ID   DGAT1_HUMAN             Reviewed;         488 AA.
AC   O75907; B2RWQ2; D3DWL6; Q96BB8;
DT   18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT   25-JUL-2003, sequence version 2.
DT   11-NOV-2015, entry version 138.
DE   RecName: Full=Diacylglycerol O-acyltransferase 1;
DE            EC=2.3.1.20;
DE   AltName: Full=ACAT-related gene product 1;
DE   AltName: Full=Acyl-CoA retinol O-fatty-acyltransferase;
DE            Short=ARAT;
DE            Short=Retinol O-fatty-acyltransferase;
DE            EC=2.3.1.76;
DE   AltName: Full=Diglyceride acyltransferase;
GN   Name=DGAT1; Synonyms=AGRP1, DGAT;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX   PubMed=9756920; DOI=10.1074/jbc.273.41.26765;
RA   Oelkers P., Behari A., Cromley D., Billheimer J.T., Sturley S.L.;
RT   "Characterization of two human genes encoding acyl coenzyme
RT   A:cholesterol acyltransferase-related enzymes.";
RL   J. Biol. Chem. 273:26765-26771(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Yamasaki Y., Watanabe T.K., Tanigami A.;
RL   Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain, and Skin;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION,
RP   AND FUNCTION.
RX   PubMed=16214399; DOI=10.1016/j.bbalip.2005.09.003;
RA   Orland M.D., Anwar K., Cromley D., Chu C.H., Chen L., Billheimer J.T.,
RA   Hussain M.M., Cheng D.;
RT   "Acyl coenzyme A dependent retinol esterification by acyl coenzyme A:
RT   diacylglycerol acyltransferase 1.";
RL   Biochim. Biophys. Acta 1737:76-82(2005).
RN   [6]
RP   INVOLVEMENT IN DIAR7.
RX   PubMed=23114594; DOI=10.1172/JCI64873;
RA   Haas J.T., Winter H.S., Lim E., Kirby A., Blumenstiel B., DeFelice M.,
RA   Gabriel S., Jalas C., Branski D., Grueter C.A., Toporovski M.S.,
RA   Walther T.C., Daly M.J., Farese R.V. Jr.;
RT   "DGAT1 mutation is linked to a congenital diarrheal disorder.";
RL   J. Clin. Invest. 122:4680-4684(2012).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17 AND SER-18, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
CC   -!- FUNCTION: Catalyzes the terminal and only committed step in
CC       triacylglycerol synthesis by using diacylglycerol and fatty acyl
CC       CoA as substrates. In contrast to DGAT2 it is not essential for
CC       survival. May be involved in VLDL (very low density lipoprotein)
CC       assembly. In liver, plays a role in esterifying exogenous fatty
CC       acids to glycerol. Functions as the major acyl-CoA retinol
CC       acyltransferase (ARAT) in the skin, where it acts to maintain
CC       retinoid homeostasis and prevent retinoid toxicity leading to skin
CC       and hair disorders. {ECO:0000269|PubMed:16214399,
CC       ECO:0000269|PubMed:9756920}.
CC   -!- CATALYTIC ACTIVITY: Acyl-CoA + 1,2-diacylglycerol = CoA +
CC       triacylglycerol. {ECO:0000269|PubMed:16214399}.
CC   -!- CATALYTIC ACTIVITY: Acyl-CoA + retinol = CoA + retinyl ester.
CC       {ECO:0000269|PubMed:16214399}.
CC   -!- ENZYME REGULATION: XP620 is a selective DGAT1 inhibitor.
CC       {ECO:0000269|PubMed:16214399}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=25.9 uM for retinol {ECO:0000269|PubMed:16214399};
CC         KM=13.9 uM for palmitoyl coenzyme A
CC         {ECO:0000269|PubMed:16214399};
CC   -!- PATHWAY: Lipid metabolism; glycerolipid metabolism.
CC   -!- SUBUNIT: Homodimer or homotetramer. {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q99IB8:- (xeno); NbExp=2; IntAct=EBI-3906527, EBI-6927873;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}.
