DS1P1_YEAST
ID DS1P1_YEAST Reviewed; 409 AA.
AC P47013; D6VW50;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Dihydrosphingosine 1-phosphate phosphatase LCB3 {ECO:0000303|PubMed:9195906};
DE EC=3.1.3.- {ECO:0000269|PubMed:25345524};
DE AltName: Full=Long-chain base protein 3 {ECO:0000303|PubMed:9195906};
DE AltName: Full=Sphingolipid resistance protein 2 {ECO:0000303|PubMed:9353337};
GN Name=LCB3 {ECO:0000303|PubMed:9195906};
GN Synonyms=LBP1 {ECO:0000303|PubMed:9419344},
GN YSR2 {ECO:0000303|PubMed:9353337}; OrderedLocusNames=YJL134W;
GN ORFNames=J0671;
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 [GENOMIC DNA].
RC STRAIN=ATCC 96604 / S288c / FY1679;
RX PubMed=8813765;
RX DOI=10.1002/(sici)1097-0061(19960630)12:8<787::aid-yea954>3.0.co;2-4;
RA Katsoulou C., Tzermia M., Tavernarakis N., Alexandraki D.;
RT "Sequence analysis of a 40.7 kb segment from the left arm of yeast
RT chromosome X reveals 14 known genes and 13 new open reading frames
RT including homologues of genes clustered on the right arm of chromosome
RT XI.";
RL Yeast 12:787-797(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8641269; DOI=10.1002/j.1460-2075.1996.tb00557.x;
RA Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C.,
RA Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D.,
RA Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J.,
RA Heumann K., Hilger F., Hollenberg C.P., Huang M.-E., Jacq C.,
RA Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E.,
RA Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T.,
RA Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R.,
RA Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N.,
RA To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H.,
RA von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.;
RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.";
RL EMBO J. 15:2031-2049(1996).
RN [3]
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 [4]
RP FUNCTION.
RX PubMed=9195906; DOI=10.1074/jbc.272.26.16110;
RA Qie L., Nagiec M.M., Baltisberger J.A., Lester R.L., Dickson R.C.;
RT "Identification of a Saccharomyces gene, LCB3, necessary for incorporation
RT of exogenous long chain bases into sphingolipids.";
RL J. Biol. Chem. 272:16110-16117(1997).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=9353337; DOI=10.1074/jbc.272.45.28690;
RA Mao C., Wadleigh M., Jenkins G.M., Hannun Y.A., Obeid L.M.;
RT "Identification and characterization of Saccharomyces cerevisiae
RT dihydrosphingosine-1-phosphate phosphatase.";
RL J. Biol. Chem. 272:28690-28694(1997).
RN [6]
RP FUNCTION.
RX PubMed=9419344; DOI=10.1073/pnas.95.1.150;
RA Mandala S.M., Thornton R., Tu Z., Kurtz M.B., Nickels J., Broach J.,
RA Menzeleev R., Spiegel S.;
RT "Sphingoid base 1-phosphate phosphatase: a key regulator of sphingolipid
RT metabolism and stress response.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:150-155(1998).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10477278; DOI=10.1042/bj3420667;
RA Mao C., Saba J.D., Obeid L.M.;
RT "The dihydrosphingosine-1-phosphate phosphatases of Saccharomyces
RT cerevisiae are important regulators of cell proliferation and heat stress
RT responses.";
RL Biochem. J. 342:667-675(1999).
RN [8]
RP FUNCTION.
RX PubMed=10856228; DOI=10.1093/emboj/19.12.2824;
RA Zanolari B., Friant S., Funato K., Suetterlin C., Stevenson B.J.,
RA Riezman H.;
RT "Sphingoid base synthesis requirement for endocytosis in Saccharomyces
RT cerevisiae.";
RL EMBO J. 19:2824-2833(2000).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10563329; DOI=10.1016/s0076-6879(00)11085-7;
RA Mao C., Obeid L.M.;
RT "Yeast sphingosine-1-phosphate phosphatases: assay, expression, deletion,
RT purification, and cellular localization by GFP tagging.";
RL Methods Enzymol. 311:223-232(2000).
RN [10]
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 [11]
RP FUNCTION.
RX PubMed=11967828; DOI=10.1002/yea.861;
RA Ferguson-Yankey S.R., Skrzypek M.S., Lester R.L., Dickson R.C.;
RT "Mutant analysis reveals complex regulation of sphingolipid long chain base
RT phosphates and long chain bases during heat stress in yeast.";
RL Yeast 19:573-586(2002).
RN [12]
RP FUNCTION.
