DGKE_HUMAN
ID DGKE_HUMAN Reviewed; 567 AA.
AC P52429; Q8TBM4; Q9UKQ3;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Diacylglycerol kinase epsilon;
DE Short=DAG kinase epsilon;
DE EC=2.7.1.107 {ECO:0000269|PubMed:15544348, ECO:0000269|PubMed:18004883, ECO:0000269|PubMed:19744926, ECO:0000269|PubMed:21477596, ECO:0000269|PubMed:22108654, ECO:0000269|PubMed:23949095};
DE AltName: Full=Diglyceride kinase epsilon;
DE Short=DGK-epsilon;
GN Name=DGKE; Synonyms=DAGK5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RC TISSUE=Umbilical vein endothelial cell;
RX PubMed=8626589; DOI=10.1074/jbc.271.17.10230;
RA Tang W., Bunting M., Zimmerman G.A., McIntyre T.M., Prescott S.M.;
RT "Molecular cloning of a novel human diacylglycerol kinase highly selective
RT for arachidonate-containing substrates.";
RL J. Biol. Chem. 271:10237-10241(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Prostate;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-154.
RX PubMed=10571048; DOI=10.1016/s0378-1119(99)00345-5;
RA Tang W., Bardien S., Bhattacharya S.S., Prescott S.M.;
RT "Characterization of the human diacylglycerol kinase epsilon gene and its
RT assessment as a candidate for inherited retinitis pigmentosa.";
RL Gene 239:185-192(1999).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND PATHWAY.
RX PubMed=15544348; DOI=10.1021/bi0484724;
RA Epand R.M., Kam A., Bridgelal N., Saiga A., Topham M.K.;
RT "The alpha isoform of diacylglycerol kinase exhibits arachidonoyl
RT specificity with alkylacylglycerol.";
RL Biochemistry 43:14778-14783(2004).
RN [6]
RP CATALYTIC ACTIVITY.
RX PubMed=18004883; DOI=10.1021/bi701584v;
RA Epand R.M., Shulga Y.V., Timmons H.C., Perri A.L., Belani J.D.,
RA Perinpanathan K., Johnson-McIntire L.B., Bajjalieh S., Dicu A.O., Elias C.,
RA Rychnovsky S.D., Topham M.K.;
RT "Substrate chirality and specificity of diacylglycerol kinases and the
RT multisubstrate lipid kinase.";
RL Biochemistry 46:14225-14231(2007).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND ACTIVITY
RP REGULATION.
RX PubMed=19744926; DOI=10.1074/jbc.m109.050617;
RA Lung M., Shulga Y.V., Ivanova P.T., Myers D.S., Milne S.B., Brown H.A.,
RA Topham M.K., Epand R.M.;
RT "Diacylglycerol kinase epsilon is selective for both acyl chains of
RT phosphatidic acid or diacylglycerol.";
RL J. Biol. Chem. 284:31062-31073(2009).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RX PubMed=22108654; DOI=10.1016/j.febslet.2011.11.016;
RA Shulga Y.V., Topham M.K., Epand R.M.;
RT "Substrate specificity of diacylglycerol kinase-epsilon and the
RT phosphatidylinositol cycle.";
RL FEBS Lett. 585:4025-4028(2011).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LEU-431; LEU-438 AND
RP PRO-439.
RX PubMed=21477596; DOI=10.1016/j.jmb.2011.03.071;
RA Shulga Y.V., Topham M.K., Epand R.M.;
RT "Study of arachidonoyl specificity in two enzymes of the PI cycle.";
RL J. Mol. Biol. 409:101-112(2011).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23949095; DOI=10.1159/000351849;
RA Sato M., Liu K., Sasaki S., Kunii N., Sakai H., Mizuno H., Saga H.,
RA Sakane F.;
RT "Evaluations of the selectivities of the diacylglycerol kinase inhibitors
RT R59022 and R59949 among diacylglycerol kinase isozymes using a new non-
RT radioactive assay method.";
RL Pharmacology 92:99-107(2013).
RN [11]
RP INVOLVEMENT IN NPHS7.
