LCB5_YEAST
ID LCB5_YEAST Reviewed; 687 AA.
AC Q06147; D6VYQ7;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Sphingoid long chain base kinase 5;
DE Short=LCB kinase 5;
DE EC=2.7.1.91 {ECO:0000269|PubMed:9677363};
DE AltName: Full=Sphinganine kinase 5;
GN Name=LCB5; OrderedLocusNames=YLR260W;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169871;
RA Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W.,
RA Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A.,
RA Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K.,
RA Heuss-Neitzel D., Hilbert H., Hilger F., Kleine K., Koetter P., Louis E.J.,
RA Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S.,
RA Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D.,
RA Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M.,
RA Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P.,
RA Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M.,
RA Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K.,
RA Zollner A., Hani J., Hoheisel J.D.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII.";
RL Nature 387:87-90(1997).
RN [2]
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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9677363; DOI=10.1074/jbc.273.31.19437;
RA Nagiec M.M., Skrzypek M.S., Nagiec E.E., Lester R.L., Dickson R.C.;
RT "The LCB4 (YOR171c) and LCB5 (YLR260w) genes of Saccharomyces encode
RT sphingoid long chain base kinases.";
RL J. Biol. Chem. 273:19437-19442(1998).
RN [4]
RP FUNCTION.
RX PubMed=11102354; DOI=10.1093/genetics/156.4.1519;
RA Kim S., Fyrst H., Saba J.D.;
RT "Accumulation of phosphorylated sphingoid long chain bases results in cell
RT growth inhibition in Saccharomyces cerevisiae.";
RL Genetics 156:1519-1529(2000).
RN [5]
RP FUNCTION.
RX PubMed=11056159; DOI=10.1074/jbc.m007425200;
RA Jenkins G.M., Hannun Y.A.;
RT "Role for de novo sphingoid base biosynthesis in the heat-induced transient
RT cell cycle arrest of Saccharomyces cerevisiae.";
RL J. Biol. Chem. 276:8574-8581(2001).
RN [6]
RP FUNCTION.
RX PubMed=11278643; DOI=10.1074/jbc.m010221200;
RA Birchwood C.J., Saba J.D., Dickson R.C., Cunningham K.W.;
RT "Calcium influx and signaling in yeast stimulated by intracellular
RT sphingosine 1-phosphate accumulation.";
RL J. Biol. Chem. 276:11712-11718(2001).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12493772; DOI=10.1074/jbc.m209925200;
RA Funato K., Lombardi R., Vallee B., Riezman H.;
RT "Lcb4p is a key regulator of ceramide synthesis from exogenous long chain
RT sphingoid base in Saccharomyces cerevisiae.";
RL J. Biol. Chem. 278:7325-7334(2003).
RN [8]
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 [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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [11]
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 [12]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=25345524; DOI=10.1038/ncomms6338;
RA Kondo N., Ohno Y., Yamagata M., Obara T., Seki N., Kitamura T.,
RA Naganuma T., Kihara A.;
RT "Identification of the phytosphingosine metabolic pathway leading to odd-
RT numbered fatty acids.";
RL Nat. Commun. 5:5338-5338(2014).
CC -!- FUNCTION: Catalyzes the phosphorylation of the sphingoid long chain
CC bases dihydrosphingosine (DHS or sphinganine) and phytosphingosine
CC (PHS) to form dihydrosphingosine 1-phosphate (DHS-1P) and
CC phytosphingosine 1-phosphate (PHS-1P) respectively (PubMed:9677363,
CC PubMed:11102354, PubMed:12493772, PubMed:25345524). Redundant to LCB4,
CC is only responsible for few percent of the total activity
CC (PubMed:9677363). Involved in the biosynthesis of sphingolipids and
CC ceramides (PubMed:9677363, PubMed:25345524). Involved in heat-induced
CC transient cell cycle arrest (PubMed:11056159). Accumulation of
CC phosphorylated sphingoid long chain bases (LCBPs) stimulates calcium
CC influx and activates calcineurin signaling (PubMed:11102354,
CC PubMed:11278643). Involved in heat-stress resistance (PubMed:11056159).
