DGKK_HUMAN
ID DGKK_HUMAN Reviewed; 1271 AA.
AC Q5KSL6; B2RP91;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Diacylglycerol kinase kappa {ECO:0000305|PubMed:16210324};
DE Short=DAG kinase kappa {ECO:0000305};
DE Short=DGK-kappa {ECO:0000303|PubMed:16210324};
DE EC=2.7.1.107 {ECO:0000269|PubMed:16210324, ECO:0000269|PubMed:23949095};
DE AltName: Full=142 kDa diacylglycerol kinase {ECO:0000303|PubMed:16210324};
DE AltName: Full=Diglyceride kinase kappa;
GN Name=DGKK {ECO:0000312|HGNC:HGNC:32395};
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, ACTIVITY
RP REGULATION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP PHOSPHORYLATION AT TYR-78, MUTAGENESIS OF TYR-78 AND TYR-1075, AND REGION.
RX PubMed=16210324; DOI=10.1074/jbc.m500669200;
RA Imai S., Kai M., Yasuda S., Kanoh H., Sakane F.;
RT "Identification and characterization of a novel human type II
RT diacylglycerol kinase, DGK kappa.";
RL J. Biol. Chem. 280:39870-39881(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP 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:16210324, 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).
CC {ECO:0000269|PubMed:16210324, ECO:0000269|PubMed:23949095,
CC 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:16210324, ECO:0000269|PubMed:23949095};
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:16210324, ECO:0000269|PubMed:23949095};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40328;
CC Evidence={ECO:0000305|PubMed:23949095};
CC -!- ACTIVITY REGULATION: Inhibited in response to H(2)O(2).
CC {ECO:0000269|PubMed:16210324}.
CC -!- PATHWAY: Lipid metabolism; glycerolipid metabolism.
CC {ECO:0000305|PubMed:16210324}.
CC -!- SUBUNIT: Does not form homooligomers. {ECO:0000269|PubMed:16210324}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16210324};
CC Peripheral membrane protein {ECO:0000269|PubMed:16210324}.
CC -!- TISSUE SPECIFICITY: Expressed in testis, and to a lesser extent in
CC placenta. {ECO:0000269|PubMed:16210324}.
CC -!- PTM: Phosphorylated at Tyr-78 by some member of the SRC family in
CC response to H(2)O(2). {ECO:0000269|PubMed:16210324}.
CC -!- SIMILARITY: Belongs to the eukaryotic diacylglycerol kinase family.
CC {ECO:0000305}.
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DR EMBL; AB183864; BAD86792.1; -; mRNA.
DR EMBL; BC137319; AAI37320.1; -; mRNA.
DR EMBL; BC137320; AAI37321.1; -; mRNA.
DR CCDS; CCDS75980.1; -.
DR RefSeq; NP_001013764.1; NM_001013742.3.
DR AlphaFoldDB; Q5KSL6; -.
DR SMR; Q5KSL6; -.
DR BioGRID; 126548; 2.
DR IntAct; Q5KSL6; 2.
DR STRING; 9606.ENSP00000477515; -.
DR DrugBank; DB14001; alpha-Tocopherol succinate.
DR SwissLipids; SLP:000000926; -.
DR iPTMnet; Q5KSL6; -.
DR PhosphoSitePlus; Q5KSL6; -.
DR BioMuta; DGKK; -.
DR DMDM; 74708075; -.
DR EPD; Q5KSL6; -.
DR MassIVE; Q5KSL6; -.
DR MaxQB; Q5KSL6; -.
DR PeptideAtlas; Q5KSL6; -.
DR PRIDE; Q5KSL6; -.
DR ProteomicsDB; 63549; -.
DR Antibodypedia; 72568; 134 antibodies from 22 providers.
DR DNASU; 139189; -.
DR Ensembl; ENST00000611977.2; ENSP00000477515.1; ENSG00000274588.2.
DR GeneID; 139189; -.
DR KEGG; hsa:139189; -.
DR MANE-Select; ENST00000611977.2; ENSP00000477515.1; NM_001013742.4; NP_001013764.1.
DR UCSC; uc033edr.2; human.
DR CTD; 139189; -.
DR DisGeNET; 139189; -.
DR GeneCards; DGKK; -.
DR HGNC; HGNC:32395; DGKK.
