DGKA_HUMAN
ID DGKA_HUMAN Reviewed; 735 AA.
AC P23743; O75481; O75482; O75483; O95217; Q3ZE25; Q8IZ56; Q8N5Q2;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2009, sequence version 3.
DT 03-AUG-2022, entry version 213.
DE RecName: Full=Diacylglycerol kinase alpha;
DE Short=DAG kinase alpha;
DE EC=2.7.1.107 {ECO:0000269|PubMed:15544348, ECO:0000269|PubMed:2175712};
DE AltName: Full=80 kDa diacylglycerol kinase;
DE AltName: Full=Diglyceride kinase alpha;
DE Short=DGK-alpha;
GN Name=DGKA; Synonyms=DAGK, DAGK1;
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), FUNCTION, CATALYTIC ACTIVITY,
RP SUBSTRATE SPECIFICITY, ACTIVITY REGULATION, PATHWAY, SUBUNIT, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Lymphocyte;
RX PubMed=2175712; DOI=10.1016/0014-5793(90)81461-v;
RA Schaap D., de Widt J., van der Wal J., Vandekerckhove J., van Damme J.,
RA Gussow D., Ploegh H.L., van Blitterswijk W.J., van der Bendl R.L.;
RT "Purification, cDNA-cloning and expression of human diacylglycerol
RT kinase.";
RL FEBS Lett. 275:151-158(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND ALTERNATIVE SPLICING.
RC TISSUE=Uterus;
RA Champagne C.M.E., Maeda H., Takashiba S., van Dyke T.E.;
RT "Alternative splicing of diacylglycerol kinase alpha expressed in human
RT neutrophils.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Batista E.L. Jr., Van Dyke T.E.;
RT "Characterization of a novel DGK alpha transcript generated by alternative
RT splicing.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT TYR-538.
RC TISSUE=Brain;
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 [6]
RP CHROMOSOMAL LOCATION.
RX PubMed=8180475; DOI=10.1007/bf00292343;
RA Hart T.C., Champagne C., Zhou J., van Dyke T.E.;
RT "Assignment of the gene for diacylglycerol kinase (DAGK) to human
RT chromosome 12.";
RL Mamm. Genome 5:123-124(1994).
RN [7]
RP CHROMOSOMAL LOCATION.
RX PubMed=7959783; DOI=10.1006/geno.1994.1376;
RA Hart T.C., Zhou J., Champagne C., van Dyke T.E., Rao P.N., Pettenati M.J.;
RT "Assignment of the human diacylglycerol kinase gene (DAGK) to 12q13.3 using
RT fluorescence in situ hybridization analysis.";
RL Genomics 22:246-247(1994).
RN [8]
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 [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-484, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP FUNCTION, AND PATHWAY.
RX PubMed=22627129; DOI=10.1016/j.bbrc.2012.05.077;
RA Gellett A.M., Kharel Y., Sunkara M., Morris A.J., Lynch K.R.;
RT "Biosynthesis of alkyl lysophosphatidic acid by diacylglycerol kinases.";
RL Biochem. Biophys. Res. Commun. 422:758-763(2012).
RN [12]
RP STRUCTURE BY NMR OF 1-118.
RG Northeast structural genomics consortium (NESG);
RT "NMR structure of diacylglycerol kinase alpha, NESGC target HR532.";
RL Submitted (JAN-2005) to the PDB data bank.
RN [13] {ECO:0007744|PDB:6IIE}
RP X-RAY CRYSTALLOGRAPHY (2.14 ANGSTROMS) OF 107-197 IN COMPLEX WITH CALCIUM,
RP SUBUNIT, AND MUTAGENESIS OF GLU-134 AND GLU-179.
RX PubMed=30653270; DOI=10.1002/pro.3572;
RA Takahashi D., Suzuki K., Sakamoto T., Iwamoto T., Murata T., Sakane F.;
RT "Crystal structure and calcium-induced conformational changes of
RT diacylglycerol kinase alpha EF-hand domains.";
RL Protein Sci. 28:694-706(2019).
CC -!- FUNCTION: Diacylglycerol kinase that converts diacylglycerol/DAG into
CC phosphatidic acid/phosphatidate/PA and regulates the respective levels
CC of these two bioactive lipids (PubMed:2175712, PubMed:15544348).
