Reviewed, UniProtKB/Swiss-Prot Q12246 (LCB4_YEAST)

Names and origin

Protein names

Recommended name:
    Sphingoid long chain base kinase 4
      Short name=LCB kinase 4
    EC=2.7.1.91
Alternative name(s):
    Sphinganine kinase 4

Gene names

Name:	LCB4
Ordered Locus Names:	YOR171C
ORF Names:	O3615

Organism

Saccharomyces cerevisiae (Baker's yeast) [Complete proteome]

Taxonomic identifier

4932 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	624 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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. 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. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.9 Ref.10 Ref.13
Catalytic activity	ATP + sphinganine = ADP + sphinganine 1-phosphate. ATP + phytosphingosine = ADP + phytosphingosine 1-phosphate.
Subcellular location	Cell membrane; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein. Late endosome membrane; Peripheral membrane protein. Golgi apparatus membrane; Peripheral membrane protein. Ref.10 Ref.13 Ref.8
Post-translational modification	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. Ref.13 Ref.12 Ref.15 Ref.16 Ref.17 Ubiquitinated. The ubiquitination leads to degradation in the vacuole. Ref.12
Miscellaneous	Present with 2840 molecules/cell in log phase SD medium. Ref.11
Sequence similarities	Contains 1 DAGKc domain.
Biophysicochemical properties	Kinetic parameters: KM=7.7 µM for dihydrosphingosine KM=25 µM for ATP

Ontologies

Keywords
Biological process	Lipid metabolism Sphingolipid metabolism
Cellular component	Cell membrane Endoplasmic reticulum Endosome Golgi apparatus Membrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Lipoprotein Palmitate Phosphoprotein Ubl conjugation
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	activation of protein kinase C activity by G-protein coupled receptor protein signaling pathway Inferred from electronic annotation. Source: InterPro calcium-mediated signaling Ref.7 Inferred from mutant phenotype. Source: SGD sphingolipid metabolic process Ref.3 Inferred from direct assay. Source: SGD
Cellular component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cortical endoplasmic reticulum Inferred from direct assay. Source: SGD endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell late endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane fraction Ref.3 Inferred from direct assay. Source: SGD plasma membrane Ref.13 Inferred from direct assay. Source: SGD soluble fraction Ref.3 Inferred from direct assay. Source: SGD
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW D-erythro-sphingosine kinase activity Ref.3 Inferred from direct assay. Source: SGD diacylglycerol kinase activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction. Source: IntAct sphinganine kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AKR2	Q12013	1	EBI-38830,EBI-34438
PMP2	P40975	1	EBI-38830,EBI-2043041
SSA1	P10591	1	EBI-38830,EBI-8591

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 624	624	Sphingoid long chain base kinase 4		PRO_0000255956
Regions
	Domain	228 – 368	141	DAGKc
Amino acid modifications
	Modified residue	120	1	Phosphoserine Ref.17
	Modified residue	158	1	Phosphoserine Ref.17
	Modified residue	160	1	Phosphoserine Ref.17
	Modified residue	451	1	Phosphoserine; by PHO85 Ref.12 Ref.15
	Modified residue	454	1	Phosphoserine Ref.15 Ref.17
	Modified residue	455	1	Phosphoserine; by PHO85 Ref.12 Ref.15 Ref.17
	Modified residue	468	1	Phosphothreonine Ref.16
	Lipidation	43	1	S-palmitoyl cysteine Ref.14
	Lipidation	46	1	S-palmitoyl cysteine Ref.14

