SOAT2_MOUSE
ID SOAT2_MOUSE Reviewed; 525 AA.
AC O88908; Q8R0Y9;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 146.
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 {ECO:0000312|MGI:MGI:1332226}; Synonyms=Acact-2, Acat2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=9756919; DOI=10.1074/jbc.273.41.26755;
RA Cases S., Novak S., Zheng Y.-W., Myers H.M., Lear S.R., Sande E.,
RA Welch C.B., Lusis A.J., Spencer T.A., Krause B.R., Erickson S.K.,
RA Farese R.V. Jr.;
RT "ACAT-2, a second mammalian acyl-CoA:cholesterol acyltransferase. Its
RT cloning, expression, and characterization.";
RL J. Biol. Chem. 273:26755-26764(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TOPOLOGY, AND SUBCELLULAR LOCATION.
RX PubMed=11071899; DOI=10.1091/mbc.11.11.3675;
RA Joyce C.W., Shelness G.S., Davis M.A., Lee R.G., Skinner K., Anderson R.A.,
RA Rudel L.L.;
RT "ACAT1 and ACAT2 membrane topology segregates a serine residue essential
RT for activity to opposite sides of the endoplasmic reticulum membrane.";
RL Mol. Biol. Cell 11:3675-3687(2000).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=28604676; DOI=10.1038/ncb3551;
RA Wang Y.J., Bian Y., Luo J., Lu M., Xiong Y., Guo S.Y., Yin H.Y., Lin X.,
RA Li Q., Chang C.C.Y., Chang T.Y., Li B.L., Song B.L.;
RT "Cholesterol and fatty acids regulate cysteine ubiquitylation of ACAT2
RT through competitive oxidation.";
RL Nat. Cell Biol. 19:808-819(2017).
RN [7]
RP ERRATUM OF PUBMED:28604676.
RX PubMed=29184177; DOI=10.1038/ncb3651;
RA Wang Y.J., Bian Y., Luo J., Lu M., Xiong Y., Guo S.Y., Yong H., Lin X.,
RA Li Q., Chang C.C.Y., Chang T.Y., Li B.L., Song B.L.;
RT "Corrigendum: Cholesterol and fatty acids regulate cysteine ubiquitylation
RT of ACAT2 through competitive oxidation.";
RL Nat. Cell Biol. 19:1441-1441(2017).
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:0000269|PubMed:11071899}; Multi-pass membrane protein
CC {ECO:0000255}.
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-280, 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-280 oxidation, preventing
CC ubiquitination at the same site, resulting in protein stabilization.
CC {ECO:0000250|UniProtKB:O75908}.
CC -!- PTM: Oxidized at Cys-280: high concentration of cholesterol and fatty
CC acid induce reactive oxygen species, which oxidizes Cys-280, preventing
CC ubiquitination at the same site, and resulting in protein
CC stabilization. {ECO:0000250|UniProtKB:O75908}.
CC -!- DISRUPTION PHENOTYPE: Mice are more susceptible to high-fat diet-
CC induced insulin resistance. {ECO:0000269|PubMed:28604676}.
CC -!- SIMILARITY: Belongs to the membrane-bound acyltransferase family.
CC Sterol o-acyltransferase subfamily. {ECO:0000305}.
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DR EMBL; AF078751; AAC64057.1; -; mRNA.
DR EMBL; CH466550; EDL04004.1; -; Genomic_DNA.
DR EMBL; BC025931; AAH25931.1; -; mRNA.
DR CCDS; CCDS27872.1; -.
DR RefSeq; NP_666176.1; NM_146064.1.
DR AlphaFoldDB; O88908; -.
DR SMR; O88908; -.
DR STRING; 10090.ENSMUSP00000023806; -.
DR ChEMBL; CHEMBL2653; -.
DR iPTMnet; O88908; -.
DR PhosphoSitePlus; O88908; -.
DR SwissPalm; O88908; -.
DR EPD; O88908; -.
DR jPOST; O88908; -.
DR MaxQB; O88908; -.
DR PaxDb; O88908; -.
DR PRIDE; O88908; -.
DR ProteomicsDB; 261313; -.
DR Antibodypedia; 43294; 146 antibodies from 21 providers.
DR Ensembl; ENSMUST00000023806; ENSMUSP00000023806; ENSMUSG00000023045.
DR GeneID; 223920; -.
DR KEGG; mmu:223920; -.
DR UCSC; uc007xut.1; mouse.
DR CTD; 8435; -.
DR MGI; MGI:1332226; Soat2.
DR VEuPathDB; HostDB:ENSMUSG00000023045; -.
DR eggNOG; KOG0380; Eukaryota.
DR GeneTree; ENSGT00950000183081; -.
DR HOGENOM; CLU_031845_1_0_1; -.
DR InParanoid; O88908; -.
DR OMA; MHDRHTG; -.
DR OrthoDB; 1275897at2759; -.
DR PhylomeDB; O88908; -.
DR TreeFam; TF315226; -.
