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 27-MAR-2024, entry version 198. 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]: CC An atypical form of hemolytic uremic syndrome characterized by acute CC onset 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 74. DR IntAct; P52429; 24. 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; 9606-ENSP00000284061; -. DR PeptideAtlas; P52429; -. DR ProteomicsDB; 56484; -. [P52429-1] DR ProteomicsDB; 74029; -. DR Pumba; P52429; -. DR Antibodypedia; 2548; 271 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 AGR; HGNC:2852; -. 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; MQPDCER; -. DR OrthoDB; 4642163at2759; -. 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; 14 hits in 1164 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 172 other cell types or tissues. DR ExpressionAtlas; P52429; baseline and differential. 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: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:ATP-dependent 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:0046339; P:diacylglycerol metabolic process; IDA:UniProtKB. 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; cd20801; C1_DGKepsilon_typeIII_rpt1; 1. DR CDD; cd20853; C1_DGKepsilon_typeIII_rpt2; 1. DR Gene3D; 2.60.200.40; -; 1. DR Gene3D; 3.30.60.20; -; 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; DIACYLGLYCEROL KINASE; 1. DR PANTHER; PTHR11255:SF117; DIACYLGLYCEROL KINASE EPSILON; 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; SSF57889; Cysteine-rich domain; 2. DR SUPFAM; SSF111331; NAD kinase/diacylglycerol kinase-like; 1. DR PROSITE; PS50146; DAGK; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 2. DR PROSITE; PS50081; ZF_DAG_PE_2; 2. DR Genevisible; P52429; HS. 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 FT 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-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-glycerol." FT /evidence="ECO:0000269|PubMed:21477596" FT MUTAGEN 438 FT /note="L->I: Decreased diacylglycerol kinase activity FT toward FT 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol." FT /evidence="ECO:0000269|PubMed:21477596" FT MUTAGEN 438 FT /note="L->M: Decreased protein abundance and diacylglycerol FT kinase activity toward FT 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-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 FT 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol." FT /evidence="ECO:0000269|PubMed:21477596" FT MUTAGEN 439 FT /note="P->G: Decreased diacylglycerol kinase activity FT toward FT 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-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 //