CC {ECO:0000269|PubMed:11056159, ECO:0000269|PubMed:11102354,
CC ECO:0000269|PubMed:11278643, ECO:0000269|PubMed:12493772,
CC ECO:0000269|PubMed:25345524, ECO:0000269|PubMed:9677363}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4R)-hydroxysphinganine + ATP = (4R)-hydroxysphinganine 1-
CC phosphate + ADP + H(+); Xref=Rhea:RHEA:33563, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:64124, ChEBI:CHEBI:64795,
CC ChEBI:CHEBI:456216; EC=2.7.1.91;
CC Evidence={ECO:0000269|PubMed:25345524, ECO:0000269|PubMed:9677363};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33564;
CC Evidence={ECO:0000269|PubMed:25345524, ECO:0000305|PubMed:9677363};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a sphingoid base + ATP = a sphingoid 1-phosphate + ADP + H(+);
CC Xref=Rhea:RHEA:51496, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:76941, ChEBI:CHEBI:84410, ChEBI:CHEBI:456216;
CC EC=2.7.1.91; Evidence={ECO:0000269|PubMed:9677363};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + sphinganine = ADP + H(+) + sphinganine 1-phosphate;
CC Xref=Rhea:RHEA:15465, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57817, ChEBI:CHEBI:57939, ChEBI:CHEBI:456216;
CC EC=2.7.1.91; Evidence={ECO:0000269|PubMed:9677363};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15466;
CC Evidence={ECO:0000305|PubMed:9677363};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2 uM for dihydrosphingosine {ECO:0000269|PubMed:9677363};
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:12493772}; Peripheral membrane protein
CC {ECO:0000269|PubMed:12493772}.
CC -!- MISCELLANEOUS: Present with 1760 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
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DR EMBL; U17244; AAB67377.1; -; Genomic_DNA.
DR EMBL; BK006945; DAA09573.1; -; Genomic_DNA.
DR PIR; S51398; S51398.
DR RefSeq; NP_013361.1; NM_001182147.1.
DR AlphaFoldDB; Q06147; -.
DR SMR; Q06147; -.
DR BioGRID; 31528; 168.
DR IntAct; Q06147; 1.
DR MINT; Q06147; -.
DR STRING; 4932.YLR260W; -.
DR SwissLipids; SLP:000000110; -.
DR iPTMnet; Q06147; -.
DR MaxQB; Q06147; -.
DR PaxDb; Q06147; -.
DR PRIDE; Q06147; -.
DR EnsemblFungi; YLR260W_mRNA; YLR260W; YLR260W.
DR GeneID; 850964; -.
DR KEGG; sce:YLR260W; -.
DR SGD; S000004250; LCB5.
DR VEuPathDB; FungiDB:YLR260W; -.
DR eggNOG; KOG1116; Eukaryota.
DR GeneTree; ENSGT00940000167991; -.
DR HOGENOM; CLU_013399_0_2_1; -.
DR InParanoid; Q06147; -.
DR OMA; DTILCAS; -.
DR BioCyc; MetaCyc:YLR260W-MON; -.
DR BioCyc; YEAST:YLR260W-MON; -.
DR Reactome; R-SCE-1483206; Glycerophospholipid biosynthesis.
DR Reactome; R-SCE-1660661; Sphingolipid de novo biosynthesis.
DR Reactome; R-SCE-390471; Association of TriC/CCT with target proteins during biosynthesis.
DR Reactome; R-SCE-5218921; VEGFR2 mediated cell proliferation.
DR Reactome; R-SCE-9009391; Extra-nuclear estrogen signaling.
DR SABIO-RK; Q06147; -.
DR PRO; PR:Q06147; -.
DR Proteomes; UP000002311; Chromosome XII.
