MBTP2_CRIGR
ID MBTP2_CRIGR Reviewed; 510 AA.
AC O54862;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Membrane-bound transcription factor site-2 protease;
DE EC=3.4.24.85 {ECO:0000250|UniProtKB:O43462};
DE AltName: Full=Endopeptidase S2P;
DE AltName: Full=Sterol regulatory element-binding proteins intramembrane protease;
DE Short=SREBPs intramembrane protease;
GN Name=MBTPS2; Synonyms=S2P;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9659902; DOI=10.1016/s1097-2765(00)80006-4;
RA Rawson R.B., Zelenski N.G., Nijhawan D., Ye J., Sakai J., Hasan M.T.,
RA Chang T.Y., Brown M.S., Goldstein J.L.;
RT "Complementation cloning of S2P, a gene encoding a putative metalloprotease
RT required for intramembrane cleavage of SREBPs.";
RL Mol. Cell 1:47-57(1997).
CC -!- FUNCTION: Zinc metalloprotease that mediates intramembrane proteolysis
CC of proteins such as ATF6, ATF6B, SREBF1/SREBP1 and SREBF2/SREBP2.
CC Catalyzes the second step in the proteolytic activation of the sterol
CC regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and
CC SREBF2/SREBP2: cleaves SREBPs within the first transmembrane segment,
CC thereby releasing the N-terminal segment with a portion of the
CC transmembrane segment attached. Mature N-terminal SREBP fragments
CC shuttle to the nucleus and activate gene transcription. Also mediates
CC the second step in the proteolytic activation of the cyclic AMP-
CC dependent transcription factor ATF-6 (ATF6 and ATF6B). Involved in
CC intramembrane proteolysis during bone formation.
CC {ECO:0000250|UniProtKB:O43462}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleaves several transcription factors that are type-2
CC transmembrane proteins within membrane-spanning domains. Known
CC substrates include sterol regulatory element-binding protein (SREBP)
CC -1, SREBP-2 and forms of the transcriptional activator ATF6. SREBP-2
CC is cleaved at the site 477-DRSRILL-|-CVLTFLCLSFNPLTSLLQWGGA-505. The
CC residues Asn-Pro, 11 residues distal to the site of cleavage in the
CC membrane-spanning domain, are important for cleavage by S2P
CC endopeptidase. Replacement of either of these residues does not
CC prevent cleavage, but there is no cleavage if both of these residues
CC are replaced.; EC=3.4.24.85; Evidence={ECO:0000250|UniProtKB:O43462};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:O43462};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:O43462};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:O43462}; Multi-
CC pass membrane protein {ECO:0000250|UniProtKB:O43462}. Cytoplasm
CC {ECO:0000250|UniProtKB:O43462}.
CC -!- SIMILARITY: Belongs to the peptidase M50A family. {ECO:0000305}.
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DR EMBL; AF019611; AAC53526.1; -; mRNA.
DR RefSeq; NP_001231018.1; NM_001244089.1.
DR AlphaFoldDB; O54862; -.
DR STRING; 10029.NP_001231018.1; -.
DR MEROPS; M50.001; -.
DR Ensembl; ENSCGRT00001022434; ENSCGRP00001018190; ENSCGRG00001018020.
DR GeneID; 100689085; -.
DR KEGG; cge:100689085; -.
DR CTD; 51360; -.
DR eggNOG; KOG2921; Eukaryota.
DR GeneTree; ENSGT00510000048066; -.
DR OMA; CMHYPYD; -.
DR OrthoDB; 1012405at2759; -.
DR BRENDA; 3.4.24.85; 1309.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0070977; P:bone maturation; ISS:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:1990440; P:positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; IMP:ParkinsonsUK-UCL.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:ParkinsonsUK-UCL.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR001193; MBTPS2.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR008915; Peptidase_M50.
DR PANTHER; PTHR13325; PTHR13325; 1.
DR Pfam; PF02163; Peptidase_M50; 1.
DR PRINTS; PR01000; SREBPS2PTASE.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 2: Evidence at transcript level;
KW Cholesterol metabolism; Cytoplasm; Glycoprotein; Hydrolase;
KW Lipid metabolism; Membrane; Metal-binding; Metalloprotease; Protease;
KW Steroid metabolism; Sterol metabolism; Transmembrane; Transmembrane helix;
KW Zinc.
FT CHAIN 1..510
FT /note="Membrane-bound transcription factor site-2 protease"
FT /id="PRO_0000088481"
FT TOPO_DOM 1..3
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O43462"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 25..74
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:O43462"
FT TRANSMEM 75..95
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 96..107
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 108..135
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:O43462"
FT TRANSMEM 136..160
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 165..177
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..200
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 220..242
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 243..437
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:O43462"
FT TRANSMEM 438..455
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 456..467
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 468..483
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 484..504
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 505..510
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 163
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 162
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 166
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT CARBOHYD 328
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 510 AA; 56499 MW; 12B6B2257C0DA7A4 CRC64;
MIPVSLVVVV VGGWTAVYLA DLVLKSSVYF KHSYEDWLEK NGLSISPFHI RWQTSVFNRA
FYSWGRRKAR MLYQWFNFGM VFGVIAMFSS FFLLGKTLMQ TLAQMMADSP SSSSSSSSSS
SSSSSSSIHN EQVLQVVVPG INLPVNQLTY FFAAVLISGV VHEIGHGIAA IREQVRFNGF
GIFLFIIYPG AFVDLFTTHL QLISPVQQLR IFCAGIWHNF VLALLGILAL VLLPVILLPF
YYTGVGVLIT EVAEDSPAIG PRGLFVGDLV THLQDCPVTN VQDWNECLDT IAYEPQIGYC
ISASTLQQLS FPVRAYKRLD GSTECCNNHS LTDVCFSYRN NFNKRLHTCL PARKAVEATQ
VCRTNKDCKT SSSSSFCIVP SLETHTRLIK VKHPPQIDML YVGHPLHLHY TVSITSFIPR
FNFLSIDLPV IVETFVKYLI SLSGALAIVN AVPCFALDGQ WILNSFLDAT LTSVIGDNDV
KDLIGFFILL GGSVLLAANV TLGLWMVTAR
