LCB1_YEAST
ID LCB1_YEAST Reviewed; 558 AA.
AC P25045; D6W0C3;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Serine palmitoyltransferase 1;
DE Short=SPT 1;
DE Short=SPT1;
DE EC=2.3.1.50;
DE AltName: Full=Long chain base biosynthesis protein 1;
GN Name=LCB1; Synonyms=END8, TSC2; OrderedLocusNames=YMR296C;
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].
RX PubMed=2066332; DOI=10.1128/jb.173.14.4325-4332.1991;
RA Buede R., Rinker-Schaffer C., Pinto W.J., Lester R.L., Dickson R.C.;
RT "Cloning and characterization of LCB1, a Saccharomyces gene required for
RT biosynthesis of the long-chain base component of sphingolipids.";
RL J. Bacteriol. 173:4325-4332(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169872;
RA Bowman S., Churcher C.M., Badcock K., Brown D., Chillingworth T.,
RA Connor R., Dedman K., Devlin K., Gentles S., Hamlin N., Hunt S., Jagels K.,
RA Lye G., Moule S., Odell C., Pearson D., Rajandream M.A., Rice P.,
RA Skelton J., Walsh S.V., Whitehead S., Barrell B.G.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII.";
RL Nature 387:90-93(1997).
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [5]
RP FUNCTION, ENZYME ACTIVITY, AND SUBUNIT.
RX PubMed=8058731; DOI=10.1073/pnas.91.17.7899;
RA Nagiec M.M., Baltisberger J.A., Wells G.B., Lester R.L., Dickson R.C.;
RT "The LCB2 gene of Saccharomyces and the related LCB1 gene encode subunits
RT of serine palmitoyltransferase, the initial enzyme in sphingolipid
RT synthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:7899-7902(1994).
RN [6]
RP ENZYME ACTIVITY, INTERACTION WITH LCB2 AND TSC3, AND SUBCELLULAR LOCATION.
RX PubMed=10713067; DOI=10.1074/jbc.275.11.7597;
RA Gable K., Slife H., Bacikova D., Monaghan E., Dunn T.M.;
RT "Tsc3p is an 80-amino acid protein associated with serine
RT palmitoyltransferase and required for optimal enzyme activity.";
RL J. Biol. Chem. 275:7597-7603(2000).
RN [7]
RP FUNCTION, ENZYME ACTIVITY, SUBUNIT, INTERACTION WITH LCB2, AND MUTAGENESIS
RP OF CYS-180 AND VAL-191.
RX PubMed=11781309; DOI=10.1074/jbc.m107873200;
RA Gable K., Han G., Monaghan E., Bacikova D., Natarajan M., Williams R.,
RA Dunn T.M.;
RT "Mutations in the yeast LCB1 and LCB2 genes, including those corresponding
RT to the hereditary sensory neuropathy type I mutations, dominantly
RT inactivate serine palmitoyltransferase.";
RL J. Biol. Chem. 277:10194-10200(2002).
RN [8]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [9]
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 [10]
RP ENZYME ACTIVITY, INTERACTION WITH LCB2, SUBCELLULAR LOCATION, TOPOLOGY,
RP TRANSMEMBRANE DOMAINS, AND MUTAGENESIS OF 24-TYR--TRP-26; 50-ALA--THR-85;
RP 66-TYR--ILE-68; 342-LEU--ARG-371; 371-ARG--HIS-386; 386-HIS--SER-416;
RP 416-SER--TYR-425; 433-GLN--THR-458 AND 549-ILE-LEU-550.
RX PubMed=15485854; DOI=10.1074/jbc.m410014200;
RA Han G., Gable K., Yan L., Natarajan M., Krishnamurthy J., Gupta S.D.,
RA Borovitskaya A., Harmon J.M., Dunn T.M.;
RT "The topology of the Lcb1p subunit of yeast serine palmitoyltransferase.";
RL J. Biol. Chem. 279:53707-53716(2004).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-121, AND IDENTIFICATION BY
RP 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 [12]
RP IDENTIFICATION IN THE SPOTS COMPLEX.
RX PubMed=20182505; DOI=10.1038/nature08787;
RA Breslow D.K., Collins S.R., Bodenmiller B., Aebersold R., Simons K.,
RA Shevchenko A., Ejsing C.S., Weissman J.S.;
RT "Orm family proteins mediate sphingolipid homeostasis.";
RL Nature 463:1048-1053(2010).
