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Protein

Sphingoid long chain base kinase 4

Gene

LCB4

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the phosphorylation of the sphingoid long chain bases dihydrosphingosine (DHS or sphinganine) and phytosphingosine (PHS) to form dihydrosphingosine 1-phosphate (DHS-1P) and phytosphingosine 1-phosphate (PHS-1P) respectively (PubMed:9677363, PubMed:11102354, PubMed:11795842, PubMed:16141212). Involved in the biosynthesis of sphingolipids and ceramides (PubMed:12493772). Required with LCB3 for an effective incorporation of DHS into ceramides through a phosphorylation-dephosphorylation cycle. Involved in heat-induced transient cell cycle arrest (PubMed:11056159). Accumulation of phosphorylated sphingoid long chain bases (LCBPs) stimulates calcium influx and activates calcineurin signaling (PubMed:11278643). Involved in heat-stress resistance (PubMed:11967828).8 Publications

Catalytic activityi

ATP + sphinganine = ADP + sphinganine 1-phosphate.1 Publication
ATP + phytosphingosine = ADP + phytosphingosine 1-phosphate.1 Publication

Kineticsi

  1. KM=7.7 µM for sphinganine1 Publication
  2. KM=25 µM for ATP1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei266 – 2661ATPPROSITE-ProRule annotation
    Active sitei293 – 2931Proton donor/acceptorBy similarity
    Binding sitei298 – 2981ATPPROSITE-ProRule annotation
    Binding sitei392 – 3921ATPPROSITE-ProRule annotation
    Binding sitei398 – 3981ATPPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi234 – 2363ATPPROSITE-ProRule annotation
    Nucleotide bindingi324 – 3263ATPPROSITE-ProRule annotation
    Nucleotide bindingi589 – 5913ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    • ATP binding Source: UniProtKB-KW
    • D-erythro-sphingosine kinase activity Source: SGD
    • sphinganine kinase activity Source: UniProtKB-EC

    GO - Biological processi

    • calcium-mediated signaling Source: SGD
    • sphingolipid metabolic process Source: SGD
    Complete GO annotation...

    Keywords - Molecular functioni

    Kinase, Transferase

    Keywords - Biological processi

    Lipid metabolism, Sphingolipid metabolism

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:YOR171C-MONOMER.
    YEAST:YOR171C-MONOMER.
    ReactomeiR-SCE-1660661. Sphingolipid de novo biosynthesis.
    R-SCE-1660662. Glycosphingolipid metabolism.
    R-SCE-390471. Association of TriC/CCT with target proteins during biosynthesis.
    R-SCE-5218921. VEGFR2 mediated cell proliferation.
    R-SCE-75105. Fatty Acyl-CoA Biosynthesis.

    Chemistry

    SwissLipidsiSLP:000000109.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sphingoid long chain base kinase 41 Publication (EC:2.7.1.911 Publication)
    Short name:
    LCB kinase 41 Publication
    Alternative name(s):
    Sphinganine kinase 4Curated
    Gene namesi
    Name:LCB41 Publication
    Ordered Locus Names:YOR171CImported
    ORF Names:O3615
    OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
    Taxonomic identifieri559292 [NCBI]
    Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
    Proteomesi
    • UP000002311 Componenti: Chromosome XV

    Organism-specific databases

    EuPathDBiFungiDB:YOR171C.
    SGDiS000005697. LCB4.

