DGKI_HUMAN
ID DGKI_HUMAN Reviewed; 1065 AA.
AC O75912; A4D1Q9; Q9NZ49;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Diacylglycerol kinase iota {ECO:0000303|PubMed:9830018};
DE Short=DAG kinase iota {ECO:0000305|PubMed:9830018};
DE Short=DGK-iota {ECO:0000303|PubMed:9830018};
DE EC=2.7.1.107 {ECO:0000269|PubMed:23949095, ECO:0000269|PubMed:9830018};
GN Name=DGKI {ECO:0000312|HGNC:HGNC:2855};
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], FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Retina;
RX PubMed=9830018; DOI=10.1074/jbc.273.49.32746;
RA Ding L., Traer E., McIntyre T.M., Zimmerman G.A., Prescott S.M.;
RT "The cloning and characterization of a novel human diacylglycerol kinase,
RT DGK-iota.";
RL J. Biol. Chem. 273:32746-32752(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 135-1065, AND VARIANT PHE-153.
RX PubMed=10706894;
RA Bowne S.J., Sullivan L.S., Ding L., Traer E., Prescott S.M., Birch D.G.,
RA Kennan A., Humphries P., Daiger S.P.;
RT "Evaluation of human diacylglycerol kinase iota, DGKI, a homolog of
RT Drosophila rdgA, in inherited retinopathy mapping to 7q.";
RL Mol. Vis. 6:6-9(2000).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=15894621; DOI=10.1073/pnas.0500663102;
RA Regier D.S., Higbee J., Lund K.M., Sakane F., Prescott S.M., Topham M.K.;
RT "Diacylglycerol kinase iota regulates Ras guanyl-releasing protein 3 and
RT inhibits Rap1 signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:7595-7600(2005).
RN [5]
RP INTERACTION WITH DLG4.
RX PubMed=21119615; DOI=10.1038/emboj.2010.286;
RA Yang J., Seo J., Nair R., Han S., Jang S., Kim K., Han K., Paik S.K.,
RA Choi J., Lee S., Bae Y.C., Topham M.K., Prescott S.M., Rhee J.S.,
RA Choi S.Y., Kim E.;
RT "DGKiota regulates presynaptic release during mGluR-dependent LTD.";
RL EMBO J. 30:165-180(2011).
RN [6]
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).
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:9830018, PubMed:23949095).
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 (Probable). Has
CC probably no preference for any of the diacylglycerols in terms of the
CC acyl chain composition, especially for the acyl chain at the sn-2
CC position (PubMed:9830018). By controlling the diacylglycerol/DAG-
CC mediated activation of RASGRP3, negatively regulates the Rap1 signaling
CC pathway. May play a role in presynaptic diacylglycerol/DAG signaling
CC and control neurotransmitter release during metabotropic glutamate
CC receptor-dependent long-term depression (By similarity).
CC {ECO:0000250|UniProtKB:D3YWQ0, ECO:0000269|PubMed:23949095,
CC ECO:0000269|PubMed:9830018, 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:23949095, ECO:0000269|PubMed:9830018};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10273;
CC Evidence={ECO:0000305|PubMed:9830018};
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:23949095, ECO:0000269|PubMed:9830018};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40328;
CC Evidence={ECO:0000305|PubMed:9830018};
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:9830018};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40324;
CC Evidence={ECO:0000305|PubMed:9830018};
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:F1MAB7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40340;
CC Evidence={ECO:0000250|UniProtKB:F1MAB7};
CC -!- PATHWAY: Lipid metabolism; glycerolipid metabolism.
CC {ECO:0000269|PubMed:9830018}.
CC -!- SUBUNIT: Interacts (via PDZ-binding motif) with DLG4; controls the
CC localization of DGKI to the synapse (PubMed:21119615). Interacts (via
CC PDZ-binding motif) with DLG1 (By similarity). Interacts (via PDZ-
CC binding motif) with DLG2 (By similarity). Interacts (via PDZ-binding
CC motif) with DLG3 (By similarity). May interact with RASGRP3; involved
CC in the regulation of RASGRP3 activity (By similarity).
CC {ECO:0000250|UniProtKB:D3YWQ0, ECO:0000250|UniProtKB:F1MAB7,
CC ECO:0000269|PubMed:21119615}.