Sequences

	Sequence		Length	Mass (Da)
	Q12246-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: E033A3BAC604D4BB	FASTA	624	69,639
	10 20 30 40 50 60 MVVQKKLRAI LTDEGVLIKS QSHHMFNKHG QLRSGDSLSL LSCLSCLDDG TLSSDGGSFD 70 80 90 100 110 120 EDDSLELLPL NTTIPFNRIL NAKYVNVGQK GFNNGKISSN PFQTENLSSS SENDDVENHS 130 140 150 160 170 180 LSNDKAPVSE SQSFPKKDKW DTKTNTVKVS PDDSQDNSPS LGIKDNQQLI ELTFAVPKGH 190 200 210 220 230 240 DVIPQKLTLL IDHVSRKSRA NTGEENISSG TVEEILEKSY ENSKRNRSIL VIINPHGGKG 250 260 270 280 290 300 TAKNLFLTKA RPILVESGCK IEIAYTKYAR HAIDIAKDLD ISKYDTIACA SGDGIPYEVI 310 320 330 340 350 360 NGLYRRPDRV DAFNKLAVTQ LPCGSGNAMS ISCHWTNNPS YAALCLVKSI ETRIDLMCCS 370 380 390 400 410 420 QPSYMNEWPR LSFLSQTYGV IAESDINTEF IRWMGPVRFN LGVAFNIIQG KKYPCEVFVK 430 440 450 460 470 480 YAAKSKKELK VHFLENKDKN KGCLTFEPNP SPNSSPDLLS KNNINNSTKD ELSPNFLNED 490 500 510 520 530 540 NFKLKYPMTE PVPRDWEKMD SELTDNLTIF YTGKMPYIAK DTKFFPAALP ADGTIDLVIT 550 560 570 580 590 600 DARIPVTRMT PILLSLDKGS HVLEPEVIHS KILAYKIIPK VESGLFSVDG EKFPLEPLQV 610 620 EIMPMLCKTL LRNGRYIDTE FESM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 8972579] [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: 9169874] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[3]	"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: 9677363] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[4]	"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: 11102354] [Abstract] Cited for: FUNCTION.
[5]	"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: 11795842] [Abstract] Cited for: FUNCTION.
[6]	"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: 11056159] [Abstract] Cited for: FUNCTION.
[7]	"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: 11278643] [Abstract] Cited for: FUNCTION.
[8]	"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: 12459470] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"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: 11967828] [Abstract] Cited for: FUNCTION.
[10]	"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: 12493772] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[11]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed: 14562106] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[12]	"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: 15598647] [Abstract] Cited for: PHOSPHORYLATION AT SER-451 AND SER-455, UBIQUITINATION.
[13]	"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: 16141212] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[14]	"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: 16227572] [Abstract] Cited for: PALMITOYLATION AT CYS-43 AND CYS-46.
[15]	"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: 17330950] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-451; SER-454 AND SER-455, MASS SPECTROMETRY.
[16]	"Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases." Smolka M.B., Albuquerque C.P., Chen S.H., Zhou H. Proc. Natl. Acad. Sci. U.S.A. 104:10364-10369(2007) [PubMed: 17563356] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-468, MASS SPECTROMETRY.
[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: 18407956] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-120; SER-158; SER-160; SER-454 AND SER-455, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U55021 Genomic DNA. Translation: AAB47416.1. Z75078 Genomic DNA. Translation: CAA99378.1.
PIR	S67059.
RefSeq	NP_014814.1.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:2844N.
IntAct	Q12246. 8 interactions.
Proteomic databases
PeptideAtlas	Q12246.
Genome annotation databases
Ensembl	YOR171C. Saccharomyces cerevisiae. [Contig view]
GeneID	854342.
GenomeReviews	Gene locus YOR171C in contig Y13140_GR.
KEGG	sce:YOR171C.
NMPDR	fig|4932.3.peg.5922.
Organism-specific databases
CYGD	YOR171c.
SGD	S000005697. LCB4.
Yeast-GFP	Search...
Phylogenomic databases
HOGENOM	Q12246.
OMA	Q12246. VITDARI.
Enzyme and pathway databases
BRENDA	2.7.1.91. 250.
Gene expression databases
ArrayExpress	Q12246.
GermOnline	YOR171C. Saccharomyces cerevisiae.
Family and domain databases
InterPro	IPR001206. Diacylglycerol_kinase_cat. [Graphical view]
Pfam	PF00781. DAGK_cat. 1 hit. [Graphical view]
ProDom	PD005043. DAGKc. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00046. DAGKc. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	976414.

Entry information

Entry name

LCB4_YEAST

Accession

Primary (citable) accession number: Q12246

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2006
Last sequence update:	November 1, 1996
Last modified:	June 16, 2009
This is version 62 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

FPAP (Fungal Proteome Annotation Project)