SOAT2_CHLAE
ID SOAT2_CHLAE Reviewed; 526 AA.
AC O77759;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Sterol O-acyltransferase 2 {ECO:0000305};
DE EC=2.3.1.26 {ECO:0000250|UniProtKB:O75908};
DE AltName: Full=Acyl-coenzyme A:cholesterol acyltransferase 2;
DE Short=ACAT-2;
DE AltName: Full=Cholesterol acyltransferase 2;
GN Name=SOAT2; Synonyms=ACAT2;
OS Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Chlorocebus.
OX NCBI_TaxID=9534;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=9756918; DOI=10.1074/jbc.273.41.26747;
RA Anderson R.A., Joyce C., Davis M., Reagan J.W., Clark M., Shelness G.S.,
RA Rudel L.L.;
RT "Identification of a form of acyl-CoA:cholesterol acyltransferase specific
RT to liver and intestine in nonhuman primates.";
RL J. Biol. Chem. 273:26747-26754(1998).
CC -!- FUNCTION: Catalyzes the formation of fatty acid-cholesterol esters,
CC which are less soluble in membranes than cholesterol. Plays a role in
CC lipoprotein assembly and dietary cholesterol absorption. Utilizes
CC oleoyl-CoA ((9Z)-octadecenoyl-CoA) and linolenoyl-CoA ((9Z,12Z,15Z)-
CC octadecatrienoyl-CoA) as substrates. May provide cholesteryl esters for
CC lipoprotein secretion from hepatocytes and intestinal mucosa.
CC {ECO:0000250|UniProtKB:O75908}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a long-chain fatty acyl-CoA + a sterol = a sterol ester + CoA;
CC Xref=Rhea:RHEA:59816, ChEBI:CHEBI:15889, ChEBI:CHEBI:35915,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:83139; EC=2.3.1.26;
CC Evidence={ECO:0000250|UniProtKB:O75908};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59817;
CC Evidence={ECO:0000250|UniProtKB:O75908};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an acyl-CoA + cholesterol = a cholesterol ester + CoA;
CC Xref=Rhea:RHEA:17729, ChEBI:CHEBI:16113, ChEBI:CHEBI:17002,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:58342;
CC Evidence={ECO:0000250|UniProtKB:O75908};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17730;
CC Evidence={ECO:0000250|UniProtKB:O75908};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + cholesterol = cholesteryl (9Z-
CC octadecenoate) + CoA; Xref=Rhea:RHEA:41436, ChEBI:CHEBI:16113,
CC ChEBI:CHEBI:46898, ChEBI:CHEBI:57287, ChEBI:CHEBI:57387;
CC Evidence={ECO:0000250|UniProtKB:O75908};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41437;
CC Evidence={ECO:0000250|UniProtKB:O75908};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA + cholesterol =
CC (5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-cholesterol + CoA;
CC Xref=Rhea:RHEA:46612, ChEBI:CHEBI:16113, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:73862, ChEBI:CHEBI:84969;
CC Evidence={ECO:0000250|UniProtKB:O75908};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46613;
CC Evidence={ECO:0000250|UniProtKB:O75908};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z,15Z)-octadecatrienoyl-CoA + cholesterol = (9Z,12Z,15Z-
CC octadecatrienoyl)-cholesterol + CoA; Xref=Rhea:RHEA:46620,
CC ChEBI:CHEBI:16113, ChEBI:CHEBI:57287, ChEBI:CHEBI:74034,
CC ChEBI:CHEBI:84341; Evidence={ECO:0000250|UniProtKB:O75908};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46621;
CC Evidence={ECO:0000250|UniProtKB:O75908};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + cholesterol =
CC cholesteryl (5Z,8Z,11Z,14Z)-eicosatetraenoate + CoA;
CC Xref=Rhea:RHEA:42816, ChEBI:CHEBI:16113, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57368, ChEBI:CHEBI:82751;
CC Evidence={ECO:0000250|UniProtKB:O75908};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42817;
CC Evidence={ECO:0000250|UniProtKB:O75908};
CC -!- SUBUNIT: May form homo- or heterodimers (By similarity). Interacts with
CC INSIG1; the interaction is direct and promotes association with
CC AMFR/gp78 (By similarity). {ECO:0000250|UniProtKB:O75908,
CC ECO:0000250|UniProtKB:P35610}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O88908}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Liver and intestine. Expression is six-fold greater
CC in hepatocytes than in kupffer cells. {ECO:0000269|PubMed:9756918}.
CC -!- DOMAIN: Each protomer consists of 9 transmembrane segments, which
CC enclose a cytosolic tunnel and a transmembrane tunnel that converge at
CC the predicted catalytic site: acyl-CoA enters the active site through
CC the cytosolic tunnel, whereas cholesterol enters from the side through
CC the transmembrane tunnel. {ECO:0000250|UniProtKB:P35610}.