RX PubMed=23274426; DOI=10.1681/asn.2012090903;
RA Ozaltin F., Li B., Rauhauser A., An S.W., Soylemezoglu O., Gonul I.I.,
RA Taskiran E.Z., Ibsirlioglu T., Korkmaz E., Bilginer Y., Duzova A., Ozen S.,
RA Topaloglu R., Besbas N., Ashraf S., Du Y., Liang C., Chen P., Lu D.,
RA Vadnagara K., Arbuckle S., Lewis D., Wakeland B., Quigg R.J., Ransom R.F.,
RA Wakeland E.K., Topham M.K., Bazan N.G., Mohan C., Hildebrandt F.,
RA Bakkaloglu A., Huang C.L., Attanasio M.;
RT "DGKE variants cause a glomerular microangiopathy that mimics
RT membranoproliferative GN.";
RL J. Am. Soc. Nephrol. 24:377-384(2013).
RN [12]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND VARIANTS AHUS7 PRO-63 AND
RP PRO-273.
RX PubMed=23542698; DOI=10.1038/ng.2590;
RA Lemaire M., Fremeaux-Bacchi V., Schaefer F., Choi M., Tang W.H.,
RA Le Quintrec M., Fakhouri F., Taque S., Nobili F., Martinez F., Ji W.,
RA Overton J.D., Mane S.M., Nuernberg G., Altmueller J., Thiele H., Morin D.,
RA Deschenes G., Baudouin V., Llanas B., Collard L., Majid M.A., Simkova E.,
RA Nuernberg P., Rioux-Leclerc N., Moeckel G.W., Gubler M.C., Hwa J.,
RA Loirat C., Lifton R.P.;
RT "Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome.";
RL Nat. Genet. 45:531-536(2013).
RN [13]
RP VARIANT [LARGE SCALE ANALYSIS] ARG-99.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Membrane-bound diacylglycerol kinase that converts
CC diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and
CC regulates the respective levels of these two bioactive lipids
CC (PubMed:15544348, PubMed:19744926, PubMed:22108654, PubMed:21477596,
CC PubMed:23949095). Thereby, acts as a central switch between the
CC signaling pathways activated by these second messengers with different
CC cellular targets and opposite effects in numerous biological processes
CC (PubMed:8626589, PubMed:15544348). Also plays an important role in the
CC biosynthesis of complex lipids (PubMed:8626589). Displays specificity
CC for diacylglycerol substrates with an arachidonoyl acyl chain at the
CC sn-2 position, with the highest activity toward 1-octadecanoyl-2-
CC (5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol the main diacylglycerol
CC intermediate within the phosphatidylinositol turnover cycle
CC (PubMed:19744926, PubMed:22108654, PubMed:23274426). Can also
CC phosphorylate diacylglycerol substrates with a linoleoyl acyl chain at
CC the sn-2 position but much less efficiently (PubMed:22108654).
CC {ECO:0000269|PubMed:15544348, ECO:0000269|PubMed:19744926,
CC ECO:0000269|PubMed:21477596, ECO:0000269|PubMed:22108654,
CC ECO:0000269|PubMed:23274426, ECO:0000269|PubMed:23949095,
CC ECO:0000303|PubMed:15544348, ECO:0000303|PubMed:8626589}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycerol + ATP = a 1,2-diacyl-sn-glycero-3-
CC phosphate + ADP + H(+); Xref=Rhea:RHEA:10272, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17815, ChEBI:CHEBI:30616, ChEBI:CHEBI:58608,
CC ChEBI:CHEBI:456216; EC=2.7.1.107;
CC Evidence={ECO:0000269|PubMed:15544348, ECO:0000269|PubMed:18004883,
CC ECO:0000269|PubMed:19744926, ECO:0000269|PubMed:21477596,
CC ECO:0000269|PubMed:22108654, ECO:0000269|PubMed:23949095};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10273;
CC Evidence={ECO:0000305|PubMed:15544348};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol
CC + ATP = 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphate + ADP + H(+); Xref=Rhea:RHEA:40335, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:72864, ChEBI:CHEBI:77096,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:19744926};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40336;
CC Evidence={ECO:0000305|PubMed:19744926};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol
CC + ATP = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphate + ADP + H(+); Xref=Rhea:RHEA:40323, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:75728, ChEBI:CHEBI:77091,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:15544348,
CC ECO:0000269|PubMed:18004883, ECO:0000269|PubMed:19744926,
CC ECO:0000269|PubMed:21477596, ECO:0000269|PubMed:22108654,
CC ECO:0000269|PubMed:23949095};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40324;
CC Evidence={ECO:0000305|PubMed:15544348};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-eicosanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycerol +
CC ATP = 1-eicosanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-
CC phosphate + ADP + H(+); Xref=Rhea:RHEA:40331, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:77093, ChEBI:CHEBI:77094,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:19744926};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40332;