CC   -!- DISEASE: Diarrhea 7 (DIAR7) [MIM:615863]: A life-threatening
CC       disease characterized by severe, intractable, watery diarrhea.
CC       {ECO:0000269|PubMed:23114594}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the membrane-bound acyltransferase family.
CC       Sterol o-acyltransferase subfamily. {ECO:0000305}.
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DR   EMBL; AF059202; AAC63997.1; -; mRNA.
DR   EMBL; AB057815; BAC66170.1; -; mRNA.
DR   EMBL; CH471162; EAW82127.1; -; Genomic_DNA.
DR   EMBL; CH471162; EAW82129.1; -; Genomic_DNA.
DR   EMBL; BC015762; AAH15762.1; -; mRNA.
DR   EMBL; BC023565; AAH23565.1; -; mRNA.
DR   EMBL; BC150649; AAI50650.1; -; mRNA.
DR   CCDS; CCDS6420.1; -.
DR   RefSeq; NP_036211.2; NM_012079.5.
DR   UniGene; Hs.521954; -.
DR   ProteinModelPortal; O75907; -.
DR   BioGrid; 114241; 10.
DR   IntAct; O75907; 3.
DR   STRING; 9606.ENSP00000332258; -.
DR   BindingDB; O75907; -.
DR   ChEMBL; CHEMBL6009; -.
DR   GuidetoPHARMACOLOGY; 2821; -.
DR   PhosphoSite; O75907; -.
DR   BioMuta; DGAT1; -.
DR   MaxQB; O75907; -.
DR   PaxDb; O75907; -.
DR   PRIDE; O75907; -.
DR   DNASU; 8694; -.
DR   Ensembl; ENST00000528718; ENSP00000482264; ENSG00000185000.
DR   GeneID; 8694; -.
DR   KEGG; hsa:8694; -.
DR   UCSC; uc003zbv.3; human.
DR   CTD; 8694; -.
DR   GeneCards; DGAT1; -.
DR   HGNC; HGNC:2843; DGAT1.
DR   HPA; CAB032853; -.
DR   MIM; 604900; gene.
DR   MIM; 615863; phenotype.
DR   neXtProt; NX_O75907; -.
DR   Orphanet; 329242; Congenital chronic diarrhea with protein-losing enteropathy.
DR   PharmGKB; PA27303; -.
DR   eggNOG; KOG0380; Eukaryota.
DR   eggNOG; COG5056; LUCA.
DR   GeneTree; ENSGT00530000063122; -.
DR   HOGENOM; HOG000213917; -.
DR   HOVERGEN; HBG051341; -.
DR   InParanoid; O75907; -.
DR   KO; K11155; -.
DR   OMA; QPDKPCH; -.
DR   PhylomeDB; O75907; -.
DR   TreeFam; TF314921; -.
DR   BRENDA; 2.3.1.20; 2681.
DR   Reactome; R-HSA-1482883; Acyl chain remodeling of DAG and TAG.
DR   Reactome; R-HSA-75109; Triglyceride Biosynthesis.
DR   UniPathway; UPA00230; -.
DR   ChiTaRS; DGAT1; human.
DR   GenomeRNAi; 8694; -.
DR   NextBio; 32607; -.
DR   PRO; PR:O75907; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   Bgee; O75907; -.
DR   CleanEx; HS_DGAT1; -.
DR   ExpressionAtlas; O75907; baseline and differential.
DR   Genevisible; O75907; HS.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR   GO; GO:0016021; C:integral component of membrane; ISS:BHF-UCL.
DR   GO; GO:0003846; F:2-acylglycerol O-acyltransferase activity; IEA:Ensembl.
DR   GO; GO:0004144; F:diacylglycerol O-acyltransferase activity; IDA:MGI.
DR   GO; GO:0050252; F:retinol O-fatty-acyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0016746; F:transferase activity, transferring acyl groups; TAS:ProtInc.
DR   GO; GO:0036155; P:acylglycerol acyl-chain remodeling; TAS:Reactome.
