DGAT1_MOUSE
ID DGAT1_MOUSE Reviewed; 498 AA.
AC Q9Z2A7; Q9D7Q5;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Diacylglycerol O-acyltransferase 1 {ECO:0000305};
DE EC=2.3.1.20 {ECO:0000269|PubMed:19028692, ECO:0000269|PubMed:20876538};
DE AltName: Full=Acyl-CoA retinol O-fatty-acyltransferase {ECO:0000303|PubMed:19028692};
DE Short=ARAT {ECO:0000303|PubMed:19028692};
DE Short=Retinol O-fatty-acyltransferase {ECO:0000303|PubMed:19028692};
DE EC=2.3.1.76 {ECO:0000269|PubMed:19028692, ECO:0000269|PubMed:20876538};
DE AltName: Full=Diglyceride acyltransferase;
GN Name=Dgat1 {ECO:0000303|PubMed:11959864, ECO:0000312|MGI:MGI:1333825};
GN Synonyms=Dgat {ECO:0000303|PubMed:10802663, ECO:0000303|PubMed:9789033};
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], AND CATALYTIC ACTIVITY.
RC STRAIN=C57BL/6J;
RX PubMed=9789033; DOI=10.1073/pnas.95.22.13018;
RA Cases S., Smith S.J., Zheng Y.-W., Myers H.M., Lear S.R., Sande E.,
RA Novak S., Collins C., Welch C.B., Lusis A.J., Erickson S.K.,
RA Farese R.V. Jr.;
RT "Identification of a gene encoding an acyl CoA:diacylglycerol
RT acyltransferase, a key enzyme in triacylglycerol synthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:13018-13023(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 DISRUPTION PHENOTYPE.
RX PubMed=10802663; DOI=10.1038/75651;
RA Smith S.J., Cases S., Jensen D.R., Chen H.C., Sande E., Tow B., Sanan D.A.,
RA Raber J., Eckel R.H., Farese R.V. Jr.;
RT "Obesity resistance and multiple mechanisms of triglyceride synthesis in
RT mice lacking Dgat.";
RL Nat. Genet. 25:87-90(2000).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11959864; DOI=10.1074/jbc.m202013200;
RA Buhman K.K., Smith S.J., Stone S.J., Repa J.J., Wong J.S.,
RA Knapp F.F.R. Jr., Burri B.J., Hamilton R.L., Abumrad N.A., Farese R.V. Jr.;
RT "DGAT1 is not essential for intestinal triacylglycerol absorption or
RT chylomicron synthesis.";
RL J. Biol. Chem. 277:25474-25479(2002).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=11956242; DOI=10.1172/jci14672;
RA Chen H.C., Smith S.J., Ladha Z., Jensen D.R., Ferreira L.D., Pulawa L.K.,
RA McGuire J.G., Pitas R.E., Eckel R.H., Farese R.V. Jr.;
RT "Increased insulin and leptin sensitivity in mice lacking acyl
RT CoA:diacylglycerol acyltransferase 1.";
RL J. Clin. Invest. 109:1049-1055(2002).
RN [7]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=19028692; DOI=10.1074/jbc.m807503200;
RA Shih M.Y., Kane M.A., Zhou P., Yen C.L., Streeper R.S., Napoli J.L.,
RA Farese R.V. Jr.;
RT "Retinol esterification by DGAT1 is essential for retinoid homeostasis in
RT murine skin.";
RL J. Biol. Chem. 284:4292-4299(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, and 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 [9]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=15834126; DOI=10.1194/jlr.m500036-jlr200;
RA Yen C.L., Monetti M., Burri B.J., Farese R.V. Jr.;
RT "The triacylglycerol synthesis enzyme DGAT1 also catalyzes the synthesis of
RT diacylglycerols, waxes, and retinyl esters.";
RL J. Lipid Res. 46:1502-1511(2005).
RN [10]
RP CATALYTIC ACTIVITY.
RX PubMed=16106050; DOI=10.1194/jlr.m500168-jlr200;
RA Yen C.-L.E., Brown C.H. IV, Monetti M., Farese R.V. Jr.;
RT "A human skin multifunctional O-acyltransferase that catalyzes the
RT synthesis of acylglycerols, waxes, and retinyl esters.";
RL J. Lipid Res. 46:2388-2397(2005).
RN [11]
RP MUTAGENESIS OF HIS-426, SUBUNIT, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION,
RP AND FUNCTION.
