LAC1_YEAST
ID LAC1_YEAST Reviewed; 418 AA.
AC P28496; D6VXS8;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 2.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Ceramide synthase LAC1;
DE AltName: Full=Very-long-chain ceramide synthase LAC1;
DE EC=2.3.1.297 {ECO:0000269|PubMed:11694577, ECO:0000269|PubMed:15692566};
GN Name=LAC1; Synonyms=DGT1; OrderedLocusNames=YKL008C; ORFNames=YKL156;
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=8488728; DOI=10.1002/yea.320090307;
RA Boyer J., Pascolo S., Richard G.-F., Dujon B.;
RT "Sequence of a 7.8 kb segment on the left arm of yeast chromosome XI
RT reveals four open reading frames, including the CAP1 gene, an intron-
RT containing gene and a gene encoding a homolog to the mammalian UOG-1
RT gene.";
RL Yeast 9:279-287(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8196765; DOI=10.1038/369371a0;
RA Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V.,
RA Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P.,
RA Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L.,
RA Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A.,
RA Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H.,
RA Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L.,
RA Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M.,
RA Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H.,
RA Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J.,
RA Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H.,
RA Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J.,
RA Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S.,
RA Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F.,
RA Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R.,
RA Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W.,
RA Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M.,
RA Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C.,
RA Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H.,
RA Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L.,
RA van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S.,
RA von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M.,
RA Becker I., Mewes H.-W.;
RT "Complete DNA sequence of yeast chromosome XI.";
RL Nature 369:371-378(1994).
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] OF 1-149.
RX PubMed=1447293; DOI=10.1083/jcb.119.5.1151;
RA Amatruda J.F., Gattermeir D.J., Karpova T.S., Cooper J.A.;
RT "Effects of null mutations and overexpression of capping protein on
RT morphogenesis, actin distribution and polarized secretion in yeast.";
RL J. Cell Biol. 119:1151-1162(1992).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10198056; DOI=10.1091/mbc.10.4.1043;
RA Barz W.P., Walter P.;
RT "Two endoplasmic reticulum (ER) membrane proteins that facilitate ER-to-
RT Golgi transport of glycosylphosphatidylinositol-anchored proteins.";
RL Mol. Biol. Cell 10:1043-1059(1999).
RN [6]
RP FUNCTION.
RX PubMed=11387200; DOI=10.1093/emboj/20.11.2655;
RA Guillas I., Kirchman P.A., Chuard R., Pfefferli M., Jiang J.C.,
RA Jazwinski S.M., Conzelmann A.;
RT "C26-CoA-dependent ceramide synthesis of Saccharomyces cerevisiae is
RT operated by Lag1p and Lac1p.";
RL EMBO J. 20:2655-2665(2001).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=11694577; DOI=10.1091/mbc.12.11.3417;
RA Schorling S., Vallee B., Barz W.P., Riezman H., Oesterhelt D.;
RT "Lag1p and Lac1p are essential for the acyl-CoA-dependent ceramide synthase
RT reaction in Saccharomyces cerevisae.";
RL Mol. Biol. Cell 12:3417-3427(2001).
RN [8]
RP DOMAIN, AND TOPOLOGY.
RX PubMed=12151215; DOI=10.1016/s0968-0004(02)02154-0;
RA Winter E., Ponting C.P.;
RT "TRAM, LAG1 and CLN8: members of a novel family of lipid-sensing domains?";
RL Trends Biochem. Sci. 27:381-383(2002).
RN [9]
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 [10]
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 [11]
RP INDUCTION.
RX PubMed=15302821; DOI=10.1128/ec.3.4.880-892.2004;
RA Kolaczkowski M., Kolaczkowska A., Gaigg B., Schneiter R., Moye-Rowley W.S.;
RT "Differential regulation of ceramide synthase components LAC1 and LAG1 in
RT Saccharomyces cerevisiae.";
RL Eukaryot. Cell 3:880-892(2004).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, IDENTIFICATION BY MASS SPECTROMETRY,
RP AND INTERACTION WITH LAG1 AND LIP1.
RX PubMed=15692566; DOI=10.1038/sj.emboj.7600562;
RA Vallee B., Riezman H.;
RT "Lip1p: a novel subunit of acyl-CoA ceramide synthase.";
RL EMBO J. 24:730-741(2005).
RN [13]
RP TOPOLOGY.
