ID   DGAT2_HUMAN             Reviewed;         388 AA.
AC   Q96PD7; A6ND76; Q5U810; Q68CL3; Q68DJ0; Q8NDB7; Q96BS0; Q9BYE5;
DT   05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2002, sequence version 2.
DT   11-NOV-2015, entry version 110.
DE   RecName: Full=Diacylglycerol O-acyltransferase 2;
DE            EC=2.3.1.20;
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 2;
GN   Name=DGAT2; ORFNames=HMFN1045, UNQ738/PRO1433;
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 TISSUE SPECIFICITY.
RC   TISSUE=Testis;
RX   PubMed=11481335; DOI=10.1074/jbc.M106219200;
RA   Cases S., Stone S.J., Zhou P., Yen C.-L.E., Tow B., Lardizabal K.D.,
RA   Voelker T., Farese R.V. Jr.;
RT   "Cloning of DGAT2, a second mammalian diacylglycerol acyltransferase,
RT   and related family members.";
RL   J. Biol. Chem. 276:38870-38876(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=14521909; DOI=10.1016/j.bbrc.2003.09.015;
RA   Wakimoto K., Chiba H., Michibata H., Seishima M., Kawasaki S.,
RA   Okubo K., Mitsui H., Torii H., Imai Y.;
RT   "A novel diacylglycerol acyltransferase (DGAT2) is decreased in human
RT   psoriatic skin and increased in diabetic mice.";
RL   Biochem. Biophys. Res. Commun. 310:296-302(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S.,
RA   Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA   Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA   Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA   Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA   Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA   Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale
RT   effort to identify novel human secreted and transmembrane proteins: a
RT   bioinformatics assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lymph node, and Uterus;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA   Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA   Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA   Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA   FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA   Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA   Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA   Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Pancreas;
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   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 4-341 (ISOFORM 2).
RC   TISSUE=Adipocyte;
RA   Reichwald K., Petz U., Platzer M.;
RT   "Evaluation of gene structure of human DGAT2 gene.";
RL   Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 66-388.
RC   TISSUE=Hepatoblastoma;
RX   PubMed=15221005; DOI=10.1038/sj.onc.1207782;
RA   Yamada S., Ohira M., Horie H., Ando K., Takayasu H., Suzuki Y.,
RA   Sugano S., Hirata T., Goto T., Matsunaga T., Hiyama E., Hayashi Y.,
RA   Ando H., Suita S., Kaneko M., Sasaki F., Hashizume K., Ohnuma N.,
RA   Nakagawara A.;
RT   "Expression profiling and differential screening between
RT   hepatoblastomas and the corresponding normal livers: identification of
RT   high expression of the PLK1 oncogene as a poor-prognostic indicator of
RT   hepatoblastomas.";
RL   Oncogene 23:5901-5911(2004).
RN   [9]
RP   CATALYTIC ACTIVITY.
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).
CC   -!- FUNCTION: Essential acyltransferase that catalyzes the terminal
CC       and only committed step in triacylglycerol synthesis by using
CC       diacylglycerol and fatty acyl CoA as substrates. Required for
CC       synthesis and storage of intracellular triglycerides. Probably
CC       plays a central role in cytosolic lipid accumulation. In liver, is
CC       primarily responsible for incorporating endogenously synthesized
CC       fatty acids into triglycerides (By similarity). Functions also as
CC       an acyl-CoA retinol acyltransferase (ARAT). {ECO:0000250}.
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: Inhibited by niacin. {ECO:0000250}.
CC   -!- PATHWAY: Glycerolipid metabolism; triacylglycerol biosynthesis.
CC   -!- SUBUNIT: Forms multimeric complexes consisting of several DGAT2
CC       subunits. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:14521909}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:14521909}. Lipid droplet {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q96PD7-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q96PD7-2; Sequence=VSP_020356;
CC   -!- TISSUE SPECIFICITY: Predominantly expressed in liver and white
CC       adipose tissue. Expressed at lower level in mammary gland, testis
CC       and peripheral blood leukocytes. Expressed in sebaceous glands of
CC       normal skin but decreased psoriatic skin.
