MBTP2_BOVIN
ID MBTP2_BOVIN Reviewed; 516 AA.
AC Q0III2;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Membrane-bound transcription factor site-2 protease {ECO:0000250|UniProtKB:O43462};
DE EC=3.4.24.85 {ECO:0000250|UniProtKB:O43462};
DE AltName: Full=Endopeptidase S2P {ECO:0000250|UniProtKB:O43462};
GN Name=MBTPS2 {ECO:0000250|UniProtKB:O43462};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Basal ganglia;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
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; BC122628; AAI22629.1; -; mRNA.
DR RefSeq; NP_001069449.1; NM_001075981.1.
DR AlphaFoldDB; Q0III2; -.
DR STRING; 9913.ENSBTAP00000010764; -.
DR MEROPS; M50.001; -.
DR PaxDb; Q0III2; -.
DR PRIDE; Q0III2; -.
DR Ensembl; ENSBTAT00000086968; ENSBTAP00000059283; ENSBTAG00000008183.
DR GeneID; 533134; -.
DR KEGG; bta:533134; -.
DR CTD; 51360; -.
DR VEuPathDB; HostDB:ENSBTAG00000008183; -.
DR VGNC; VGNC:31292; MBTPS2.
DR eggNOG; KOG2921; Eukaryota.
DR GeneTree; ENSGT00940000167584; -.
DR HOGENOM; CLU_032523_1_0_1; -.
DR InParanoid; Q0III2; -.
DR OMA; CMHYPYD; -.
DR OrthoDB; 1318335at2759; -.
DR TreeFam; TF314478; -.
DR Proteomes; UP000009136; Chromosome X.
DR Bgee; ENSBTAG00000008183; Expressed in granulosa cell and 106 other tissues.
DR ExpressionAtlas; Q0III2; baseline and differential.
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; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IBA:GO_Central.
DR GO; GO:1990440; P:positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; IBA:GO_Central.
DR GO; GO:1905897; P:regulation of response to endoplasmic reticulum stress; IBA:GO_Central.
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 Reference proteome; Steroid metabolism; Sterol metabolism; Transmembrane;
KW Transmembrane helix; Zinc.
FT CHAIN 1..516
FT /note="Membrane-bound transcription factor site-2 protease"
FT /id="PRO_0000261591"
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..141
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:O43462"
FT TRANSMEM 142..166
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 171..183
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 184..206
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 226..248
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 249..443
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:O43462"
FT TRANSMEM 444..461
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 462..473
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 474..489
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 490..510
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 511..516
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT ACT_SITE 169
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 168
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 172
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT CARBOHYD 334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 516 AA; 57214 MW; F2E18EC52C644074 CRC64;
MIPVSLVVVV VGGWTAVYLT DLVLKSSVYF KHSYEDWLEN NGLSISPFHI RWQTAVFNRA
FYSWGRRKAR MLYQWFNFGM VFGVIAMFSS FFLLGKTLIQ TLGQMMADSS YSSSSSSSSH
SSSSSSSSSS SSSLYNEQVL QVVVPGINLP VNQLTYFFAA VLISGVVHEI GHGIAAIREQ
VRFNGFGIFL FIIYPGAFVD LFTTHLQLIS PVQQLRIFCA GIWHNFILAL LGILALILLP
VILLPFYYTG VGVLITEVAE DSPAIGPRGL FVGDLVTHLQ DCPVTNVQDW NECLDTITYE
PQIGYCISAS TLQQLSFPVR AYKRLDGSTE CCNNHSLTDV CFSYRNNFNK RLHTCLPARK
AVEATQVCRT NKDCKKSSSS SFCIIPSLET HTRLIKVKHP PQIDMLYVGH PLHLHYTVSI
TSFIPRFKFL SIDLPVVVET FVKYLISLSG ALAIVNAVPC FALDGQWILN SFLDATLTSV
IGDNDVKDLI GFFILLGGSI LLAANVALGL WMVTAR