RX PubMed=20876538; DOI=10.1074/jbc.m110.163691;
RA McFie P.J., Stone S.L., Banman S.L., Stone S.J.;
RT "Acyl CoA:diacylglycerol acyltransferase-1 (DGAT1): topological
RT orientation, identification of a putative active site histidine and the
RT role of the N-terminus in dimer/tetramer formation.";
RL J. Biol. Chem. 285:37377-37387(2010).
RN [12]
RP FUNCTION.
RX PubMed=22493088; DOI=10.1194/jlr.m020156;
RA Qi J., Lang W., Geisler J.G., Wang P., Petrounia I., Mai S., Smith C.,
RA Askari H., Struble G.T., Williams R., Bhanot S., Monia B.P., Bayoumy S.,
RA Grant E., Caldwell G.W., Todd M.J., Liang Y., Gaul M.D., Demarest K.T.,
RA Connelly M.A.;
RT "The use of stable isotope-labeled glycerol and oleic acid to differentiate
RT the hepatic functions of DGAT1 and -2.";
RL J. Lipid Res. 53:1106-1116(2012).
RN [13]
RP CATALYTIC ACTIVITY.
RX PubMed=23066022; DOI=10.1074/jbc.m112.400416;
RA Eichmann T.O., Kumari M., Haas J.T., Farese R.V. Jr., Zimmermann R.,
RA Lass A., Zechner R.;
RT "Studies on the substrate and stereo/regioselectivity of adipose
RT triglyceride lipase, hormone-sensitive lipase, and diacylglycerol-O-
RT acyltransferases.";
RL J. Biol. Chem. 287:41446-41457(2012).
RN [14]
RP CATALYTIC ACTIVITY, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28420705; DOI=10.1194/jlr.m073445;
RA Ma Z., Onorato J.M., Chen L., Nelson D.W., Yen C.E., Cheng D.;
RT "Synthesis of neutral ether lipid monoalkyl-diacylglycerol by lipid
RT acyltransferases.";
RL J. Lipid Res. 58:1091-1099(2017).
CC -!- FUNCTION: Catalyzes the terminal and only committed step in
CC triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as
CC substrates (PubMed:15834126, PubMed:19028692, PubMed:20876538,
CC PubMed:22493088, PubMed:28420705). Highly expressed in epithelial cells
CC of the small intestine and its activity is essential for the absorption
CC of dietary fats (By similarity). In liver, plays a role in esterifying
CC exogenous fatty acids to glycerol, and is required to synthesize fat
CC for storage (PubMed:15834126). Also present in female mammary glands,
CC where it produces fat in the milk (By similarity). May be involved in
CC VLDL (very low density lipoprotein) assembly (By similarity). In
CC contrast to DGAT2 it is not essential for survival (PubMed:11959864).
CC Functions as the major acyl-CoA retinol acyltransferase (ARAT) in the
CC skin, where it acts to maintain retinoid homeostasis and prevent
CC retinoid toxicity leading to skin and hair disorders (PubMed:19028692).
CC Exhibits additional acyltransferase activities, includin acyl
CC CoA:monoacylglycerol acyltransferase (MGAT), wax monoester and wax
CC diester synthases (PubMed:15834126). Also able to use 1-
CC monoalkylglycerol (1-MAkG) as an acyl acceptor for the synthesis of
CC monoalkyl-monoacylglycerol (MAMAG) (PubMed:28420705).