DR RNAct; Q06147; protein.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; HDA:SGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:SGD.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IDA:SGD.
DR GO; GO:0005634; C:nucleus; HDA:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0017050; F:D-erythro-sphingosine kinase activity; IDA:SGD.
DR GO; GO:0001727; F:lipid kinase activity; IBA:GO_Central.
DR GO; GO:0003951; F:NAD+ kinase activity; IEA:InterPro.
DR GO; GO:0008481; F:sphinganine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0019722; P:calcium-mediated signaling; IMP:SGD.
DR GO; GO:0016310; P:phosphorylation; IBA:GO_Central.
DR GO; GO:0009408; P:response to heat; IDA:SGD.
DR GO; GO:0006665; P:sphingolipid metabolic process; IDA:SGD.
DR GO; GO:0046512; P:sphingosine biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.40.50.10330; -; 1.
DR InterPro; IPR017438; ATP-NAD_kinase_N.
DR InterPro; IPR001206; Diacylglycerol_kinase_cat_dom.
DR InterPro; IPR016064; NAD/diacylglycerol_kinase_sf.
DR Pfam; PF00781; DAGK_cat; 1.
DR SMART; SM00046; DAGKc; 1.
DR SUPFAM; SSF111331; SSF111331; 1.
DR PROSITE; PS50146; DAGK; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Golgi apparatus; Kinase; Lipid metabolism; Lipoprotein;
KW Membrane; Nucleotide-binding; Palmitate; Reference proteome;
KW Sphingolipid metabolism; Transferase.
FT CHAIN 1..687
FT /note="Sphingoid long chain base kinase 5"
FT /id="PRO_0000255957"
FT DOMAIN 266..405
FT /note="DAGKc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 101..130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 180..207
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 506..525
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..19
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 180..194
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 506..522
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 335
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 276..278
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 308
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 333..336
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 340
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 366..368
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 434
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 440
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 652..654
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT LIPID 91
FT /note="S-palmitoyl cysteine; by AKR1"
FT /evidence="ECO:0000250|UniProtKB:Q12246"
FT LIPID 94
FT /note="S-palmitoyl cysteine; by AKR1"
FT /evidence="ECO:0000250|UniProtKB:Q12246"
SQ SEQUENCE 687 AA; 77566 MW; 205C32F3570042FA CRC64;
MTLKPSKRRK GRSRHSRKKQ ITSAILTEEG IMIKAKPSSP YTYANRMADK RSRSSIDNIS
RTSFQSNISR TSFQSNSDNN SIFETASLIS CVTCLSDTDT IDRSETSTTD TSKDDLSANP
KLHYPSVNGQ LPANTVIPYG RILDARYIEK EPLHYYDANS SPSSPLSSSM SNISEKCDLD
ELESSQKKER KGNSLSRGSN SSSSLLTSRS PFTKLVEVIF ARPRRHDVVP KRVSLYIDYK
PHSSSHLKEE DDLVEEILKR SYKNTRRNKS IFVIINPFGG KGKAKKLFMT KAKPLLLASR
CSIEVVYTKY PGHAIEIARE MDIDKYDTIA CASGDGIPHE VINGLYQRPD HVKAFNNIAI
TEIPCGSGNA MSVSCHWTNN PSYSTLCLIK SIETRIDLMC CSQPSYAREH PKLSFLSQTY
GLIAETDINT EFIRWMGPAR FELGVAFNII QKKKYPCEIY VKYAAKSKNE LKNHYLEHKN
KGSLEFQHIT MNKDNEDCDN YNYENEYETE NEDEDEDADA DDEDSHLISR DLADSSADQI
KEEDFKIKYP LDEGIPSDWE RLDPNISNNL GIFYTGKMPY VAADTKFFPA ALPSDGTMDM
VITDARTSLT RMAPILLGLD KGSHVLQPEV LHSKILAYKI IPKLGNGLFS VDGEKFPLEP
LQVEIMPRLC KTLLRNGRYV DTDFDSM
