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Protein

Diacylglycerol O-acyltransferase 1

Gene

DGAT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

Acyl-CoA + 1,2-diacylglycerol = CoA + triacylglycerol.1 Publication
Acyl-CoA + retinol = CoA + retinyl ester.1 Publication

Enzyme regulationi

XP620 is a selective DGAT1 inhibitor.1 Publication

Kineticsi

  1. KM=25.9 µM for retinol1 Publication
  2. KM=13.9 µM for palmitoyl coenzyme A1 Publication

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei415 – 4151By similarity

GO - Molecular functioni

  1. 2-acylglycerol O-acyltransferase activity Source: Ensembl
  2. diacylglycerol O-acyltransferase activity Source: MGI
  3. retinol O-fatty-acyltransferase activity Source: UniProtKB-EC
  4. transferase activity, transferring acyl groups Source: ProtInc

GO - Biological processi

  1. acylglycerol acyl-chain remodeling Source: Reactome
  2. cellular lipid metabolic process Source: Reactome
  3. diacylglycerol metabolic process Source: BHF-UCL
  4. fatty acid homeostasis Source: Ensembl
  5. glycerophospholipid biosynthetic process Source: Reactome
  6. lipid storage Source: BHF-UCL
  7. long-chain fatty-acyl-CoA metabolic process Source: BHF-UCL
  8. phospholipid metabolic process Source: Reactome
  9. small molecule metabolic process Source: Reactome
  10. triglyceride biosynthetic process Source: UniProtKB
  11. triglyceride metabolic process Source: ProtInc
  12. very-low-density lipoprotein particle assembly Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Acyltransferase, Transferase

Enzyme and pathway databases

BRENDAi2.3.1.20. 2681.
ReactomeiREACT_1190. Triglyceride Biosynthesis.
REACT_121122. Acyl chain remodeling of DAG and TAG.
UniPathwayiUPA00230.

Names & Taxonomyi

Protein namesi
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 (EC:2.3.1.76)
Short name:
ARAT
Short name:
Retinol O-fatty-acyltransferase
Diglyceride acyltransferase
Gene namesi
Name:DGAT1
Synonyms:AGRP1, DGAT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:2843. DGAT1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 8787CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei88 – 10922HelicalSequence AnalysisAdd
BLAST
Topological domaini110 – 220111LumenalSequence AnalysisAdd
BLAST
Transmembranei221 – 2299HelicalSequence Analysis
Topological domaini230 – 2301CytoplasmicSequence Analysis
Transmembranei231 – 2399HelicalSequence Analysis
Topological domaini240 – 488249LumenalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. endoplasmic reticulum membrane Source: Reactome
  2. integral component of membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Diarrhea 7 (DIAR7)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA life-threatening disease characterized by severe, intractable, watery diarrhea.

See also OMIM:615863

Organism-specific databases

MIMi615863. phenotype.
Orphaneti329242. Congenital chronic diarrhea with protein-losing enteropathy.
PharmGKBiPA27303.

Polymorphism and mutation databases

BioMutaiDGAT1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 488488Diacylglycerol O-acyltransferase 1PRO_0000207654Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei17 – 171Phosphoserine1 Publication
Modified residuei18 – 181Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO75907.
PaxDbiO75907.
PRIDEiO75907.

PTM databases

PhosphoSiteiO75907.

Expressioni

Gene expression databases

BgeeiO75907.
CleanExiHS_DGAT1.
ExpressionAtlasiO75907. baseline.
GenevestigatoriO75907.

Organism-specific databases

HPAiCAB032853.

Interactioni

Subunit structurei

Homodimer or homotetramer.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Q99IB82EBI-3906527,EBI-6927873From a different organism.

Protein-protein interaction databases

BioGridi114241. 7 interactions.
IntActiO75907. 3 interactions.
STRINGi9606.ENSP00000332258.

Structurei

3D structure databases

ProteinModelPortaliO75907.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 9191Involved in homomerizationBy similarityAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG5056.
GeneTreeiENSGT00530000063122.
HOGENOMiHOG000213917.
HOVERGENiHBG051341.
InParanoidiO75907.
KOiK11155.
OMAiLWAFTAM.
PhylomeDBiO75907.
TreeFamiTF314921.

Family and domain databases

InterProiIPR027251. Diacylglycerol_acylTrfase1.
IPR004299. MBOAT_fam.
IPR014371. Oat_ACAT_DAG_ARE.
[Graphical view]
PANTHERiPTHR10408. PTHR10408. 1 hit.
PTHR10408:SF7. PTHR10408:SF7. 1 hit.
PfamiPF03062. MBOAT. 1 hit.
[Graphical view]
PIRSFiPIRSF000439. Oat_ACAT_DAG_ARE. 1 hit.
PIRSF500231. Oat_dag. 1 hit.

Sequencei

Sequence statusi: Complete.

