ELO3_YEAST
ID ELO3_YEAST Reviewed; 345 AA.
AC P40319; D6VZ09;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Elongation of fatty acids protein 3 {ECO:0000303|PubMed:9211877};
DE EC=2.3.1.199 {ECO:0000269|PubMed:12684876};
DE AltName: Full=3-keto acyl-CoA synthase ELO3 {ECO:0000305};
DE AltName: Full=Affecting plasma membrane ATPase activity protein 1 {ECO:0000303|PubMed:8027068};
DE AltName: Full=Suppressor of RAD3 essential function protein 1 {ECO:0000303|PubMed:3323825};
DE AltName: Full=Suppressor of Rvs161 and Rvs167 mutations protein 4 {ECO:0000303|PubMed:8488727};
DE AltName: Full=Very-long-chain 3-oxoacyl-CoA synthase 3 {ECO:0000305};
DE AltName: Full=v-SNARE bypass mutant gene 1 protein {ECO:0000303|PubMed:9832547};
GN Name=ELO3 {ECO:0000303|PubMed:9211877};
GN Synonyms=APA1 {ECO:0000303|PubMed:8027068},
GN SRE1 {ECO:0000303|PubMed:3323825}, SUR4 {ECO:0000303|PubMed:8488727},
GN VBM1 {ECO:0000303|PubMed:9832547};
GN OrderedLocusNames=YLR372W {ECO:0000312|SGD:S000004364}; ORFNames=L8039.2;
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 44827 / SKQ2N;
RA Revardel E.;
RL Thesis (1994), University of Bordeaux II, France.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=8027068; DOI=10.1016/s0021-9258(17)32419-5;
RA Garcia-Arranz M., Maldonado A.M., Mazon M.J., Portillo F.;
RT "Transcriptional control of yeast plasma membrane H(+)-ATPase by glucose.
RT Cloning and characterization of a new gene involved in this regulation.";
RL J. Biol. Chem. 269:18076-18082(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8649379; DOI=10.1128/mcb.16.6.2719;
RA Silve S., Leplatois P., Josse A., Dupuy P.-H., Lanau C., Kaghad M.,
RA Dhers C., Picard C., Rahier A., Taton M., Le Fur G., Caput D., Ferrara P.,
RA Loison G.;
RT "The immunosuppressant SR 31747 blocks cell proliferation by inhibiting a
RT steroid isomerase in Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 16:2719-2727(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SUBCELLULAR LOCATION.
RX PubMed=9832547; DOI=10.1083/jcb.143.5.1167;
RA David D., Sundarababu S., Gerst J.E.;
RT "Involvement of long chain fatty acid elongation in the trafficking of
RT secretory vesicles in yeast.";
RL J. Cell Biol. 143:1167-1182(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169871;
RA Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W.,
RA Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A.,
RA Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K.,
RA Heuss-Neitzel D., Hilbert H., Hilger F., Kleine K., Koetter P., Louis E.J.,
RA Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S.,
RA Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D.,
RA Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M.,
RA Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P.,
RA Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M.,
RA Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K.,
RA Zollner A., Hani J., Hoheisel J.D.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII.";
RL Nature 387:87-90(1997).
RN [6]
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 [7]
RP GENE NAME.
RX PubMed=3323825; DOI=10.1007/bf00331150;
RA Naumovski L., Friedberg E.C.;
RT "The RAD3 gene of Saccharomyces cerevisiae: isolation and characterization
RT of a temperature-sensitive mutant in the essential function and of
RT extragenic suppressors of this mutant.";
RL Mol. Gen. Genet. 209:458-466(1987).
RN [8]
RP IDENTIFICATION.
RX PubMed=8488727; DOI=10.1002/yea.320090306;
RA Desfarges L., Durrens P., Juguelin H., Cassagne C., Bonneu M., Aigle M.;
RT "Yeast mutants affected in viability upon starvation have a modified
RT phospholipid composition.";
RL Yeast 9:267-277(1993).