CC Evidence={ECO:0000305|PubMed:19744926};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycerol + ATP =
CC 1,2-di-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphate + ADP
CC + H(+); Xref=Rhea:RHEA:40351, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:77125, ChEBI:CHEBI:77126, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:22108654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40352;
CC Evidence={ECO:0000305|PubMed:22108654};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(9Z,12Z)-octadecadienoyl-sn-glycerol + ATP =
CC 1-octadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphate +
CC ADP + H(+); Xref=Rhea:RHEA:40339, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:77097, ChEBI:CHEBI:77098,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:19744926,
CC ECO:0000269|PubMed:22108654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40340;
CC Evidence={ECO:0000305|PubMed:19744926};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycerol + ATP = 1,2-di-
CC (9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphate + ADP + H(+);
CC Xref=Rhea:RHEA:40355, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:77127, ChEBI:CHEBI:77128, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:22108654};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40356;
CC Evidence={ECO:0000305|PubMed:22108654};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycerol + ATP = 1,2-di-(9Z-
CC octadecenoyl)-sn-glycero-3-phosphate + ADP + H(+);
CC Xref=Rhea:RHEA:40327, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:52333, ChEBI:CHEBI:74546, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:15544348, ECO:0000269|PubMed:19744926};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40328;
CC Evidence={ECO:0000305|PubMed:15544348};
CC -!- ACTIVITY REGULATION: Undergoes competitive inhibition by its own
CC product 1,2-diacyl-sn-glycero-3-phosphate/phosphatidic acid. The
CC strongest inhibition being observed in vitro with 1-octadecanoyl-2-
CC (5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate, a major
CC intermediate in the phosphatidylinositol turnover cycle and more
CC generally by diacylglycerols with an arachidonoyl acyl chain at the sn-
CC 2 position. {ECO:0000269|PubMed:19744926}.
CC -!- PATHWAY: Lipid metabolism; glycerolipid metabolism.
CC {ECO:0000305|PubMed:15544348}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:23542698}; Single-
CC pass membrane protein {ECO:0000255}. Cytoplasm
CC {ECO:0000269|PubMed:23542698}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P52429-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P52429-2; Sequence=VSP_056957, VSP_056958;
CC -!- TISSUE SPECIFICITY: Expressed predominantly in testis. Expressed in
CC endothelium, platelets and podocytes (at protein level).
CC {ECO:0000269|PubMed:23542698}.
CC -!- DISEASE: Nephrotic syndrome 7 (NPHS7) [MIM:615008]: A form of nephrotic
CC syndrome, a renal disease clinically characterized by severe
CC proteinuria, resulting in complications such as hypoalbuminemia,
CC hyperlipidemia and edema. NPHS7 is an autosomal recessive form
CC characterized by onset of proteinuria usually in the first decade of
CC life. The disorder is progressive, and some patients develop end-stage
CC renal disease within several years. Renal biopsy typically shows
CC membranoproliferative glomerulonephritis.
CC {ECO:0000269|PubMed:23274426}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Hemolytic uremic syndrome atypical 7 (AHUS7) [MIM:615008]: An
CC atypical form of hemolytic uremic syndrome characterized by acute onset
CC in the first year of life of microangiopathic hemolytic anemia,
CC thrombocytopenia, and renal failure. After the acute episode, most
CC patients develop chronic renal insufficiency. Unlike other genetic
CC forms of aHUS, AHUS7 is not related to abnormal activation of the
CC complement system. {ECO:0000269|PubMed:23542698}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the eukaryotic diacylglycerol kinase family.
CC {ECO:0000305}.
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DR EMBL; U49379; AAC50497.1; -; mRNA.
DR EMBL; AC015912; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC106858; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC022297; AAH22297.1; -; mRNA.
DR EMBL; AF136745; AAD45666.1; -; Genomic_DNA.
DR CCDS; CCDS11590.1; -. [P52429-1]
DR RefSeq; NP_003638.1; NM_003647.2. [P52429-1]
DR AlphaFoldDB; P52429; -.
DR SMR; P52429; -.
DR BioGRID; 114096; 55.
DR IntAct; P52429; 21.
DR STRING; 9606.ENSP00000284061; -.
DR ChEMBL; CHEMBL1075187; -.