CC -!- FUNCTION: Component of serine palmitoyltransferase (SPT), which
CC catalyzes the committed step in the synthesis of sphingolipids, the
CC condensation of serine with palmitoyl CoA to form the long chain base
CC 3-ketosphinganine. {ECO:0000269|PubMed:11781309,
CC ECO:0000269|PubMed:8058731}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hexadecanoyl-CoA + L-serine = 3-oxosphinganine + CO2 +
CC CoA; Xref=Rhea:RHEA:14761, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:33384, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379,
CC ChEBI:CHEBI:58299; EC=2.3.1.50;
CC Evidence={ECO:0000269|PubMed:10713067, ECO:0000269|PubMed:11781309,
CC ECO:0000269|PubMed:15485854, ECO:0000269|PubMed:8058731};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC -!- SUBUNIT: LCB1 and LCB2 encode essential subunits of the enzyme and form
CC a heterodimer. Component of the SPOTS complex, at least composed of
CC LCB1/2 (LCB1 and/or LCB2), ORM1/2 (ORM1 and/or ORM2), SAC1 and TSC3.
CC Interacts with LCB2 and TSC3. {ECO:0000269|PubMed:10713067,
CC ECO:0000269|PubMed:11781309, ECO:0000269|PubMed:15485854,
CC ECO:0000269|PubMed:20182505, ECO:0000269|PubMed:8058731}.
CC -!- INTERACTION:
CC P25045; P40970: LCB2; NbExp=9; IntAct=EBI-10059, EBI-10067;
CC P25045; P53224: ORM1; NbExp=5; IntAct=EBI-10059, EBI-12592;
CC P25045; Q06144: ORM2; NbExp=7; IntAct=EBI-10059, EBI-34916;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Endoplasmic reticulum membrane; Multi-
CC pass membrane protein.
CC -!- DOMAIN: The first transmembrane domain is not required for stability,
CC membrane association, interaction with LCB2, or enzymatic activity. The
CC second and third transmembrane domains are required for stability and
CC interaction with LCB2.
CC -!- MISCELLANEOUS: Present with 22400 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the class-II pyridoxal-phosphate-dependent
CC aminotransferase family. {ECO:0000305}.
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DR EMBL; M63674; AAA34739.1; -; Genomic_DNA.
DR EMBL; X80836; CAA56805.1; -; Genomic_DNA.
DR EMBL; AY693052; AAT93071.1; -; Genomic_DNA.
DR EMBL; BK006946; DAA10197.1; -; Genomic_DNA.
DR PIR; A43667; A43667.
DR RefSeq; NP_014025.1; NM_001182805.1.
DR AlphaFoldDB; P25045; -.
DR SMR; P25045; -.
DR BioGRID; 35476; 642.
DR ComplexPortal; CPX-3158; SPOTS complex.
DR DIP; DIP-5249N; -.
DR IntAct; P25045; 12.
DR MINT; P25045; -.
DR STRING; 4932.YMR296C; -.
DR iPTMnet; P25045; -.
DR MaxQB; P25045; -.
DR PaxDb; P25045; -.
DR PRIDE; P25045; -.
DR EnsemblFungi; YMR296C_mRNA; YMR296C; YMR296C.
DR GeneID; 855342; -.
DR KEGG; sce:YMR296C; -.
DR SGD; S000004911; LCB1.
DR VEuPathDB; FungiDB:YMR296C; -.
DR eggNOG; KOG1358; Eukaryota.
DR GeneTree; ENSGT00550000074872; -.
DR HOGENOM; CLU_015846_0_2_1; -.
DR InParanoid; P25045; -.
DR OMA; RNTPTFA; -.
DR BioCyc; MetaCyc:YMR296C-MON; -.
DR BioCyc; YEAST:YMR296C-MON; -.
DR UniPathway; UPA00222; -.
DR PRO; PR:P25045; -.
DR Proteomes; UP000002311; Chromosome XIII.
DR RNAct; P25045; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:SGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0035339; C:SPOTS complex; IDA:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0004758; F:serine C-palmitoyltransferase activity; IMP:SGD.
DR GO; GO:0090156; P:cellular sphingolipid homeostasis; IC:ComplexPortal.
DR GO; GO:0046513; P:ceramide biosynthetic process; IBA:GO_Central.
DR GO; GO:0046512; P:sphingosine biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.40.640.10; -; 1.
