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 04-NOV-2026, entry version 202. 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). RN [22] {ECO:0000305} RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=26726837; DOI=10.1080/15384101.2015.1127475; RA Villasmil M.L., Francisco J., Gallo-Ebert C., Donigan M., Liu H.Y., RA Brower M., Nickels J.T. Jr.; RT "Ceramide signals for initiation of yeast mating-specific cell cycle RT arrest."; RL Cell Cycle 15:441-454(2016). RN [23] {ECO:0000305} RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=31164445; DOI=10.1242/jcs.228411; RA Megyeri M., Prasad R., Volpert G., Sliwa-Gonzalez A., Haribowo A.G., RA Aguilera-Romero A., Riezman H., Barral Y., Futerman A.H., Schuldiner M.; RT "Yeast ceramide synthases, Lag1 and Lac1, have distinct substrate RT specificity."; RL J. Cell Sci. 132:0-0(2019). RN [24] {ECO:0000305} RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-23 AND SER-24, AND RP MUTAGENESIS OF SER-23 AND SER-24. RX PubMed=34492164; DOI=10.1111/febs.16189; RA Ishino Y., Komatsu N., Sakata K.T., Yoshikawa D., Tani M., Maeda T., RA Morishige K., Yoshizawa K., Tanaka N., Tabuchi M.; RT "Regulation of sphingolipid biosynthesis in the endoplasmic reticulum via RT signals from the plasma membrane in budding yeast."; RL FEBS J. 289:457-472(2022). RN [25] {ECO:0000305} RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF HIS-255 AND RP HIS-256. RX PubMed=37953642; DOI=10.15252/embj.2023114889; RA Xie T., Fang Q., Zhang Z., Wang Y., Dong F., Gong X.; RT "Structure and mechanism of a eukaryotic ceramide synthase complex."; RL EMBO J. 42:e114889-e114889(2023). RN [26] {ECO:0007744|PDB:8QTN, ECO:0007744|PDB:8QTR} RP STRUCTURE BY ELECTRON MICROSCOPY IN COMPLEX WITH LAC1; LIP1; HEXACOSANOIC RP ACID; 1,2-DISTEAROYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE AND FUMONISIN B1, RP FUNCTION, SUBUNIT, AND DISRUPTION PHENOTYPE. RX PubMed=39528796; DOI=10.1038/s41594-024-01415-2; RA Schafer J.H., Clausmeyer L., Korner C., Esch B.M., Wolf V.N., Sapia J., RA Ahmed Y., Walter S., Vanni S., Januliene D., Moeller A., Frohlich F.; RT "Structure of the yeast ceramide synthase."; RL Nat. Struct. Mol. Biol. 0:0-0(2024). 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:11694577, CC PubMed:12869556, PubMed:37953642). N-acylates sphinganine and CC phytosphingosine bases to form dihydroceramides and phytoceramides, CC respectively (PubMed:12869556). Has a higher affinity for CC phytosphingosine (PHS) than dihydrosphingosine (DHS), and thus CC preferentially produces phytoceramides for the establishment of lateral CC diffusion barriers in the cortical endoplasmic reticulum and nuclear CC envelope (PubMed:31164445). Redundant with LAC1 but requires SUR2 to CC compensate for sphingolipid biosynthesis (PubMed:31164445, CC PubMed:39528796). Disruption or inhibition of sphingolipid synthesis CC leads to the activation and phosphorylation of YPK1 through the TORC2 CC and PKH1 pathways, which phosphorylates ORM1 and LAG1 to activate CC sphingolipid synthesis (PubMed:34492164). Facilitates ER-to-Golgi CC transport of GPI-anchored proteins. Involved in the aging process. CC Along with LAC1, plays a role in pheromone-induced MAP kinase- CC activation of mating and formation of diploid cells (PubMed:26726837). CC May also play a role, together with LAC1, in the polarized membrane CC distribution of phosphatidylinositol 4,5 