DR DrugBank; DB14001; alpha-Tocopherol succinate.
DR SwissLipids; SLP:000000546; -.
DR iPTMnet; P52429; -.
DR PhosphoSitePlus; P52429; -.
DR SwissPalm; P52429; -.
DR BioMuta; DGKE; -.
DR DMDM; 1708625; -.
DR EPD; P52429; -.
DR jPOST; P52429; -.
DR MassIVE; P52429; -.
DR MaxQB; P52429; -.
DR PaxDb; P52429; -.
DR PeptideAtlas; P52429; -.
DR PRIDE; P52429; -.
DR ProteomicsDB; 56484; -. [P52429-1]
DR ProteomicsDB; 74029; -.
DR Antibodypedia; 2548; 242 antibodies from 30 providers.
DR DNASU; 8526; -.
DR Ensembl; ENST00000284061.8; ENSP00000284061.3; ENSG00000153933.10. [P52429-1]
DR Ensembl; ENST00000572810.1; ENSP00000459295.1; ENSG00000153933.10. [P52429-2]
DR GeneID; 8526; -.
DR KEGG; hsa:8526; -.
DR MANE-Select; ENST00000284061.8; ENSP00000284061.3; NM_003647.3; NP_003638.1.
DR UCSC; uc002iur.4; human. [P52429-1]
DR CTD; 8526; -.
DR DisGeNET; 8526; -.
DR GeneCards; DGKE; -.
DR GeneReviews; DGKE; -.
DR HGNC; HGNC:2852; DGKE.
DR HPA; ENSG00000153933; Tissue enhanced (retina).
DR MalaCards; DGKE; -.
DR MIM; 601440; gene.
DR MIM; 615008; phenotype.
DR neXtProt; NX_P52429; -.
DR OpenTargets; ENSG00000153933; -.
DR Orphanet; 357008; Hemolytic uremic syndrome with DGKE deficiency.
DR Orphanet; 329903; Immunoglobulin-mediated membranoproliferative glomerulonephritis.
DR PharmGKB; PA27313; -.
DR VEuPathDB; HostDB:ENSG00000153933; -.
DR eggNOG; KOG1169; Eukaryota.
DR GeneTree; ENSGT00940000158604; -.
DR HOGENOM; CLU_1517427_0_0_1; -.
DR InParanoid; P52429; -.
DR OMA; GMMEVFG; -.
DR OrthoDB; 1275907at2759; -.
DR PhylomeDB; P52429; -.
DR TreeFam; TF313104; -.
DR BRENDA; 2.7.1.107; 2681.
DR PathwayCommons; P52429; -.
DR Reactome; R-HSA-114508; Effects of PIP2 hydrolysis.
DR SignaLink; P52429; -.
DR UniPathway; UPA00230; -.
DR BioGRID-ORCS; 8526; 12 hits in 1081 CRISPR screens.
DR ChiTaRS; DGKE; human.
DR GenomeRNAi; 8526; -.
DR Pharos; P52429; Tbio.
DR PRO; PR:P52429; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P52429; protein.
DR Bgee; ENSG00000153933; Expressed in Brodmann (1909) area 23 and 170 other tissues.
DR ExpressionAtlas; P52429; baseline and differential.
DR Genevisible; P52429; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004143; F:diacylglycerol kinase activity; IDA:UniProtKB.
DR GO; GO:0016301; F:kinase activity; IDA:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003951; F:NAD+ kinase activity; IEA:InterPro.
DR GO; GO:0046339; P:diacylglycerol metabolic process; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0046834; P:lipid phosphorylation; IDA:UniProtKB.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IEA:Ensembl.
DR GO; GO:0006654; P:phosphatidic acid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; IEA:Ensembl.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0007205; P:protein kinase C-activating G protein-coupled receptor signaling pathway; IEA:InterPro.
DR CDD; cd00029; C1; 2.
DR Gene3D; 3.40.50.10330; -; 1.
DR InterPro; IPR017438; ATP-NAD_kinase_N.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR037607; DGK.
DR InterPro; IPR000756; Diacylglycerol_kin_accessory.
DR InterPro; IPR001206; Diacylglycerol_kinase_cat_dom.
DR InterPro; IPR016064; NAD/diacylglycerol_kinase_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR PANTHER; PTHR11255; PTHR11255; 1.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF00609; DAGK_acc; 1.
DR Pfam; PF00781; DAGK_cat; 1.