CC {ECO:0000250|UniProtKB:O75907, ECO:0000250|UniProtKB:Q8MK44,
CC ECO:0000269|PubMed:11959864, ECO:0000269|PubMed:15834126,
CC ECO:0000269|PubMed:19028692, ECO:0000269|PubMed:20876538,
CC ECO:0000269|PubMed:22493088, ECO:0000269|PubMed:28420705}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycerol + an acyl-CoA = a triacyl-sn-glycerol
CC + CoA; Xref=Rhea:RHEA:10868, ChEBI:CHEBI:17815, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:58342, ChEBI:CHEBI:64615; EC=2.3.1.20;
CC Evidence={ECO:0000269|PubMed:19028692, ECO:0000269|PubMed:20876538};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10869;
CC Evidence={ECO:0000305};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinol + an acyl-CoA = an all-trans-retinyl ester +
CC CoA; Xref=Rhea:RHEA:11488, ChEBI:CHEBI:17336, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:58342, ChEBI:CHEBI:63410; EC=2.3.1.76;
CC Evidence={ECO:0000269|PubMed:19028692, ECO:0000269|PubMed:20876538};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11489;
CC Evidence={ECO:0000305};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-sn-glycerol = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-
CC eicosatetraenoyl-3-(9Z)-octadecenoyl-sn-glycerol + CoA;
CC Xref=Rhea:RHEA:38307, ChEBI:CHEBI:57287, ChEBI:CHEBI:57387,
CC ChEBI:CHEBI:75728, ChEBI:CHEBI:75729;
CC Evidence={ECO:0000269|PubMed:9789033};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38308;
CC Evidence={ECO:0000305|PubMed:9789033};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecane-1,2-diol + 2 hexadecanoyl-CoA = 1,2-O,O-
CC dihexadecanoyl-1,2-hexadecanediol + 2 CoA; Xref=Rhea:RHEA:38211,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:75586,
CC ChEBI:CHEBI:75608; Evidence={ECO:0000269|PubMed:15834126,
CC ECO:0000269|PubMed:16106050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38212;
CC Evidence={ECO:0000305|PubMed:15834126, ECO:0000305|PubMed:16106050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecane-1,2-diol + hexadecanoyl-CoA = 2-hydroxyhexadecyl
CC hexadecanoate + CoA; Xref=Rhea:RHEA:38171, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57379, ChEBI:CHEBI:75586, ChEBI:CHEBI:75587;
CC Evidence={ECO:0000269|PubMed:16106050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38172;
CC Evidence={ECO:0000305|PubMed:16106050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(9Z-octadecenoyl)-glycerol + hexadecanoyl-CoA = 1-
CC hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + CoA;
CC Xref=Rhea:RHEA:38071, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379,
CC ChEBI:CHEBI:73990, ChEBI:CHEBI:75466;
CC Evidence={ECO:0000269|PubMed:15834126, ECO:0000269|PubMed:16106050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38072;
CC Evidence={ECO:0000305|PubMed:15834126, ECO:0000305|PubMed:16106050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycerol + hexadecanoyl-CoA = 1,2-
CC di-(9Z)-octadecenoyl-3-hexadecanoyl-sn-glycerol + CoA;
CC Xref=Rhea:RHEA:38163, ChEBI:CHEBI:52333, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57379, ChEBI:CHEBI:75583;
CC Evidence={ECO:0000269|PubMed:15834126, ECO:0000269|PubMed:16106050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38164;
CC Evidence={ECO:0000305|PubMed:15834126, ECO:0000305|PubMed:16106050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecan-1-ol + hexadecanoyl-CoA = CoA + hexadecanyl
CC hexadecanoate; Xref=Rhea:RHEA:38167, ChEBI:CHEBI:16125,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:75584;
CC Evidence={ECO:0000269|PubMed:15834126, ECO:0000269|PubMed:16106050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38168;
CC Evidence={ECO:0000305|PubMed:15834126, ECO:0000305|PubMed:16106050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinol + hexadecanoyl-CoA = all-trans-retinyl
CC hexadecanoate + CoA; Xref=Rhea:RHEA:38175, ChEBI:CHEBI:17336,
CC ChEBI:CHEBI:17616, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379;
CC Evidence={ECO:0000269|PubMed:15834126, ECO:0000269|PubMed:16106050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38176;
CC Evidence={ECO:0000305|PubMed:15834126, ECO:0000305|PubMed:16106050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=13-cis-retinol + hexadecanoyl-CoA = 13-cis-retinyl
CC hexadecanoate + CoA; Xref=Rhea:RHEA:55296, ChEBI:CHEBI:45479,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:138722;
CC Evidence={ECO:0000269|PubMed:15834126};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55297;
CC Evidence={ECO:0000305|PubMed:15834126};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + 1,2-di-(9Z-octadecenoyl)-sn-glycerol =
CC 1,2,3-tri-(9Z-octadecenoyl)-glycerol + CoA; Xref=Rhea:RHEA:38219,