RN [9]
RP FUNCTION.
RX PubMed=9211877; DOI=10.1074/jbc.272.28.17376;
RA Oh C.-S., Toke D.A., Mandala S., Martin C.E.;
RT "ELO2 and ELO3, homologues of the Saccharomyces cerevisiae ELO1 gene,
RT function in fatty acid elongation and are required for sphingolipid
RT formation.";
RL J. Biol. Chem. 272:17376-17384(1997).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=12087109; DOI=10.1074/jbc.m205620200;
RA Han G., Gable K., Kohlwein S.D., Beaudoin F., Napier J.A., Dunn T.M.;
RT "The Saccharomyces cerevisiae YBR159w gene encodes the 3-ketoreductase of
RT the microsomal fatty acid elongase.";
RL J. Biol. Chem. 277:35440-35449(2002).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=12684876; DOI=10.1007/s00438-003-0836-0;
RA Roessler H., Rieck C., Delong T., Hoja U., Schweizer E.;
RT "Functional differentiation and selective inactivation of multiple
RT Saccharomyces cerevisiae genes involved in very-long-chain fatty acid
RT synthesis.";
RL Mol. Genet. Genomics 269:290-298(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 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 [14]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF PHE-262 AND LYS-266.
RX PubMed=17719544; DOI=10.1016/j.cell.2007.06.031;
RA Denic V., Weissman J.S.;
RT "A molecular caliper mechanism for determining very long-chain fatty acid
RT length.";
RL Cell 130:663-677(2007).
RN [15]
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 [16]
RP FUNCTION.
RX PubMed=29458843; DOI=10.1016/j.micres.2017.11.001;
RA Wang Q., Du X., Ma K., Shi P., Liu W., Sun J., Peng M., Huang Z.;
RT "A critical role for very long-chain fatty acid elongases in oleic acid-
RT mediated Saccharomyces cerevisiae cytotoxicity.";
RL Microbiol. Res. 207:1-7(2018).
CC -!- FUNCTION: Component of a microsomal membrane bound long-chain fatty
CC acid elongation system, which produces the 20-26-carbon very long-chain
CC fatty acids (VLCFA) from long-chain fatty acid precursors and is
CC involved ceramide and inositol sphingolipid biosynthesis. Component of
CC elongase III, which synthesizes 20-26-carbon fatty acids from 18-
CC carbon-fatty acyl-CoA primers such as stearoyl-CoA by incorporation of
CC malonyl-CoA (PubMed:9211877, PubMed:12684876). The enzymes active site
CC faces the cytosol, whereas VLCFA length is determined by a lysine near
CC the luminal end of transmembrane helix 6 (PubMed:17719544). Plays an
CC important role in lipotoxic cell death induced by oleic acid through
CC maintaining a balanced fatty acid composition in thr plasma membrane
CC (PubMed:29458843). Affects plasma membrane H(+)-ATPase activity. May
CC act on a glucose-signaling pathway that controls the expression of
CC several genes that are transcriptionally regulated by glucose such as
CC PMA1, HXT3 and SNF3 (PubMed:8027068). {ECO:0000269|PubMed:12684876,
CC ECO:0000269|PubMed:17719544, ECO:0000269|PubMed:29458843,
CC ECO:0000269|PubMed:8027068, ECO:0000269|PubMed:9211877}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a very-long-chain acyl-CoA + H(+) + malonyl-CoA = a very-long-
CC chain 3-oxoacyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:32727,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:90725, ChEBI:CHEBI:90736;
CC EC=2.3.1.199; Evidence={ECO:0000269|PubMed:12684876};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + malonyl-CoA + octadecanoyl-CoA = 3-oxoeicosanoyl-CoA +
