LAG1_YEAST
ID LAG1_YEAST Reviewed; 411 AA.
AC P38703; D3DKR1; Q6LD26;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Ceramide synthase LAG1;
DE AltName: Full=Longevity assurance factor 1;
DE AltName: Full=Longevity assurance gene 1 protein;
DE AltName: Full=Longevity assurance protein 1;
DE AltName: Full=Very-long-chain ceramide synthase LAG1;
DE EC=2.3.1.297 {ECO:0000269|PubMed:11694577, ECO:0000269|PubMed:12869556};
GN Name=LAG1; OrderedLocusNames=YHL003C;
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 26786 / X2180-1A;
RX PubMed=8195187; DOI=10.1016/s0021-9258(17)40700-9;
RA D'Mello N.P., Childress A.M., Franklin D.S., Kale S.P., Pinswasdi C.,
RA Jazwinski S.M.;
RT "Cloning and characterization of LAG1, a longevity-assurance gene in
RT yeast.";
RL J. Biol. Chem. 269:15451-15459(1994).
RN [2]
RP SEQUENCE REVISION TO 173-174; 220 AND 301-411.
RA Jazwinski S.M.;
RL Submitted (MAR-1994) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Manske M., Sommer T., Prehn S., Rapoport T.A., Hartmann E.;
RL Submitted (JAN-1994) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8091229; DOI=10.1126/science.8091229;
RA Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Dover J., Du Z.,
RA Favello A., Fulton L., Gattung S., Geisel C., Kirsten J., Kucaba T.,
RA Hillier L.W., Jier M., Johnston L., Langston Y., Latreille P., Louis E.J.,
RA Macri C., Mardis E., Menezes S., Mouser L., Nhan M., Rifkin L., Riles L.,
RA St Peter H., Trevaskis E., Vaughan K., Vignati D., Wilcox L., Wohldman P.,
RA Waterston R., Wilson R., Vaudin M.;
RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome
RT VIII.";
RL Science 265:2077-2082(1994).
RN [5]
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 [6]
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 [7]
RP FUNCTION.
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 [8]
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 [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 [10]
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 [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=12869556; DOI=10.1074/jbc.m307554200;
RA Guillas I., Jiang J.C., Vionnet C., Roubaty C., Uldry D., Chuard R.,
RA Wang J., Jazwinski S.M., Conzelmann A.;
RT "Human homologues of LAG1 reconstitute Acyl-CoA-dependent ceramide
RT synthesis in yeast.";
RL J. Biol. Chem. 278:37083-37091(2003).
RN [12]
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 [13]
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 [14]
RP FUNCTION.
RX PubMed=15236759; DOI=10.1016/j.exger.2004.03.026;
RA Jiang J.C., Kirchman P.A., Allen M., Jazwinski S.M.;
RT "Suppressor analysis points to the subtle role of the LAG1 ceramide
RT synthase gene in determining yeast longevity.";
RL Exp. Gerontol. 39:999-1009(2004).
RN [15]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH LAC1
RP 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 [16]
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 [17]
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 [18]
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 [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23 AND SER-24, 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 [21]
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).
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:12869556,
CC PubMed:11694577). N-acylates sphinganine and phytosphingosine bases to
CC form dihydroceramides and phytoceramides, respectively
CC (PubMed:12869556). Redundant with LAC1. Facilitates ER-to-Golgi
CC transport of GPI-anchored proteins. Involved in the aging process.
CC Deletion of LAG1 results in a pronounced increase (approximately 50%)
CC in mean and in maximum life span. {ECO:0000269|PubMed:10198056,
CC ECO:0000269|PubMed:11387200, ECO:0000269|PubMed:11694577,
CC ECO:0000269|PubMed:12869556, ECO:0000269|PubMed:15236759,
CC 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:12869556};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61481;
CC Evidence={ECO:0000269|PubMed:11694577, ECO:0000269|PubMed:12869556};
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:12869556};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33352;
CC Evidence={ECO:0000269|PubMed:12869556};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=sphinganine + tetracosanoyl-CoA = CoA + H(+) + N-
CC tetracosanoylsphinganine; Xref=Rhea:RHEA:33591, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:52961, ChEBI:CHEBI:57287, ChEBI:CHEBI:57817,
CC ChEBI:CHEBI:65052; Evidence={ECO:0000269|PubMed:12869556};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33592;
CC Evidence={ECO:0000269|PubMed:12869556};
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:12869556};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36556;
CC Evidence={ECO:0000269|PubMed:12869556};
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:12869556}.