CC ChEBI:CHEBI:52333, ChEBI:CHEBI:53753, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57387; Evidence={ECO:0000269|PubMed:23066022};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38220;
CC Evidence={ECO:0000305|PubMed:23066022};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + 1,3-di-(9Z-octadecenoyl)-glycerol =
CC 1,2,3-tri-(9Z-octadecenoyl)-glycerol + CoA; Xref=Rhea:RHEA:38435,
CC ChEBI:CHEBI:53753, ChEBI:CHEBI:57287, ChEBI:CHEBI:57387,
CC ChEBI:CHEBI:75735; Evidence={ECO:0000269|PubMed:23066022};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38436;
CC Evidence={ECO:0000305|PubMed:23066022};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + 2,3-di-(9Z)-octadecenoyl-sn-glycerol =
CC 1,2,3-tri-(9Z-octadecenoyl)-glycerol + CoA; Xref=Rhea:RHEA:38439,
CC ChEBI:CHEBI:53753, ChEBI:CHEBI:57287, ChEBI:CHEBI:57387,
CC ChEBI:CHEBI:75824; Evidence={ECO:0000269|PubMed:23066022};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38440;
CC Evidence={ECO:0000305|PubMed:23066022};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + 1-O-(9Z-octadecenyl)-glycerol = 1-O-
CC (9Z-octadecenyl)-mono-(9Z-octadecenoyl)-glycerol + CoA;
CC Xref=Rhea:RHEA:55340, ChEBI:CHEBI:34116, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57387, ChEBI:CHEBI:138734;
CC Evidence={ECO:0000269|PubMed:28420705};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55341;
CC Evidence={ECO:0000269|PubMed:28420705};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + 1-(9Z-octadecenoyl)-glycerol = 1,2-di-
CC (9Z-octadecenoyl)-glycerol + CoA; Xref=Rhea:RHEA:37915,
CC ChEBI:CHEBI:52323, ChEBI:CHEBI:57287, ChEBI:CHEBI:57387,
CC ChEBI:CHEBI:75342; Evidence={ECO:0000269|PubMed:28420705};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37916;
CC Evidence={ECO:0000269|PubMed:28420705};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + 2-(9Z-octadecenoyl)-glycerol = 1,2-di-
CC (9Z-octadecenoyl)-sn-glycerol + CoA; Xref=Rhea:RHEA:37911,
CC ChEBI:CHEBI:52333, ChEBI:CHEBI:57287, ChEBI:CHEBI:57387,
CC ChEBI:CHEBI:73990; Evidence={ECO:0000250|UniProtKB:O75907};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37912;
CC Evidence={ECO:0000250|UniProtKB:O75907};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + 1-O-(9Z-octadecenyl)-mono-(9Z-
CC octadecenoyl)-glycerol = 1-O-(9Z-octadecenyl)-2,3-di-(9Z-
CC octadecenoyl)glycerol + CoA; Xref=Rhea:RHEA:55344, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57387, ChEBI:CHEBI:138734, ChEBI:CHEBI:138735;
CC Evidence={ECO:0000250|UniProtKB:O75907};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55345;
CC Evidence={ECO:0000250|UniProtKB:O75907};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoate + 1,2-di-(9Z-octadecenoyl)-glycerol + H(+)
CC = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O; Xref=Rhea:RHEA:38379,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:52323, ChEBI:CHEBI:53753;
CC Evidence={ECO:0000250|UniProtKB:O75907};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38380;
CC Evidence={ECO:0000250|UniProtKB:O75907};
CC -!- PATHWAY: Lipid metabolism; glycerolipid metabolism.
CC -!- SUBUNIT: Homodimer or homotetramer; both forms have similar enzymatic
CC activities. {ECO:0000269|PubMed:20876538}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:20876538}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:20876538}.
CC -!- DOMAIN: The disordered N-terminal region is required for the
CC diacylglycerol O-acyltransferase activity and may regulate enzymatic
CC function via its interaction with the MBOAT fold.
CC {ECO:0000250|UniProtKB:O75907}.
CC -!- DOMAIN: The MBOAT fold forms a reaction chamber in the endoplasmic
CC reticulum membrane that encloses the active sites. The reaction chamber
CC has a tunnel to the cytosolic side and its entrance recognizes the
CC hydrophilic CoA motif of an acyl-CoA molecule. The chamber has separate
CC entrances for each of the two substrates, acyl-CoA and 1,2-diacyl-sn-
CC glycerol. {ECO:0000250|UniProtKB:O75907}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and live well, but show
CC substantially reduced levels of triacylglycerides in all tissues
CC (PubMed:10802663, PubMed:11959864, PubMed:11956242). Mice are resistant
CC to obesity when kept on a high-fat diet due to increased energy
CC expenditure: they display reduced postabsorptive chylomicronemia and
CC accumulate neutral-lipid droplets in the cytoplasm of enterocytes
CC (PubMed:10802663, PubMed:11959864, PubMed:11956242). Mice also show
CC increased sensitivity to insulin and to leptin and are protected
CC against insulin resistance (PubMed:11956242). Mutant mice show reduced
CC levels of monoalkyl-monoacylglycerol (MADAG) in the adrenal gland
CC (PubMed:28420705). {ECO:0000269|PubMed:10802663,
CC ECO:0000269|PubMed:11956242, ECO:0000269|PubMed:11959864,
CC ECO:0000269|PubMed:28420705}.
