DGKI_MOUSE
ID DGKI_MOUSE Reviewed; 1071 AA.
AC D3YWQ0; D3Z2W1;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Diacylglycerol kinase iota {ECO:0000303|PubMed:15894621};
DE Short=DAG kinase iota {ECO:0000305|PubMed:15894621};
DE EC=2.7.1.107 {ECO:0000250|UniProtKB:O75912};
GN Name=Dgki {ECO:0000312|MGI:MGI:2443430};
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 [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 [2]
RP FUNCTION, INTERACTION WITH RASGRP3, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [4]
RP FUNCTION, INTERACTION WITH DLG3, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
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).
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. Thereby, acts as a central switch
CC between the signaling pathways activated by these second messengers
CC with different cellular targets and opposite effects in numerous
CC biological processes. Has probably no preference for any of the
CC diacylglycerols in terms of the acyl chain composition, especially for
CC the acyl chain at the sn-2 position (By similarity). By controlling the
CC diacylglycerol/DAG-mediated activation of RASGRP3, negatively regulates
CC the Rap1 signaling pathway (PubMed:15894621). May play a role in
CC presynaptic diacylglycerol/DAG signaling and control neurotransmitter
CC release during metabotropic glutamate receptor-dependent long-term
CC depression (PubMed:21119615). {ECO:0000250|UniProtKB:O75912,
CC ECO:0000269|PubMed:15894621, ECO:0000269|PubMed:21119615}.
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:0000250|UniProtKB:O75912};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10273;
CC Evidence={ECO:0000250|UniProtKB:O75912};
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:O75912};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40328;
CC Evidence={ECO:0000250|UniProtKB:O75912};
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:O75912};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40324;
CC Evidence={ECO:0000250|UniProtKB:O75912};
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:0000250|UniProtKB:O75912}.
CC -!- SUBUNIT: Interacts (via PDZ-binding motif) with DLG4; controls the
CC localization of DGKI to the synapse (By similarity). 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 (PubMed:21119615). May interact with RASGRP3; involved
CC in the regulation of RASGRP3 activity (Probable).
CC {ECO:0000250|UniProtKB:F1MAB7, ECO:0000269|PubMed:21119615,
CC ECO:0000305|PubMed:15894621}.
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:0000250|UniProtKB:O75912}. Nucleus
CC {ECO:0000250|UniProtKB:O75912}. Note=Excluded from inhibitory synapses
CC (By similarity). Localization between cytoplasm and nucleus is
CC regulated by protein kinase C (By similarity). Both in the detergent
CC soluble and particulate fractions (By similarity).
CC {ECO:0000250|UniProtKB:F1MAB7, ECO:0000250|UniProtKB:O75912}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=D3YWQ0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=D3YWQ0-2; Sequence=VSP_060832;
CC -!- TISSUE SPECIFICITY: In brain, expressed in the hippocampus and
CC cerebellum with stronger expression in the Purkinje cell layer (at
CC protein level) (PubMed:21119615). Expressed in kidney
CC (PubMed:15894621). {ECO:0000269|PubMed:15894621,
CC ECO:0000269|PubMed:21119615}.
CC -!- DISRUPTION PHENOTYPE: Homozygous knockout mice lacking Dgki do not
CC display overt phenotype (PubMed:15894621). They are slower to
CC habituation to a novel environment, but have normal levels of locomotor
CC activity, anxiety, and motor coordination (PubMed:21119615). They
CC display a small increase in presynaptic release probability and
CC synapses show a reduction in metabotropic glutamate receptor-dependent
CC long-term depression (PubMed:21119615). {ECO:0000269|PubMed:15894621,
CC ECO:0000269|PubMed:21119615}.
CC -!- SIMILARITY: Belongs to the eukaryotic diacylglycerol kinase family.
CC {ECO:0000305}.