CC CO2 + CoA; Xref=Rhea:RHEA:35319, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:57394, ChEBI:CHEBI:65115;
CC Evidence={ECO:0000269|PubMed:17719544};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35320;
CC Evidence={ECO:0000269|PubMed:17719544};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hexadecanoyl-CoA + malonyl-CoA = 3-oxooctadecanoyl-CoA
CC + CO2 + CoA; Xref=Rhea:RHEA:35315, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:71407;
CC Evidence={ECO:0000269|PubMed:17719544};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35316;
CC Evidence={ECO:0000269|PubMed:17719544};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=eicosanoyl-CoA + H(+) + malonyl-CoA = 3-oxodocosanoyl-CoA +
CC CO2 + CoA; Xref=Rhea:RHEA:35327, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57380,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:71451;
CC Evidence={ECO:0000269|PubMed:17719544};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35328;
CC Evidence={ECO:0000269|PubMed:17719544};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=docosanoyl-CoA + H(+) + malonyl-CoA = 3-oxotetracosanoyl-CoA +
CC CO2 + CoA; Xref=Rhea:RHEA:36507, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:65059, ChEBI:CHEBI:73977;
CC Evidence={ECO:0000269|PubMed:17719544};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36508;
CC Evidence={ECO:0000269|PubMed:17719544};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:12087109, ECO:0000269|PubMed:14562095,
CC ECO:0000269|PubMed:9832547}; Multi-pass membrane protein {ECO:0000305}.
CC -!- DOMAIN: The HxxHH motif is essential for ELOp function in vivo and 3-
CC keto acyl-CoA synthase activity in vitro.
CC {ECO:0000269|PubMed:17719544}.
CC -!- DOMAIN: The C-terminal di-lysine motifs may confer endoplasmic
CC reticulum localization. {ECO:0000303|PubMed:9832547}.
CC -!- SIMILARITY: Belongs to the ELO family. {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; L28723; AAA35134.1; -; Genomic_DNA.
DR EMBL; X78326; CAA55129.1; -; Genomic_DNA.
DR EMBL; X82033; CAA57553.1; -; Genomic_DNA.
DR EMBL; U19103; AAB67563.1; -; Genomic_DNA.
DR EMBL; AF011409; AAC28398.1; -; Genomic_DNA.
DR EMBL; BK006945; DAA09675.1; -; Genomic_DNA.
DR PIR; S48517; S48517.
DR RefSeq; NP_013476.3; NM_001182261.3.
DR AlphaFoldDB; P40319; -.
DR SMR; P40319; -.
DR BioGRID; 31632; 592.
DR DIP; DIP-4024N; -.
DR IntAct; P40319; 56.
DR MINT; P40319; -.
DR STRING; 4932.YLR372W; -.
DR SwissLipids; SLP:000000494; -.
DR iPTMnet; P40319; -.
DR MaxQB; P40319; -.
DR PaxDb; P40319; -.
DR PRIDE; P40319; -.
DR EnsemblFungi; YLR372W_mRNA; YLR372W; YLR372W.
DR GeneID; 851087; -.
DR KEGG; sce:YLR372W; -.
DR SGD; S000004364; ELO3.
DR VEuPathDB; FungiDB:YLR372W; -.
DR eggNOG; KOG3071; Eukaryota.
DR GeneTree; ENSGT01050000244965; -.
DR HOGENOM; CLU_048483_6_1_1; -.
DR InParanoid; P40319; -.
DR OMA; AACGPKF; -.
DR BioCyc; MetaCyc:MON3O-70; -.
DR BioCyc; YEAST:MON3O-70; -.
DR PRO; PR:P40319; -.
DR Proteomes; UP000002311; Chromosome XII.
DR RNAct; P40319; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:SGD.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0102336; F:3-oxo-arachidoyl-CoA synthase activity; IEA:RHEA.
DR GO; GO:0102338; F:3-oxo-lignoceronyl-CoA synthase activity; IEA:RHEA.
DR GO; GO:0009922; F:fatty acid elongase activity; IMP:SGD.
