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Identification
NameSphingoid long chain base kinase 4
Synonyms
  • LCB kinase 4
  • Sphinganine kinase 4
Gene NameLCB4
Enzyme Class
Biological Properties
General FunctionInvolved in diacylglycerol kinase activity
Specific FunctionCatalyzes 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. Involved in the biosynthesis of sphingolipids and ceramides. Required with LCB3 for an effective incorporation of DHS into ceramides through a phosphorylation-dephosphorylation cycle. Involved in heat-induced transient cell cycle arrest. Accumulation of phosphorylated sphingoid long chain bases (LCBPs) stimulates calcium influx and activates calcineurin signaling. Involved in heat-stress resistance
Cellular LocationCell membrane; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein. Late endosome membrane; Peripheral membrane protein. Golgi apparatus membrane; Peripheral membrane protein
SMPDB Pathways
Sphingolipid metabolismPW002479 ThumbThumb?image type=greyscaleThumb?image type=simple
KEGG Pathways
Sphingolipid metabolismec00600 Map00600
SMPDB ReactionsNot Available
KEGG Reactions
Adenosine triphosphate + PhytosphingosinePhytosphingosine 1-phosphate + hydron + ADP
Sphinganine + Adenosine triphosphatehydron + Sphinganine 1-phosphate + ADP
Metabolites
YMDB IDNameView
YMDB00109Adenosine triphosphateShow
YMDB00190SphingosineShow
YMDB00285PhytosphingosineShow
YMDB00299Sphinganine 1-phosphateShow
YMDB00327SphinganineShow
YMDB00762Phytosphingosine 1-phosphateShow
YMDB00862hydronShow
YMDB00914ADPShow
GO Classification
Component
Not Available
Function
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
diacylglycerol kinase activity
Process
activation of protein kinase C activity by G-protein coupled receptor protein signaling pathway
signaling
signaling pathway
cell surface receptor linked signaling pathway
G-protein coupled receptor protein signaling pathway
Gene Properties
Chromosome Locationchromosome 15
LocusYOR171C
Gene Sequence>1875 bp ATGGTGGTGCAGAAAAAACTTAGGGCTATCTTGACCGATGAAGGTGTATTGATCAAATCG CAATCACACCATATGTTCAATAAGCATGGTCAACTCAGAAGCGGAGATTCTTTATCCTTG TTGAGCTGCTTGTCCTGTCTGGATGATGGAACTTTGAGCTCTGATGGAGGTTCTTTTGAT GAGGATGATTCCCTGGAACTGTTGCCTCTTAATACTACCATTCCGTTCAACAGAATTTTG AACGCAAAATATGTGAATGTCGGTCAGAAAGGCTTCAATAATGGCAAAATTTCTTCGAAT CCTTTTCAAACGGAAAATCTGAGTTCTTCGTCTGAAAATGACGACGTTGAGAATCATAGT TTGAGCAATGATAAGGCTCCTGTAAGCGAATCACAGTCATTTCCCAAAAAAGACAAGTGG GATACAAAAACGAACACTGTGAAGGTGTCTCCCGATGATTCACAGGATAACTCACCATCT TTAGGGATAAAAGATAATCAACAGTTAATTGAGTTAACTTTTGCTGTACCCAAGGGCCAT GATGTTATACCACAAAAATTAACCTTGTTAATAGATCACGTTTCTAGGAAATCGAGAGCA AATACCGGAGAGGAGAACATTTCTTCTGGTACTGTGGAAGAAATCCTGGAAAAAAGTTAT GAAAATTCCAAGAGAAACAGATCGATATTAGTCATTATTAATCCCCACGGTGGTAAAGGT ACTGCTAAAAATTTATTCCTGACAAAAGCAAGGCCAATACTAGTGGAAAGTGGCTGCAAA ATAGAAATTGCATACACAAAATATGCCCGTCACGCCATCGATATTGCCAAAGATTTAGAT