CC Thereby, acts as a central switch between the signaling pathways
CC activated by these second messengers with different cellular targets
CC and opposite effects in numerous biological processes (PubMed:2175712,
CC PubMed:15544348). Also plays an important role in the biosynthesis of
CC complex lipids (Probable). Can also phosphorylate 1-alkyl-2-
CC acylglycerol in vitro as efficiently as diacylglycerol provided it
CC contains an arachidonoyl group (PubMed:15544348). Also involved in the
CC production of alkyl-lysophosphatidic acid, another bioactive lipid,
CC through the phosphorylation of 1-alkyl-2-acetyl glycerol
CC (PubMed:22627129). {ECO:0000269|PubMed:15544348,
CC ECO:0000269|PubMed:2175712, ECO:0000269|PubMed:22627129, ECO:0000305}.
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:2175712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10273;
CC Evidence={ECO:0000305|PubMed:2175712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycerol + ATP = 1,2-dihexadecanoyl-sn-
CC glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:63324,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:72859,
CC ChEBI:CHEBI:82929, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:2175712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63325;
CC Evidence={ECO:0000305|PubMed:2175712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + ATP = 1-
CC hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + ADP + H(+);
CC Xref=Rhea:RHEA:43416, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:64839, ChEBI:CHEBI:75466, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:2175712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43417;
CC Evidence={ECO:0000305|PubMed:2175712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(9Z-octadecenoyl)-glycerol + ATP = 2-(9Z-octadecenoyl)-sn-
CC glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:63328,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:73990,
CC ChEBI:CHEBI:77593, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:2175712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63329;
CC Evidence={ECO:0000305|PubMed:2175712};
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:2175712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40328;
CC Evidence={ECO:0000305|PubMed:2175712};
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:2175712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40324;
CC Evidence={ECO:0000305|PubMed:2175712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-didecanoyl-sn-glycerol + ATP = 1,2-didecanoyl-sn-glycero-
CC 3-phosphate + ADP + H(+); Xref=Rhea:RHEA:43428, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:18155, ChEBI:CHEBI:30616, ChEBI:CHEBI:78227,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P20192};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43429;
CC Evidence={ECO:0000250|UniProtKB:P20192};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-alkyl-2-acyl-sn-glycerol + ATP = 1-O-alkyl-2-acyl-sn-
CC glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:44072,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:52595,
CC ChEBI:CHEBI:73332, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:15544348, ECO:0000269|PubMed:2175712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44073;
CC Evidence={ECO:0000305|PubMed:2175712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-hexadecyl-2-acetyl-sn-glycerol + ATP = 1-O-hexadecyl-2-
CC acetyl-sn-glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:41676,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:75936,
CC ChEBI:CHEBI:78385, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:P51556};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41677;
CC Evidence={ECO:0000250|UniProtKB:P51556};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-hexadecyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol +
CC ATP = 1-O-hexadecyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-
CC phosphate + ADP + H(+); Xref=Rhea:RHEA:40403, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:77184, ChEBI:CHEBI:77186,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:15544348};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40404;
CC Evidence={ECO:0000305|PubMed:15544348};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-hexadecyl-2-(9Z-octadecenoyl)-sn-glycerol + ATP = 1-O-
CC hexadecyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + ADP + H(+);
CC Xref=Rhea:RHEA:40407, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:77185, ChEBI:CHEBI:77187, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:15544348, ECO:0000269|PubMed:2175712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40408;
CC Evidence={ECO:0000305|PubMed:2175712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-hexadecyl-sn-glycerol + ATP = 1-O-hexadecyl-sn-glycero-3-
CC phosphate + ADP + H(+); Xref=Rhea:RHEA:41672, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:34115, ChEBI:CHEBI:77580,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P51556};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41673;
CC Evidence={ECO:0000250|UniProtKB:P51556};
CC -!- ACTIVITY REGULATION: Stimulated by calcium and phosphatidylserine.
CC {ECO:0000269|PubMed:2175712}.
CC -!- PATHWAY: Lipid metabolism; glycerolipid metabolism.
CC {ECO:0000305|PubMed:15544348, ECO:0000305|PubMed:2175712,
CC ECO:0000305|PubMed:22627129}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:2175712,
CC ECO:0000269|PubMed:30653270}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:2175712}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P23743-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P23743-2; Sequence=VSP_032212, VSP_032213;
CC Name=3;
CC IsoId=P23743-3; Sequence=VSP_047702, VSP_047703;
CC -!- TISSUE SPECIFICITY: Expressed in lymphocytes.