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DR EMBL; AC114574; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC154019; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC159480; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC184160; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC185507; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS39459.1; -. [D3YWQ0-1]
DR CCDS; CCDS85032.1; -. [D3YWQ0-2]
DR RefSeq; NP_001074675.1; NM_001081206.1. [D3YWQ0-1]
DR RefSeq; NP_001334033.1; NM_001347104.1. [D3YWQ0-2]
DR AlphaFoldDB; D3YWQ0; -.
DR SMR; D3YWQ0; -.
DR IntAct; D3YWQ0; 1.
DR STRING; 10090.ENSMUSP00000099071; -.
DR iPTMnet; D3YWQ0; -.
DR PhosphoSitePlus; D3YWQ0; -.
DR SwissPalm; D3YWQ0; -.
DR MaxQB; D3YWQ0; -.
DR PaxDb; D3YWQ0; -.
DR PeptideAtlas; D3YWQ0; -.
DR PRIDE; D3YWQ0; -.
DR ProteomicsDB; 350765; -.
DR ProteomicsDB; 361049; -. [D3YWQ0-1]
DR Antibodypedia; 32299; 192 antibodies from 29 providers.
DR DNASU; 320127; -.
DR Ensembl; ENSMUST00000090314; ENSMUSP00000087788; ENSMUSG00000038665. [D3YWQ0-2]
DR Ensembl; ENSMUST00000101532; ENSMUSP00000099071; ENSMUSG00000038665. [D3YWQ0-1]
DR GeneID; 320127; -.
DR KEGG; mmu:320127; -.
DR UCSC; uc009bjb.1; mouse. [D3YWQ0-1]
DR CTD; 9162; -.
DR MGI; MGI:2443430; Dgki.
DR VEuPathDB; HostDB:ENSMUSG00000038665; -.
DR eggNOG; KOG0782; Eukaryota.
DR GeneTree; ENSGT00940000158094; -.
DR InParanoid; D3YWQ0; -.
DR OMA; CFLDSCT; -.
DR OrthoDB; 274339at2759; -.
DR PhylomeDB; D3YWQ0; -.
DR TreeFam; TF312817; -.
DR Reactome; R-MMU-114508; Effects of PIP2 hydrolysis.
DR UniPathway; UPA00230; -.
DR BioGRID-ORCS; 320127; 5 hits in 77 CRISPR screens.
DR ChiTaRS; Dgki; mouse.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; D3YWQ0; protein.
DR Bgee; ENSMUSG00000038665; Expressed in lumbar dorsal root ganglion and 55 other tissues.
DR ExpressionAtlas; D3YWQ0; baseline and differential.
DR Genevisible; D3YWQ0; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0043679; C:axon terminus; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR GO; GO:0060076; C:excitatory synapse; ISO:MGI.
DR GO; GO:0099147; C:extrinsic component of postsynaptic density membrane; ISO:MGI.
DR GO; GO:0098891; C:extrinsic component of presynaptic active zone membrane; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IMP:SynGO.
DR GO; GO:0032045; C:guanyl-nucleotide exchange factor complex; IDA:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0048786; C:presynaptic active zone; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IMP:SynGO.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0097060; C:synaptic membrane; ISO:MGI.
DR GO; GO:0008021; C:synaptic vesicle; ISO:MGI.
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:MGI.
DR GO; GO:0005095; F:GTPase inhibitor activity; IDA: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:0031267; F:small GTPase binding; IPI:MGI.
DR GO; GO:0046339; P:diacylglycerol metabolic process; ISO:MGI.
DR GO; GO:0060079; P:excitatory postsynaptic potential; IMP:MGI.
DR GO; GO:0046959; P:habituation; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0046834; P:lipid phosphorylation; ISO:MGI.
DR GO; GO:0007269; P:neurotransmitter secretion; IMP:MGI.
DR GO; GO:0006654; P:phosphatidic acid biosynthetic process; ISO:MGI.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IMP:MGI.
DR GO; GO:0007205; P:protein kinase C-activating G protein-coupled receptor signaling pathway; IEA:InterPro.