    Subcellular locationi

    GO - Cellular componenti

    • cortical endoplasmic reticulum Source: SGD
    • endoplasmic reticulum Source: SGD
    • endoplasmic reticulum membrane Source: UniProtKB-SubCell
    • Golgi apparatus Source: SGD
    • Golgi membrane Source: UniProtKB-SubCell
    • late endosome membrane Source: UniProtKB-SubCell
    • plasma membrane Source: SGD
    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Endoplasmic reticulum, Endosome, Golgi apparatus, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 624624Sphingoid long chain base kinase 4PRO_0000255956Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi43 – 431S-palmitoyl cysteine1 Publication
    Lipidationi46 – 461S-palmitoyl cysteine1 Publication
    Modified residuei111 – 1111PhosphoserineCombined sources
    Modified residuei120 – 1201PhosphoserineCombined sources
    Modified residuei154 – 1541PhosphoserineCombined sources
    Modified residuei160 – 1601PhosphoserineCombined sources
    Modified residuei451 – 4511Phosphoserine; by PHO85Combined sources1 Publication
    Modified residuei454 – 4541PhosphoserineCombined sources
    Modified residuei455 – 4551Phosphoserine; by PHO85Combined sources1 Publication
    Modified residuei460 – 4601PhosphoserineCombined sources

    Post-translational modificationi

    Phosphorylated by the cyclin-CDKs PCL1-PHO85 and PCL2-PHO85. Phosphorylation is a prerequisite to ubiquitination. The phosphorylation level depends on sterol composition and may also be involved in subcellular location (PubMed:16141212).2 Publications
    Ubiquitinated. The ubiquitination leads to degradation in the vacuole.1 Publication

    Keywords - PTMi

    Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ12246.
    PeptideAtlasiQ12246.

    PTM databases

    iPTMnetiQ12246.
    SwissPalmiQ12246.

    Interactioni

    Protein-protein interaction databases

    BioGridi34565. 103 interactions.
    DIPiDIP-2844N.
    IntActiQ12246. 4 interactions.
    MINTiMINT-502657.

    Structurei

    3D structure databases

    ProteinModelPortaliQ12246.
    SMRiQ12246. Positions 229-604.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini224 – 363140DAGKcPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni291 – 2944Substrate bindingBy similarity

    Sequence similaritiesi

    Contains 1 DAGKc domain.PROSITE-ProRule annotation

    Phylogenomic databases

    GeneTreeiENSGT00690000101761.
    HOGENOMiHOG000207396.
    InParanoidiQ12246.
    KOiK04718.
    OMAiTIDETIG.
    OrthoDBiEOG7KH9TK.

    Family and domain databases

    InterProiIPR001206. Diacylglycerol_kinase_cat_dom.
    IPR016064. NAD/diacylglycerol_kinase.
    [Graphical view]
    PfamiPF00781. DAGK_cat. 1 hit.
    [Graphical view]
    SMARTiSM00046. DAGKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF111331. SSF111331. 2 hits.
    PROSITEiPS50146. DAGK. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q12246-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MVVQKKLRAI LTDEGVLIKS QSHHMFNKHG QLRSGDSLSL LSCLSCLDDG
    60 70 80 90 100
    TLSSDGGSFD EDDSLELLPL NTTIPFNRIL NAKYVNVGQK GFNNGKISSN
    110 120 130 140 150
    PFQTENLSSS SENDDVENHS LSNDKAPVSE SQSFPKKDKW DTKTNTVKVS
    160 170 180 190 200
    PDDSQDNSPS LGIKDNQQLI ELTFAVPKGH DVIPQKLTLL IDHVSRKSRA
    210 220 230 240 250
    NTGEENISSG TVEEILEKSY ENSKRNRSIL VIINPHGGKG TAKNLFLTKA
    260 270 280 290 300
    RPILVESGCK IEIAYTKYAR HAIDIAKDLD ISKYDTIACA SGDGIPYEVI
    310 320 330 340 350
    NGLYRRPDRV DAFNKLAVTQ LPCGSGNAMS ISCHWTNNPS YAALCLVKSI
    360 370 380 390 400
    ETRIDLMCCS QPSYMNEWPR LSFLSQTYGV IAESDINTEF IRWMGPVRFN
    410 420 430 440 450
    LGVAFNIIQG KKYPCEVFVK YAAKSKKELK VHFLENKDKN KGCLTFEPNP
    460 470 480 490 500
    SPNSSPDLLS KNNINNSTKD ELSPNFLNED NFKLKYPMTE PVPRDWEKMD
    510 520 530 540 550
    SELTDNLTIF YTGKMPYIAK DTKFFPAALP ADGTIDLVIT DARIPVTRMT
    560 570 580 590 600
    PILLSLDKGS HVLEPEVIHS KILAYKIIPK VESGLFSVDG EKFPLEPLQV
    610 620
    EIMPMLCKTL LRNGRYIDTE FESM
    Length:624
    Mass (Da):69,639
    Last modified:November 1, 1996 - v1
    Checksum:iE033A3BAC604D4BB
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U55021 Genomic DNA. Translation: AAB47416.1.
    Z75078 Genomic DNA. Translation: CAA99378.1.
    BK006948 Genomic DNA. Translation: DAA10943.1.
    PIRiS67059.
    RefSeqiNP_014814.1. NM_001183590.1.