CC       {ECO:0000269|PubMed:11481335, ECO:0000269|PubMed:14521909}.
CC   -!- SIMILARITY: Belongs to the diacylglycerol acyltransferase family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAD38635.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC       Sequence=CAD38961.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AF384161; AAK84176.2; -; mRNA.
DR   EMBL; AB048286; BAB40641.2; -; mRNA.
DR   EMBL; AY358532; AAQ88896.1; -; mRNA.
DR   EMBL; AL834287; CAD38961.1; ALT_INIT; mRNA.
DR   EMBL; CR749377; CAH18230.1; -; mRNA.
DR   EMBL; AP001922; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC015234; AAH15234.1; -; mRNA.
DR   EMBL; AY780647; AAV35727.1; -; mRNA.
DR   EMBL; AB073384; BAD38635.1; ALT_INIT; mRNA.
DR   CCDS; CCDS31642.1; -. [Q96PD7-1]
DR   CCDS; CCDS58162.1; -. [Q96PD7-2]
DR   RefSeq; NP_001240820.1; NM_001253891.1. [Q96PD7-2]
DR   RefSeq; NP_115953.2; NM_032564.4. [Q96PD7-1]
DR   UniGene; Hs.129798; -.
DR   ProteinModelPortal; Q96PD7; -.
DR   BioGrid; 124172; 2.
DR   IntAct; Q96PD7; 2.
DR   STRING; 9606.ENSP00000228027; -.
DR   BindingDB; Q96PD7; -.
DR   ChEMBL; CHEMBL5853; -.
DR   PhosphoSite; Q96PD7; -.
DR   BioMuta; DGAT2; -.
DR   DMDM; 74732654; -.
DR   PaxDb; Q96PD7; -.
DR   PRIDE; Q96PD7; -.
DR   DNASU; 84649; -.
DR   Ensembl; ENST00000228027; ENSP00000228027; ENSG00000062282. [Q96PD7-1]
DR   Ensembl; ENST00000376262; ENSP00000365438; ENSG00000062282. [Q96PD7-2]
DR   GeneID; 84649; -.
DR   KEGG; hsa:84649; -.
DR   UCSC; uc001oxa.3; human. [Q96PD7-1]
DR   UCSC; uc001oxb.3; human. [Q96PD7-2]
DR   CTD; 84649; -.
DR   GeneCards; DGAT2; -.
DR   HGNC; HGNC:16940; DGAT2.
DR   HPA; HPA013351; -.
DR   MIM; 606983; gene.
DR   neXtProt; NX_Q96PD7; -.
DR   PharmGKB; PA27304; -.
DR   eggNOG; KOG0831; Eukaryota.
DR   eggNOG; ENOG410XTG3; LUCA.
DR   GeneTree; ENSGT00750000117391; -.
DR   HOVERGEN; HBG065791; -.
DR   InParanoid; Q96PD7; -.
DR   KO; K11160; -.
DR   OMA; AILMYTF; -.
DR   OrthoDB; EOG7KH9KB; -.
DR   PhylomeDB; Q96PD7; -.
DR   TreeFam; TF314707; -.
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   SABIO-RK; Q96PD7; -.
DR   UniPathway; UPA00282; -.
DR   ChiTaRS; DGAT2; human.
DR   GenomeRNAi; 84649; -.
DR   NextBio; 74602; -.
DR   PRO; PR:Q96PD7; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   Bgee; Q96PD7; -.
DR   CleanEx; HS_DGAT2; -.
DR   ExpressionAtlas; Q96PD7; baseline and differential.
DR   Genevisible; Q96PD7; HS.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS:BHF-UCL.
DR   GO; GO:0016021; C:integral component of membrane; IDA:BHF-UCL.
DR   GO; GO:0005811; C:lipid particle; IEA:UniProtKB-SubCell.
DR   GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; 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:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:BHF-UCL.