DR GO; GO:0007265; P:Ras protein signal transduction; IMP:MGI.
DR GO; GO:0043087; P:regulation of GTPase activity; IMP:MGI.
DR GO; GO:1900452; P:regulation of long-term synaptic depression; IMP:MGI.
DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IMP:MGI.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IMP:SynGO.
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; 1.
DR PROSITE; PS50146; DAGK; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ANK repeat; ATP-binding; Cell membrane;
KW Cell projection; Cytoplasm; Cytoplasmic vesicle; Kinase; Lipid metabolism;
KW Membrane; Metal-binding; Nucleotide-binding; Nucleus; Reference proteome;
KW Repeat; Synapse; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..1071
FT /note="Diacylglycerol kinase iota"
FT /id="PRO_0000451698"
FT DOMAIN 367..502
FT /note="DAGKc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT REPEAT 964..993
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 1000..1029
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT ZN_FING 172..227
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 245..304
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 53..74
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 92..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 328..356
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1069..1071
FT /note="PDZ-binding"
FT /evidence="ECO:0000250|UniProtKB:F1MAB7"
FT COMPBIAS 57..74
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 328..344
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 712..732
FT /note="Missing (in isoform 2)"
FT /id="VSP_060832"
SQ SEQUENCE 1071 AA; 118209 MW; 407FD700231F89ED CRC64;
MDAAGRGCHL LPLPAARGPA RAPAASSALS PTGLCSGTTS ASFAAAGAVA MNPSSSAGEE
RGATGGSSSS GSGAGSCCLG AEGGADPRGA GAAAAAALEE PAAAGQKEKE EALEEKLRDL
TFRKQVSYRK AISRTGLQHL APAHPLGLPV ANGPAKEPRA TLDWSENAVN GEHLWLETNV
SGDLCYLGEE NCQVRFAKSA LRRKCAVCKI VVHTACIEQL EKINFRCKPT FREGGSRSPR
ENFVRHHWVH RRRQEGKCKQ CGKGFQQKFS FHSKEIVAIS CSWCKQAFHN KVTCFMLHHI
EEPCSLGAHA AVIVPPTWII KVKKPQNSLK ASNRKKKRTS FKRKASKRGT EQETKGRPFV
IKPISSPLMK PLLVFVNPKS GGNQGTKVLQ MFMWYLNPRQ VFDLSQEGPK DALEMYRKVP
NLRILACGGD GTVGWILSIL DELQLSPQPP VGVLPLGTGN DLARTLNWGG GYTDEPVSKI
LCQVEDGTIV QLDRWNLHVE RNPDLPPEEL EDGVCKLPLN VFNNYFSLGF DAHVTLEFHE
SREANPEKFN SRFRNKMFYA GAAFSDFLQR SSRDLSKHVK VVCDGTDLTP KIQDLKFQCI
VFLNIPRYCA GTMPWGNPGD HHDFEPQRHD DGYIEVIGFT MASLAALQVG GHGERLHQCR
EVMLLTYKSI PMQVDGEPCR LAPAMIRISL RNQANMVQKS KRRTSMPLLN DIHQVQAADL
RRVSAPPGSF TIPQSVPDRL RIRVNKISLQ DYEGLHYDKD KLREASIPLG ILVVRGDCDL
ETCRMYIDRL QEDLQSVSSG SQRVHYQDQE TSFPRALSAQ RLSPRWCFLD ATSADRFYRI
DRSQEHLHFV MEISHDEIFI LDPDMVVSQQ AGTPPGMPDL VVEQASGLSD WWNPALRKRM
LSDSGMITPH YEDSDLKDFS HSRVLQSPVS SEDHAILQAV LTGDLMKLME SYKNGGSLLI
QGPGHCSLLH YAAKTGNGDI VKYILDHGPA ELLDMADSET GETALHKAAC QRNRAVCQLL
VDAGASLRQT DSKGKTPQER AQQAGDPDLA AYLESRQNYK IIGHEDLETA V