RX PubMed=16756512; DOI=10.1042/bj20060697;
RA Kageyama-Yahara N., Riezman H.;
RT "Transmembrane topology of ceramide synthase in yeast.";
RL Biochem. J. 398:585-593(2006).
RN [14]
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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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).
CC -!- FUNCTION: Component of the ceramide synthase complex that catalyzes the
CC transfer of the acyl chain from acyl-CoA to a sphingoid base, with high
CC selectivity toward hexacosanoyl-CoA (C26:0-CoA) (PubMed:15692566,
CC PubMed:11694577). N-acylates sphinganine and phytosphingosine bases to
CC form dihydroceramides and phytoceramides, respectively
CC (PubMed:15692566, PubMed:11694577). Redundant with LAG1. Facilitates
CC ER-to-Golgi transport of GPI-anchored proteins.
CC {ECO:0000269|PubMed:10198056, ECO:0000269|PubMed:11387200,
CC ECO:0000269|PubMed:11694577, ECO:0000269|PubMed:15692566}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a sphingoid base + a very long-chain fatty acyl-CoA = an N-
CC (very-long-chain fatty acyl)-sphingoid base + CoA + H(+);
CC Xref=Rhea:RHEA:61480, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:84410, ChEBI:CHEBI:138261, ChEBI:CHEBI:144712;
CC EC=2.3.1.297; Evidence={ECO:0000269|PubMed:11694577,
CC ECO:0000269|PubMed:15692566};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61481;
CC Evidence={ECO:0000269|PubMed:11694577, ECO:0000269|PubMed:15692566};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexacosanoyl-CoA + sphinganine = CoA + H(+) + N-
CC hexacosanoylsphinganine; Xref=Rhea:RHEA:33351, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:52962, ChEBI:CHEBI:57287, ChEBI:CHEBI:57817,
CC ChEBI:CHEBI:64868; Evidence={ECO:0000269|PubMed:15692566};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33352;
CC Evidence={ECO:0000269|PubMed:15692566};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=eicosanoyl-CoA + sphinganine = CoA + H(+) + N-
CC eicosanoylsphinganine; Xref=Rhea:RHEA:36555, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57380, ChEBI:CHEBI:57817,
CC ChEBI:CHEBI:67027; Evidence={ECO:0000269|PubMed:15692566};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36556;
CC Evidence={ECO:0000269|PubMed:15692566};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a fatty acyl-CoA + sphinganine = an N-acylsphinganine + CoA +
CC H(+); Xref=Rhea:RHEA:34735, ChEBI:CHEBI:15378, ChEBI:CHEBI:31488,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57817, ChEBI:CHEBI:77636;
CC Evidence={ECO:0000269|PubMed:11694577};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34736;
CC Evidence={ECO:0000269|PubMed:11694577};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4R)-hydroxysphinganine + a fatty acyl-CoA = an N-acyl-(4R)-4-
CC hydroxysphinganine + CoA + H(+); Xref=Rhea:RHEA:35651,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:31998, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:64124, ChEBI:CHEBI:77636;
CC Evidence={ECO:0000269|PubMed:11694577};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35652;
CC Evidence={ECO:0000269|PubMed:11694577};
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC {ECO:0000269|PubMed:11694577, ECO:0000269|PubMed:15692566}.
CC -!- SUBUNIT: Composed of the ceramide synthase complex composed of at least
CC LAC1, LAG1 and LIP1.
CC -!- INTERACTION:
CC P28496; P38703: LAG1; NbExp=6; IntAct=EBI-26585, EBI-10035;
CC P28496; Q03579: LIP1; NbExp=5; IntAct=EBI-26585, EBI-27640;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10198056, ECO:0000269|PubMed:14562095}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:10198056,
CC ECO:0000269|PubMed:14562095}.
CC -!- INDUCTION: Expression is controlled by PDR1 and PDR3 which bind its
CC propmoter PDRE element, and by ROX1 and CBF1.
CC {ECO:0000269|PubMed:15302821}.
CC -!- MISCELLANEOUS: Present with 2840 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the sphingosine N-acyltransferase family.
CC {ECO:0000305}.
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DR EMBL; X61398; CAA43670.1; -; Genomic_DNA.
DR EMBL; S59773; AAC60549.1; -; Genomic_DNA.
DR EMBL; Z28008; CAA81843.1; -; Genomic_DNA.