CC -!- SIMILARITY: Belongs to the membrane-bound acyltransferase family.
CC Sterol o-acyltransferase subfamily. {ECO:0000305}.
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DR EMBL; AF078752; AAC72917.1; -; mRNA.
DR EMBL; AK008995; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC003717; AAH03717.1; -; mRNA.
DR CCDS; CCDS27573.1; -.
DR RefSeq; NP_034176.1; NM_010046.3.
DR AlphaFoldDB; Q9Z2A7; -.
DR SMR; Q9Z2A7; -.
DR BioGRID; 199213; 1.
DR IntAct; Q9Z2A7; 2.
DR STRING; 10090.ENSMUSP00000023214; -.
DR BindingDB; Q9Z2A7; -.
DR ChEMBL; CHEMBL1075284; -.
DR SwissLipids; SLP:000000302; -.
DR iPTMnet; Q9Z2A7; -.
DR PhosphoSitePlus; Q9Z2A7; -.
DR EPD; Q9Z2A7; -.
DR jPOST; Q9Z2A7; -.
DR MaxQB; Q9Z2A7; -.
DR PaxDb; Q9Z2A7; -.
DR PRIDE; Q9Z2A7; -.
DR ProteomicsDB; 277318; -.
DR Antibodypedia; 28443; 324 antibodies from 31 providers.
DR DNASU; 13350; -.
DR Ensembl; ENSMUST00000023214; ENSMUSP00000023214; ENSMUSG00000022555.
DR GeneID; 13350; -.
DR KEGG; mmu:13350; -.
DR UCSC; uc007wkn.1; mouse.
DR CTD; 8694; -.
DR MGI; MGI:1333825; Dgat1.
DR VEuPathDB; HostDB:ENSMUSG00000022555; -.
DR eggNOG; KOG0380; Eukaryota.
DR GeneTree; ENSGT00950000183081; -.
DR HOGENOM; CLU_018190_0_0_1; -.
DR InParanoid; Q9Z2A7; -.
DR OMA; HAIIVWL; -.
DR OrthoDB; 1275897at2759; -.
DR PhylomeDB; Q9Z2A7; -.
DR TreeFam; TF314921; -.
DR BRENDA; 2.3.1.20; 3474.
DR Reactome; R-MMU-1482883; Acyl chain remodeling of DAG and TAG.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-75109; Triglyceride biosynthesis.
DR UniPathway; UPA00230; -.
DR BioGRID-ORCS; 13350; 6 hits in 75 CRISPR screens.
DR ChiTaRS; Dgat1; mouse.
DR PRO; PR:Q9Z2A7; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q9Z2A7; protein.
DR Bgee; ENSMUSG00000022555; Expressed in granulocyte and 269 other tissues.
DR ExpressionAtlas; Q9Z2A7; baseline and differential.
DR Genevisible; Q9Z2A7; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IMP:BHF-UCL.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0003846; F:2-acylglycerol O-acyltransferase activity; IDA:MGI.
DR GO; GO:0016746; F:acyltransferase activity; ISO:MGI.
DR GO; GO:0019992; F:diacylglycerol binding; ISO:MGI.
DR GO; GO:0004144; F:diacylglycerol O-acyltransferase activity; IDA:BHF-UCL.
DR GO; GO:0005504; F:fatty acid binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008374; F:O-acyltransferase activity; IBA:GO_Central.
DR GO; GO:0050252; F:retinol O-fatty-acyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0046339; P:diacylglycerol metabolic process; IDA:BHF-UCL.
DR GO; GO:0055089; P:fatty acid homeostasis; IMP:UniProtKB.
DR GO; GO:0046486; P:glycerolipid metabolic process; ISO:MGI.
DR GO; GO:0030073; P:insulin secretion; ISO:MGI.
DR GO; GO:1902224; P:ketone body metabolic process; ISO:MGI.
DR GO; GO:0019915; P:lipid storage; IMP:UniProtKB.
DR GO; GO:0035336; P:long-chain fatty-acyl-CoA metabolic process; IDA:BHF-UCL.
DR GO; GO:0006640; P:monoacylglycerol biosynthetic process; IMP:UniProtKB.
