DGKE_MOUSE
ID DGKE_MOUSE Reviewed; 564 AA.
AC Q9R1C6; Q5SU69;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Diacylglycerol kinase epsilon;
DE Short=DAG kinase epsilon;
DE EC=2.7.1.107 {ECO:0000269|PubMed:11287665};
DE AltName: Full=Diglyceride kinase epsilon;
DE Short=DGK-epsilon;
GN Name=Dgke;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=11287665; DOI=10.1073/pnas.081536298;
RA Rodriguez de Turco E.B., Tang W., Topham M.K., Sakane F., Marcheselli V.L.,
RA Chen C., Taketomi A., Prescott S.M., Bazan N.G.;
RT "Diacylglycerol kinase epsilon regulates seizure susceptibility and long-
RT term potentiation through arachidonoyl-inositol lipid signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:4740-4745(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP FUNCTION, SUBSTRATE SPECIFICITY, AND PATHWAY.
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP TISSUE SPECIFICITY.
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).
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:11287665). 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:11287665). Also plays an important role in the biosynthesis of
CC complex lipids (By similarity). Displays specificity for diacylglycerol
CC substrates with an arachidonoyl acyl chain at the sn-2 position, with
CC the highest activity toward 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-sn-glycerol the main diacylglycerol intermediate
CC within the phosphatidylinositol turnover cycle (PubMed:11287665,
CC PubMed:19744926). Can also phosphorylate diacylglycerol substrates with
CC a linoleoyl acyl chain at the sn-2 position but much less efficiently
CC (By similarity). {ECO:0000250|UniProtKB:P52429,
CC ECO:0000269|PubMed:11287665, ECO:0000269|PubMed:19744926}.
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:11287665};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10273;
CC Evidence={ECO:0000269|PubMed:11287665};
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:0000250|UniProtKB:P52429};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40336;
CC Evidence={ECO:0000250|UniProtKB:P52429};
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:0000250|UniProtKB:P52429};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40324;
CC Evidence={ECO:0000250|UniProtKB:P52429};
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:0000250|UniProtKB:P52429};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40332;
CC Evidence={ECO:0000250|UniProtKB:P52429};
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:0000250|UniProtKB:P52429};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40352;
CC Evidence={ECO:0000250|UniProtKB:P52429};
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:0000250|UniProtKB:P52429};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40340;
CC Evidence={ECO:0000250|UniProtKB:P52429};
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:0000250|UniProtKB:P52429};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40356;
CC Evidence={ECO:0000250|UniProtKB:P52429};
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:0000250|UniProtKB:P52429};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40328;
CC Evidence={ECO:0000250|UniProtKB:P52429};
CC -!- PATHWAY: Lipid metabolism; glycerolipid metabolism.
CC {ECO:0000269|PubMed:11287665, ECO:0000269|PubMed:19744926}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P52429}; Single-
CC pass membrane protein {ECO:0000255}. Cytoplasm
CC {ECO:0000250|UniProtKB:P52429}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and heart
CC (PubMed:11287665). In brain, highly expressed in Purkinje cells of the
CC cerebellum, pyramidal cells of the hippocampus, mitral cells of the
CC olfactory bulb, and neurons of the substantia nigra (PubMed:11287665).
CC Lower expression in neurons of the thalamus, superior olive, and
CC lateral reticular nucleus is also detected (PubMed:11287665). Expressed
CC in platelets (PubMed:23542698). {ECO:0000269|PubMed:11287665,
CC ECO:0000269|PubMed:23542698}.
CC -!- DISRUPTION PHENOTYPE: Homozygous knockout mice are normal, reproduce
CC and behave normally. No gross or histological abnormalities in major
CC organs, including the brain are observed (PubMed:11287665). The
CC phosphatidylinositol 4,5- bisphosphate-signaling pathway in cerebral
CC cortex and long-term potentiation are affected (PubMed:11287665).
CC {ECO:0000269|PubMed:11287665}.
CC -!- SIMILARITY: Belongs to the eukaryotic diacylglycerol kinase family.
CC {ECO:0000305}.
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DR EMBL; AF136744; AAD45665.1; -; mRNA.
DR EMBL; AL646096; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS25234.1; -.
DR RefSeq; NP_062378.1; NM_019505.3.
DR AlphaFoldDB; Q9R1C6; -.
DR BioGRID; 207804; 3.
DR STRING; 10090.ENSMUSP00000103526; -.
DR iPTMnet; Q9R1C6; -.
