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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: glycerolipid metabolism

    This protein is involved in the pathway glycerolipid metabolism, which is part of Lipid metabolism.
    View all proteins of this organism that are known to be involved in the pathway glycerolipid metabolism and in Lipid metabolism.

    Sites

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

    GO - Molecular functioni

    GO - Biological processi

    • acylglycerol acyl-chain remodeling Source: Reactome
    • diacylglycerol metabolic process Source: BHF-UCL
    • fatty acid homeostasis Source: Ensembl
    • lipid storage Source: BHF-UCL
    • long-chain fatty-acyl-CoA metabolic process Source: BHF-UCL
    • triglyceride biosynthetic process Source: UniProtKB
    • triglyceride metabolic process Source: ProtInc
    • 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.
    ReactomeiR-HSA-1482883. Acyl chain remodeling of DAG and TAG.
    R-HSA-75109. Triglyceride Biosynthesis.
    UniPathwayiUPA00230.

    Chemistry

    SwissLipidsiSLP:000000308.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Diacylglycerol O-acyltransferase 1 (EC:2.3.1.201 Publication)
    Alternative name(s):
    ACAT-related gene product 1
    Acyl-CoA retinol O-fatty-acyltransferase (EC:2.3.1.761 Publication)
    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
    Proteomesi
    • UP000005640 Componenti: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:2843. DGAT1.

    Subcellular locationi

    • Endoplasmic reticulum membrane By similarity; Multi-pass membrane protein By similarity

    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

    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

    MalaCardsiDGAT1.
    MIMi615863. phenotype.
    Orphaneti329242. Congenital chronic diarrhea with protein-losing enteropathy.
    PharmGKBiPA27303.

    Chemistry

    ChEMBLiCHEMBL6009.
    GuidetoPHARMACOLOGYi2821.

    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 – 171PhosphoserineCombined sources
    Modified residuei18 – 181PhosphoserineCombined sources

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    EPDiO75907.
    MaxQBiO75907.
    PaxDbiO75907.
    PRIDEiO75907.

    PTM databases

    iPTMnetiO75907.
    PhosphoSiteiO75907.

    Expressioni

    Gene expression databases

    BgeeiO75907.
    CleanExiHS_DGAT1.
    ExpressionAtlasiO75907. baseline and differential.
    GenevisibleiO75907. HS.

    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. 11 interactions.
    IntActiO75907. 4 interactions.
    STRINGi9606.ENSP00000332258.

    Chemistry

    BindingDBiO75907.

    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

    eggNOGiKOG0380. Eukaryota.
    COG5056. LUCA.
    GeneTreeiENSGT00530000063122.
    HOGENOMiHOG000213917.
    HOVERGENiHBG051341.
    InParanoidiO75907.
    KOiK11155.
    OMAiQPDKPCH.
    PhylomeDBiO75907.
    TreeFamiTF314921.

    Family and domain databases

    InterProiIPR027251. Diacylglycerol_acylTrfase1.
    IPR004299. MBOAT_fam.
    IPR014371. Oat_ACAT_DAG_ARE.
    [Graphical view]
    PANTHERiPTHR10408. PTHR10408. 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.5. human.

    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. 11 interactions.
    IntActiO75907. 4 interactions.
    STRINGi9606.ENSP00000332258.

    Chemistry

    BindingDBiO75907.
    ChEMBLiCHEMBL6009.
    GuidetoPHARMACOLOGYi2821.
    SwissLipidsiSLP:000000308.

    PTM databases

    iPTMnetiO75907.
    PhosphoSiteiO75907.

    Polymorphism and mutation databases

    BioMutaiDGAT1.

    Proteomic databases

    EPDiO75907.
    MaxQBiO75907.
    PaxDbiO75907.
    PRIDEiO75907.

    Protocols and materials databases

    DNASUi8694.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000528718; ENSP00000482264; ENSG00000185000.
    GeneIDi8694.
    KEGGihsa:8694.
    UCSCiuc003zbv.5. human.

    Organism-specific databases

    CTDi8694.
    GeneCardsiDGAT1.
    HGNCiHGNC:2843. DGAT1.
    HPAiCAB032853.
    MalaCardsiDGAT1.
    MIMi604900. gene.
    615863. phenotype.
    neXtProtiNX_O75907.
    Orphaneti329242. Congenital chronic diarrhea with protein-losing enteropathy.
    PharmGKBiPA27303.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG0380. Eukaryota.
    COG5056. LUCA.
    GeneTreeiENSGT00530000063122.
    HOGENOMiHOG000213917.
    HOVERGENiHBG051341.
    InParanoidiO75907.
    KOiK11155.
    OMAiQPDKPCH.
    PhylomeDBiO75907.
    TreeFamiTF314921.

    Enzyme and pathway databases

    UniPathwayiUPA00230.
    BRENDAi2.3.1.20. 2681.
    ReactomeiR-HSA-1482883. Acyl chain remodeling of DAG and TAG.
    R-HSA-75109. Triglyceride Biosynthesis.

    Miscellaneous databases

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

    Gene expression databases

    BgeeiO75907.
    CleanExiHS_DGAT1.
    ExpressionAtlasiO75907. baseline and differential.
    GenevisibleiO75907. HS.

    Family and domain databases

    InterProiIPR027251. Diacylglycerol_acylTrfase1.
    IPR004299. MBOAT_fam.
    IPR014371. Oat_ACAT_DAG_ARE.
    [Graphical view]
    PANTHERiPTHR10408. PTHR10408. 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: June 8, 2016
    This is version 143 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

    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 one 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.