CC {ECO:0000269|PubMed:2175712}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the eukaryotic diacylglycerol kinase family.
CC {ECO:0000305}.
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DR EMBL; X62535; CAA44396.1; -; mRNA.
DR EMBL; AF064767; AAC34802.1; -; mRNA.
DR EMBL; AF064768; AAC34803.1; -; mRNA.
DR EMBL; AF064769; AAC34804.1; -; mRNA.
DR EMBL; AF064771; AAC34806.1; -; mRNA.
DR EMBL; AY930112; AAY20994.1; -; mRNA.
DR EMBL; AC025162; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC023523; AAH23523.1; -; mRNA.
DR EMBL; BC031870; AAH31870.1; -; mRNA.
DR CCDS; CCDS8896.1; -. [P23743-1]
DR PIR; S12969; S12969.
DR RefSeq; NP_001336.2; NM_001345.4. [P23743-1]
DR RefSeq; NP_958852.1; NM_201444.2. [P23743-1]
DR RefSeq; NP_958853.1; NM_201445.1. [P23743-1]
DR RefSeq; NP_963848.1; NM_201554.1. [P23743-1]
DR RefSeq; XP_011536293.1; XM_011537991.2.
DR RefSeq; XP_011536295.1; XM_011537993.2. [P23743-1]
DR PDB; 1TUZ; NMR; -; A=1-116.
DR PDB; 6IIE; X-ray; 2.14 A; A=107-197.
DR PDBsum; 1TUZ; -.
DR PDBsum; 6IIE; -.
DR AlphaFoldDB; P23743; -.
DR BMRB; P23743; -.
DR SMR; P23743; -.
DR BioGRID; 107976; 31.
DR IntAct; P23743; 4.
DR MINT; P23743; -.
DR STRING; 9606.ENSP00000328405; -.
DR BindingDB; P23743; -.
DR ChEMBL; CHEMBL4105787; -.
DR DrugBank; DB14001; alpha-Tocopherol succinate.
DR DrugBank; DB00163; Vitamin E.
DR SwissLipids; SLP:000000555; -.
DR SwissLipids; SLP:000000739; -.
DR GlyGen; P23743; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P23743; -.
DR MetOSite; P23743; -.
DR PhosphoSitePlus; P23743; -.
DR BioMuta; DGKA; -.
DR DMDM; 281185505; -.
DR EPD; P23743; -.
DR jPOST; P23743; -.
DR MassIVE; P23743; -.
DR MaxQB; P23743; -.
DR PaxDb; P23743; -.
DR PeptideAtlas; P23743; -.
DR PRIDE; P23743; -.
DR ProteomicsDB; 54146; -. [P23743-1]
DR ProteomicsDB; 54147; -. [P23743-2]
DR Antibodypedia; 27785; 458 antibodies from 31 providers.
DR DNASU; 1606; -.
DR Ensembl; ENST00000331886.10; ENSP00000328405.5; ENSG00000065357.20. [P23743-1]
DR Ensembl; ENST00000394147.5; ENSP00000377703.1; ENSG00000065357.20. [P23743-1]
DR Ensembl; ENST00000402956.7; ENSP00000385792.3; ENSG00000065357.20. [P23743-3]
DR Ensembl; ENST00000548549.5; ENSP00000448565.1; ENSG00000065357.20. [P23743-2]
DR Ensembl; ENST00000551156.5; ENSP00000450359.1; ENSG00000065357.20. [P23743-1]
DR Ensembl; ENST00000553084.5; ENSP00000446605.1; ENSG00000065357.20. [P23743-2]
DR GeneID; 1606; -.
DR KEGG; hsa:1606; -.
DR MANE-Select; ENST00000331886.10; ENSP00000328405.5; NM_001345.5; NP_001336.2.
DR UCSC; uc001sij.4; human. [P23743-1]
DR CTD; 1606; -.
DR DisGeNET; 1606; -.
DR GeneCards; DGKA; -.
DR HGNC; HGNC:2849; DGKA.
DR HPA; ENSG00000065357; Tissue enhanced (esophagus, lymphoid tissue).
DR MIM; 125855; gene.
DR neXtProt; NX_P23743; -.
DR OpenTargets; ENSG00000065357; -.
DR PharmGKB; PA27310; -.
DR VEuPathDB; HostDB:ENSG00000065357; -.