DR HPA; ENSG00000274588; Group enriched (adrenal gland, brain, pituitary gland).
DR MIM; 300837; gene.
DR neXtProt; NX_Q5KSL6; -.
DR OpenTargets; ENSG00000274588; -.
DR PharmGKB; PA142671978; -.
DR VEuPathDB; HostDB:ENSG00000274588; -.
DR eggNOG; KOG1170; Eukaryota.
DR GeneTree; ENSGT00940000162262; -.
DR HOGENOM; CLU_001799_3_3_1; -.
DR InParanoid; Q5KSL6; -.
DR OMA; ECKHTEI; -.
DR OrthoDB; 43384at2759; -.
DR PhylomeDB; Q5KSL6; -.
DR BRENDA; 2.7.1.107; 2681.
DR PathwayCommons; Q5KSL6; -.
DR Reactome; R-HSA-114508; Effects of PIP2 hydrolysis.
DR SignaLink; Q5KSL6; -.
DR UniPathway; UPA00230; -.
DR BioGRID-ORCS; 139189; 8 hits in 207 CRISPR screens.
DR ChiTaRS; DGKK; human.
DR GenomeRNAi; 139189; -.
DR Pharos; Q5KSL6; Tbio.
DR PRO; PR:Q5KSL6; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q5KSL6; protein.
DR Bgee; ENSG00000274588; Expressed in ventricular zone and 33 other tissues.
DR Genevisible; Q5KSL6; HS.
DR GO; GO:0005886; C:plasma membrane; IDA:HGNC-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004143; F:diacylglycerol kinase activity; IDA:HGNC-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; IDA:HGNC-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:HGNC-UCL.
DR GO; GO:0046834; P:lipid phosphorylation; IBA:GO_Central.
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:0006979; P:response to oxidative stress; IDA:HGNC-UCL.
DR CDD; cd00029; C1; 2.
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; 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 PANTHER; PTHR11255; PTHR11255; 1.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF00609; DAGK_acc; 1.
DR Pfam; PF00781; DAGK_cat; 1.
DR Pfam; PF00169; PH; 1.
DR SMART; SM00109; C1; 2.
DR SMART; SM00045; DAGKa; 1.
DR SMART; SM00046; DAGKc; 1.
DR SMART; SM00233; PH; 1.
DR SUPFAM; SSF111331; SSF111331; 1.
DR SUPFAM; SSF57889; SSF57889; 2.
DR PROSITE; PS50146; DAGK; 1.
DR PROSITE; PS50003; PH_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; Kinase; Lipid metabolism; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Repeat; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..1271
FT /note="Diacylglycerol kinase kappa"
FT /id="PRO_0000239368"
FT REPEAT 48..51
FT /note="1"
FT REPEAT 52..55
FT /note="2"
FT REPEAT 56..59
FT /note="3"
FT REPEAT 60..63
FT /note="4"
FT REPEAT 64..67
FT /note="5"
FT REPEAT 68..71
FT /note="6"
FT REPEAT 72..75
FT /note="7"
FT REPEAT 76..79
FT /note="8"
FT REPEAT 80..83
FT /note="9"
FT REPEAT 84..87
FT /note="10"
FT REPEAT 88..91
FT /note="11"
FT REPEAT 92..95
FT /note="12"
FT REPEAT 96..99
FT /note="13"
FT REPEAT 100..103
FT /note="14"
FT REPEAT 104..107
FT /note="15"
FT REPEAT 108..111
FT /note="16"
FT REPEAT 112..115
FT /note="17"
FT REPEAT 116..119
FT /note="18"
FT REPEAT 120..123
FT /note="19"
FT REPEAT 124..127
FT /note="20"
FT REPEAT 128..131
FT /note="21"
FT REPEAT 132..135
FT /note="22"
FT REPEAT 136..139
FT /note="23"
FT REPEAT 140..143
FT /note="24"
FT REPEAT 144..147
FT /note="25"
FT REPEAT 148..151
FT /note="26"
FT REPEAT 152..155
FT /note="27"
FT REPEAT 156..159
FT /note="28"
FT REPEAT 160..163
FT /note="29"
FT REPEAT 164..167
FT /note="30"
FT REPEAT 168..171
FT /note="31"
FT REPEAT 172..175
FT /note="32"
FT REPEAT 176..179
FT /note="33"
FT DOMAIN 216..309
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 487..622
FT /note="DAGKc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT ZN_FING 327..377
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 398..449
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 1..160
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 48..179
FT /note="33 X 4 AA approximate tandem repeats of E-P-A-P"
FT REGION 190..209
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 805..825
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1199..1268
FT /note="Required for localization to the plasma membrane"
FT /evidence="ECO:0000269|PubMed:16210324"
FT REGION 1252..1271
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 19..64
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 86..160
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 78
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:16210324"
FT VARIANT 1118
FT /note="D -> N (in dbSNP:rs4074320)"
FT /id="VAR_048859"
FT MUTAGEN 78
FT /note="Y->F: Induces a strong reduction in phosphorylation
FT but is still sensitive to H(2)O(2)."
