SOAT2_HUMAN
ID SOAT2_HUMAN Reviewed; 522 AA.
AC O75908; F5H7W4; I6L9H9; Q4VB99; Q4VBA1; Q96TD4; Q9UNR2;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Sterol O-acyltransferase 2 {ECO:0000305};
DE EC=2.3.1.26 {ECO:0000269|PubMed:16647063, ECO:0000305|PubMed:11294643};
DE AltName: Full=Acyl-coenzyme A:cholesterol acyltransferase 2;
DE Short=ACAT-2;
DE AltName: Full=Cholesterol acyltransferase 2;
GN Name=SOAT2 {ECO:0000312|HGNC:HGNC:11178}; Synonyms=ACACT2, ACAT2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9756920; DOI=10.1074/jbc.273.41.26765;
RA Oelkers P., Behari A., Cromley D., Billheimer J.T., Sturley S.L.;
RT "Characterization of two human genes encoding acyl coenzyme A:cholesterol
RT acyltransferase-related enzymes.";
RL J. Biol. Chem. 273:26765-26771(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ILE-254.
RC TISSUE=Intestine;
RX PubMed=10846185; DOI=10.1074/jbc.m003927200;
RA Chang C.C.Y., Sakashita N., Ornvold K., Lee O., Chang E.T., Dong R.,
RA Lin S., Lee C.-Y.G., Strom S.C., Kashyap R., Fung J.J., Farese R.V. Jr.,
RA Patoiseau J.-F., Delhon A., Chang T.-Y.;
RT "Immunological quantitation and localization of ACAT-1 and ACAT-2 in human
RT liver and small intestine.";
RL J. Biol. Chem. 275:28083-28092(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11325614; DOI=10.1016/s1388-1981(01)00106-8;
RA Katsuren K., Tamura T., Arashiro R., Takata K., Matsuura T., Niikawa N.,
RA Ohta T.;
RT "Structure of the human acyl-CoA:cholesterol acyltransferase-2 (ACAT-2)
RT gene and its relation to dyslipidemia.";
RL Biochim. Biophys. Acta 1531:230-240(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11401500; DOI=10.1006/bbrc.2001.4612;
RA Song B.L., Qi W., Yang X.Y., Chang C.C.Y., Zhu J.Q., Chang T.Y., Li B.L.;
RT "Organization of human ACAT-2 gene and its cell-type-specific promoter
RT activity.";
RL Biochem. Biophys. Res. Commun. 282:580-588(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4), AND VARIANTS
RP GLY-14 AND ILE-254.
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 [7]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF HIS-360 AND
RP HIS-399.
RX PubMed=16647063; DOI=10.1016/j.febslet.2006.04.035;
RA An S., Cho K.H., Lee W.S., Lee J.O., Paik Y.K., Jeong T.S.;
RT "A critical role for the histidine residues in the catalytic function of
RT acyl-CoA:cholesterol acyltransferase catalysis: evidence for catalytic
RT difference between ACAT1 and ACAT2.";
RL FEBS Lett. 580:2741-2749(2006).
RN [8]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=11294643; DOI=10.1021/bi0022947;
RA Seo T., Oelkers P.M., Giattina M.R., Worgall T.S., Sturley S.L.,
RA Deckelbaum R.J.;
RT "Differential modulation of ACAT1 and ACAT2 transcription and activity by
RT long chain free fatty acids in cultured cells.";
RL Biochemistry 40:4756-4762(2001).
RN [9]
RP TISSUE SPECIFICITY, FUNCTION (ISOFORMS 2 AND 3), AND ALTERNATIVE SPLICING
RP (ISOFORMS 2 AND 3).
RX PubMed=16331323; DOI=10.1111/j.1745-7270.2005.00118.x;
RA Yao X.M., Wang C.H., Song B.L., Yang X.Y., Wang Z.Z., Qi W., Lin Z.X.,
RA Chang C.C., Chang T.Y., Li B.L.;
RT "Two human ACAT2 mRNA variants produced by alternative splicing and coding
RT for novel isoenzymes.";
RL Acta Biochim. Biophys. Sin. 37:797-806(2005).
RN [10]
RP INTERACTION WITH INSIG1, UBIQUITINATION AT CYS-277, OXIDATION AT CYS-277,
RP AND MUTAGENESIS OF LYS-49; LYS-80; LYS-100; LYS-102; LYS-108; LYS-242;
RP THR-254; 267-SER--SER-270; CYS-277; THR-279 AND LYS-299.