DR GO; GO:0102756; F:very-long-chain 3-ketoacyl-CoA synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IMP:SGD.
DR GO; GO:0030497; P:fatty acid elongation; IMP:SGD.
DR GO; GO:0034625; P:fatty acid elongation, monounsaturated fatty acid; IBA:GO_Central.
DR GO; GO:0034626; P:fatty acid elongation, polyunsaturated fatty acid; IBA:GO_Central.
DR GO; GO:0019367; P:fatty acid elongation, saturated fatty acid; IBA:GO_Central.
DR GO; GO:0032511; P:late endosome to vacuole transport via multivesicular body sorting pathway; IGI:SGD.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; IMP:SGD.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; IMP:SGD.
DR GO; GO:0042761; P:very long-chain fatty acid biosynthetic process; IMP:SGD.
DR InterPro; IPR030457; ELO_CS.
DR InterPro; IPR002076; ELO_fam.
DR PANTHER; PTHR11157; PTHR11157; 1.
DR Pfam; PF01151; ELO; 1.
DR PROSITE; PS01188; ELO; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Fatty acid biosynthesis; Fatty acid metabolism;
KW Glycoprotein; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..345
FT /note="Elongation of fatty acids protein 3"
FT /id="PRO_0000207550"
FT TOPO_DOM 1..73
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 74..94
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 95..105
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 106..126
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 127..155
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 156..176
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 177..180
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 181..201
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 202..207
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 208..228
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 229..242
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 243..263
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 264..283
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:16847258"
FT TRANSMEM 284..304
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 305..345
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:16847258"
FT REGION 318..345
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 185..189
FT /note="HxxHH motif"
FT /evidence="ECO:0000305|PubMed:17719544"
FT MOTIF 308..311
FT /note="Di-lysine motif 1"
FT /evidence="ECO:0000303|PubMed:9832547"
FT MOTIF 312..315
FT /note="Di-lysine motif 2"
FT /evidence="ECO:0000303|PubMed:9832547"
FT MOTIF 316..319
FT /note="Di-lysine motif 3"
FT /evidence="ECO:0000303|PubMed:9832547"
FT COMPBIAS 320..339
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 266
FT /note="Determines the chain length of the elongated VLCFA"
FT /evidence="ECO:0000305|PubMed:17719544"
FT CARBOHYD 2
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 20
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 66
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 262
FT /note="F->K: Terminates elongation following the production
FT of C22 instead of C-26; when associated with L-266."
FT /evidence="ECO:0000269|PubMed:17719544"
FT MUTAGEN 266
FT /note="K->L: Terminates elongation following the production
FT of C22 instead of C-26; when associated with K-262."
FT /evidence="ECO:0000269|PubMed:17719544"
FT CONFLICT 35
FT /note="E -> D (in Ref. 2; CAA55129)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="W -> R (in Ref. 2; CAA55129)"
FT /evidence="ECO:0000305"
FT CONFLICT 330..331
FT /note="ST -> FY (in Ref. 2; CAA55129)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 345 AA; 39465 MW; 1303A9AC54BFFCC5 CRC64;
MNTTTSTVIA AVADQFQSLN SSSSCFLKVH VPSIENPFGI ELWPIFSKVF EYFSGYPAEQ
FEFIHNKTFL ANGYHAVSII IVYYIIIFGG QAILRALNAS PLKFKLLFEI HNLFLTSISL
VLWLLMLEQL VPMVYHNGLF WSICSKEAFA PKLVTLYYLN YLTKFVELID TVFLVLRRKK
LLFLHTYHHG ATALLCYTQL IGRTSVEWVV ILLNLGVHVI MYWYYFLSSC GIRVWWKQWV
TRFQIIQFLI DLVFVYFATY TFYAHKYLDG ILPNKGTCYG TQAAAAYGYL ILTSYLLLFI
SFYIQSYKKG GKKTVKKESE VSGSVASGSS TGVKTSNTKV SSRKA
