615 112505915
PSOM : 113348309 113349054
TAES : 123154733 123159906 123169567
PVIR : 120669830 120702713
ACAK : 137945591 137950480
SMO : SELMODRAFT_50575 SELMODRAFT_85837
DDI : DDB_G0282397(mbtps1)
DFA : DFA_02038(mbtps1) DFA_02083
SPAR : SPRG_09285 SPRG_15469
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Taxonomy
Reference
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
Reference
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
Reference
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
Sequence
Reference
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
Reference
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
Reference
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
Reference
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
Reference
8
Authors
Seidah NG, Chretien M.
Title
Proprotein convertase SKI-1/S1P.
Journal
In: Barrett AJ, Rawlings ND, Woessner JF (eds). Handbook of Proteolytic Enzymes. 2nd ed. Vol. 2. London: Elsevier; 2004. p. 1845-1847.
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