ATCAGCAAATACGATACCATTGCATGTGCCTCGGGTGATGGTATTCCATACGAAGTAATT AATGGGCTTTATAGAAGACCCGACAGAGTGGATGCGTTCAATAAACTAGCCGTAACTCAG CTACCTTGCGGTTCAGGAAATGCTATGAGCATTTCATGTCATTGGACAAATAACCCATCG TACGCCGCTCTGTGCCTTGTCAAATCCATTGAAACAAGAATAGACTTAATGTGTTGTTCC CAACCTTCTTATATGAACGAATGGCCAAGATTATCCTTTTTGAGTCAGACGTACGGCGTT ATTGCAGAATCTGATATTAACACTGAATTCATCAGATGGATGGGTCCCGTTAGGTTTAAT TTGGGTGTAGCATTCAACATTATCCAAGGTAAGAAATATCCCTGCGAAGTTTTCGTCAAA TATGCTGCCAAATCTAAAAAGGAATTAAAAGTTCATTTCTTAGAAAATAAAGATAAAAAC AAAGGATGTTTAACCTTCGAACCAAATCCTAGCCCAAACTCTTCGCCGGATTTACTATCT AAAAACAATATCAACAACAGTACAAAAGATGAACTTTCACCGAATTTTCTCAACGAGGAC AACTTTAAATTAAAGTATCCGATGACGGAACCAGTACCTAGAGACTGGGAGAAAATGGAT TCAGAGCTAACTGATAACTTAACAATCTTTTACACAGGGAAAATGCCGTATATTGCTAAG GACACCAAATTTTTTCCCGCTGCTTTACCAGCGGATGGTACCATTGATTTAGTCATAACG GATGCAAGAATCCCAGTGACAAGAATGACACCAATTTTATTATCCTTGGATAAAGGTTCT CATGTATTAGAGCCAGAAGTTATTCACTCAAAAATATTGGCTTATAAGATTATACCAAAA GTGGAGTCAGGTTTATTTTCAGTGGATGGTGAAAAGTTTCCTTTGGAACCCTTGCAAGTG GAAATAATGCCCATGTTATGCAAGACGTTGCTAAGGAATGGTAGATATATCGATACAGAG TTTGAATCCATGTAG
Protein Properties
Pfam Domain Function
Protein Residues624
Protein Molecular Weight69638.60156
Protein Theoretical pI6.39
Signalling Regions
  • None
Transmembrane Regions
  • None
Protein Sequence>Sphingoid long chain base kinase 4 MVVQKKLRAILTDEGVLIKSQSHHMFNKHGQLRSGDSLSLLSCLSCLDDGTLSSDGGSFD EDDSLELLPLNTTIPFNRILNAKYVNVGQKGFNNGKISSNPFQTENLSSSSENDDVENHS LSNDKAPVSESQSFPKKDKWDTKTNTVKVSPDDSQDNSPSLGIKDNQQLIELTFAVPKGH DVIPQKLTLLIDHVSRKSRANTGEENISSGTVEEILEKSYENSKRNRSILVIINPHGGKG TAKNLFLTKARPILVESGCKIEIAYTKYARHAIDIAKDLDISKYDTIACASGDGIPYEVI NGLYRRPDRVDAFNKLAVTQLPCGSGNAMSISCHWTNNPSYAALCLVKSIETRIDLMCCS QPSYMNEWPRLSFLSQTYGVIAESDINTEFIRWMGPVRFNLGVAFNIIQGKKYPCEVFVK YAAKSKKELKVHFLENKDKNKGCLTFEPNPSPNSSPDLLSKNNINNSTKDELSPNFLNED NFKLKYPMTEPVPRDWEKMDSELTDNLTIFYTGKMPYIAKDTKFFPAALPADGTIDLVIT DARIPVTRMTPILLSLDKGSHVLEPEVIHSKILAYKIIPKVESGLFSVDGEKFPLEPLQV EIMPMLCKTLLRNGRYIDTEFESM
References
External Links
ResourceLink
Saccharomyces Genome Database LCB4
Uniprot IDQ12246
Uniprot NameLCB4_YEAST
GenBank Gene IDZ75078
Genebank Protein ID1420417
General Reference
  • Madania, A., Poch, O., Tarassov, I., Winsor, B., Martin, R. (1996). "Analysis of a 22,956 bp region on the right arm of Saccharomyces cerevisiae chromosome XV." Yeast 12:1563-1573.8972579
  • 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, D. V., de Haan, M., Delius, H., Durand, P., Fairhead, C., Feldmann, H., Gaillon, L., Kleine, K., et, a. l. .. (1997). "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV." Nature 387:98-102.9169874
  • Nagiec, M. M., Skrzypek, M., Nagiec, E. E., Lester, R. L., Dickson, R. C. (1998). "The LCB4 (YOR171c) and LCB5 (YLR260w) genes of Saccharomyces encode sphingoid long chain base kinases." J Biol Chem 273:19437-19442.9677363