biphosphate required for STE5 CC localization to the plasma membrane (PubMed:26726837). CC {ECO:0000269|PubMed:10198056, ECO:0000269|PubMed:11387200, CC ECO:0000269|PubMed:11694577, ECO:0000269|PubMed:12869556, CC ECO:0000269|PubMed:15236759, ECO:0000269|PubMed:15692566, CC ECO:0000269|PubMed:26726837, ECO:0000269|PubMed:31164445, CC ECO:0000269|PubMed:34492164, ECO:0000269|PubMed:37953642, CC ECO:0000269|PubMed:39528796}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a very long-chain fatty acyl-CoA + a sphingoid base = 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, ECO:0000269|PubMed:37953642}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61481; CC Evidence={ECO:0000269|PubMed:11694577, ECO:0000269|PubMed:12869556, CC ECO:0000269|PubMed:37953642}; CC -!- CATALYTIC ACTIVITY: CC Reaction=hexacosanoyl-CoA + sphinganine = N-hexacosanoylsphinganine + CC CoA + H(+); 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=tetracosanoyl-CoA + sphinganine = N-tetracosanoylsphinganine + CC CoA + H(+); 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 = N-eicosanoylsphinganine + CoA + CC H(+); Xref=Rhea:RHEA:36555, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, CC ChEBI:CHEBI:57380, ChEBI:CHEBI:57817, ChEBI:CHEBI:67027; CC 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=sphinganine + a fatty acyl-CoA = 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 -!- ACTIVITY REGULATION: As part of the ceramide synthase complex, CC inhibited by the sphinganine analog mycotoxin, fumonisin B1 (FB1) CC (PubMed:39528796). Activated by ACB1, as part of the ceramide synthase CC complex (PubMed:39528796). {ECO:0000269|PubMed:39528796}. CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism. CC {ECO:0000269|PubMed:11694577, ECO:0000269|PubMed:12869556}. CC -!- SUBUNIT: Component of the ceramide synthase complex composed of at CC least LAC1, LAG1 and LIP1 (PubMed:37953642, PubMed:39528796). Forms a CC heterotetrameric complex, where one unit of the LIP1 homodimer CC interacts with LAC1 and the other with either LAC1 or LAG1 CC (PubMed:39528796). {ECO:0000269|PubMed:37953642, CC ECO:0000269|PubMed:39528796}. CC -!- INTERACTION: CC P38703; P28496: LAC1; NbExp=7; IntAct=EBI-10035, EBI-26585; CC P38703; Q03579: LIP1; NbExp=3; IntAct=EBI-10035, EBI-27640; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:34492164}; Multi-pass membrane protein CC {ECO:0000269|PubMed:34492164, ECO:0000269|PubMed:37953642}. CC Note=Localized to both cortical and nuclear endoplasmic reticulum. CC {ECO:0000269|PubMed:34492164}. CC -!- INDUCTION: Expression is controlled by CBF1. CC {ECO:0000269|PubMed:15302821}. CC -!- PTM: Phosphorylated; phosphorylation is induced upon disruption of CC sphingolipid synthesis. {ECO:0000269|PubMed:34492164}. CC -!- DISRUPTION PHENOTYPE: Deletion of LAG1 results in a pronounced increase CC (approximately 50%) in mean and in maximum life span (PubMed:15236759). CC Does not affect the level of total sphingolipids (PubMed:31164445). CC Exhibits weak diffusion barriers in both cortical ER and nuclear CC envelope (PubMed:31164445). Double knockout of LAC1 and LAG1 abolishes CC growth and leads to mating defects including defects in diploid cell CC formation, pheromone-induced shmoo formation, induction of cell cycle CC arrest and activation of mating-specific MAP kinase (PubMed:26726837, CC PubMed:39528796). Also defective in the localization of STE5 to the CC plasma membrane (PubMed:26726837). {ECO:0000269|PubMed:15236759, CC ECO:0000269|PubMed:26726837, ECO:0000269|PubMed:31164445, CC ECO:0000269|PubMed:39528796}. CC -!