FT /evidence="ECO:0000269|PubMed:16210324"
FT MUTAGEN 1075
FT /note="Y->F: Does not affect phosphorylation."
FT /evidence="ECO:0000269|PubMed:16210324"
SQ SEQUENCE 1271 AA; 141829 MW; 1EB8BD12B1992DDB CRC64;
MDRGAAAAQG TAPPQDGEQP AESPEPPPPW PPPPPPPAPP PAPPLLSEAS PEPIPEPCPE
LAPGPCPEAT SESATELYTE PTPEPATEPA SEPAPEPATE PAPEPATEPA PEPAPEPATE
SAPEPTPEPA LESVPEPAPE LTPEVAPELA PEPTPEPVTE LAPEFCPEAA PEFRPSPAPC
LLQCPVDTRE RGLKTSPSPS PSPSPRTPMS WSRIKKILKE GPMLKNCNSF KRWKLRYFLV
QGQKLYFAHH PAFAHFETID LSQATVAESS CRNLCHSFCV ITPQRKITLA APNRKDMEEW
INIIKTIQQG EIYKIPAAEN NPFLVGMHCW YSSYSHRTQH CNVCRESIPA LSRDAIICEV
CKVKSHRLCA LRASKDCKWN TLSITDDLLL PADEVNMPHQ WVEGNMPVSS QCAVCHESCG
SYQRLQDFRC LWCNSTVHDD CRRRFSKECC FRSHRSSVIP PTALSDPKGD GQLVVSSDFW
NLDWSSACSC PLLIFINSKS GDHQGIVFLR KFKQYLNPSQ VFDLLKGGPE AGLSMFKNFA
RFRILVCGGD GSVSWVLSLI DAFGLHEKCQ LAVIPLGTGN DLARVLGWGA FWNKSKSPLD
ILNRVEQASV RILDRWSVMI RETPRQTPLL KGQVEMDVPR FEAAAIQHLE SAATELNKIL
KAKYPTEMII ATRFLCSAVE DFVVDIVKAW GQIKQNNTAI VSVILKSDLM YDRLSVLIDV
LAEEAAATSA EKSATEYADS SKADRKPFIP QIDHIAKCKL ELATKAQSLQ KSLKLIIFQV
EQALDEESRQ TISVKNFSST FFLEDDPEDI NQTSPRRRSR RGTLSSISSL KSEDLDNLNL
DHLHFTPESI RFKEKCVMNN YFGIGLDAKI SLDFNTRRDE HPGQYNSRLK NKMWYGLLGT
KELLQRSYRK LEERVHLECD GETISLPNLQ GIVVLNITSY AGGINFWGSN TATTEYEAPA
IDDGKLEVVA IFGSVQMAMS RIINLHHHRI AQCHEVMITI DGEEGIPVQV DGEAWIQRPG
LIKIRYKNAA QMLTRDRDFE NSMKMWEYKH TEIQAAPQPQ LDFQDSQESL SDEEYAQMQH
LARLAENLIS KLNDLSKIHQ HVSVLMGSVN ASANILNDIF YGQDSGNEMG AASCIPIETL
SRNDAVDVTF SLKGLYDDTT AFLDEKLLRS AEDETALQSA LDAMNKEFKK LSEIDWMNPI
FVPEEKSSDT DSRSLRLKIK FPKLGKKKVE EERKPKSGQS VQSFIGNLWH RRHREDEAEG
DDPLTPSRSQ L