  • Kim, S., Fyrst, H., Saba, J. (2000). "Accumulation of phosphorylated sphingoid long chain bases results in cell growth inhibition in Saccharomyces cerevisiae." Genetics 156:1519-1529.11102354
  • Zhang, X., Skrzypek, M. S., Lester, R. L., Dickson, R. C. (2001). "Elevation of endogenous sphingolipid long-chain base phosphates kills Saccharomyces cerevisiae cells." Curr Genet 40:221-233.11795842
  • Jenkins, G. M., Hannun, Y. A. (2001). "Role for de novo sphingoid base biosynthesis in the heat-induced transient cell cycle arrest of Saccharomyces cerevisiae." J Biol Chem 276:8574-8581.11056159
  • Birchwood, C. J., Saba, J. D., Dickson, R. C., Cunningham, K. W. (2001). "Calcium influx and signaling in yeast stimulated by intracellular sphingosine 1-phosphate accumulation." J Biol Chem 276:11712-11718.11278643
  • Hait, N. C., Fujita, K., Lester, R. L., Dickson, R. C. (2002). "Lcb4p sphingoid base kinase localizes to the Golgi and late endosomes." FEBS Lett 532:97-102.12459470
  • Ferguson-Yankey, S. R., Skrzypek, M. S., Lester, R. L., Dickson, R. C. (2002). "Mutant analysis reveals complex regulation of sphingolipid long chain base phosphates and long chain bases during heat stress in yeast." Yeast 19:573-586.11967828
  • Funato, K., Lombardi, R., Vallee, B., Riezman, H. (2003). "Lcb4p is a key regulator of ceramide synthesis from exogenous long chain sphingoid base in Saccharomyces cerevisiae." J Biol Chem 278:7325-7334.12493772
  • Ghaemmaghami, S., Huh, W. K., Bower, K., Howson, R. W., Belle, A., Dephoure, N., O'Shea, E. K., Weissman, J. S. (2003). "Global analysis of protein expression in yeast." Nature 425:737-741.14562106
  • Iwaki, S., Kihara, A., Sano, T., Igarashi, Y. (2005). "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." J Biol Chem 280:6520-6527.15598647
  • Sano, T., Kihara, A., Kurotsu, F., Iwaki, S., Igarashi, Y. (2005). "Regulation of the sphingoid long-chain base kinase Lcb4p by ergosterol and heme: studies in phytosphingosine-resistant mutants." J Biol Chem 280:36674-36682.16141212
  • Kihara, A., Kurotsu, F., Sano, T., Iwaki, S., Igarashi, Y. (2005). "Long-chain base kinase Lcb4 Is anchored to the membrane through its palmitoylation by Akr1." Mol Cell Biol 25:9189-9197.16227572
  • Li, X., Gerber, S. A., Rudner, A. D., Beausoleil, S. A., Haas, W., Villen, J., Elias, J. E., Gygi, S. P. (2007). "Large-scale phosphorylation analysis of alpha-factor-arrested Saccharomyces cerevisiae." J Proteome Res 6:1190-1197.17330950
  • Smolka, M. B., Albuquerque, C. P., Chen, S. H., Zhou, H. (2007). "Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases." Proc Natl Acad Sci U S A 104:10364-10369.17563356
  • Albuquerque, C. P., Smolka, M. B., Payne, S. H., Bafna, V., Eng, J., Zhou, H. (2008). "A multidimensional chromatography technology for in-depth phosphoproteome analysis." Mol Cell Proteomics 7:1389-1396.18407956