DGK1_YEAST
ID DGK1_YEAST Reviewed; 290 AA.
AC Q12382; D6W310;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=CTP-dependent diacylglycerol kinase 1;
DE EC=2.7.1.174;
DE AltName: Full=Diglyceride kinase 1;
DE Short=DAG kinase 1;
DE AltName: Full=High-copy suppressor of SLY1 defect protein 1 {ECO:0000303|PubMed:11481671};
GN Name=DGK1; Synonyms=HSD1 {ECO:0000303|PubMed:11481671};
GN OrderedLocusNames=YOR311C; ORFNames=O6111;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 96604 / S288c / FY1679;
RX PubMed=8896266;
RX DOI=10.1002/(sici)1097-0061(199609)12:10b<1021::aid-yea981>3.0.co;2-7;
RA Pearson B.M., Hernando Y., Payne J., Wolf S.S., Kalogeropoulos A.,
RA Schweizer M.;
RT "Sequencing of a 35.71 kb DNA segment on the right arm of yeast chromosome
RT XV reveals regions of similarity to chromosomes I and XIII.";
RL Yeast 12:1021-1031(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169874;
RA Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL Nature 387:98-102(1997).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP FUNCTION.
RX PubMed=10407277;
RX DOI=10.1002/(sici)1097-0061(199907)15:10b<973::aid-yea402>3.0.co;2-l;
RA Rieger K.-J., El-Alama M., Stein G., Bradshaw C., Slonimski P.P.,
RA Maundrell K.;
RT "Chemotyping of yeast mutants using robotics.";
RL Yeast 15:973-986(1999).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11481671; DOI=10.1002/yea.747.abs;
RA Kosodo Y., Imai K., Hirata A., Noda Y., Takatsuki A., Adachi H., Yoda K.;
RT "Multicopy suppressors of the sly1 temperature-sensitive mutation in the
RT ER-Golgi vesicular transport in Saccharomyces cerevisiae.";
RL Yeast 18:1003-1014(2001).
RN [6]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [7]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [8]
RP TOPOLOGY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 208353 / W303-1A;
RX PubMed=16847258; DOI=10.1073/pnas.0604075103;
RA Kim H., Melen K., Oesterberg M., von Heijne G.;
RT "A global topology map of the Saccharomyces cerevisiae membrane proteome.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TRANSMEMBRANE DOMAINS,
RP OVEREXPRESSION PHENOTYPE, KNOCKOUT, AND MUTAGENESIS OF ASP-177.
RX PubMed=18458075; DOI=10.1074/jbc.m802903200;
RA Han G.-S., O'Hara L., Carman G.M., Siniossoglou S.;
RT "An unconventional diacylglycerol kinase that regulates phospholipid
RT synthesis and nuclear membrane growth.";
RL J. Biol. Chem. 283:20433-20442(2008).
RN [11]
RP SYNTHESIS OF 133-145 AND 188-201, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF
RP 1-MET--GLY-66; 1-MET--THR-70; 1-MET--LYS-77; ARG-76; LYS-77; ASP-177 AND
RP GLY-184.
RX PubMed=18458076; DOI=10.1074/jbc.m802866200;
RA Han G.-S., O'Hara L., Siniossoglou S., Carman G.M.;
RT "Characterization of the yeast DGK1-encoded CTP-dependent diacylglycerol
RT kinase.";
RL J. Biol. Chem. 283:20443-20453(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44; SER-45 AND SER-46, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [13]
RP FUNCTION.
RX PubMed=21071438; DOI=10.1074/jbc.m110.194308;
RA Fakas S., Konstantinou C., Carman G.M.;
RT "DGK1-encoded diacylglycerol kinase activity is required for phospholipid
RT synthesis during growth resumption from stationary phase in Saccharomyces
RT cerevisiae.";
RL J. Biol. Chem. 286:1464-1474(2011).
RN [14]
RP FUNCTION, PHOSPHORYLATION AT SER-45 AND SER-46, AND MUTAGENESIS OF
RP 45-SER-SER-46 AND SER-46.
RX PubMed=27834677; DOI=10.1074/jbc.m116.763839;
RA Qiu Y., Hassaninasab A., Han G.S., Carman G.M.;
RT "Phosphorylation of Dgk1 diacylglycerol kinase by casein kinase II
RT regulates phosphatidic acid production in Saccharomyces cerevisiae.";
RL J. Biol. Chem. 291:26455-26467(2016).