- SIMILARITY: Belongs to the sphingosine N-acyltransferase 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; 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 PDB; 8QTN; EM; 3.00 A; A=75-383. DR PDB; 8QTR; EM; 3.20 A; A=75-383. DR AlphaFoldDB; P38703; -. DR EMDB; EMD-18652; -. DR EMDB; EMD-18653; -. DR SMR; P38703; -. DR BioGRID; 36422; 115. DR ComplexPortal; CPX-1706; Acyl-CoA ceramide synthase complex. DR DIP; DIP-4393N; -. DR FunCoup; P38703; 563. DR IntAct; P38703; 41. DR MINT; P38703; -. DR STRING; 4932.YHL003C; -. DR SwissLipids; SLP:000000276; -. DR GlyCosmos; P38703; 1 site, No reported glycans. DR GlyGen; P38703; 1 site. DR iPTMnet; P38703; -. DR PaxDb; 4932-YHL003C; -. DR PeptideAtlas; P38703; -. DR EnsemblFungi; YHL003C_mRNA; YHL003C; YHL003C. DR GeneID; 856386; -. DR KEGG; sce:YHL003C; -. DR AGR; SGD:S000000995; -. DR SGD; S000000995; LAG1. DR VEuPathDB; FungiDB:YHL003C; -. DR eggNOG; KOG1607; Eukaryota. DR HOGENOM; CLU_028277_4_0_1; -. DR InParanoid; P38703; -. DR OMA; AAGQYKC; -. DR OrthoDB; 3053196at2759; -. DR BioCyc; MetaCyc:MONOMER3O-370; -. DR BioCyc; YEAST:MONOMER3O-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 BioGRID-ORCS; 856386; 0 hits in 10 CRISPR screens. 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:0050291; F:sphingosine N-acyltransferase activity; IDA:SGD. DR GO; GO:0046513; P:ceramide biosynthetic process; IDA:ComplexPortal. DR InterPro; IPR016439; Lag1/Lac1-like. DR InterPro; IPR006634; TLC-dom. DR PANTHER; PTHR12560:SF11; CERAMIDE SYNTHASE LAC1-RELATED; 1. DR PANTHER; PTHR12560; LONGEVITY ASSURANCE FACTOR 1 LAG1; 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 3D-structure; Endoplasmic reticulum; Glycoprotein; Lipid biosynthesis; KW Lipid metabolism; Membrane; Phosphoprotein; Reference proteome; KW Transferase; Transmembrane; 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:0000269|PubMed:39528796" FT TOPO_DOM 103..130 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:39528796" FT TRANSMEM 131..155 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:39528796" FT TOPO_DOM 156..172 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:39528796" FT TRANSMEM 173..194 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:39528796" FT TOPO_DOM 195..217 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:39528796" FT TRANSMEM 218..240 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:39528796" FT TOPO_DOM 241..249 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:39528796" FT TRANSMEM 250..268 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:39528796" FT TOPO_DOM 269..273 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:39528796" FT TRANSMEM 274..295 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:39528796" FT TOPO_DOM 296..305 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:39528796" FT TRANSMEM 306..334 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:39528796" FT TOPO_DOM 335..353 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:39528796" FT TRANSMEM 354..382 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:39528796" FT TOPO_DOM 383..411 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:39528796" FT DOMAIN 168..385 FT /note="TLC" FT /evidence="ECO:0000250|UniProtKB:P28496, FT