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 [11]
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 (PubMed:16647063,
CC PubMed:11294643). Plays a role in lipoprotein assembly and dietary
CC cholesterol absorption (PubMed:11294643). Utilizes oleoyl-CoA ((9Z)-
CC octadecenoyl-CoA) and linolenoyl-CoA ((9Z,12Z,15Z)-octadecatrienoyl-
CC CoA) as substrates (PubMed:11294643). May provide cholesteryl esters
CC for lipoprotein secretion from hepatocytes and intestinal mucosa
CC (PubMed:11294643). {ECO:0000269|PubMed:11294643,
CC ECO:0000269|PubMed:16647063}.
CC -!- FUNCTION: [Isoform 2]: Has lower enzymatic activity compared to isoform
CC 1. {ECO:0000269|PubMed:16331323}.
CC -!- FUNCTION: [Isoform 3]: Has lower enzymatic activity compared to isoform
CC 1. {ECO:0000269|PubMed:16331323}.
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:0000269|PubMed:16647063, ECO:0000305|PubMed:11294643};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59817;
CC Evidence={ECO:0000269|PubMed:16647063, ECO:0000305|PubMed:11294643};
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:0000269|PubMed:16647063, ECO:0000305|PubMed:11294643};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17730;
CC Evidence={ECO:0000269|PubMed:16647063, ECO:0000305|PubMed:11294643};
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:0000269|PubMed:11294643};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41437;
CC Evidence={ECO:0000305|PubMed:11294643};
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:0000269|PubMed:11294643};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46613;
CC Evidence={ECO:0000305|PubMed:11294643};
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:0000269|PubMed:11294643};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46621;
CC Evidence={ECO:0000305|PubMed:11294643};
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:0000269|PubMed:11294643};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42817;
CC Evidence={ECO:0000305|PubMed:11294643};
CC -!- SUBUNIT: May form homo- or heterodimers (By similarity). Interacts with
CC INSIG1; the interaction is direct and promotes association with
CC AMFR/gp78 (PubMed:28604676). {ECO:0000250|UniProtKB:P35610,
CC ECO:0000269|PubMed:28604676}.
CC -!- INTERACTION:
CC O75908; P55061: TMBIM6; NbExp=3; IntAct=EBI-9055438, EBI-1045825;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O88908}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=ACAD2a;
CC IsoId=O75908-1; Sequence=Displayed;
CC Name=2; Synonyms=ACAD2b;
CC IsoId=O75908-2; Sequence=VSP_057159;
CC Name=3; Synonyms=ACAD2c;
CC IsoId=O75908-3; Sequence=VSP_057158, VSP_057160;
CC Name=4;
CC IsoId=O75908-4; Sequence=VSP_057161, VSP_057162;
CC -!- TISSUE SPECIFICITY: Expression seems confined in hepatocytes and
CC enterocytes. {ECO:0000269|PubMed:16331323}.
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-277, leading to its
CC degradation when the lipid levels are low (PubMed:28604676).
CC Association with AMFR/gp78 is mediated via interaction with INSIG1
CC (PubMed:28604676). High concentration of cholesterol and fatty acid
CC results in Cys-277 oxidation, preventing ubiquitination at the same
CC site, resulting in protein stabilization (PubMed:28604676).
CC {ECO:0000269|PubMed:28604676}.
CC -!- PTM: Oxidized at Cys-277: high concentration of cholesterol and fatty
CC acid induce reactive oxygen species, which oxidizes Cys-277, preventing
CC ubiquitination at the same site, and resulting in protein
CC stabilization. {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; AF059203; AAC63998.1; -; mRNA.
DR EMBL; AF099031; AAC78335.2; -; mRNA.
DR EMBL; AF331516; AAK18275.1; -; Genomic_DNA.
DR EMBL; AF331502; AAK18275.1; JOINED; Genomic_DNA.
DR EMBL; AF331503; AAK18275.1; JOINED; Genomic_DNA.
DR EMBL; AF331504; AAK18275.1; JOINED; Genomic_DNA.
DR EMBL; AF331505; AAK18275.1; JOINED; Genomic_DNA.
DR EMBL; AF331506; AAK18275.1; JOINED; Genomic_DNA.
