DGKD_MOUSE
ID DGKD_MOUSE Reviewed; 1220 AA.
AC E9PUQ8;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=Diacylglycerol kinase delta {ECO:0000305};
DE Short=DAG kinase delta;
DE EC=2.7.1.107 {ECO:0000269|PubMed:17021016};
GN Name=Dgkd {ECO:0000312|MGI:MGI:2138334};
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 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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RX PubMed=17021016; DOI=10.1073/pnas.0604104103;
RA Crotty T., Cai J., Sakane F., Taketomi A., Prescott S.M., Topham M.K.;
RT "Diacylglycerol kinase delta regulates protein kinase C and epidermal
RT growth factor receptor signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:15485-15490(2006).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
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:17021016). Thereby, acts as a
CC central switch between the signaling pathways activated by these second
CC messengers with different cellular targets and opposite effects in
CC numerous biological processes (PubMed:17021016). By controlling the
CC levels of diacylglycerol, regulates for instance the PKC and EGF
CC receptor signaling pathways and plays a crucial role during development
CC (PubMed:17021016). May also regulate clathrin-dependent endocytosis (By
CC similarity). {ECO:0000250|UniProtKB:Q16760,
CC ECO:0000269|PubMed:17021016}.
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:17021016};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10273;
CC Evidence={ECO:0000269|PubMed:17021016};
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:Q16760};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40328;
CC Evidence={ECO:0000250|UniProtKB:Q16760};
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:Q16760};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40324;
CC Evidence={ECO:0000250|UniProtKB:Q16760};
CC -!- PATHWAY: Lipid metabolism; glycerolipid metabolism.
CC {ECO:0000269|PubMed:17021016}.
CC -!- SUBUNIT: Homooligomer. Monomer. Interacts with AP2A2; regulates
CC clathrin-dependent endocytosis. {ECO:0000250|UniProtKB:Q16760}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q16760};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q16760}. Membrane,
CC clathrin-coated pit {ECO:0000250|UniProtKB:Q16760}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q16760}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:17021016}.
CC -!- DOMAIN: The SAM domain mediates homooligomerization.
CC {ECO:0000250|UniProtKB:Q16760}.
CC -!- DOMAIN: The PH domain mediates association with membranes.
CC {ECO:0000250|UniProtKB:Q16760}.
CC -!- DISRUPTION PHENOTYPE: Homozygous knockout of dgkd is lethal
CC (PubMed:17021016). Fetuses are smaller and newborn mice develop
CC respiratory difficulty and die within 24 hours after birth
CC (PubMed:17021016). They show an abnormal open-eyelids phenotype which
CC is associated with significant reduction of the expression of the EGF
CC receptor/EGFR in the basal layer of the epidermis (PubMed:17021016).
CC {ECO:0000269|PubMed:17021016}.
CC -!- SIMILARITY: Belongs to the eukaryotic diacylglycerol kinase family.
CC {ECO:0000305}.
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DR EMBL; AC102630; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC162281; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS48312.1; -.
DR RefSeq; NP_808314.2; NM_177646.3.
DR AlphaFoldDB; E9PUQ8; -.
DR SMR; E9PUQ8; -.
DR STRING; 10090.ENSMUSP00000027517; -.
DR iPTMnet; E9PUQ8; -.
DR PhosphoSitePlus; E9PUQ8; -.
DR EPD; E9PUQ8; -.
DR MaxQB; E9PUQ8; -.
DR PaxDb; E9PUQ8; -.
DR PeptideAtlas; E9PUQ8; -.
DR PRIDE; E9PUQ8; -.
DR ProteomicsDB; 320440; -.
DR Antibodypedia; 34452; 172 antibodies from 28 providers.
DR Ensembl; ENSMUST00000027517; ENSMUSP00000027517; ENSMUSG00000070738.
DR GeneID; 227333; -.
DR KEGG; mmu:227333; -.
DR UCSC; uc011wos.1; mouse.
DR CTD; 8527; -.
DR MGI; MGI:2138334; Dgkd.
DR VEuPathDB; HostDB:ENSMUSG00000070738; -.
DR eggNOG; KOG1170; Eukaryota.
DR GeneTree; ENSGT00940000159041; -.
DR HOGENOM; CLU_001799_3_0_1; -.
DR InParanoid; E9PUQ8; -.
DR OMA; SKAPCEK; -.
DR OrthoDB; 43384at2759; -.
DR PhylomeDB; E9PUQ8; -.
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; 227333; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Dgkq; mouse.
DR PRO; PR:E9PUQ8; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; E9PUQ8; protein.
DR Bgee; ENSMUSG00000070738; Expressed in spermatocyte and 230 other tissues.
DR ExpressionAtlas; E9PUQ8; baseline and differential.
DR Genevisible; E9PUQ8; MM.
DR GO; GO:0005905; C:clathrin-coated pit; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004143; F:diacylglycerol kinase activity; IMP:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0019900; F:kinase binding; 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:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0046339; P:diacylglycerol metabolic process; IMP:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0046834; P:lipid phosphorylation; IMP:UniProtKB.
