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   27-MAR-2024, entry version 146.
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; 3.
DR   IntAct; Q5KSL6; 2.
DR   STRING; 9606.ENSP00000477515; -.
DR   DrugBank; DB14001; alpha-Tocopherol succinate.
DR   SwissLipids; SLP:000000926; -.
DR   GlyGen; Q5KSL6; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q5KSL6; -.
DR   PhosphoSitePlus; Q5KSL6; -.
DR   BioMuta; DGKK; -.
DR   DMDM; 74708075; -.
DR   EPD; Q5KSL6; -.
DR   MassIVE; Q5KSL6; -.
DR   MaxQB; Q5KSL6; -.
DR   PaxDb; 9606-ENSP00000477515; -.
DR   PeptideAtlas; Q5KSL6; -.
DR   ProteomicsDB; 63549; -.
DR   Antibodypedia; 72568; 152 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   AGR; HGNC:32395; -.
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; 4642163at2759; -.
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; 10 hits in 272 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 male germ line stem cell (sensu Vertebrata) in testis and 33 other cell types or tissues.
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:ATP-dependent diacylglycerol kinase activity; IDA:HGNC-UCL.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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; cd20800; C1_DGK_typeII_rpt1; 1.
DR   CDD; cd20852; C1_DGK_typeII_rpt2; 1.
DR   CDD; cd13274; PH_DGK_type2; 1.
DR   Gene3D; 2.60.200.40; -; 1.
DR   Gene3D; 3.30.60.20; -; 2.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 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; DIACYLGLYCEROL KINASE; 1.
DR   PANTHER; PTHR11255:SF33; DIACYLGLYCEROL KINASE KAPPA; 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; SSF57889; Cysteine-rich domain; 2.
DR   SUPFAM; SSF111331; NAD kinase/diacylglycerol kinase-like; 1.
DR   SUPFAM; SSF50729; PH domain-like; 1.
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.
DR   Genevisible; Q5KSL6; HS.
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
//