    Genome annotation databases

    EnsemblFungiiYOR171C; YOR171C; YOR171C.
    GeneIDi854342.
    KEGGisce:YOR171C.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U55021 Genomic DNA. Translation: AAB47416.1.
    Z75078 Genomic DNA. Translation: CAA99378.1.
    BK006948 Genomic DNA. Translation: DAA10943.1.
    PIRiS67059.
    RefSeqiNP_014814.1. NM_001183590.1.

    3D structure databases

    ProteinModelPortaliQ12246.
    SMRiQ12246. Positions 229-604.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi34565. 103 interactions.
    DIPiDIP-2844N.
    IntActiQ12246. 4 interactions.
    MINTiMINT-502657.

    Chemistry

    SwissLipidsiSLP:000000109.

    PTM databases

    iPTMnetiQ12246.
    SwissPalmiQ12246.

    Proteomic databases

    MaxQBiQ12246.
    PeptideAtlasiQ12246.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblFungiiYOR171C; YOR171C; YOR171C.
    GeneIDi854342.
    KEGGisce:YOR171C.

    Organism-specific databases

    EuPathDBiFungiDB:YOR171C.
    SGDiS000005697. LCB4.

    Phylogenomic databases

    GeneTreeiENSGT00690000101761.
    HOGENOMiHOG000207396.
    InParanoidiQ12246.
    KOiK04718.
    OMAiTIDETIG.
    OrthoDBiEOG7KH9TK.

    Enzyme and pathway databases

    BioCyciMetaCyc:YOR171C-MONOMER.
    YEAST:YOR171C-MONOMER.
    ReactomeiR-SCE-1660661. Sphingolipid de novo biosynthesis.
    R-SCE-1660662. Glycosphingolipid metabolism.
    R-SCE-390471. Association of TriC/CCT with target proteins during biosynthesis.
    R-SCE-5218921. VEGFR2 mediated cell proliferation.
    R-SCE-75105. Fatty Acyl-CoA Biosynthesis.

    Miscellaneous databases

    NextBioi976414.
    PROiQ12246.

