O75907 (DGAT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Diacylglycerol O-acyltransferase 1
EC=2.3.1.20

Alternative name(s):
ACAT-related gene product 1
Acyl-CoA retinol O-fatty-acyltransferase
Short name=ARAT
Short name=Retinol O-fatty-acyltransferase
EC=2.3.1.76
Diglyceride acyltransferase

Gene names

Name:	DGAT1
Synonyms:	AGRP1, DGAT

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	488 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates. In contrast to DGAT2 it is not essential for survival. May be involved in VLDL (very low density lipoprotein) assembly. In liver, plays a role in esterifying exogenous fatty acids to glycerol. 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.
Catalytic activity	Acyl-CoA + 1,2-diacylglycerol = CoA + triacylglycerol. Ref.5 Acyl-CoA + retinol = CoA + retinyl ester. Ref.5
Enzyme regulation	XP620 is a selective DGAT1 inhibitor. Ref.5
Pathway	Lipid metabolism; glycerolipid metabolism.
Subunit structure	Homodimer or homotetramer By similarity.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein By similarity.
Sequence similarities	Belongs to the membrane-bound acyltransferase family. Sterol o-acyltransferase subfamily.
Biophysicochemical properties	Kinetic parameters: KM=25.9 µM for retinol Ref.5 KM=13.9 µM for palmitoyl coenzyme A

