Catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates (PubMed:16214399, PubMed:18768481, PubMed:28420705, PubMed:9756920, PubMed:32433611, PubMed:32433610). Highly expressed in epithelial cells of the small intestine and its activity is essential for the absorption of dietary fats (PubMed:18768481). In liver, plays a role in esterifying exogenous fatty acids to glycerol, and is required to synthesize fat for storage (PubMed:16214399). Also present in female mammary glands, where it produces fat in the milk (By similarity). May be involved in VLDL (very low density lipoprotein) assembly (PubMed:18768481). In contrast to DGAT2 it is not essential for survival (By similarity). Functions as the major acyl-CoA retinol acyltransferase (ARAT) in the skin, where it acts to maintain retinoid homeostasis and prevent retinoid toxicity leading to skin and hair disorders (PubMed:16214399). Exhibits additional acyltransferase activities, includin acyl CoA:monoacylglycerol acyltransferase (MGAT), wax monoester and wax diester synthases (By similarity). Also able to use 1-monoalkylglycerol (1-MAkG) as an acyl acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG) (PubMed:28420705). a 1,2-diacyl-sn-glycerol + an acyl-CoA = a triacyl-sn-glycerol + CoA all-trans-retinol + an acyl-CoA = an all-trans-retinyl ester + CoA (9Z)-octadecenoyl-CoA + 2-(9Z-octadecenoyl)-glycerol = 1,2-di-(9Z-octadecenoyl)-sn-glycerol + CoA (9Z)-octadecenoyl-CoA + 1,2-di-(9Z-octadecenoyl)-sn-glycerol = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + CoA all-trans-retinol + hexadecanoyl-CoA = all-trans-retinyl hexadecanoate + CoA (9Z)-octadecenoyl-CoA + 1-O-(9Z-octadecenyl)-glycerol = 1-O-(9Z-octadecenyl)-mono-(9Z-octadecenoyl)-glycerol + CoA (9Z)-octadecenoyl-CoA + 1-O-(9Z-octadecenyl)-mono-(9Z-octadecenoyl)-glycerol = 1-O-(9Z-octadecenyl)-2,3-di-(9Z-octadecenoyl)glycerol + CoA (9Z)-octadecenoyl-CoA + 1-(9Z-octadecenoyl)-glycerol = 1,2-di-(9Z-octadecenoyl)-glycerol + CoA (9Z)-octadecenoate + 1,2-di-(9Z-octadecenoyl)-glycerol + H(+) = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O (9Z)-octadecenoyl-CoA + 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-3-(9Z)-octadecenoyl-sn-glycerol + CoA hexadecane-1,2-diol + 2 hexadecanoyl-CoA = 1,2-O,O-dihexadecanoyl-1,2-hexadecanediol + 2 CoA hexadecane-1,2-diol + hexadecanoyl-CoA = 2-hydroxyhexadecyl hexadecanoate + CoA 2-(9Z-octadecenoyl)-glycerol + hexadecanoyl-CoA = 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + CoA 1,2-di-(9Z-octadecenoyl)-sn-glycerol + hexadecanoyl-CoA = 1,2-di-(9Z)-octadecenoyl-3-hexadecanoyl-sn-glycerol + CoA hexadecan-1-ol + hexadecanoyl-CoA = CoA + hexadecanyl hexadecanoate 13-cis-retinol + hexadecanoyl-CoA = 13-cis-retinyl hexadecanoate + CoA (9Z)-octadecenoyl-CoA + 1,3-di-(9Z-octadecenoyl)-glycerol = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + CoA (9Z)-octadecenoyl-CoA + 2,3-di-(9Z)-octadecenoyl-sn-glycerol = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + CoA XP620 is a selective DGAT1 inhibitor. Lipid metabolism; glycerolipid metabolism. Homodimer or homotetramer; both forms have similar enzymatic activities. The disordered N-terminal region is required for the diacylglycerol O-acyltransferase activity and may regulate enzymatic function via its interaction with the MBOAT fold. The MBOAT fold forms a reaction chamber in the endoplasmic reticulum membrane that encloses the active sites (PubMed:32433611, PubMed:32433610). The reaction chamber has a tunnel to the cytosolic side and its entrance recognizes the hydrophilic CoA motif of an acyl-CoA molecule (PubMed:32433610). The chamber has separate entrances for each of the two substrates, acyl-CoA and 1,2-diacyl-sn-glycerol (PubMed:32433610). The disease is caused by variants affecting the gene represented in this entry. Belongs to the membrane-bound acyltransferase family. Sterol o-acyltransferase subfamily.