CC -!- INTERACTION:
CC O75912; P40337-3: VHL; NbExp=3; IntAct=EBI-1765520, EBI-301270;
CC -!- SUBCELLULAR LOCATION: Cell projection, axon
CC {ECO:0000250|UniProtKB:F1MAB7}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:F1MAB7}. Presynapse
CC {ECO:0000250|UniProtKB:F1MAB7}. Postsynapse
CC {ECO:0000250|UniProtKB:F1MAB7}. Postsynaptic density
CC {ECO:0000250|UniProtKB:F1MAB7}. Synaptic cell membrane
CC {ECO:0000250|UniProtKB:F1MAB7}. Cytoplasmic vesicle, secretory vesicle,
CC synaptic vesicle membrane {ECO:0000250|UniProtKB:F1MAB7}. Cytoplasm,
CC cytosol {ECO:0000269|PubMed:9830018}. Nucleus
CC {ECO:0000269|PubMed:9830018}. Note=Excluded from inhibitory synapses
CC (By similarity). Localization between cytoplasm and nucleus is
CC regulated by protein kinase C (PubMed:9830018). Both in the detergent
CC soluble and particulate fractions (By similarity).
CC {ECO:0000250|UniProtKB:F1MAB7, ECO:0000269|PubMed:9830018}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in brain and retina
CC (PubMed:9830018). In brain, highly expressed in hippocampus, caudate
CC nucleus, occipital pole, cerebral cortex, and cerebellum
CC (PubMed:9830018). Also detected in kidney (PubMed:15894621).
CC {ECO:0000269|PubMed:15894621, ECO:0000269|PubMed:9830018}.
CC -!- SIMILARITY: Belongs to the eukaryotic diacylglycerol kinase family.
CC {ECO:0000305}.
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DR EMBL; AF061936; AAC62010.1; -; mRNA.
DR EMBL; CH236950; EAL24051.1; -; Genomic_DNA.
DR EMBL; AH009185; AAF43006.1; -; Genomic_DNA.
DR CCDS; CCDS5845.1; -.
DR RefSeq; NP_001308637.1; NM_001321708.1.
DR RefSeq; NP_001308638.1; NM_001321709.1.
DR RefSeq; NP_001308639.1; NM_001321710.1.
DR RefSeq; NP_004708.1; NM_004717.3.
DR AlphaFoldDB; O75912; -.
DR SMR; O75912; -.
DR BioGRID; 114605; 6.
DR IntAct; O75912; 4.
DR STRING; 9606.ENSP00000288490; -.
DR DrugBank; DB14001; alpha-Tocopherol succinate.
DR SwissLipids; SLP:000000925; -.
DR iPTMnet; O75912; -.
DR PhosphoSitePlus; O75912; -.
DR BioMuta; DGKI; -.
DR jPOST; O75912; -.
DR MassIVE; O75912; -.
DR MaxQB; O75912; -.
DR PaxDb; O75912; -.
DR PeptideAtlas; O75912; -.
DR PRIDE; O75912; -.
DR ProteomicsDB; 50265; -.
DR Antibodypedia; 32299; 192 antibodies from 29 providers.
DR DNASU; 9162; -.
DR Ensembl; ENST00000288490.9; ENSP00000288490.4; ENSG00000157680.16.
DR GeneID; 9162; -.
DR KEGG; hsa:9162; -.
DR UCSC; uc003vtt.4; human.
DR CTD; 9162; -.
DR DisGeNET; 9162; -.
DR GeneCards; DGKI; -.
DR HGNC; HGNC:2855; DGKI.
DR HPA; ENSG00000157680; Tissue enhanced (brain, choroid plexus, retina, thyroid gland).
DR MIM; 604072; gene.
DR neXtProt; NX_O75912; -.
DR OpenTargets; ENSG00000157680; -.
DR PharmGKB; PA27316; -.
DR VEuPathDB; HostDB:ENSG00000157680; -.
DR eggNOG; KOG0782; Eukaryota.
DR GeneTree; ENSGT00940000158094; -.
DR InParanoid; O75912; -.
DR PhylomeDB; O75912; -.
DR TreeFam; TF312817; -.
DR BRENDA; 2.7.1.107; 2681.
DR PathwayCommons; O75912; -.
DR Reactome; R-HSA-114508; Effects of PIP2 hydrolysis.
DR SignaLink; O75912; -.
DR UniPathway; UPA00230; -.
DR BioGRID-ORCS; 9162; 19 hits in 1080 CRISPR screens.
DR ChiTaRS; DGKI; human.
DR GenomeRNAi; 9162; -.
DR Pharos; O75912; Tbio.
DR PRO; PR:O75912; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; O75912; protein.
DR Bgee; ENSG00000157680; Expressed in cortical plate and 127 other tissues.
DR ExpressionAtlas; O75912; baseline and differential.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0043197; C:dendritic spine; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0097060; C:synaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030672; C:synaptic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004143; F:diacylglycerol 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; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0046834; P:lipid phosphorylation; IDA:BHF-UCL.