DR GO; GO:0046321; P:positive regulation of fatty acid oxidation; ISO:MGI.
DR GO; GO:2000491; P:positive regulation of hepatic stellate cell activation; ISO:MGI.
DR GO; GO:0010867; P:positive regulation of triglyceride biosynthetic process; ISO:MGI.
DR GO; GO:1903998; P:regulation of eating behavior; ISO:MGI.
DR GO; GO:1904729; P:regulation of intestinal lipid absorption; ISO:MGI.
DR GO; GO:1901738; P:regulation of vitamin A metabolic process; ISO:MGI.
DR GO; GO:0019432; P:triglyceride biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0034379; P:very-low-density lipoprotein particle assembly; ISO:MGI.
DR InterPro; IPR027251; Diacylglycerol_acylTrfase1.
DR InterPro; IPR004299; MBOAT_fam.
DR InterPro; IPR014371; Oat_ACAT_DAG_ARE.
DR PANTHER; PTHR10408; PTHR10408; 1.
DR Pfam; PF03062; MBOAT; 1.
DR PIRSF; PIRSF000439; Oat_ACAT_DAG_ARE; 1.
DR PIRSF; PIRSF500231; Oat_dag; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Endoplasmic reticulum; Lipid metabolism; Membrane;
KW Phosphoprotein; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..498
FT /note="Diacylglycerol O-acyltransferase 1"
FT /id="PRO_0000207655"
FT TOPO_DOM 1..92
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 93..127
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT TOPO_DOM 128..139
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 140..165
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT TOPO_DOM 166..170
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 171..193
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT TOPO_DOM 194..200
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 201..232
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT TOPO_DOM 233..284
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 285..319
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT TOPO_DOM 320..326
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 327..364
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT TOPO_DOM 365..410
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 411..431
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT TOPO_DOM 432..439
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 440..458
FT /note="Helical; Name=8"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT TOPO_DOM 459..460
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 461..492
FT /note="Helical; Name=9"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT TOPO_DOM 493..498
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT REGION 1..100
FT /note="Involved in homomerization"
FT /evidence="ECO:0000269|PubMed:20876538"
FT REGION 1..66
FT /note="Disordered"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT REGION 128..139
FT /note="Extracellular loop 1 (EL1)"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT REGION 140..498
FT /note="MBOAT fold"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT REGION 235..287
FT /note="Intracellular loop 1 (IL1)"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT REGION 365..410
FT /note="Intracellular loop 2 (IL2)"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT REGION 391..405
FT /note="Amphipathic helix (AH)"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT MOTIF 371..377
FT /note="FYXDWWN motif"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT ACT_SITE 426
FT /evidence="ECO:0000305|PubMed:20876538"
FT BINDING 385..393
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT BINDING 401
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT BINDING 415
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT BINDING 488
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT SITE 427
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75907"
FT MUTAGEN 426
FT /note="H->A: Impairs the ability to synthesize
FT triacylglycerols, as well as retinyl and wax esters, in an
FT in vitro acyltransferase assay."
FT /evidence="ECO:0000269|PubMed:20876538"
SQ SEQUENCE 498 AA; 56790 MW; E7B0DD6DDCF1EC2B CRC64;
MGDRGGAGSS RRRRTGSRVS VQGGSGPKVE EDEVRDAAVS PDLGAGGDAP APAPAPAHTR
DKDGRTSVGD GYWDLRCHRL QDSLFSSDSG FSNYRGILNW CVVMLILSNA RLFLENLIKY
GILVDPIQVV SLFLKDPYSW PAPCVIIASN IFVVAAFQIE KRLAVGALTE QMGLLLHVVN
LATIICFPAA VALLVESITP VGSVFALASY SIMFLKLYSY RDVNLWCRQR RVKAKAVSTG
KKVSGAAAQQ AVSYPDNLTY RDLYYFIFAP TLCYELNFPR SPRIRKRFLL RRVLEMLFFT
QLQVGLIQQW MVPTIQNSMK PFKDMDYSRI IERLLKLAVP NHLIWLIFFY WFFHSCLNAV
AELLQFGDRE FYRDWWNAES VTYFWQNWNI PVHKWCIRHF YKPMLRHGSS KWVARTGVFL
TSAFFHEYLV SVPLRMFRLW AFTAMMAQVP LAWIVGRFFQ GNYGNAAVWV TLIIGQPVAV
LMYVHDYYVL NYDAPVGV