DR PhosphoSitePlus; Q9R1C6; -.
DR SwissPalm; Q9R1C6; -.
DR EPD; Q9R1C6; -.
DR MaxQB; Q9R1C6; -.
DR PaxDb; Q9R1C6; -.
DR PeptideAtlas; Q9R1C6; -.
DR PRIDE; Q9R1C6; -.
DR ProteomicsDB; 277324; -.
DR Antibodypedia; 2548; 242 antibodies from 30 providers.
DR DNASU; 56077; -.
DR Ensembl; ENSMUST00000000285; ENSMUSP00000000285; ENSMUSG00000000276.
DR Ensembl; ENSMUST00000107894; ENSMUSP00000103526; ENSMUSG00000000276.
DR GeneID; 56077; -.
DR KEGG; mmu:56077; -.
DR UCSC; uc007kwd.1; mouse.
DR CTD; 8526; -.
DR MGI; MGI:1889276; Dgke.
DR VEuPathDB; HostDB:ENSMUSG00000000276; -.
DR eggNOG; KOG1169; Eukaryota.
DR GeneTree; ENSGT00940000158604; -.
DR HOGENOM; CLU_003770_3_1_1; -.
DR InParanoid; Q9R1C6; -.
DR OMA; GMMEVFG; -.
DR OrthoDB; 1275907at2759; -.
DR PhylomeDB; Q9R1C6; -.
DR TreeFam; TF313104; -.
DR BRENDA; 2.7.1.107; 3474.
DR Reactome; R-MMU-114508; Effects of PIP2 hydrolysis.
DR UniPathway; UPA00230; -.
DR BioGRID-ORCS; 56077; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Dgke; mouse.
DR PRO; PR:Q9R1C6; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9R1C6; protein.
DR Bgee; ENSMUSG00000000276; Expressed in retinal neural layer and 190 other tissues.
DR ExpressionAtlas; Q9R1C6; baseline and differential.
DR Genevisible; Q9R1C6; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IMP:SynGO.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004143; F:diacylglycerol kinase activity; ISS:UniProtKB.
DR GO; GO:0016301; F:kinase activity; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0046834; P:lipid phosphorylation; ISS:UniProtKB.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IMP:SynGO.
DR GO; GO:0006654; P:phosphatidic acid biosynthetic process; ISO:MGI.
DR GO; GO:0006661; P:phosphatidylinositol biosynthetic process; IMP:UniProtKB.
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; 1.
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 ATP-binding; Cytoplasm; Kinase; Lipid metabolism; Membrane; Metal-binding;
KW Nucleotide-binding; Reference proteome; Repeat; Transferase; Transmembrane;
KW Transmembrane helix; Zinc; Zinc-finger.
FT CHAIN 1..564
FT /note="Diacylglycerol kinase epsilon"
FT /id="PRO_0000218465"
FT TRANSMEM 20..40
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 212..353
FT /note="DAGKc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT ZN_FING 57..106
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 121..174
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
SQ SEQUENCE 564 AA; 63635 MW; C900BEC2CE9DD109 CRC64;
MEGDQRSGPP AQSLLPDGHL VLWTLCSVLL PVFITLWCSL QRSRRQLHRR DIFRKSKHCW
RDTDLFSHPT YCCVCAQHIL QGAFCDCCGL RVDEGCLKKV DKRFPCKEIM LKNDKAADAM
PHHWIRGNVP LCSYCVFCRQ QCGSQPKLCD YRCIWCQKTV HDECMRGSLR SEKCDFGEFR
NLIIPPSYLT SINQMRKDKN TNYEGLASKF GKQWTPLIIL ANSRSGTNMG EGLLGEFKIL
LNPVQVFDVT KTPPIKALQL CTLLPYYSVR VLVCGGDGTV GWVLDAIDEM KIKGQEKYIP
EVAVLPLGTG NDLSNTLGWG TGYAGEIPVA QVLRNVMEAD GIKLDRWKVQ VTNKGYYNLR
KPKEFTMNNY FSVGPDALMA LNFHAHREKA PSLFSSRILN KAVYLFYGTK DCLVQECKDL
NKKIELELDG ERVELPNLEG IIVLNIGYWG GGCRLWEGMG DETYPLARHD DGLLEIVGVY
GSFHCAQIQV KLANPFRIGQ AHTVRLTLKC SMMPMQVDGE PWAQGPCTVT ITHKTHALML
YFSGEQSDDD ISSPSDHEDV KEAE