DR   GO; GO:0044255; P:cellular lipid metabolic process; TAS:Reactome.
DR   GO; GO:0046339; P:diacylglycerol metabolic process; ISS:BHF-UCL.
DR   GO; GO:0055089; P:fatty acid homeostasis; IEA:Ensembl.
DR   GO; GO:0046474; P:glycerophospholipid biosynthetic process; TAS:Reactome.
DR   GO; GO:0019915; P:lipid storage; ISS:BHF-UCL.
DR   GO; GO:0035336; P:long-chain fatty-acyl-CoA metabolic process; ISS:BHF-UCL.
DR   GO; GO:0006644; P:phospholipid metabolic process; TAS:Reactome.
DR   GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR   GO; GO:0019432; P:triglyceride biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0006641; P:triglyceride metabolic process; TAS:ProtInc.
DR   GO; GO:0034379; P:very-low-density lipoprotein particle assembly; IMP:BHF-UCL.
DR   InterPro; IPR027251; Diacylglycerol_acylTrfase1.
DR   InterPro; IPR004299; MBOAT_fam.
DR   InterPro; IPR014371; Oat_ACAT_DAG_ARE.
DR   PANTHER; PTHR10408; PTHR10408; 1.
DR   Pfam; PF03062; MBOAT; 1.
DR   PIRSF; PIRSF000439; Oat_ACAT_DAG_ARE; 1.
DR   PIRSF; PIRSF500231; Oat_dag; 1.
PE   1: Evidence at protein level;
KW   Acyltransferase; Complete proteome; Endoplasmic reticulum; Membrane;
KW   Phosphoprotein; Reference proteome; Transferase; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN         1    488       Diacylglycerol O-acyltransferase 1.
FT                                /FTId=PRO_0000207654.
FT   TOPO_DOM      1     87       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM     88    109       Helical. {ECO:0000255}.
FT   TOPO_DOM    110    220       Lumenal. {ECO:0000255}.
FT   TRANSMEM    221    229       Helical. {ECO:0000255}.
FT   TOPO_DOM    230    230       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    231    239       Helical. {ECO:0000255}.
FT   TOPO_DOM    240    488       Lumenal. {ECO:0000255}.
FT   REGION        1     91       Involved in homomerization.
FT                                {ECO:0000250}.
FT   ACT_SITE    415    415       {ECO:0000250}.
FT   MOD_RES      17     17       Phosphoserine.
FT                                {ECO:0000244|PubMed:24275569}.
FT   MOD_RES      18     18       Phosphoserine.
FT                                {ECO:0000244|PubMed:24275569}.
FT   CONFLICT    129    129       Y -> H (in Ref. 1; AAC63997).
FT                                {ECO:0000305}.
SQ   SEQUENCE   488 AA;  55278 MW;  6574D5DBF15D6171 CRC64;
     MGDRGSSRRR RTGSRPSSHG GGGPAAAEEE VRDAAAGPDV GAAGDAPAPA PNKDGDAGVG
     SGHWELRCHR LQDSLFSSDS GFSNYRGILN WCVVMLILSN ARLFLENLIK YGILVDPIQV
     VSLFLKDPYS WPAPCLVIAA NVFAVAAFQV EKRLAVGALT EQAGLLLHVA NLATILCFPA
     AVVLLVESIT PVGSLLALMA HTILFLKLFS YRDVNSWCRR ARAKAASAGK KASSAAAPHT
     VSYPDNLTYR DLYYFLFAPT LCYELNFPRS PRIRKRFLLR RILEMLFFTQ LQVGLIQQWM
     VPTIQNSMKP FKDMDYSRII ERLLKLAVPN HLIWLIFFYW LFHSCLNAVA ELMQFGDREF
     YRDWWNSESV TYFWQNWNIP VHKWCIRHFY KPMLRRGSSK WMARTGVFLA SAFFHEYLVS
     VPLRMFRLWA FTGMMAQIPL AWFVGRFFQG NYGNAAVWLS LIIGQPIAVL MYVHDYYVLN
     YEAPAAEA
//