CC -!- FUNCTION: CTP-dependent diacylglycerol kinase that catalyzes the
CC phosphorylation of diacylglycerol (DAG) to phosphatidate (PA). Controls
CC phosphatidate levels at the nuclear envelope. Counteracts the activity
CC of PA phosphatase PAH1/SMP2, controlling the levels of PA and DAG for
CC the synthesis of triacylglycerol and membrane phospholipids
CC (PubMed:18458075, PubMed:27834677). May be involved in vesicle
CC trafficking between the endoplasmic reticulum and the Golgi apparatus
CC (PubMed:11481671). Required to convert triacylglycerol-derived DAG to
CC PA for phospholipid synthesis during growth resumption from stationary
CC phase in the absence of de novo fatty acid synthesis (PubMed:21071438).
CC Involved in the resistance to nickel chloride and nalidixic acid
CC (PubMed:10407277). {ECO:0000269|PubMed:10407277,
CC ECO:0000269|PubMed:11481671, ECO:0000269|PubMed:18458075,
CC ECO:0000269|PubMed:21071438, ECO:0000269|PubMed:27834677}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycerol + CTP = a 1,2-diacyl-sn-glycero-3-
CC phosphate + CDP + H(+); Xref=Rhea:RHEA:25948, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17815, ChEBI:CHEBI:37563, ChEBI:CHEBI:58069,
CC ChEBI:CHEBI:58608; EC=2.7.1.174;
CC Evidence={ECO:0000269|PubMed:18458075, ECO:0000269|PubMed:18458076};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycerol + CTP = 1,2-di-(9Z-
CC octadecenoyl)-sn-glycero-3-phosphate + CDP + H(+);
CC Xref=Rhea:RHEA:43656, ChEBI:CHEBI:15378, ChEBI:CHEBI:37563,
CC ChEBI:CHEBI:52333, ChEBI:CHEBI:58069, ChEBI:CHEBI:74546;
CC Evidence={ECO:0000269|PubMed:18458076};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43657;
CC Evidence={ECO:0000305|PubMed:18458076};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:18458076};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:18458076};
CC -!- ACTIVITY REGULATION: Inhibited by N-ethylmaleimide, dCTP, and sphingoid
CC bases including sphinganine, sphingosine and phytosphingosine. DAG
CC pyrophosphate, cardiolipin, CDP-DAG, and lyso-PA inhibited activity by
CC 23-66%. Also inhibited by Ca(2+) concentrations of more than 1 mM, by
CC addition of EDTA or EGTA at 5 mM, and by 5 mM Mn(2+) and Zn(2+).
CC Stimulated by major membrane phospholipids including
CC phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol,
CC phosphatidylserine, phosphatidylglycerol, and phosphatidate. Also
CC stimulated to a maximum by addition of TritonX-100 at a concentration
CC of 1 mM, followed by an apparent inhibition of activity at
CC concentrations above 1 mM. {ECO:0000269|PubMed:18458076}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.3 mM for CTP {ECO:0000269|PubMed:18458076};
CC KM=0.4 mM for dCTP {ECO:0000269|PubMed:18458076};
CC Vmax=0.018 nM/min/mg enzyme {ECO:0000269|PubMed:18458076};
CC pH dependence:
CC Optimum pH is 7.0-7.5. {ECO:0000269|PubMed:18458076};
CC Temperature dependence:
CC Maximum activity at 30 degrees Celsius. Labile above 40 degrees
CC Celsius. {ECO:0000269|PubMed:18458076};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:11481671, ECO:0000269|PubMed:14562095,
CC ECO:0000269|PubMed:18458075}; Multi-pass membrane protein
CC {ECO:0000305|PubMed:11481671, ECO:0000305|PubMed:18458075}. Nucleus
CC membrane {ECO:0000269|PubMed:18458075}; Multi-pass membrane protein
CC {ECO:0000305|PubMed:18458075}.
CC -!- PTM: CKII-mediated phosphorylation of Ser-45 and Ser-46 regulates its
CC function in the production of PA. {ECO:0000269|PubMed:27834677}.
CC -!- MISCELLANEOUS: Present with 784 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- MISCELLANEOUS: Rescues the lethality of dephosphorylated PAH1/SMP2.
CC Overexpression causes the appearance of phosphatidate-enriched
CC membranes around the nucleus, leading to expansion of the nuclear
CC membrane without proliferation of the cortical endoplasmic reticulum
CC membrane. Deletion restores normal nuclear structure in PAH1/SMP2
CC deleted cells and returns the level of INO1 mRNA to normal. Deletion
CC does not affect the abnormal levels of phosphatidylinositol and major
CC neutral lipid triacylglycerol seen in the PAH1/SMP2 deletion mutant.
CC {ECO:0000305|PubMed:18458075}.
CC -!- SIMILARITY: Belongs to the DGK1 family. {ECO:0000305}.
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DR EMBL; X90565; CAA62166.1; -; Genomic_DNA.
DR EMBL; Z75219; CAA99631.1; -; Genomic_DNA.
DR EMBL; BK006948; DAA11076.1; -; Genomic_DNA.
DR PIR; S58323; S58323.