CC -!- PTM: Polyubiquitinated by AMFR/gp78 at Cys-281, leading to its
CC degradation when the lipid levels are low. Association with AMFR/gp78
CC is mediated via interaction with INSIG1. High concentration of
CC cholesterol and fatty acid results in Cys-281 oxidation, preventing
CC ubiquitination at the same site, resulting in protein stabilization.
CC {ECO:0000250|UniProtKB:O75908}.
CC -!- PTM: Oxidized at Cys-281: high concentration of cholesterol and fatty
CC acid induce reactive oxygen species, which oxidizes Cys-281, preventing
CC ubiquitination at the same site, and resulting in protein
CC stabilization. {ECO:0000250|UniProtKB:O75908}.
CC -!- SIMILARITY: Belongs to the membrane-bound acyltransferase family.
CC Sterol o-acyltransferase subfamily. {ECO:0000305}.
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DR EMBL; AF053234; AAC62929.1; -; mRNA.
DR AlphaFoldDB; O77759; -.
DR SMR; O77759; -.
DR BindingDB; O77759; -.
DR ChEMBL; CHEMBL3879854; -.
DR BRENDA; 2.3.1.26; 175.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0034736; F:cholesterol O-acyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0004772; F:sterol O-acyltransferase activity; ISS:UniProtKB.
DR GO; GO:0034435; P:cholesterol esterification; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IEA:InterPro.
DR GO; GO:0008203; P:cholesterol metabolic process; ISS:UniProtKB.
DR InterPro; IPR004299; MBOAT_fam.
DR InterPro; IPR014371; Oat_ACAT_DAG_ARE.
DR InterPro; IPR030687; Sterol_acyltranf_meta.
DR PANTHER; PTHR10408; PTHR10408; 1.
DR Pfam; PF03062; MBOAT; 1.
DR PIRSF; PIRSF000439; Oat_ACAT_DAG_ARE; 1.
DR PIRSF; PIRSF500230; Sterol_acyltranf_ACAT; 1.
PE 2: Evidence at transcript level;
KW Acyltransferase; Cholesterol metabolism; Endoplasmic reticulum;
KW Lipid metabolism; Membrane; Oxidation; Steroid metabolism;
KW Sterol metabolism; Thioester bond; Transferase; Transmembrane;
KW Transmembrane helix; Ubl conjugation.
FT CHAIN 1..526
FT /note="Sterol O-acyltransferase 2"
FT /id="PRO_0000207644"
FT TOPO_DOM 1..120
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 121..142
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 143..162
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 163..188
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 189..200
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 201..224
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 225..232
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 233..256
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 257..297
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 298..330
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 331..347
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 348..373
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 374..421
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 422..446
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 447..452
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 453..468
FT /note="Helical; Name=8"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 469..474
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 475..506
FT /note="Helical; Name=9"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 507..526
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 75..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 381..387
FT /note="FYXDWWN motif"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT COMPBIAS 13..37
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 438
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT BINDING 119
FT /ligand="cholesterol"
FT /ligand_id="ChEBI:CHEBI:16113"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT BINDING 393
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT BINDING 396
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT BINDING 399
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT BINDING 403
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT BINDING 411
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT BINDING 434
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT MOD_RES 281
FT /note="Cysteine sulfenic acid (-SOH); alternate"
FT /evidence="ECO:0000250|UniProtKB:O75908"
FT CROSSLNK 281
FT /note="Glycyl cysteine thioester (Cys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:O75908"
SQ SEQUENCE 526 AA; 60412 MW; FA5E29F48386DB43 CRC64;
MEPGGARLRL QRTEGPGGER EHQPCRDGNT ETHRAPDLVK WTRHMEAVKA QLLEQAQGQL
RELLDRAMWE AIQSYPSQDK PPPLPPPDSL SRTQEPSLGK QKVFIIRKSL LDELMEVQHF
RTIYHMFIAG LCVFIISTLA IDFIDEGRLL LEFDLLIFSF GQLPLALVTW VPMFLSTLLA
PYQALRLWAR PGARGTWTLG AGLGCALLAA HALVLCALPV HVAVEHQLPP ASRCVLVFEQ
VRFLMKSYSF LREAVPGTLR ARRGEGIQAP SFSSYLYFLF CPTLIYRETY PRTPYIRWNY
VAKNFAQALG CVLYACFILG RLCVPVFANM SREPFSTRAL VLSILHATLP GIFMLLLIFF
AFLHCWLNAF AEMLRFGDRM FYRDWWNSTS FSNYYRTWNV VVHDWLYSYV YQDGLWLLGA
QARGVAMLGV FLVSAVAHEY IFCFVLGFFY PVMLILFLVI GGMLNFMMHD QHTGPAWNVL
MWTMLFLGQG IQVSLYCQEW YARRHCPLPQ TTFWGLVTPR SWSCHT
