Diacylglycerol O-acyltransferase 1

UniProt O75907 Organism Homo sapiens Gene AGRP1, DGAT, DGAT1 EC 2.3.1.20, 2.3.1.76

Also known as: AGRP1, DGAT, DGAT1

Function

Catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates. Highly expressed in epithelial cells of the small intestine and its activity is essential for the absorption of dietary fats. In liver, plays a role in esterifying exogenous fatty acids to glycerol, and is required to synthesize fat for storage. 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. 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. 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).

Classification

Family (Pfam): PF03062 MBOAT
InterPro: Diacylglycerol_acylTrfase1, MBOAT_fam, Oat_ACAT_DAG_ARE
Functional cluster: Mixed Regulatory & Membrane Proteins

Experimental structures · PDB · 5

6VP0 EM 3.10A
6VYI EM 3.00A
6VZ1 EM 3.20A
8ESM EM 3.20A
8ETM EM 3.20A

A predicted model is available from AlphaFold.

Gene Ontology · 17

Disease associations

congenital diarrhea 7 with exudative enteropathy MONDO:0014375

Drugs targeting this protein · 2

PRADIGASTAT inhibitor
AZD-7687 inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

2-acylglycerol O-acyltransferase 3 3 shared papers
Sterol O-acyltransferase 2 1 shared papers
Diacylglycerol O-acyltransferase 2 3 shared papers
2-acylglycerol O-acyltransferase 2 2 shared papers
Diacylglycerol O-acyltransferase 2-like protein 6 1 shared papers
Diacylglycerol O-acyltransferase 1 1 shared papers
Acyl-CoA wax alcohol acyltransferase 2 1 shared papers
T-box transcription factor T 1 shared papers
Katanin-interacting protein 1 shared papers
Leukocyte receptor cluster member 8 1 shared papers
THUMP domain-containing protein 1 1 shared papers
Alpha-(1,6)-fucosyltransferase 1 shared papers

Literature · 10 cited papers

Structure and catalytic mechanism of a human triacylglycerol-synthesis enzyme. Nature · 2020
Structure and mechanism of human diacylglycerol O-acyltransferase 1. Nature · 2020
Autozygome and high throughput confirmation of disease genes candidacy. Genet. Med. · 2019
Synthesis of neutral ether lipid monoalkyl-diacylglycerol by lipid acyltransferases. J. Lipid Res. · 2017
An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
DGAT1 mutation is linked to a congenital diarrheal disorder. J. Clin. Invest. · 2012
Acylation of acylglycerols by acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1). Functional importance of DGAT1 in the intestinal fat absorption. J. Biol. Chem. · 2008
Acyl coenzyme A dependent retinol esterification by acyl coenzyme A: diacylglycerol acyltransferase 1. Biochim. Biophys. Acta · 2005
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Characterization of two human genes encoding acyl coenzyme A:cholesterol acyltransferase-related enzymes. J. Biol. Chem. · 1998

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