DR EMBL; AF331507; AAK18275.1; JOINED; Genomic_DNA.
DR EMBL; AF331508; AAK18275.1; JOINED; Genomic_DNA.
DR EMBL; AF331509; AAK18275.1; JOINED; Genomic_DNA.
DR EMBL; AF331510; AAK18275.1; JOINED; Genomic_DNA.
DR EMBL; AF331511; AAK18275.1; JOINED; Genomic_DNA.
DR EMBL; AF331512; AAK18275.1; JOINED; Genomic_DNA.
DR EMBL; AF331513; AAK18275.1; JOINED; Genomic_DNA.
DR EMBL; AF331514; AAK18275.1; JOINED; Genomic_DNA.
DR EMBL; AF331515; AAK18275.1; JOINED; Genomic_DNA.
DR EMBL; AF332858; AAK48829.1; -; Genomic_DNA.
DR EMBL; AF332857; AAK48829.1; JOINED; Genomic_DNA.
DR EMBL; AC073573; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC096090; AAH96090.1; -; mRNA.
DR EMBL; BC096091; AAH96091.1; -; mRNA.
DR EMBL; BC096092; AAH96092.1; -; mRNA.
DR EMBL; BC099626; AAH99626.1; -; mRNA.
DR CCDS; CCDS8847.1; -. [O75908-1]
DR RefSeq; NP_003569.1; NM_003578.3. [O75908-1]
DR PDB; 7N6Q; EM; 3.87 A; A/B/C/D=2-522.
DR PDB; 7N6R; EM; 3.93 A; A/B/C/D=2-522.
DR PDBsum; 7N6Q; -.
DR PDBsum; 7N6R; -.
DR AlphaFoldDB; O75908; -.
DR SMR; O75908; -.
DR BioGRID; 114015; 6.
DR IntAct; O75908; 3.
DR MINT; O75908; -.
DR STRING; 9606.ENSP00000301466; -.
DR BindingDB; O75908; -.
DR ChEMBL; CHEMBL4465; -.
DR DrugBank; DB01094; Hesperetin.
DR SwissLipids; SLP:000001262; -. [O75908-1]
DR TCDB; 2.A.50.4.11; the glycerol uptake (gup) or membrane-bound acyl transferase (mboat) family.
DR iPTMnet; O75908; -.
DR PhosphoSitePlus; O75908; -.
DR SwissPalm; O75908; -.
DR BioMuta; SOAT2; -.
DR MassIVE; O75908; -.
DR PaxDb; O75908; -.
DR PeptideAtlas; O75908; -.
DR PRIDE; O75908; -.
DR ProteomicsDB; 27608; -.
DR ProteomicsDB; 50258; -. [O75908-1]
DR Antibodypedia; 43294; 146 antibodies from 21 providers.
DR DNASU; 8435; -.
DR Ensembl; ENST00000301466.8; ENSP00000301466.3; ENSG00000167780.12. [O75908-1]
DR Ensembl; ENST00000542365.1; ENSP00000442234.1; ENSG00000167780.12. [O75908-4]
DR GeneID; 8435; -.
DR KEGG; hsa:8435; -.
DR MANE-Select; ENST00000301466.8; ENSP00000301466.3; NM_003578.4; NP_003569.1.
DR UCSC; uc001sbv.4; human. [O75908-1]
DR CTD; 8435; -.
DR DisGeNET; 8435; -.
DR GeneCards; SOAT2; -.
DR HGNC; HGNC:11178; SOAT2.
DR HPA; ENSG00000167780; Tissue enriched (intestine).
DR MIM; 601311; gene.
DR neXtProt; NX_O75908; -.
DR OpenTargets; ENSG00000167780; -.
DR PharmGKB; PA36016; -.
DR VEuPathDB; HostDB:ENSG00000167780; -.
DR eggNOG; KOG0380; Eukaryota.
DR GeneTree; ENSGT00950000183081; -.
DR HOGENOM; CLU_031845_1_0_1; -.
DR InParanoid; O75908; -.
DR OMA; MHDRHTG; -.
DR OrthoDB; 1275897at2759; -.
DR PhylomeDB; O75908; -.
DR TreeFam; TF315226; -.
DR BioCyc; MetaCyc:HS09636-MON; -.
DR BRENDA; 2.3.1.26; 2681.