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 GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IBA:GO_Central.
DR Gene3D; 1.25.40.20; -; 1.
DR Gene3D; 3.40.50.10330; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR017438; ATP-NAD_kinase_N.
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; PF12796; Ank_2; 1.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF00609; DAGK_acc; 1.
DR Pfam; PF00781; DAGK_cat; 1.
DR SMART; SM00248; ANK; 2.
DR SMART; SM00109; C1; 2.
DR SMART; SM00045; DAGKa; 1.
DR SMART; SM00046; DAGKc; 1.
DR SUPFAM; SSF111331; SSF111331; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 2.
DR PROSITE; PS50146; DAGK; 1.
PE 1: Evidence at protein level;
KW ANK repeat; ATP-binding; Cell membrane; Cell projection; Cytoplasm;
KW Cytoplasmic vesicle; Kinase; Lipid metabolism; Membrane; Metal-binding;
KW Nucleotide-binding; Nucleus; Reference proteome; Repeat; Synapse;
KW Transferase; Zinc; Zinc-finger.
FT CHAIN 1..1065
FT /note="Diacylglycerol kinase iota"
FT /id="PRO_0000218466"
FT DOMAIN 372..507
FT /note="DAGKc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT REPEAT 958..987
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 994..1023
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT ZN_FING 177..232
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 250..309
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 15..74
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 334..358
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1022..1041
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1063..1065
FT /note="PDZ-binding"
FT /evidence="ECO:0000250|UniProtKB:F1MAB7"
FT COMPBIAS 59..74
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 334..349
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 153
FT /note="L -> F (in dbSNP:rs61757580)"
FT /evidence="ECO:0000269|PubMed:10706894"
FT /id="VAR_010190"
FT CONFLICT 160
FT /note="A -> P (in Ref. 3; AAF43006)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1065 AA; 116997 MW; B84971AA7630A799 CRC64;
MDAAGRGCHL LPLPAARGPA RAPAAAAAAA ASPPGPCSGA ACAPSAAAGA GAMNPSSSAG
EEKGATGGSS SSGSGAGSCC LGAEGGADPR GAGSAAAAGA AALDEPAAAG QKEKDEALEE
KLRNLTFRKQ VSYRKAISRA GLQHLAPAHP LSLPVANGPA KEPRATLDWS ENAVNGEHLW
LETNVSGDLC YLGEENCQVR FAKSALRRKC AVCKIVVHTA CIEQLEKINF RCKPTFREGG
SRSPRENFVR HHWVHRRRQE GKCKQCGKGF QQKFSFHSKE IVAISCSWCK QAFHNKVTCF
MLHHIEEPCS LGAHAAVIVP PTWIIKVKKP QNSLKASNRK KKRTSFKRKA SKRGMEQENK
GRPFVIKPIS SPLMKPLLVF VNPKSGGNQG TKVLQMFMWY LNPRQVFDLS QEGPKDALEL
YRKVPNLRIL ACGGDGTVGW ILSILDELQL SPQPPVGVLP LGTGNDLART LNWGGGYTDE
PVSKILCQVE DGTVVQLDRW NLHVERNPDL PPEELEDGVC KLPLNVFNNY FSLGFDAHVT
LEFHESREAN PEKFNSRFRN KMFYAGAAFS DFLQRSSRDL SKHVKVVCDG TDLTPKIQEL
KFQCIVFLNI PRYCAGTMPW GNPGDHHDFE PQRHDDGYIE VIGFTMASLA ALQVGGHGER
LHQCREVMLL TYKSIPMQVD GEPCRLAPAM IRISLRNQAN MVQKSKRRTS MPLLNDPQSV
PDRLRIRVNK ISLQDYEGFH YDKEKLREAS ISDWLRTIAG ELVQSFGAIP LGILVVRGDC
DLETCRMYID RLQEDLQSVS SGSQRVHYQD HETSFPRALS AQRLSPRWCF LDDRSQEHLH
FVMEISQDEI FILDPDMVVS QPAGTPPGMP DLVVEQASGI SDWWNPALRK RMLSDSGLGM
IAPYYEDSDL KDLSHSRVLQ SPVSSEDHAI LQAVIAGDLM KLIESYKNGG SLLIQGPDHC
SLLHYAAKTG NGEIVKYILD HGPSELLDMA DSETGETALH KAACQRNRAV CQLLVDAGAS
LRKTDSKGKT PQERAQQAGD PDLAAYLESR QNYKVIGHED LETAV