DR GO; GO:0090038; P:negative regulation of protein kinase C signaling; IMP:UniProtKB.
DR GO; GO:0006654; P:phosphatidic acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:2000370; P:positive regulation of clathrin-dependent endocytosis; ISS:UniProtKB.
DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0007205; P:protein kinase C-activating G protein-coupled receptor signaling pathway; IEA:InterPro.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0010033; P:response to organic substance; ISO:MGI.
DR CDD; cd00029; C1; 2.
DR CDD; cd09575; SAM_DGK-delta; 1.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
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; IPR037606; DGK-delta_SAM.
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 InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR PANTHER; PTHR11255; PTHR11255; 1.
DR Pfam; PF00130; C1_1; 2.
DR Pfam; PF00609; DAGK_acc; 1.
DR Pfam; PF00781; DAGK_cat; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF07647; SAM_2; 1.
DR SMART; SM00109; C1; 2.
DR SMART; SM00045; DAGKa; 1.
DR SMART; SM00046; DAGKc; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF111331; SSF111331; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF57889; SSF57889; 2.
DR PROSITE; PS50146; DAGK; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 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; Cell membrane; Coated pit; Coiled coil; Cytoplasm;
KW Endocytosis; Kinase; Lipid metabolism; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Protein transport; Reference proteome;
KW Repeat; Transferase; Transport; Zinc; Zinc-finger.
FT CHAIN 1..1220
FT /note="Diacylglycerol kinase delta"
FT /id="PRO_0000450663"
FT DOMAIN 53..146
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 317..451
FT /note="DAGKc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT DOMAIN 1151..1214
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT ZN_FING 163..213
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 235..286
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 1..52
FT /note="Regulates association with membranes"
FT /evidence="ECO:0000250|UniProtKB:Q16760"
FT REGION 1..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 554..584
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..24
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 554..568
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1220 AA; 135208 MW; 1635F45B96741B7E CRC64;
MAAAAGAPPP GPPQPPPPPP PEESSDSEPE AEPGSPQKLI RKVSTSGQIR QKTILKEGML
TKQNNSFQRS KRRYFKLRGR TLYYAKTAKS IIFDEVDLTD ASVAESSTKN VNNSFTVITP
CRKLILCADN RKEMEDWIAA LKTVQNKEHF EPTQYSMDHF SGMHNWYACS HARPTYCNVC
REVLSGVTSH GLSCEVCKFK AHKRCAVRAT SNCKWTTLAS IGKDIIEDED GIAMPHQWLE
GNLPVSAKCI VCDKTCGSVL RLQDWRCLWC KAMVHTSCKE SLVMKCPLGL CKVSVIPPTA
LNSIDSDGFW KATCPPSCTS PLLVFVNSKS GDNQGVKFLR RFKQLLNPAQ VFDLMNGGPH
LGLRLFQKFD TFRILVCGGD GSVGWVLSEI DSLNLHKQCQ LGVLPLGTGN DLARVLGWGS
ACDDDTQLPQ ILAKLERAST KMLDRWSVMA YETKLPRQAS SSTVTEDFSE DSEVQQILFY
EDSVAAHLSK ILTSDQHSVV ISSAKVLCET VKDFVARVGK AYEKTTESSQ ESEVMAKKCS
VLKEKLDSLL KTLDDESQAS SSLSNPPPTI AEEAEDGDGS GNICSSTGDH LVGSACPSRP
QIFRPREQLM LRANSLKKAI RQIIEHTEKA VDEQNAQTQE QQGFVLGLSE SEKKDLKTDN
RVCTSSVHSE SCVIAKGRSQ RKASRAPCEK LVSKGLSLGS SASLPPGTGS RDSLPALNTK
ILYPSVRAGM SGSLPGGSVI SRLLINADPF NAEPENLEYY TEKCVMNNYF GIGLDAKISL
DFNNKRDEHP EKCRSRTKNM MWYGVLGTKE LLHRTYRNLE QKVLLECDGR PIPLPSLQGI
AVLNIPSYAG GTNFWGGTKE DDTFAAPSFD DKILEVVAVF GSMQMAVSRV IKLQHHRIAQ
CRTVKISILG DEGVPVQVDG EAWIQPPGYI RIVHKNRAQT LTRDRAFENT LKSWEDKQKC
ELSRPPSFSL HPEILSEEEA TQMDQFGQAA GGLIHSIREI AQSHRAMEQE LAHAVNASSK
AMERVYGKPR TAEGLNCSFV LEMVNNIRAL RSETELLLAG KMALQLDPPQ KERLGAALIE
MDQQLRKLTD TPWLCQPLEP GEEESLQQNV MLDLTKRSRS GKFRLVTKFK KEKNNKNKEV
HSNLGGPVHL WGTEEVAAWL EHLSLCEYKD IFTRHDIRGS ELLHLERRDL KDLGVTKVGH
MKRILCGIKE LSRSSPAAEA