O75907-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGDRGSSRRR RTGSRPSSHG GGGPAAAEEE VRDAAAGPDV GAAGDAPAPA
60 70 80 90 100
PNKDGDAGVG SGHWELRCHR LQDSLFSSDS GFSNYRGILN WCVVMLILSN
110 120 130 140 150
ARLFLENLIK YGILVDPIQV VSLFLKDPYS WPAPCLVIAA NVFAVAAFQV
160 170 180 190 200
EKRLAVGALT EQAGLLLHVA NLATILCFPA AVVLLVESIT PVGSLLALMA
210 220 230 240 250
HTILFLKLFS YRDVNSWCRR ARAKAASAGK KASSAAAPHT VSYPDNLTYR
260 270 280 290 300
DLYYFLFAPT LCYELNFPRS PRIRKRFLLR RILEMLFFTQ LQVGLIQQWM
310 320 330 340 350
VPTIQNSMKP FKDMDYSRII ERLLKLAVPN HLIWLIFFYW LFHSCLNAVA
360 370 380 390 400
ELMQFGDREF YRDWWNSESV TYFWQNWNIP VHKWCIRHFY KPMLRRGSSK
410 420 430 440 450
WMARTGVFLA SAFFHEYLVS VPLRMFRLWA FTGMMAQIPL AWFVGRFFQG
460 470 480
NYGNAAVWLS LIIGQPIAVL MYVHDYYVLN YEAPAAEA
Length:488
Mass (Da):55,278
Last modified:July 25, 2003 - v2
Checksum:i6574D5DBF15D6171
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti129 – 1291Y → H in AAC63997 (PubMed:9756920).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS6420.1.
RefSeqiNP_036211.2. NM_012079.5.
UniGeneiHs.521954.

Genome annotation databases

EnsembliENST00000528718; ENSP00000482264; ENSG00000185000.
GeneIDi8694.
KEGGihsa:8694.
UCSCiuc003zbv.3. human.

Polymorphism and mutation databases

BioMutaiDGAT1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS6420.1.
RefSeqiNP_036211.2. NM_012079.5.
UniGeneiHs.521954.

3D structure databases

ProteinModelPortaliO75907.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114241. 7 interactions.
IntActiO75907. 3 interactions.
STRINGi9606.ENSP00000332258.

Chemistry

BindingDBiO75907.
ChEMBLiCHEMBL6009.
GuidetoPHARMACOLOGYi2821.

PTM databases

PhosphoSiteiO75907.

Polymorphism and mutation databases

BioMutaiDGAT1.

Proteomic databases

MaxQBiO75907.
PaxDbiO75907.
PRIDEiO75907.

Protocols and materials databases

DNASUi8694.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000528718; ENSP00000482264; ENSG00000185000.
GeneIDi8694.
KEGGihsa:8694.
UCSCiuc003zbv.3. human.

Organism-specific databases

CTDi8694.
GeneCardsiGC08M145539.
HGNCiHGNC:2843. DGAT1.
HPAiCAB032853.
MIMi604900. gene.
615863. phenotype.
neXtProtiNX_O75907.
Orphaneti329242. Congenital chronic diarrhea with protein-losing enteropathy.
PharmGKBiPA27303.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5056.
GeneTreeiENSGT00530000063122.
HOGENOMiHOG000213917.
HOVERGENiHBG051341.
InParanoidiO75907.
KOiK11155.
OMAiLWAFTAM.
PhylomeDBiO75907.
TreeFamiTF314921.

Enzyme and pathway databases

UniPathwayiUPA00230.
BRENDAi2.3.1.20. 2681.
ReactomeiREACT_1190. Triglyceride Biosynthesis.
REACT_121122. Acyl chain remodeling of DAG and TAG.

Miscellaneous databases

ChiTaRSiDGAT1. human.
GenomeRNAii8694.
NextBioi32607.
PROiO75907.
SOURCEiSearch...

Gene expression databases

BgeeiO75907.
CleanExiHS_DGAT1.
ExpressionAtlasiO75907. baseline.
GenevestigatoriO75907.

Family and domain databases

InterProiIPR027251. Diacylglycerol_acylTrfase1.
IPR004299. MBOAT_fam.
IPR014371. Oat_ACAT_DAG_ARE.
[Graphical view]
PANTHERiPTHR10408. PTHR10408. 1 hit.
PTHR10408:SF7. PTHR10408:SF7. 1 hit.
PfamiPF03062. MBOAT. 1 hit.
[Graphical view]
PIRSFiPIRSF000439. Oat_ACAT_DAG_ARE. 1 hit.
PIRSF500231. Oat_dag. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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], FUNCTION.
  2. Yamasaki Y., Watanabe T.K., Tanigami A.
    Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. 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, FUNCTION.
  6. Cited for: INVOLVEMENT IN DIAR7.
  7. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17 AND SER-18, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiDGAT1_HUMAN
AccessioniPrimary (citable) accession number: O75907
Secondary accession number(s): B2RWQ2, D3DWL6, Q96BB8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: July 25, 2003
Last modified: April 29, 2015
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.