    Family and domain databases

    InterProiIPR001206. Diacylglycerol_kinase_cat_dom.
    IPR016064. NAD/diacylglycerol_kinase.
    [Graphical view]
    PfamiPF00781. DAGK_cat. 1 hit.
    [Graphical view]
    SMARTiSM00046. DAGKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF111331. SSF111331. 2 hits.
    PROSITEiPS50146. DAGK. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Analysis of a 22,956 bp region on the right arm of Saccharomyces cerevisiae chromosome XV."
      Madania A., Poch O., Tarassov I.A., Winsor B., Martin R.P.
      Yeast 12:1563-1573(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: ATCC 96604 / S288c / FY1679.
    2. "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV."
      Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J., Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A., Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B., Dang V.-D.
      , de Haan M., Delius H., Durand P., Fairhead C., Feldmann H., Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E., Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U., Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B., Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A., Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C., Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G., Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B., Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B., Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F., Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E., Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I., Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H., Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.
      Nature 387:98-102(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 204508 / S288c.
    3. Cited for: GENOME REANNOTATION.
      Strain: ATCC 204508 / S288c.
    4. "The LCB4 (YOR171c) and LCB5 (YLR260w) genes of Saccharomyces encode sphingoid long chain base kinases."
      Nagiec M.M., Skrzypek M.S., Nagiec E.E., Lester R.L., Dickson R.C.
      J. Biol. Chem. 273:19437-19442(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
    5. "Accumulation of phosphorylated sphingoid long chain bases results in cell growth inhibition in Saccharomyces cerevisiae."
      Kim S., Fyrst H., Saba J.D.
      Genetics 156:1519-1529(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    6. "Elevation of endogenous sphingolipid long-chain base phosphates kills Saccharomyces cerevisiae cells."
      Zhang X., Skrzypek M.S., Lester R.L., Dickson R.C.
      Curr. Genet. 40:221-233(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    7. "Role for de novo sphingoid base biosynthesis in the heat-induced transient cell cycle arrest of Saccharomyces cerevisiae."
      Jenkins G.M., Hannun Y.A.
      J. Biol. Chem. 276:8574-8581(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    8. "Calcium influx and signaling in yeast stimulated by intracellular sphingosine 1-phosphate accumulation."
      Birchwood C.J., Saba J.D., Dickson R.C., Cunningham K.W.
      J. Biol. Chem. 276:11712-11718(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    9. "Lcb4p sphingoid base kinase localizes to the Golgi and late endosomes."
      Hait N.C., Fujita K., Lester R.L., Dickson R.C.
      FEBS Lett. 532:97-102(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    10. "Mutant analysis reveals complex regulation of sphingolipid long chain base phosphates and long chain bases during heat stress in yeast."
      Ferguson-Yankey S.R., Skrzypek M.S., Lester R.L., Dickson R.C.
      Yeast 19:573-586(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    11. "Lcb4p is a key regulator of ceramide synthesis from exogenous long chain sphingoid base in Saccharomyces cerevisiae."
      Funato K., Lombardi R., Vallee B., Riezman H.
      J. Biol. Chem. 278:7325-7334(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    12. Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
    13. "Phosphorylation by Pho85 cyclin-dependent kinase acts as a signal for the down-regulation of the yeast sphingoid long-chain base kinase Lcb4 during the stationary phase."
      Iwaki S., Kihara A., Sano T., Igarashi Y.
      J. Biol. Chem. 280:6520-6527(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-451 AND SER-455, UBIQUITINATION.
    14. "Regulation of the sphingoid long-chain base kinase Lcb4p by ergosterol and heme: studies in phytosphingosine-resistant mutants."
      Sano T., Kihara A., Kurotsu F., Iwaki S., Igarashi Y.
      J. Biol. Chem. 280:36674-36682(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION.
    15. "Long-chain base kinase Lcb4 Is anchored to the membrane through its palmitoylation by Akr1."
      Kihara A., Kurotsu F., Sano T., Iwaki S., Igarashi Y.
      Mol. Cell. Biol. 25:9189-9197(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PALMITOYLATION AT CYS-43 AND CYS-46.
    16. "Large-scale phosphorylation analysis of alpha-factor-arrested Saccharomyces cerevisiae."
      Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J., Elias J.E., Gygi S.P.
      J. Proteome Res. 6:1190-1197(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-451; SER-454 AND SER-455, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Strain: ADR376.
    17. "A multidimensional chromatography technology for in-depth phosphoproteome analysis."
      Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.
      Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-160, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    18. "Global analysis of Cdk1 substrate phosphorylation sites provides insights into evolution."
      Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.
      Science 325:1682-1686(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-111; SER-120; SER-154; SER-451; SER-454; SER-455 AND SER-460, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    19. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    20. "Sites of ubiquitin attachment in Saccharomyces cerevisiae."
      Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.
      Proteomics 12:236-240(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiLCB4_YEAST
    AccessioniPrimary (citable) accession number: Q12246
    Secondary accession number(s): D6W2M7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 31, 2006
    Last sequence update: November 1, 1996
    Last modified: May 11, 2016
    This is version 129 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programFungal Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Present with 2840 molecules/cell in log phase SD medium.1 Publication

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Yeast
      Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
    3. Yeast chromosome XV
      Yeast (Saccharomyces cerevisiae) chromosome XV: entries and gene names

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.