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Entry
EC 3.4.24.85                Enzyme                                 

Name
S2P endopeptidase
Class
Hydrolases;
Acting on peptide bonds (peptidases);
Metalloendopeptidases
BRITE hierarchy
Reaction(IUBMB)
Cleaves several transcription factors that are type-2 transmembrane proteins within membrane-spanning domains. Known substrates include sterol regulatory element-binding protein (SREBP) -1, SREBP-2 and forms of the transcriptional activator ATF6. SREBP-2 is cleaved at the site DRSR_ILL_483!CVLTFLCLSFNPLTSLLQWGGA, in which the membrane-spanning segment is underlined. The residues NP (bold), 11 residues distal to the site of cleavage in the membrane-spanning domain, are important for cleavage by S2P endopeptidase. Replacement of either of these residues does not prevent cleavage, but there is no cleavage if both of these residues are replaced.
Comment
Type example of peptidase family M50. The transcription factors SREBP-1 and -2 are synthesized as precursor proteins that are attached to the membranes of the endoplasmic reticulum and two cleavages are needed to release the active factor so that it can move to the nucleus. This enzyme cleaves the second of these, and is thus the "site 2 protease", S2P.
History
EC 3.4.24.85 created 2003
Orthology
K07765  
S2P endopeptidase
Genes
HSA: 
51360(MBTPS2)
PTR: 
465532(MBTPS2)
PPS: 
100988592(MBTPS2)
GGO: 
101135564(MBTPS2)
PON: 
100454671(MBTPS2)
MCC: 
696540(MBTPS2)
MCF: 
102140645(MBTPS2)
MMU: 
270669(Mbtps2)
RNO: 
302705(Mbtps2)
CGE: 
100689085(Mbtps2)
HGL: 
101726620(Mbtps2)
TUP: 
102496221(MBTPS2)
CFA: 
491771(MBTPS2)
AML: 
FCA: 
101084262(MBTPS2)
PTG: 
102954190(MBTPS2)
BTA: 
533134(MBTPS2)
BOM: 
102280586(MBTPS2)
PHD: 
102340351(MBTPS2)
CHX: 
102190948(MBTPS2)
OAS: 
101106915(MBTPS2)
SSC: 
CFR: 
102512896(MBTPS2)
LVE: 
103072780(MBTPS2)
ECB: 
100051796(MBTPS2)
MYB: 
102251140(MBTPS2)
MYD: 
102759985(MBTPS2)
PALE: 
MDO: 
100011019(MBTPS2)
SHR: 
100929394(MBTPS2)
OAA: 
100083166(MBTPS2)
GGA: 
427996(MBTPS2)
MGP: 
TGU: 
100221191(MBTPS2)
FAB: 
101809571(MBTPS2)
PHI: 
102114211(MBTPS2)
APLA: 
101791896(MBTPS2)
FPG: 
101923038(MBTPS2)
FCH: 
102049253(MBTPS2)
CLV: 
102083546(MBTPS2)
ASN: 
102387796(MBTPS2)
AMJ: 
102575368(MBTPS2)
PSS: 
102444548(MBTPS2)
CMY: 
102933913(MBTPS2)
ACS: 
100560770(mbtps2)
PBI: 
103049752(MBTPS2)
XTR: 
549815(mbtps2)
DRE: 
334658(mbtps2)
TRU: 
MZE: 
OLA: 
XMA: 
LCM: 
CMK: 
103189988(mbtps2)
BFO: 
CIN: 
SPU: 
DME: 
DPO: 
DAN: 
DER: 
DPE: 
DSE: 
DSI: 
DWI: 
DYA: 
DGR: 
DMO: 
DVI: 
AGA: 
AAG: 
CQU: 
AME: 
724553(GB13283)
NVI: 
TCA: 
API: 
PHU: 
ISC: 
CEL: 
CELE_Y56A3A.2(Y56A3A.2)
CBR: 
BMY: 
LOA: 
TSP: 
SMM: 
NVE: 
HMG: 
TAD: 
AQU: 
ATH: 
ALY: 
CRB: 
EUS: 
CIT: 
CIC: 
TCC: 
GMX: 
PVU: 
MTR: 
CAM: 
FVE: 
PPER: 
PMUM: 
MDM: 
CSV: 
CMO: 
RCU: 
POP: 
POPTR_0003s15640g(POPTRDRAFT_757770)
SLY: 
SOT: 
OBR: 
BDI: 
ZMA: 
SITA: 
ATR: 
s00068p00204430(AMTR_s00068p00204430)
SMO: 
CSL: 
CVR: 
CME: 
GSL: 
CCP: 
TMS: 
DSQ: 
SHS: 
PCO: 
ADL: 
FME: 
GTR: 
LBC: 
MRR: 
ABP: 
AGABI1DRAFT114978(AGABI1DRAFT_114978)
CPUT: 
SLA: 
PGR: 
MLR: 
WSE: 
MBR: 
DDI: 
DDB_G0275939(mbtps2)
DPP: 
DFA: 
DFA_01538(mbtps2)
ACAN: 
GTT: 
 » show all
Taxonomy
Reference
1  [PMID:10693756]
  Authors
Brown MS, Ye J, Rawson RB, Goldstein JL.
  Title
Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans.
  Journal
Cell. 100 (2000) 391-8.
Other DBs
ExplorEnz - The Enzyme Database: 
IUBMB Enzyme Nomenclature: 
ExPASy - ENZYME nomenclature database: 
BRENDA, the Enzyme Database: 
CAS: 
752251-31-3

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