DR EMBL; BK006944; DAA09148.1; -; Genomic_DNA.
DR PIR; S30134; S30134.
DR RefSeq; NP_012917.3; NM_001179574.3.
DR AlphaFoldDB; P28496; -.
DR BioGRID; 34124; 101.
DR ComplexPortal; CPX-1706; acyl-CoA ceramide synthase complex.
DR DIP; DIP-4348N; -.
DR IntAct; P28496; 58.
DR MINT; P28496; -.
DR STRING; 4932.YKL008C; -.
DR SwissLipids; SLP:000000277; -.
DR iPTMnet; P28496; -.
DR MaxQB; P28496; -.
DR PaxDb; P28496; -.
DR PRIDE; P28496; -.
DR EnsemblFungi; YKL008C_mRNA; YKL008C; YKL008C.
DR GeneID; 853861; -.
DR KEGG; sce:YKL008C; -.
DR SGD; S000001491; LAC1.
DR VEuPathDB; FungiDB:YKL008C; -.
DR eggNOG; KOG1607; Eukaryota.
DR GeneTree; ENSGT01030000234515; -.
DR HOGENOM; CLU_028277_4_0_1; -.
DR InParanoid; P28496; -.
DR OMA; FRIAYRF; -.
DR BioCyc; MetaCyc:MON3O-373; -.
DR BioCyc; YEAST:MON3O-373; -.
DR BRENDA; 2.3.1.297; 984.
DR Reactome; R-SCE-1660661; Sphingolipid de novo biosynthesis.
DR UniPathway; UPA00222; -.
DR PRO; PR:P28496; -.
DR Proteomes; UP000002311; Chromosome XI.
DR RNAct; P28496; protein.
DR GO; GO:0061576; C:acyl-CoA ceramide synthase complex; IDA:SGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:SGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0034399; C:nuclear periphery; HDA:SGD.
DR GO; GO:0016410; F:N-acyltransferase activity; IBA:GO_Central.
DR GO; GO:0050291; F:sphingosine N-acyltransferase activity; IDA:SGD.
DR GO; GO:0046513; P:ceramide biosynthetic process; IDA:SGD.
DR InterPro; IPR016439; Lag1/Lac1-like.
DR InterPro; IPR006634; TLC-dom.
DR InterPro; IPR013599; TRAM1.
DR PANTHER; PTHR12560; PTHR12560; 1.
DR Pfam; PF08390; TRAM1; 1.
DR Pfam; PF03798; TRAM_LAG1_CLN8; 1.
DR PIRSF; PIRSF005225; LAG1_LAC1; 1.
DR SMART; SM00724; TLC; 1.
DR PROSITE; PS50922; TLC; 1.
PE 1: Evidence at protein level;
KW Acetylation; Endoplasmic reticulum; Glycoprotein; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Phosphoprotein; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..418
FT /note="Ceramide synthase LAC1"
FT /id="PRO_0000185535"
FT TOPO_DOM 2..81
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 82..102
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 103..134
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 135..155
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 156..172
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 173..193
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 194..221
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 222..242
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 243..259
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 260..280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 281..296
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 297..317
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 318..355
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 356..376
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 377..418
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 168..384
FT /note="TLC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00205"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 390..418
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38703"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38703"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 418 AA; 48992 MW; 7691BA623AC0460A CRC64;
MSTIKPSPSN NNLKVRSRPR RKSSIGKIDL GDTVPSLGTM FETKESKTAA KRRMQRLSEA
TKNDSDLVKK IWFSFREISY RHAWIAPLMI LIAVYSAYFT SGNTTKTNVL HRFVAVSYQI
GDTNAYGKGI NDLCFVFYYM IFFTFLREFL MDVVIRPFAI RLHVTSKHRI KRIMEQMYAI
FYTGVSGPFG IYCMYHSDLW FFNTKAMYRT YPDFTNPFLF KVFYLGQAAF WAQQACILVL
QLEKPRKDHN ELTFHHIVTL LLIWSSYVFH FTKMGLPIYI TMDVSDFLLS FSKTLNYLDS
GLAFFSFAIF VVAWIYLRHY INLKILWSVL TQFRTEGNYV LNFATQQYKC WISLPIVFVL
IGALQLVNLY WLFLIFRVLY RILWRGILKD DRSDSESDEE SDESSTTPTD STPTKKDI