DR InterPro; IPR004839; Aminotransferase_I/II.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR Pfam; PF00155; Aminotran_1_2; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Cytoplasm; Endoplasmic reticulum; Lipid metabolism;
KW Membrane; Phosphoprotein; Pyridoxal phosphate; Reference proteome;
KW Sphingolipid metabolism; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..558
FT /note="Serine palmitoyltransferase 1"
FT /id="PRO_0000163856"
FT TOPO_DOM 1..49
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:15485854"
FT TRANSMEM 50..84
FT /note="Helical"
FT TOPO_DOM 85..341
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:15485854"
FT TRANSMEM 342..371
FT /note="Helical"
FT TOPO_DOM 372..424
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:15485854"
FT TRANSMEM 425..457
FT /note="Helical"
FT TOPO_DOM 458..558
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:15485854"
FT MOD_RES 121
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17330950"
FT MUTAGEN 24..26
FT /note="YLW->DRS: No effect on stability. No effect on LCB2
FT stabilization."
FT /evidence="ECO:0000269|PubMed:15485854"
FT MUTAGEN 50..85
FT /note="Missing: No effect on stability. No effect on LCB2
FT stabilization."
FT /evidence="ECO:0000269|PubMed:15485854"
FT MUTAGEN 66..68
FT /note="YGI->DVK: No effect on stability. No effect on LCB2
FT stabilization."
FT /evidence="ECO:0000269|PubMed:15485854"
FT MUTAGEN 180
FT /note="C->W,Y: Loss of activity. No effect on interaction
FT with LCB2."
FT /evidence="ECO:0000269|PubMed:11781309"
FT MUTAGEN 191
FT /note="V->D: Loss of activity. No effect on interaction
FT with LCB2."
FT /evidence="ECO:0000269|PubMed:11781309"
FT MUTAGEN 342..371
FT /note="Missing: Unstable. Destabilizes LCB2."
FT /evidence="ECO:0000269|PubMed:15485854"
FT MUTAGEN 371..386
FT /note="Missing: No effect on stability. Destabilizes LCB2."
FT /evidence="ECO:0000269|PubMed:15485854"
FT MUTAGEN 386..416
FT /note="Missing: Unstable. Destabilizes LCB2."
FT /evidence="ECO:0000269|PubMed:15485854"
FT MUTAGEN 416..425
FT /note="Missing: No effect on stability. Destabilizes LCB2."
FT /evidence="ECO:0000269|PubMed:15485854"
FT MUTAGEN 433..458
FT /note="Missing: Unstable. Destabilizes LCB2."
FT /evidence="ECO:0000269|PubMed:15485854"
FT MUTAGEN 549..550
FT /note="IL->AS: No effect on stability. Partially stabilizes
FT LCB2."
FT /evidence="ECO:0000269|PubMed:15485854"
FT MUTAGEN 549..550
FT /note="IL->PR: No effect on stability. Partially stabilizes
FT LCB2."
FT /evidence="ECO:0000269|PubMed:15485854"
FT CONFLICT 443
FT /note="A -> P (in Ref. 1; AAA34739)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 558 AA; 62207 MW; 9F7F93E4B2C70FDB CRC64;
MAHIPEVLPK SIPIPAFIVT TSSYLWYYFN LVLTQIPGGQ FIVSYIKKSH HDDPYRTTVE
IGLILYGIIY YLSKPQQKKS LQAQKPNLSP QEIDALIEDW EPEPLVDPSA TDEQSWRVAK
TPVTMEMPIQ NHITITRNNL QEKYTNVFNL ASNNFLQLSA TEPVKEVVKT TIKNYGVGAC
GPAGFYGNQD VHYTLEYDLA QFFGTQGSVL YGQDFCAAPS VLPAFTKRGD VIVADDQVSL
PVQNALQLSR STVYYFNHND MNSLECLLNE LTEQEKLEKL PAIPRKFIVT EGIFHNSGDL
APLPELTKLK NKYKFRLFVD ETFSIGVLGA TGRGLSEHFN MDRATAIDIT VGSMATALGS
TGGFVLGDSV MCLHQRIGSN AYCFSACLPA YTVTSVSKVL KLMDSNNDAV QTLQKLSKSL
HDSFASDDSL RSYVIVTSSP VSAVLHLQLT PAYRSRKFGY TCEQLFETMS ALQKKSQTNK
FIEPYEEEEK FLQSIVDHAL INYNVLITRN TIVLKQETLP IVPSLKICCN AAMSPEELKN
ACESVKQSIL ACCQESNK