DR   GO; GO:0050252; F:retinol O-fatty-acyltransferase activity; IEA:UniProtKB-EC.
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:0071400; P:cellular response to oleic acid; ISS:BHF-UCL.
DR   GO; GO:0035356; P:cellular triglyceride homeostasis; ISS:BHF-UCL.
DR   GO; GO:0042632; P:cholesterol homeostasis; ISS:BHF-UCL.
DR   GO; GO:0046339; P:diacylglycerol metabolic process; IDA:BHF-UCL.
DR   GO; GO:0060613; P:fat pad development; ISS:BHF-UCL.
DR   GO; GO:0055089; P:fatty acid homeostasis; ISS:BHF-UCL.
DR   GO; GO:0006071; P:glycerol metabolic process; IEA:UniProtKB-KW.
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; IDA:BHF-UCL.
DR   GO; GO:0034383; P:low-density lipoprotein particle clearance; ISS:BHF-UCL.
DR   GO; GO:0006644; P:phospholipid metabolic process; TAS:Reactome.
DR   GO; GO:0097006; P:regulation of plasma lipoprotein particle levels; ISS:BHF-UCL.
DR   GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR   GO; GO:0019432; P:triglyceride biosynthetic process; IDA:UniProtKB.
DR   InterPro; IPR007130; DAGAT.
DR   Pfam; PF03982; DAGAT; 1.
PE   1: Evidence at protein level;
KW   Acyltransferase; Alternative splicing; Complete proteome;
KW   Endoplasmic reticulum; Glycerol metabolism; Lipid biosynthesis;
KW   Lipid droplet; Lipid metabolism; Membrane; Polymorphism;
KW   Reference proteome; Transferase; Transmembrane; Transmembrane helix.
FT   CHAIN         1    388       Diacylglycerol O-acyltransferase 2.
FT                                /FTId=PRO_0000249045.
FT   TOPO_DOM      1     69       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM     70     88       Helical. {ECO:0000255}.
FT   TOPO_DOM     89     92       Lumenal. {ECO:0000255}.
FT   TRANSMEM     93    112       Helical. {ECO:0000255}.
FT   TOPO_DOM    113    388       Cytoplasmic. {ECO:0000255}.
FT   VAR_SEQ      41     83       Missing (in isoform 2).
FT                                {ECO:0000303|Ref.7}.
FT                                /FTId=VSP_020356.
FT   VARIANT     317    317       R -> G (in dbSNP:rs34421064).
FT                                /FTId=VAR_033864.
FT   VARIANT     361    361       M -> I (in dbSNP:rs34113941).
FT                                /FTId=VAR_033865.
FT   CONFLICT    295    295       W -> C (in Ref. 7; AAV35727).
FT                                {ECO:0000305}.
FT   CONFLICT    304    304       Q -> H (in Ref. 7; AAV35727).
FT                                {ECO:0000305}.
SQ   SEQUENCE   388 AA;  43831 MW;  39EE7783A3F06593 CRC64;
     MKTLIAAYSG VLRGERQAEA DRSQRSHGGP ALSREGSGRW GTGSSILSAL QDLFSVTWLN
     RSKVEKQLQV ISVLQWVLSF LVLGVACSAI LMYIFCTDCW LIAVLYFTWL VFDWNTPKKG
     GRRSQWVRNW AVWRYFRDYF PIQLVKTHNL LTTRNYIFGY HPHGIMGLGA FCNFSTEATE
     VSKKFPGIRP YLATLAGNFR MPVLREYLMS GGICPVSRDT IDYLLSKNGS GNAIIIVVGG
     AAESLSSMPG KNAVTLRNRK GFVKLALRHG ADLVPIYSFG ENEVYKQVIF EEGSWGRWVQ
     KKFQKYIGFA PCIFHGRGLF SSDTWGLVPY SKPITTVVGE PITIPKLEHP TQQDIDLYHT
     MYMEALVKLF DKHKTKFGLP ETEVLEVN
//