DR SMART; SM00109; C1; 2.
DR SMART; SM00045; DAGKa; 1.
DR SMART; SM00046; DAGKc; 1.
DR SUPFAM; SSF111331; SSF111331; 1.
DR SUPFAM; SSF57889; SSF57889; 2.
DR PROSITE; PS50146; DAGK; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 2.
DR PROSITE; PS50081; ZF_DAG_PE_2; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cytoplasm; Disease variant;
KW Hemolytic uremic syndrome; Kinase; Lipid metabolism; Membrane;
KW Metal-binding; Nucleotide-binding; Reference proteome; Repeat; Transferase;
KW Transmembrane; Transmembrane helix; Zinc; Zinc-finger.
FT CHAIN 1..567
FT /note="Diacylglycerol kinase epsilon"
FT /id="PRO_0000218464"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 215..356
FT /note="DAGKc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT ZN_FING 59..108
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 124..177
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT VAR_SEQ 156..177
FT /note="CIWCQKTVHDECMKNSLKNEKC -> YGLRGHSLSQNAPWESGFHRVV (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056957"
FT VAR_SEQ 178..567
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056958"
FT VARIANT 63
FT /note="R -> P (in AHUS7; dbSNP:rs312262694)"
FT /evidence="ECO:0000269|PubMed:23542698"
FT /id="VAR_069804"
FT VARIANT 99
FT /note="L -> R (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036120"
FT VARIANT 273
FT /note="R -> P (in AHUS7; dbSNP:rs312262695)"
FT /evidence="ECO:0000269|PubMed:23542698"
FT /id="VAR_069805"
FT MUTAGEN 431
FT /note="L->I: Decreased diacylglycerol kinase activity
FT toward 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-
FT sn-glycerol."
FT /evidence="ECO:0000269|PubMed:21477596"
FT MUTAGEN 431
FT /note="L->S: Loss of diacylglycerol kinase activity toward
FT 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-
FT glycerol."
FT /evidence="ECO:0000269|PubMed:21477596"
FT MUTAGEN 438
FT /note="L->I: Decreased diacylglycerol kinase activity
FT toward 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-
FT sn-glycerol."
FT /evidence="ECO:0000269|PubMed:21477596"
FT MUTAGEN 438
FT /note="L->M: Decreased protein abundance and diacylglycerol
FT kinase activity toward 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-
FT eicosatetraenoyl)-sn-glycerol."
FT /evidence="ECO:0000269|PubMed:21477596"
FT MUTAGEN 438
FT /note="L->S,A,G: Loss of diacylglycerol kinase activity
FT toward 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-
FT sn-glycerol."
FT /evidence="ECO:0000269|PubMed:21477596"
FT MUTAGEN 439
FT /note="P->G: Decreased diacylglycerol kinase activity
FT toward 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-
FT sn-glycerol."
FT /evidence="ECO:0000269|PubMed:21477596"
SQ SEQUENCE 567 AA; 63927 MW; BC334AD15FB4D0B4 CRC64;
MEAERRPAPG SPSEGLFADG HLILWTLCSV LLPVFITFWC SLQRSRRQLH RRDIFRKSKH
GWRDTDLFSQ PTYCCVCAQH ILQGAFCDCC GLRVDEGCLR KADKRFQCKE IMLKNDTKVL
DAMPHHWIRG NVPLCSYCMV CKQQCGCQPK LCDYRCIWCQ KTVHDECMKN SLKNEKCDFG
EFKNLIIPPS YLTSINQMRK DKKTDYEVLA SKLGKQWTPL IILANSRSGT NMGEGLLGEF
RILLNPVQVF DVTKTPPIKA LQLCTLLPYY SARVLVCGGD GTVGWVLDAV DDMKIKGQEK
YIPQVAVLPL GTGNDLSNTL GWGTGYAGEI PVAQVLRNVM EADGIKLDRW KVQVTNKGYY
NLRKPKEFTM NNYFSVGPDA LMALNFHAHR EKAPSLFSSR ILNKAVYLFY GTKDCLVQEC
KDLNKKVELE LDGERVALPS LEGIIVLNIG YWGGGCRLWE GMGDETYPLA RHDDGLLEVV
GVYGSFHCAQ IQVKLANPFR IGQAHTVRLI LKCSMMPMQV DGEPWAQGPC TVTITHKTHA
MMLYFSGEQT DDDISSTSDQ EDIKATE
