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   27-MAR-2024, entry version 168.
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; 185.
DR   IntAct; Q06147; 1.
DR   MINT; Q06147; -.
DR   STRING; 4932.YLR260W; -.
DR   SwissLipids; SLP:000000110; -.
DR   iPTMnet; Q06147; -.
DR   MaxQB; Q06147; -.
DR   PaxDb; 4932-YLR260W; -.
DR   PeptideAtlas; Q06147; -.
DR   EnsemblFungi; YLR260W_mRNA; YLR260W; YLR260W.
DR   GeneID; 850964; -.
DR   KEGG; sce:YLR260W; -.
DR   AGR; SGD:S000004250; -.
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   OrthoDB; 374620at2759; -.
DR   BioCyc; MetaCyc:YLR260W-MONOMER; -.
DR   BioCyc; YEAST:YLR260W-MONOMER; -.
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   Reactome; R-SCE-9833482; PKR-mediated signaling.
DR   SABIO-RK; Q06147; -.
DR   BioGRID-ORCS; 850964; 0 hits in 10 CRISPR screens.
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: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; 2.60.200.40; -; 1.
DR   InterPro; IPR017438; ATP-NAD_kinase_N.
DR   InterPro; IPR001206; Diacylglycerol_kinase_cat_dom.
DR   InterPro; IPR016064; NAD/diacylglycerol_kinase_sf.
DR   PANTHER; PTHR12358:SF31; LD11247P-RELATED; 1.
DR   PANTHER; PTHR12358; SPHINGOSINE KINASE; 1.
DR   Pfam; PF00781; DAGK_cat; 1.
DR   SMART; SM00046; DAGKc; 1.
DR   SUPFAM; SSF111331; NAD kinase/diacylglycerol kinase-like; 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
//