DR BRENDA; 2.3.1.26; 3474.
DR Reactome; R-MMU-8964038; LDL clearance.
DR BioGRID-ORCS; 223920; 6 hits in 75 CRISPR screens.
DR ChiTaRS; Soat2; mouse.
DR PRO; PR:O88908; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; O88908; protein.
DR Bgee; ENSMUSG00000023045; Expressed in small intestine Peyer's patch and 59 other tissues.
DR ExpressionAtlas; O88908; baseline and differential.
DR Genevisible; O88908; MM.
DR GO; GO:0005903; C:brush border; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0015485; F:cholesterol binding; ISO:MGI.
DR GO; GO:0034736; F:cholesterol O-acyltransferase activity; ISO:MGI.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; ISO:MGI.
DR GO; GO:0008374; F:O-acyltransferase activity; IBA:GO_Central.
DR GO; GO:0004772; F:sterol O-acyltransferase activity; IDA:MGI.
DR GO; GO:0033344; P:cholesterol efflux; ISO:MGI.
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; IDA:MGI.
DR GO; GO:0034379; P:very-low-density lipoprotein particle assembly; ISO:MGI.
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 1: Evidence at protein level;
KW Acyltransferase; Cholesterol metabolism; Endoplasmic reticulum;
KW Lipid metabolism; Membrane; Oxidation; Reference proteome;
KW Steroid metabolism; Sterol metabolism; Thioester bond; Transferase;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..525
FT /note="Sterol O-acyltransferase 2"
FT /id="PRO_0000207646"
FT TOPO_DOM 1..119
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 120..141
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 142..161
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 162..187
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 188..199
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 200..223
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 224..231
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 232..255
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 256..296
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 297..329
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 330..346
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 347..372
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 373..420
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 421..445
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 446..451
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 452..467
FT /note="Helical; Name=8"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 468..473
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 474..505
FT /note="Helical; Name=9"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 506..525
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 77..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 380..386
FT /note="FYXDWWN motif"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT COMPBIAS 9..26
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 437
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT BINDING 118
FT /ligand="cholesterol"
FT /ligand_id="ChEBI:CHEBI:16113"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT BINDING 392
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT BINDING 395
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT BINDING 398
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT BINDING 402
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT BINDING 410
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT BINDING 433
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT MOD_RES 280
FT /note="Cysteine sulfenic acid (-SOH); alternate"
FT /evidence="ECO:0000250|UniProtKB:O75908"
FT CROSSLNK 280
FT /note="Glycyl cysteine thioester (Cys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:O75908"
FT CONFLICT 93
FT /note="Q -> P (in Ref. 1; AAC64057)"
FT /evidence="ECO:0000305"
FT CONFLICT 96
FT /note="H -> R (in Ref. 1; AAC64057)"
FT /evidence="ECO:0000305"
FT CONFLICT 104..105
FT /note="IT -> VA (in Ref. 1; AAC64057)"
FT /evidence="ECO:0000305"
FT CONFLICT 131..132
FT /note="CV -> WF (in Ref. 1; AAC64057)"
FT /evidence="ECO:0000305"
FT CONFLICT 175
FT /note="S -> Y (in Ref. 1; AAC64057)"
FT /evidence="ECO:0000305"
FT CONFLICT 262
FT /note="G -> R (in Ref. 1; AAC64057)"
FT /evidence="ECO:0000305"
FT CONFLICT 519
FT /note="R -> Q (in Ref. 1; AAC64057)"
FT /evidence="ECO:0000305"
FT CONFLICT 525
FT /note="P -> T (in Ref. 1; AAC64057)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 525 AA; 60597 MW; F1C2DFEB5AB6CCA8 CRC64;
MQPKVPQLRR REGLGEEQEK GARGGEGNAR THGTPDLVQW TRHMEAVKTQ FLEQAQRELA
ELLDRALWEA MQAYPKQDRP LPSAAPDSTS KTQELHPGKR KVFITRKSLI DELMEVQHFR
TIYHMFIAGL CVLIISTLAI DFIDEGRLML EFDLLLFSFG QLPLALMTWV PMFLSTLLVP
YQTLWLWARP RAGGAWMLGA SLGCVLLAAH AVVLCVLPVH VSVRHELPPA SRCVLVFEQV
RLLMKSYSFL RETVPGIFCV RGGKGISPPS FSSYLYFLFC PTLIYRETYP RTPSIRWNYV
AKNFAQVLGC LLYACFILGR LCVPVFANMS REPFSTRALL LSILHATGPG IFMLLLIFFA
FLHCWLNAFA EMLRFGDRMF YRDWWNSTSF SNYYRTWNVV VHDWLYSYVY QDGLWLLGRR
ARGVAMLGVF LVSAVVHEYI FCFVLGFFYP VMLMLFLVFG GLLNFTMNDR HTGPAWNILM
WTFLFMGQGI QVSLYCQEWY ARRHCPLPQT TFWGMVTPRS WSCHP