CC -!- INTERACTION:
CC P38703; P28496: LAC1; NbExp=6; IntAct=EBI-10035, EBI-26585;
CC P38703; Q03579: LIP1; NbExp=3; IntAct=EBI-10035, EBI-27640;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Multi-pass membrane protein {ECO:0000250}.
CC -!- INDUCTION: Expression is controlled by CBF1.
CC {ECO:0000269|PubMed:15302821}.
CC -!- SIMILARITY: Belongs to the sphingosine N-acyltransferase family.
CC {ECO:0000305}.
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DR EMBL; U08133; AAA21579.1; -; Genomic_DNA.
DR EMBL; U05335; AAF21442.1; -; Genomic_DNA.
DR EMBL; U10555; AAB68429.1; -; Genomic_DNA.
DR EMBL; AY558514; AAS56840.1; -; Genomic_DNA.
DR EMBL; BK006934; DAA06684.1; -; Genomic_DNA.
DR PIR; S46800; S46800.
DR RefSeq; NP_011860.1; NM_001179083.1.
DR AlphaFoldDB; P38703; -.
DR BioGRID; 36422; 92.
DR ComplexPortal; CPX-1706; acyl-CoA ceramide synthase complex.
DR DIP; DIP-4393N; -.
DR IntAct; P38703; 20.
DR MINT; P38703; -.
DR STRING; 4932.YHL003C; -.
DR SwissLipids; SLP:000000276; -.
DR iPTMnet; P38703; -.
DR MaxQB; P38703; -.
DR PaxDb; P38703; -.
DR PRIDE; P38703; -.
DR EnsemblFungi; YHL003C_mRNA; YHL003C; YHL003C.
DR GeneID; 856386; -.
DR KEGG; sce:YHL003C; -.
DR SGD; S000000995; LAG1.
DR VEuPathDB; FungiDB:YHL003C; -.
DR eggNOG; KOG1607; Eukaryota.
DR GeneTree; ENSGT01030000234515; -.
DR HOGENOM; CLU_028277_4_0_1; -.
DR InParanoid; P38703; -.
DR OMA; HVLNLKI; -.
DR BioCyc; MetaCyc:MON3O-370; -.
DR BioCyc; YEAST:MON3O-370; -.
DR BRENDA; 2.3.1.24; 984.
DR BRENDA; 2.3.1.297; 984.
DR Reactome; R-SCE-1660661; Sphingolipid de novo biosynthesis.
DR UniPathway; UPA00222; -.
DR PRO; PR:P38703; -.
DR Proteomes; UP000002311; Chromosome VIII.
DR RNAct; P38703; protein.
DR GO; GO:0061576; C:acyl-CoA ceramide synthase complex; IDA:SGD.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA: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: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 SMART; SM00724; TLC; 1.
DR PROSITE; PS50922; TLC; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Phosphoprotein; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..411
FT /note="Ceramide synthase LAG1"
FT /id="PRO_0000185527"
FT TOPO_DOM 1..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..176
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 177..197
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 198..211
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 212..232
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 233..251
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 252..272
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 273..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..411
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 168..384
FT /note="TLC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00205"
FT REGION 390..411
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 411 AA; 48455 MW; 91676D56AC053F3C CRC64;
MTSATDKSID RLVVNAKTRR RNSSVGKIDL GDTVPGFAAM PESAASKNEA KKRMKALTGD
SKKDSDLLWK VWFSYREMNY RHSWLTPFFI LVCVYSAYFL SGNRTESNPL HMFVAISYQV
DGTDSYAKGI KDLSFVFFYM IFFTFLREFL MDVVIRPFTV YLNVTSEHRQ KRMLEQMYAI
FYCGVSGPFG LYIMYHSDLW LFKTKPMYRT YPVITNPFLF KIFYLGQAAF WAQQACVLVL
QLEKPRKDYK ELVFHHIVTL LLIWSSYVFH FTKMGLAIYI TMDVSDFFLS LSKTLNYLNS
VFTPFVFGLF VFFWIYLRHV VNIRILWSVL TEFRHEGNYV LNFATQQYKC WISLPIVFVL
IAALQLVNLY WLFLILRILY RLIWQGIQKD ERSDSDSDES AENEESKEKC E