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Domain	Transmembrane Transmembrane helix
Molecular function	Acyltransferase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	acylglycerol acyl-chain remodeling Traceable author statement. Source: Reactome diacylglycerol metabolic process Inferred from sequence or structural similarity. Source: BHF-UCL fatty acid homeostasis Inferred from electronic annotation. Source: Compara glycerophospholipid biosynthetic process Traceable author statement. Source: Reactome lipid storage Inferred from sequence or structural similarity. Source: BHF-UCL long-chain fatty-acyl-CoA metabolic process Inferred from sequence or structural similarity. Source: BHF-UCL small molecule metabolic process Traceable author statement. Source: Reactome triglyceride biosynthetic process Inferred from direct assay PubMed 18238778. Source: UniProtKB very-low-density lipoprotein particle assembly Inferred from mutant phenotype PubMed 15308631. Source: BHF-UCL
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular_function	2-acylglycerol O-acyltransferase activity Inferred from electronic annotation. Source: Compara diacylglycerol O-acyltransferase activity Inferred from experiment. Source: Reactome retinol O-fatty-acyltransferase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 488	488	Diacylglycerol O-acyltransferase 1		PRO_0000207654
Regions
	Topological domain	1 – 87	87	Cytoplasmic Potential
	Transmembrane	88 – 109	22	Helical; Potential
	Topological domain	110 – 220	111	Lumenal Potential
	Transmembrane	221 – 229	9	Helical; Potential
	Topological domain	230	1	Cytoplasmic Potential
	Transmembrane	231 – 239	9	Helical; Potential
	Topological domain	240 – 488	249	Lumenal Potential
	Region	1 – 91	91	Involved in homomerization By similarity
Sites
	Active site	415	1	By similarity
Amino acid modifications
	Modified residue	17	1	Phosphoserine By similarity
Experimental info
	Sequence conflict	129	1	Y → H in AAC63997. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O75907 [UniParc]. Last modified July 25, 2003. Version 2. Checksum: 6574D5DBF15D6171	FASTA	488	55,278
	10 20 30 40 50 60 MGDRGSSRRR RTGSRPSSHG GGGPAAAEEE VRDAAAGPDV GAAGDAPAPA PNKDGDAGVG 70 80 90 100 110 120 SGHWELRCHR LQDSLFSSDS GFSNYRGILN WCVVMLILSN ARLFLENLIK YGILVDPIQV 130 140 150 160 170 180 VSLFLKDPYS WPAPCLVIAA NVFAVAAFQV EKRLAVGALT EQAGLLLHVA NLATILCFPA 190 200 210 220 230 240 AVVLLVESIT PVGSLLALMA HTILFLKLFS YRDVNSWCRR ARAKAASAGK KASSAAAPHT 250 260 270 280 290 300 VSYPDNLTYR DLYYFLFAPT LCYELNFPRS PRIRKRFLLR RILEMLFFTQ LQVGLIQQWM 310 320 330 340 350 360 VPTIQNSMKP FKDMDYSRII ERLLKLAVPN HLIWLIFFYW LFHSCLNAVA ELMQFGDREF 370 380 390 400 410 420 YRDWWNSESV TYFWQNWNIP VHKWCIRHFY KPMLRRGSSK WMARTGVFLA SAFFHEYLVS 430 440 450 460 470 480 VPLRMFRLWA FTGMMAQIPL AWFVGRFFQG NYGNAAVWLS LIIGQPIAVL MYVHDYYVLN YEAPAAEA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of two human genes encoding acyl coenzyme A:cholesterol acyltransferase-related enzymes." Oelkers P., Behari A., Cromley D., Billheimer J.T., Sturley S.L. J. Biol. Chem. 273:26765-26771(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Yamasaki Y., Watanabe T.K., Tanigami A. Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Skin.
[5]	"Acyl coenzyme A dependent retinol esterification by acyl coenzyme A: diacylglycerol acyltransferase 1." Orland M.D., Anwar K., Cromley D., Chu C.H., Chen L., Billheimer J.T., Hussain M.M., Cheng D. Biochim. Biophys. Acta 1737:76-82(2005) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF059202 mRNA. Translation: AAC63997.1. AB057815 mRNA. Translation: BAC66170.1. CH471162 Genomic DNA. Translation: EAW82127.1. CH471162 Genomic DNA. Translation: EAW82129.1. BC015762 mRNA. Translation: AAH15762.1. BC023565 mRNA. Translation: AAH23565.1. BC150649 mRNA. Translation: AAI50650.1.
IPI	IPI00015799.
RefSeq	NP_036211.2. NM_012079.4.
UniGene	Hs.521954.
3D structure databases
ProteinModelPortal	O75907.
ModBase	Search...
Protein-protein interaction databases
IntAct	O75907. 2 interactions.
STRING	9606.ENSP00000332258.
PTM databases
PhosphoSite	O75907.
Proteomic databases
PaxDb	O75907.
PRIDE	O75907.
Protocols and materials databases
DNASU	8694.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000332324; ENSP00000332258; ENSG00000185000. ENST00000565657; ENSP00000454624; ENSG00000261698.
GeneID	8694.
KEGG	hsa:8694.
UCSC	uc003zbv.3. human.
Organism-specific databases
CTD	8694.
GeneCards	GC08M145510.
HGNC	HGNC:2843. DGAT1.
HPA	CAB032853.
MIM	604900. gene.
neXtProt	NX_O75907.
PharmGKB	PA27303.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5056.
HOGENOM	HOG000213917.
HOVERGEN	HBG051341.
InParanoid	O75907.
KO	K11155.
OMA	FSWSSGF.
OrthoDB	EOG4VT5X5.
PhylomeDB	O75907.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00230.
Gene expression databases
ArrayExpress	O75907.
Bgee	O75907.
CleanEx	HS_DGAT1.
Genevestigator	O75907.
GermOnline	ENSG00000185000. Homo sapiens.
Family and domain databases
InterPro	IPR027251. Diacylglycerol_acylTrfase1. IPR004299. MBOAT_fam. IPR014371. Oat_ACAT_DAG_ARE. [Graphical view]
PANTHER	PTHR10408. PTHR10408. 1 hit.
Pfam	PF03062. MBOAT. 1 hit. [Graphical view]
PIRSF	PIRSF000439. Oat_ACAT_DAG_ARE. 1 hit. PIRSF500231. Oat_dag. 1 hit.
ProtoNet	Search...
Other
BindingDB	O75907.
ChEMBL	CHEMBL6009.
ChiTaRS	DGAT1. human.
GenomeRNAi	8694.
NextBio	32607.
SOURCE	Search...

Entry information

Entry name

DGAT1_HUMAN

Accession

Primary (citable) accession number: O75907
Secondary accession number(s): B2RWQ2, D3DWL6, Q96BB8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 18, 2001
Last sequence update:	July 25, 2003
Last modified:	April 3, 2013
This is version 115 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.