DR eggNOG; KOG1169; Eukaryota.
DR GeneTree; ENSGT00940000157144; -.
DR HOGENOM; CLU_059202_0_0_1; -.
DR InParanoid; P23743; -.
DR OMA; MTQTDGQ; -.
DR OrthoDB; 633642at2759; -.
DR PhylomeDB; P23743; -.
DR TreeFam; TF313104; -.
DR BRENDA; 2.7.1.107; 2681.
DR PathwayCommons; P23743; -.
DR Reactome; R-HSA-114508; Effects of PIP2 hydrolysis.
DR SABIO-RK; P23743; -.
DR SignaLink; P23743; -.
DR SIGNOR; P23743; -.
DR UniPathway; UPA00230; -.
DR BioGRID-ORCS; 1606; 19 hits in 1080 CRISPR screens.
DR ChiTaRS; DGKA; human.
DR EvolutionaryTrace; P23743; -.
DR GeneWiki; DGKA; -.
DR GenomeRNAi; 1606; -.
DR Pharos; P23743; Tbio.
DR PRO; PR:P23743; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P23743; protein.
DR Bgee; ENSG00000065357; Expressed in lower esophagus mucosa and 178 other tissues.
DR ExpressionAtlas; P23743; baseline and differential.
DR Genevisible; P23743; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004143; F:diacylglycerol kinase activity; IDA:UniProtKB.
DR GO; GO:0016301; F:kinase activity; IDA:BHF-UCL.
DR GO; GO:0008289; F:lipid binding; IDA:BHF-UCL.
DR GO; GO:0003951; F:NAD+ kinase activity; IEA:InterPro.
DR GO; GO:0005543; F:phospholipid binding; IEA:Ensembl.
DR GO; GO:0046339; P:diacylglycerol metabolic process; IDA:UniProtKB.
DR GO; GO:0046486; P:glycerolipid metabolic process; IDA:BHF-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0046834; P:lipid phosphorylation; IDA:UniProtKB.
DR GO; GO:0006654; P:phosphatidic acid biosynthetic process; IDA:UniProtKB.
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; 1.
DR CDD; cd00051; EFh; 1.
DR Gene3D; 1.10.238.110; -; 1.
DR Gene3D; 3.40.50.10330; -; 1.
DR InterPro; IPR017438; ATP-NAD_kinase_N.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR029477; DAG_kinase_typeI_N.
DR InterPro; IPR037607; DGK.
DR InterPro; IPR038199; DGK_typeI_N_sf.
DR InterPro; IPR000756; Diacylglycerol_kin_accessory.
DR InterPro; IPR001206; Diacylglycerol_kinase_cat_dom.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR016064; NAD/diacylglycerol_kinase_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR PANTHER; PTHR11255; PTHR11255; 1.
DR Pfam; PF00130; C1_1; 2.
DR Pfam; PF14513; DAG_kinase_N; 2.
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 SMART; SM00054; EFh; 2.
DR SUPFAM; SSF111331; SSF111331; 1.
DR SUPFAM; SSF47473; SSF47473; 2.
DR SUPFAM; SSF57889; SSF57889; 2.
DR PROSITE; PS50146; DAGK; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 2.
DR PROSITE; PS00479; ZF_DAG_PE_1; 2.
DR PROSITE; PS50081; ZF_DAG_PE_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Calcium;
KW Cytoplasm; Kinase; Lipid metabolism; Metal-binding; Nucleotide-binding;
KW Reference proteome; Repeat; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..735
FT /note="Diacylglycerol kinase alpha"
FT /id="PRO_0000218453"
FT DOMAIN 110..145
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 155..190
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 372..506
FT /note="DAGKc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT ZN_FING 205..253
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 269..319
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT BINDING 123
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:30653270"
FT BINDING 125
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:30653270"
FT BINDING 127
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:30653270"
FT BINDING 134
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:30653270"
FT BINDING 168
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:30653270"
FT BINDING 170
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:30653270"
FT BINDING 172
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:30653270"
FT BINDING 174
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:30653270"
FT BINDING 179
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:30653270"
FT MOD_RES 484
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 117..118
FT /note="FT -> WS (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_032212"
FT VAR_SEQ 119..735
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_032213"
FT VAR_SEQ 237..247
FT /note="LCKYTVHDQCA -> RPITCVGARRL (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_047702"
FT VAR_SEQ 248..735
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_047703"
FT VARIANT 538
FT /note="H -> Y (in dbSNP:rs17852990)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_031563"
FT MUTAGEN 134
FT /note="E->Q: Binds calcium but with decreased affinity."