DR RefSeq; NP_014956.3; NM_001183731.3.
DR AlphaFoldDB; Q12382; -.
DR BioGRID; 34699; 473.
DR DIP; DIP-5021N; -.
DR IntAct; Q12382; 1.
DR STRING; 4932.YOR311C; -.
DR SwissLipids; SLP:000000046; -.
DR iPTMnet; Q12382; -.
DR MaxQB; Q12382; -.
DR PaxDb; Q12382; -.
DR PRIDE; Q12382; -.
DR EnsemblFungi; YOR311C_mRNA; YOR311C; YOR311C.
DR GeneID; 854488; -.
DR KEGG; sce:YOR311C; -.
DR SGD; S000005838; DGK1.
DR VEuPathDB; FungiDB:YOR311C; -.
DR eggNOG; KOG4453; Eukaryota.
DR HOGENOM; CLU_031477_0_1_1; -.
DR InParanoid; Q12382; -.
DR OMA; LPVTEIH; -.
DR BioCyc; MetaCyc:G3O-33794-MON; -.
DR BioCyc; YEAST:G3O-33794-MON; -.
DR BRENDA; 2.7.1.174; 984.
DR SABIO-RK; Q12382; -.
DR PRO; PR:Q12382; -.
DR Proteomes; UP000002311; Chromosome XV.
DR RNAct; Q12382; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:SGD.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:SGD.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004143; F:diacylglycerol kinase activity; IDA:SGD.
DR GO; GO:0006654; P:phosphatidic acid biosynthetic process; IDA:SGD.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:2001210; P:regulation of isopentenyl diphosphate biosynthetic process, mevalonate pathway; IMP:SGD.
DR GO; GO:0016192; P:vesicle-mediated transport; IEA:UniProtKB-KW.
DR InterPro; IPR037997; Dgk1-like.
DR PANTHER; PTHR31303; PTHR31303; 1.
PE 1: Evidence at protein level;
KW Calcium; Endoplasmic reticulum; ER-Golgi transport; Glycoprotein; Kinase;
KW Magnesium; Membrane; Nucleus; Phosphoprotein; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..290
FT /note="CTP-dependent diacylglycerol kinase 1"
FT /id="PRO_0000240382"
FT TOPO_DOM 1..77
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 78..95
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 96..103
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 104..124
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 125..140
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 141..161
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 162..163
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 164..184
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 185..203
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 204..224
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 225..244
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 245..265
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 266..290
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:16847258"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 15..33
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 44
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 45
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27834677,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27834677,
FT ECO:0007744|PubMed:19779198"
FT CARBOHYD 11
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 197
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 270
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 45..46
FT /note="SS->AA: Abolishes the stationary phase-dependent
FT stimulation of DAG kinase activity."
FT /evidence="ECO:0000269|PubMed:27834677"
FT MUTAGEN 46
FT /note="S->A: Abolishes the stationary phase-dependent
FT stimulation of DAG kinase activity."
FT /evidence="ECO:0000269|PubMed:27834677"
FT MUTAGEN 76
FT /note="R->A: Loss of kinase activity. Not temperature-
FT sensitive for growth. Regular shaped nuclear membrane
FT structure."
FT /evidence="ECO:0000269|PubMed:18458076"
FT MUTAGEN 77
FT /note="K->A: Loss of kinase activity. Not temperature-
FT sensitive for growth. Regular shaped nuclear membrane
FT structure."
FT /evidence="ECO:0000269|PubMed:18458076"
FT MUTAGEN 177
FT /note="D->A: No kinase activity. Not temperature-sensitive
FT for growth. Does not trigger nuclear membrane expansion."
FT /evidence="ECO:0000269|PubMed:18458075,
FT ECO:0000269|PubMed:18458076"
FT MUTAGEN 184
FT /note="G->A: 70% reduction in kinase activity. Not
FT temperature-sensitive for growth. Regular shaped nuclear
FT membrane structure."
FT /evidence="ECO:0000269|PubMed:18458076"
SQ SEQUENCE 290 AA; 32840 MW; F8A0EE6F1018025B CRC64;
MGTEDAIALP NSTLEPRTEA KQRLSSKSHQ VSAKVTIPAK EEISSSDDDA HVPVTEIHLK
SHEWFGDFIT KHEIPRKVFH SSIGFITLYL YTQGINYKNV LWPLIYAFII LFILDLIRLN
WPFFNMLYCR TVGALMRKKE IHTYNGVLWY ILGLIFSFNF FSKDVTLISL FLLSWSDTAA
ATIGRKYGHL TPKVARNKSL AGSIAAFTVG VITCWVFYGY FVPAYSYVNK PGEIQWSPET
SRLSLNMLSL LGGVVAALSE GIDLFNWDDN FTIPVLSSLF MNAVIKTFKK
