MBTP2_PONAB
ID MBTP2_PONAB Reviewed; 521 AA.
AC Q5RAC8;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 64.
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;
GN Name=MBTPS2;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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; CR859090; CAH91282.1; -; mRNA.
DR AlphaFoldDB; Q5RAC8; -.
DR STRING; 9601.ENSPPYP00000022583; -.
DR MEROPS; M50.001; -.
DR eggNOG; KOG2921; Eukaryota.
DR InParanoid; Q5RAC8; -.
DR Proteomes; UP000001595; Unplaced.
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:0006508; P:proteolysis; IEA:UniProtKB-KW.
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..521
FT /note="Membrane-bound transcription factor site-2 protease"
FT /id="PRO_0000261593"
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..146
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:O43462"
FT TRANSMEM 147..171
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 176..188
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 189..211
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 231..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 254..448
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:O43462"
FT TRANSMEM 449..466
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 467..478
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 479..494
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 495..515
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 516..521
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 113..137
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 174
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 173
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 177
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT CARBOHYD 339
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 521 AA; 57561 MW; A24D71CD3073E58C CRC64;
MIPVSLVVVV VGGWTVVYLT DLVLKSSVYF KHSYEDWLES NGLSISPFHI RWQTAVFNRA
FYSWGRRKAR MLYQWFNFGM VFGVIAMFSS FFLLGKTLMQ TLAQMMADSP SSYSSSSSSS
SSSSSSSSSS SSSSSSSSLH NEQVLQVVVP GINLPVNQLT YFFAAVLISG VVHEIGHGIA
AIREQVRFNG FGIFLFIIYP GAFVDLFTTH LQLISPVQQL RIFCAGIWHN FVLALLGILA
LVLLPVILLP FYYTGVGVLI TEVAEDSPAI GPRGLFVGDL VTHLQDCPVT NVQDWNECLD
TIAYEPQIGY CISASTLQQL SFPVRAYKRL DGSTECCNNH SLTDVCFSYR NNFNKRLHTC
LPARKAVEAT QVCRTNKDCK KSSSSSFCII PSLETHTRLI KVKHPPQIDM LYVGHPLHLH
YTVSITSFIP RFNFLSIDLP VVVETFVKYL ISLSGALAIV NAVPCFALDG QWILNSFLDA
TLTSVIGDND VKDLIGFFIL LGGSVLLAAN VTLGLWMVTA R