FT /evidence="ECO:0000269|PubMed:30653270"
FT MUTAGEN 179
FT /note="E->Q: Loss of calcium-binding."
FT /evidence="ECO:0000269|PubMed:30653270"
FT CONFLICT 339
FT /note="L -> P (in Ref. 2; AAC34804)"
FT /evidence="ECO:0000305"
FT CONFLICT 379
FT /note="V -> L (in Ref. 2; AAC34802)"
FT /evidence="ECO:0000305"
FT CONFLICT 385
FT /note="S -> W (in Ref. 2; AAC34802)"
FT /evidence="ECO:0000305"
FT CONFLICT 684
FT /note="E -> G (in Ref. 2; AAC34803)"
FT /evidence="ECO:0000305"
FT CONFLICT 699
FT /note="G -> V (in Ref. 1; CAA44396)"
FT /evidence="ECO:0000305"
FT CONFLICT 715
FT /note="N -> K (in Ref. 2; AAC34803)"
FT /evidence="ECO:0000305"
FT HELIX 10..22
FT /evidence="ECO:0007829|PDB:1TUZ"
FT HELIX 27..35
FT /evidence="ECO:0007829|PDB:1TUZ"
FT HELIX 38..42
FT /evidence="ECO:0007829|PDB:1TUZ"
FT HELIX 50..60
FT /evidence="ECO:0007829|PDB:1TUZ"
FT HELIX 68..77
FT /evidence="ECO:0007829|PDB:1TUZ"
FT HELIX 96..107
FT /evidence="ECO:0007829|PDB:1TUZ"
FT HELIX 112..122
FT /evidence="ECO:0007829|PDB:6IIE"
FT STRAND 127..130
FT /evidence="ECO:0007829|PDB:6IIE"
FT HELIX 132..148
FT /evidence="ECO:0007829|PDB:6IIE"
FT TURN 154..156
FT /evidence="ECO:0007829|PDB:6IIE"
FT HELIX 157..167
FT /evidence="ECO:0007829|PDB:6IIE"
FT STRAND 173..176
FT /evidence="ECO:0007829|PDB:6IIE"
FT HELIX 177..185
FT /evidence="ECO:0007829|PDB:6IIE"
FT HELIX 190..193
FT /evidence="ECO:0007829|PDB:6IIE"
SQ SEQUENCE 735 AA; 82630 MW; ACAA0AD186EE64A0 CRC64;
MAKERGLISP SDFAQLQKYM EYSTKKVSDV LKLFEDGEMA KYVQGDAIGY EGFQQFLKIY
LEVDNVPRHL SLALFQSFET GHCLNETNVT KDVVCLNDVS CYFSLLEGGR PEDKLEFTFK
LYDTDRNGIL DSSEVDKIIL QMMRVAEYLD WDVSELRPIL QEMMKEIDYD GSGSVSQAEW
VRAGATTVPL LVLLGLEMTL KDDGQHMWRP KRFPRPVYCN LCESSIGLGK QGLSCNLCKY
TVHDQCAMKA LPCEVSTYAK SRKDIGVQSH VWVRGGCESG RCDRCQKKIR IYHSLTGLHC
VWCHLEIHDD CLQAVGHECD CGLLRDHILP PSSIYPSVLA SGPDRKNSKT SQKTMDDLNL
STSEALRIDP VPNTHPLLVF VNPKSGGKQG QRVLWKFQYI LNPRQVFNLL KDGPEIGLRL
FKDVPDSRIL VCGGDGTVGW ILETIDKANL PVLPPVAVLP LGTGNDLARC LRWGGGYEGQ
NLAKILKDLE MSKVVHMDRW SVEVIPQQTE EKSDPVPFQI INNYFSIGVD ASIAHRFHIM
REKYPEKFNS RMKNKLWYFE FATSESIFST CKKLEESLTV EICGKPLDLS NLSLEGIAVL
NIPSMHGGSN LWGDTRRPHG DIYGINQALG ATAKVITDPD ILKTCVPDLS DKRLEVVGLE
GAIEMGQIYT KLKNAGRRLA KCSEITFHTT KTLPMQIDGE PWMQTPCTIK ITHKNQMPML
MGPPPRSTNF FGFLS