ECO:0000255|PROSITE-ProRule:PRU00205" FT REGION 390..411 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 252 FT /ligand="fumonisin B1" FT /ligand_id="ChEBI:CHEBI:62554" FT /evidence="ECO:0000269|PubMed:39528796, FT ECO:0007744|PDB:8QTR" FT BINDING 258 FT /ligand="hexacosanoate" FT /ligand_id="ChEBI:CHEBI:31013" FT /evidence="ECO:0000269|PubMed:39528796, FT ECO:0007744|PDB:8QTR" FT BINDING 303 FT /ligand="fumonisin B1" FT /ligand_id="ChEBI:CHEBI:62554" FT /evidence="ECO:0000269|PubMed:39528796, FT ECO:0007744|PDB:8QTR" FT BINDING 304 FT /ligand="fumonisin B1" FT /ligand_id="ChEBI:CHEBI:62554" FT /evidence="ECO:0000269|PubMed:39528796, FT ECO:0007744|PDB:8QTR" FT BINDING 318 FT /ligand="fumonisin B1" FT /ligand_id="ChEBI:CHEBI:62554" FT /evidence="ECO:0000269|PubMed:39528796, FT ECO:0007744|PDB:8QTR" FT BINDING 341 FT /ligand="hexacosanoate" FT /ligand_id="ChEBI:CHEBI:31013" FT /evidence="ECO:0000269|PubMed:39528796, FT ECO:0007744|PDB:8QTR" FT BINDING 350 FT /ligand="hexacosanoate" FT /ligand_id="ChEBI:CHEBI:31013" FT /evidence="ECO:0000269|PubMed:39528796, FT ECO:0007744|PDB:8QTR" FT BINDING 364 FT /ligand="hexacosanoate" FT /ligand_id="ChEBI:CHEBI:31013" FT /evidence="ECO:0000269|PubMed:39528796, FT ECO:0007744|PDB:8QTR" FT BINDING 378 FT /ligand="fumonisin B1" FT /ligand_id="ChEBI:CHEBI:62554" FT /evidence="ECO:0000269|PubMed:39528796, FT ECO:0007744|PDB:8QTR" FT BINDING 381 FT /ligand="fumonisin B1" FT /ligand_id="ChEBI:CHEBI:62554" FT /evidence="ECO:0000269|PubMed:39528796, FT ECO:0007744|PDB:8QTR" FT BINDING 382 FT /ligand="fumonisin B1" FT /ligand_id="ChEBI:CHEBI:62554" FT /evidence="ECO:0000269|PubMed:39528796, FT ECO:0007744|PDB:8QTR" FT MOD_RES 23 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:34492164, FT ECO:0007744|PubMed:19779198" FT MOD_RES 24 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:34492164, FT ECO:0007744|PubMed:19779198" FT CARBOHYD 103 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT MUTAGEN 23..24 FT /note="SS->AA: Exhibits higher sensitivity to myriocin FT disruption of sphingolipid synthesis in a LIP1 mutant FT background." FT /evidence="ECO:0000269|PubMed:34492164" FT MUTAGEN 255..256 FT /note="HH->AA: Abolishes the enzymatic activity of the FT LAG1-LIP1 complex." FT /evidence="ECO:0000269|PubMed:37953642" FT HELIX 76..81 FT /evidence="ECO:0007829|PDB:8QTN" FT HELIX 85..100 FT /evidence="ECO:0007829|PDB:8QTN" FT HELIX 111..114 FT /evidence="ECO:0007829|PDB:8QTN" FT STRAND 123..126 FT /evidence="ECO:0007829|PDB:8QTR" FT HELIX 131..149 FT /evidence="ECO:0007829|PDB:8QTN" FT HELIX 150..155 FT /evidence="ECO:0007829|PDB:8QTN" FT HELIX 156..162 FT /evidence="ECO:0007829|PDB:8QTN" FT HELIX 167..195 FT /evidence="ECO:0007829|PDB:8QTN" FT TURN 198..202 FT /evidence="ECO:0007829|PDB:8QTN" FT HELIX 206..209 FT /evidence="ECO:0007829|PDB:8QTN" FT STRAND 215..217 FT /evidence="ECO:0007829|PDB:8QTR" FT HELIX 218..240 FT /evidence="ECO:0007829|PDB:8QTN" FT HELIX 249..268 FT /evidence="ECO:0007829|PDB:8QTN" FT HELIX 272..297 FT /evidence="ECO:0007829|PDB:8QTN" FT HELIX 302..314 FT /evidence="ECO:0007829|PDB:8QTN" FT HELIX 315..321 FT /evidence="ECO:0007829|PDB:8QTN" FT HELIX 322..331 FT /evidence="ECO:0007829|PDB:8QTN" FT TURN 332..335 FT /evidence="ECO:0007829|PDB:8QTN" FT TURN 343..346 FT /evidence="ECO:0007829|PDB:8QTN" FT HELIX 353..382 FT /evidence="ECO:0007829|PDB:8QTN" 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 //