RX PubMed=12684378; DOI=10.1128/ec.2.2.284-294.2003;
RA Kobayashi S.D., Nagiec M.M.;
RT "Ceramide/long-chain base phosphate rheostat in Saccharomyces cerevisiae:
RT regulation of ceramide synthesis by Elo3p and Cka2p.";
RL Eukaryot. Cell 2:284-294(2003).
RN [13]
RP FUNCTION, MUTAGENESIS OF LYS-128; HIS-160 AND HIS-210, GLYCOSYLATION, AND
RP TOPOLOGY.
RX PubMed=12786943; DOI=10.1046/j.1365-2443.2003.00653.x;
RA Kihara A., Sano T., Iwaki S., Igarashi Y.;
RT "Transmembrane topology of sphingoid long-chain base-1-phosphate
RT phosphatase, Lcb3p.";
RL Genes Cells 8:525-535(2003).
RN [14]
RP FUNCTION.
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 [15]
RP TOPOLOGY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 208353 / W303-1A;
RX PubMed=16847258; DOI=10.1073/pnas.0604075103;
RA Kim H., Melen K., Oesterberg M., von Heijne G.;
RT "A global topology map of the Saccharomyces cerevisiae membrane proteome.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-16 AND SER-18, AND
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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-16 AND SER-18, AND
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 [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [19]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
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: Dihydrosphingosine 1-phosphate phosphatase required for
CC efficient ceramide synthesis from exogenous sphingoid bases
CC (PubMed:10477278, PubMed:10563329, PubMed:10856228, PubMed:11278643,
CC PubMed:11967828, PubMed:12493772, PubMed:12684378, PubMed:12786943,
CC PubMed:9195906, PubMed:9353337, PubMed:9419344, PubMed:25345524).
CC Involved in endocytosis and calcium-mediated signaling
CC (PubMed:10856228, PubMed:11278643). {ECO:0000269|PubMed:10477278,
CC ECO:0000269|PubMed:10563329, ECO:0000269|PubMed:10856228,
CC ECO:0000269|PubMed:11278643, ECO:0000269|PubMed:11967828,
CC ECO:0000269|PubMed:12493772, ECO:0000269|PubMed:12684378,
CC ECO:0000269|PubMed:12786943, ECO:0000269|PubMed:25345524,
CC ECO:0000269|PubMed:9195906, ECO:0000269|PubMed:9353337,
CC ECO:0000269|PubMed:9419344}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4R)-hydroxysphinganine 1-phosphate + H2O = (4R)-
CC hydroxysphinganine + phosphate; Xref=Rhea:RHEA:33067,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:64124,
CC ChEBI:CHEBI:64795; Evidence={ECO:0000269|PubMed:25345524};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33068;
CC Evidence={ECO:0000269|PubMed:25345524};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + sphinganine 1-phosphate = phosphate + sphinganine;
CC Xref=Rhea:RHEA:27514, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57817, ChEBI:CHEBI:57939;
CC Evidence={ECO:0000269|PubMed:25345524, ECO:0000269|PubMed:9353337};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27515;
CC Evidence={ECO:0000305|PubMed:25345524, ECO:0000305|PubMed:9353337};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8.3 uM for dihydrosphingosin 1-phosphate
CC {ECO:0000269|PubMed:25345524};
CC KM=17.4 uM for phytosphingosin 1-phosphate
CC {ECO:0000269|PubMed:25345524};
CC Vmax=6.0 nmol/min/ug enzyme toward dihydrosphingosin 1-phosphate
CC {ECO:0000269|PubMed:25345524};
CC Vmax=7.3 nmol/min/ug enzyme toward phytosphingosin 1-phosphate
CC {ECO:0000269|PubMed:25345524};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10477278, ECO:0000269|PubMed:10563329,
CC ECO:0000269|PubMed:9353337}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:10477278, ECO:0000269|PubMed:10563329,
CC ECO:0000269|PubMed:9353337}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:12786943}.
CC -!- SIMILARITY: Belongs to the type 2 lipid phosphate phosphatase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X87371; CAA60821.1; -; Genomic_DNA.
DR EMBL; Z49410; CAA89430.1; -; Genomic_DNA.
DR EMBL; BK006943; DAA08666.1; -; Genomic_DNA.
DR PIR; S55178; S55178.
DR RefSeq; NP_012401.1; NM_001181567.1.
DR AlphaFoldDB; P47013; -.
DR BioGRID; 33622; 122.
DR DIP; DIP-5685N; -.
DR IntAct; P47013; 4.
DR MINT; P47013; -.
DR STRING; 4932.YJL134W; -.
DR SwissLipids; SLP:000000932; -.
DR iPTMnet; P47013; -.
DR MaxQB; P47013; -.