DR PathwayCommons; O75908; -.
DR Reactome; R-HSA-8964038; LDL clearance.
DR SABIO-RK; O75908; -.
DR SignaLink; O75908; -.
DR BioGRID-ORCS; 8435; 18 hits in 1068 CRISPR screens.
DR GeneWiki; SOAT2; -.
DR GenomeRNAi; 8435; -.
DR Pharos; O75908; Tchem.
DR PRO; PR:O75908; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; O75908; protein.
DR Bgee; ENSG00000167780; Expressed in jejunal mucosa and 86 other tissues.
DR ExpressionAtlas; O75908; baseline and differential.
DR Genevisible; O75908; HS.
DR GO; GO:0005903; C:brush border; IDA:BHF-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016746; F:acyltransferase activity; TAS:ProtInc.
DR GO; GO:0015485; F:cholesterol binding; IDA:BHF-UCL.
DR GO; GO:0034736; F:cholesterol O-acyltransferase activity; IDA:BHF-UCL.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; IDA:BHF-UCL.
DR GO; GO:0008374; F:O-acyltransferase activity; IBA:GO_Central.
DR GO; GO:0004772; F:sterol O-acyltransferase activity; IDA:UniProtKB.
DR GO; GO:0033344; P:cholesterol efflux; IMP:BHF-UCL.
DR GO; GO:0034435; P:cholesterol esterification; IDA:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; TAS:BHF-UCL.
DR GO; GO:0008203; P:cholesterol metabolic process; IDA:UniProtKB.
DR GO; GO:0030299; P:intestinal cholesterol absorption; IC:BHF-UCL.
DR GO; GO:0034383; P:low-density lipoprotein particle clearance; TAS:Reactome.
DR GO; GO:0010742; P:macrophage derived foam cell differentiation; TAS:BHF-UCL.
DR GO; GO:0034379; P:very-low-density lipoprotein particle assembly; IMP:BHF-UCL.
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 3D-structure; Acyltransferase; Alternative splicing;
KW Cholesterol metabolism; Endoplasmic reticulum; Lipid metabolism; Membrane;
KW Oxidation; Reference proteome; Steroid metabolism; Sterol metabolism;
KW Thioester bond; Transferase; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT CHAIN 1..522
FT /note="Sterol O-acyltransferase 2"
FT /id="PRO_0000207645"
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..196
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 197..220
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 221..228
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 229..252
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 253..293
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 294..326
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 327..343
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 344..369
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 370..417
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 418..442
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 443..448
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 449..464
FT /note="Helical; Name=8"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 465..470
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 471..502
FT /note="Helical; Name=9"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT TOPO_DOM 503..522
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT REGION 1..36
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 74..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 377..383
FT /note="FYXDWWN motif"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT COMPBIAS 13..28
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 434
FT /evidence="ECO:0000305|PubMed:16647063"
FT BINDING 119
FT /ligand="cholesterol"
FT /ligand_id="ChEBI:CHEBI:16113"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT BINDING 389
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
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 399
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT BINDING 407
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT BINDING 430
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:P35610"
FT MOD_RES 277
FT /note="Cysteine sulfenic acid (-SOH); alternate"
FT /evidence="ECO:0000269|PubMed:28604676"
FT CROSSLNK 277
FT /note="Glycyl cysteine thioester (Cys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000269|PubMed:28604676"
FT VAR_SEQ 93..148
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000269|PubMed:16331323"
FT /id="VSP_057158"
FT VAR_SEQ 93..112
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000269|PubMed:16331323"
FT /id="VSP_057159"
FT VAR_SEQ 236..261
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000269|PubMed:16331323"
FT /id="VSP_057160"
FT VAR_SEQ 289..310
FT /note="TPYVRWNYVAKNFAQALGCVLY -> PWDVCSMPASSWAASVFLSLPT (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_057161"
FT VAR_SEQ 311..522
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_057162"
FT VARIANT 14
FT /note="E -> G (in dbSNP:rs9658625)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_020373"
FT VARIANT 254
FT /note="T -> I (in dbSNP:rs2272296)"
FT /evidence="ECO:0000269|PubMed:10846185,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_020374"
FT MUTAGEN 49
FT /note="K->R: In K-null mutant; does not affect
FT ubiquitination and sterol-regulated stabilization; when
FT associated with R-80, R-100, R-102, R-108, R-242 and R-
FT 299."
FT /evidence="ECO:0000269|PubMed:28604676"
FT MUTAGEN 80
FT /note="K->R: In K-null mutant; does not affect
FT ubiquitination and sterol-regulated stabilization; when
FT associated with R-49, R-100, R-102, R-108, R-242 and R-
FT 299."
FT /evidence="ECO:0000269|PubMed:28604676"
FT MUTAGEN 100
FT /note="K->R: In K-null mutant; does not affect
FT ubiquitination and sterol-regulated stabilization; when
FT associated with R-49, R-80, R-102, R-108, R-242 and R-299."
FT /evidence="ECO:0000269|PubMed:28604676"
FT MUTAGEN 102
FT /note="K->R: In K-null mutant; does not affect
FT ubiquitination and sterol-regulated stabilization; when
FT associated with R-49, R-80, R-100, R-108, R-242 and R-299."
FT /evidence="ECO:0000269|PubMed:28604676"
FT MUTAGEN 108
FT /note="K->R: In K-null mutant; does not affect
FT ubiquitination and sterol-regulated stabilization; when
FT associated with R-49, R-80, R-100, R-102, R-242 and R-299."
FT /evidence="ECO:0000269|PubMed:28604676"
FT MUTAGEN 242
FT /note="K->R: In K-null mutant; does not affect
FT ubiquitination and sterol-regulated stabilization; when
FT associated with R-49, R-80, R-100, R-102, R-108 and R-299."
FT /evidence="ECO:0000269|PubMed:28604676"
FT MUTAGEN 254
FT /note="T->A: Does not affect ubiquitination and sterol-
FT regulated stabilization; when associated with R-279."
FT /evidence="ECO:0000269|PubMed:28604676"
FT MUTAGEN 267..270
FT /note="SFSS->AFAA: Does not affect ubiquitination and
FT sterol-regulated stabilization."
FT /evidence="ECO:0000269|PubMed:28604676"
FT MUTAGEN 277
FT /note="C->A: Abolished ubiquitination and sterol-regulated
FT stabilization."
FT /evidence="ECO:0000269|PubMed:28604676"
FT MUTAGEN 279
FT /note="T->A: Does not affect ubiquitination and sterol-
FT regulated stabilization; when associated with R-54."
FT /evidence="ECO:0000269|PubMed:28604676"
FT MUTAGEN 299
FT /note="K->R: In K-null mutant; does not affect
FT ubiquitination and sterol-regulated stabilization; when
FT associated with R-49, R-80, R-100, R-102, R-108 and R-242."
FT /evidence="ECO:0000269|PubMed:28604676"
FT MUTAGEN 360
FT /note="H->A: Abolished cholesterol O-acyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:16647063"
FT MUTAGEN 399
FT /note="H->A: Abolished cholesterol O-acyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:16647063"
FT CONFLICT 22
FT /note="R -> P (in Ref. 4; AAK48829)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 522 AA; 59896 MW; EEAC2DB569FFE729 CRC64;
MEPGGARLRL QRTEGLGGER ERQPCGDGNT ETHRAPDLVQ WTRHMEAVKA QLLEQAQGQL
RELLDRAMRE AIQSYPSQDK PLPPPPPGSL SRTQEPSLGK QKVFIIRKSL LDELMEVQHF
RTIYHMFIAG LCVFIISTLA IDFIDEGRLL LEFDLLIFSF GQLPLALVTW VPMFLSTLLA
PYQALRLWAR GTWTQATGLG CALLAAHAVV LCALPVHVAV EHQLPPASRC VLVFEQVRFL
MKSYSFLREA VPGTLRARRG EGIQAPSFSS YLYFLFCPTL IYRETYPRTP YVRWNYVAKN
FAQALGCVLY ACFILGRLCV PVFANMSREP FSTRALVLSI LHATLPGIFM LLLIFFAFLH
CWLNAFAEML RFGDRMFYRD WWNSTSFSNY YRTWNVVVHD WLYSYVYQDG LRLLGARARG
VAMLGVFLVS AVAHEYIFCF VLGFFYPVML ILFLVIGGML NFMMHDQRTG PAWNVLMWTM
LFLGQGIQVS LYCQEWYARR HCPLPQATFW GLVTPRSWSC HT