DR PaxDb; P47013; -.
DR PRIDE; P47013; -.
DR EnsemblFungi; YJL134W_mRNA; YJL134W; YJL134W.
DR GeneID; 853307; -.
DR KEGG; sce:YJL134W; -.
DR SGD; S000003670; LCB3.
DR VEuPathDB; FungiDB:YJL134W; -.
DR eggNOG; KOG2822; Eukaryota.
DR GeneTree; ENSGT00660000096503; -.
DR HOGENOM; CLU_019266_1_1_1; -.
DR InParanoid; P47013; -.
DR OMA; HYLQDPH; -.
DR BioCyc; MetaCyc:MON3O-419; -.
DR BioCyc; YEAST:MON3O-419; -.
DR Reactome; R-SCE-1660661; Sphingolipid de novo biosynthesis.
DR PRO; PR:P47013; -.
DR Proteomes; UP000002311; Chromosome X.
DR RNAct; P47013; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:SGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0070780; F:dihydrosphingosine-1-phosphate phosphatase activity; IEA:RHEA.
DR GO; GO:0042392; F:sphingosine-1-phosphate phosphatase activity; IDA:SGD.
DR GO; GO:0019722; P:calcium-mediated signaling; IMP:SGD.
DR GO; GO:0046839; P:phospholipid dephosphorylation; IBA:GO_Central.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; TAS:SGD.
DR InterPro; IPR036938; P_Acid_Pase_2/haloperoxi_sf.
DR InterPro; IPR000326; P_Acid_Pase_2/haloperoxidase.
DR Pfam; PF01569; PAP2; 1.
DR SMART; SM00014; acidPPc; 1.
DR SUPFAM; SSF48317; SSF48317; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Hydrolase; Lipid metabolism; Membrane;
KW Phosphoprotein; Reference proteome; Sphingolipid metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..409
FT /note="Dihydrosphingosine 1-phosphate phosphatase LCB3"
FT /id="PRO_0000203037"
FT TOPO_DOM 1..86
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 87..107
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 108..112
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 113..133
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 134..182
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 183..203
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 204..207
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 208..228
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 229..245
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 246..266
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 267..276
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 277..297
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 298..315
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 316..336
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 337..384
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 385..405
FT /note="Helical; Name=8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 406..409
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:16847258"
FT REGION 15..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 128..136
FT /note="Phosphatase sequence motif I"
FT /evidence="ECO:0000305"
FT REGION 157..160
FT /note="Phosphatase sequence motif II"
FT /evidence="ECO:0000305"
FT REGION 203..214
FT /note="Phosphatase sequence motif III"
FT /evidence="ECO:0000305"
FT ACT_SITE 160
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P0A924"
FT ACT_SITE 210
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P0A924"
FT SITE 214
FT /note="Stabilizes the active site histidine for
FT nucleophilic attack"
FT /evidence="ECO:0000250|UniProtKB:P0A924"
FT MOD_RES 16
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
FT MUTAGEN 128
FT /note="K->A: Impairs dihydrosphingosine 1-phosphate
FT phosphatase activity."
FT /evidence="ECO:0000269|PubMed:12786943"
FT MUTAGEN 160
FT /note="H->A: Impairs dihydrosphingosine 1-phosphate
FT phosphatase activity."
FT /evidence="ECO:0000269|PubMed:12786943"
FT MUTAGEN 210
FT /note="H->A: Impairs dihydrosphingosine 1-phosphate
FT phosphatase activity."
FT /evidence="ECO:0000269|PubMed:12786943"
SQ SEQUENCE 409 AA; 47372 MW; E0CD7D0F169447C3 CRC64;
MVDGLNTSNI RKRARTLSNP NDFQEPNYLL DPGNHPSDHF RTRMSKFRFN IREKLLVFTN
NQSFTLSRWQ KKYRSAFNDL YFTYTSLMGS HTFYVLCLPM PVWFGYFETT KDMVYILGYS
IYLSGFFKDY WCLPRPRAPP LHRITLSEYT TKEYGAPSSH TANATGVSLL FLYNIWRMQE
SSVMVQLLLS CVVLFYYMTL VFGRIYCGMH GILDLVSGGL IGIVCFIVRM YFKYRFPGLR
IEEHWWFPLF SVGWGLLLLF KHVKPVDECP CFQDSVAFMG VVSGIECCDW LGKVFGVTLV
YNLEPNCGWR LTLARLLVGL PCVVIWKYVI SKPMIYTLLI KVFHLKDDRN VAARKRLEAT
HKEGASKYEC PLYIGEPKID ILGRFIIYAG VPFTVVMCSP VLFSLLNIA
