MKAR_YEAST
ID MKAR_YEAST Reviewed; 347 AA.
AC P38286; D6VQF4;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Very-long-chain 3-oxoacyl-CoA reductase {ECO:0000255|HAMAP-Rule:MF_03107};
DE EC=1.1.1.330 {ECO:0000255|HAMAP-Rule:MF_03107};
DE AltName: Full=3-ketoacyl-CoA reductase {ECO:0000255|HAMAP-Rule:MF_03107};
DE Short=3-ketoreductase {ECO:0000255|HAMAP-Rule:MF_03107};
DE Short=KAR {ECO:0000255|HAMAP-Rule:MF_03107};
DE AltName: Full=Microsomal beta-keto-reductase {ECO:0000255|HAMAP-Rule:MF_03107};
GN Name=IFA38; OrderedLocusNames=YBR159W; ORFNames=YBR1209;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7813418; DOI=10.1002/j.1460-2075.1994.tb06923.x;
RA Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C.,
RA Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M.,
RA Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M.,
RA Cziepluch C., Demolis N., Delaveau T., Doignon F., Domdey H.,
RA Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D.,
RA Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N.,
RA Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J.,
RA Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C.,
RA Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P.,
RA Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y.,
RA Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F.,
RA Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E.,
RA Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M.,
RA Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B.,
RA Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L.,
RA Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M.,
RA Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S.,
RA Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K.,
RA Mewes H.-W., Kleine K.;
RT "Complete DNA sequence of yeast chromosome II.";
RL EMBO J. 13:5795-5809(1994).
RN [2]
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 [3]
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 [4]
RP FUNCTION.
RX PubMed=11792704; DOI=10.1074/jbc.m111441200;
RA Beaudoin F., Gable K., Sayanova O., Dunn T., Napier J.A.;
RT "A Saccharomyces cerevisiae gene required for heterologous fatty acid
RT elongase activity encodes a microsomal beta-keto-reductase.";
RL J. Biol. Chem. 277:11481-11488(2002).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND SUBUNIT.
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 [6]
RP FUNCTION.
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 [7]
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 [8]
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 [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 [10]
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 [11]
RP SUBCELLULAR LOCATION.
RX PubMed=23263984; DOI=10.1128/mcb.00811-12;
RA Browne C.M., Samir P., Fites J.S., Villarreal S.A., Link A.J.;
RT "The yeast eukaryotic translation initiation factor 2B translation
RT initiation complex interacts with the fatty acid synthesis enzyme YBR159W
RT and endoplasmic reticulum membranes.";
RL Mol. Cell. Biol. 33:1041-1056(2013).
RN [12]
RP CATALYTIC ACTIVITY.
RX PubMed=25003994; DOI=10.1371/journal.pone.0101823;
RA Naganuma T., Kihara A.;
RT "Two modes of regulation of the fatty acid elongase ELOVL6 by the 3-
RT ketoacyl-CoA reductase KAR in the fatty acid elongation cycle.";
RL PLoS ONE 9:E101823-E101823(2014).
CC -!- FUNCTION: Component of the microsomal membrane bound fatty acid
CC elongation system, which produces the 26-carbon very long-chain fatty
CC acids (VLCFA) from palmitate. Catalyzes the reduction of the 3-
CC ketoacyl-CoA intermediate that is formed in each cycle of fatty acid
CC elongation. VLCFAs serve as precursors for ceramide and sphingolipids.
CC {ECO:0000255|HAMAP-Rule:MF_03107, ECO:0000269|PubMed:11792704,
CC ECO:0000269|PubMed:12087109, ECO:0000269|PubMed:12684876,
CC ECO:0000269|PubMed:17719544}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a very-long-chain (3R)-3-hydroxyacyl-CoA + NADP(+) = a very-
CC long-chain 3-oxoacyl-CoA + H(+) + NADPH; Xref=Rhea:RHEA:48680,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:85440, ChEBI:CHEBI:90725; EC=1.1.1.330;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03107,
CC ECO:0000269|PubMed:12087109};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxooctadecanoyl-CoA + H(+) + NADPH = (3R)-
CC hydroxyoctadecanoyl-CoA + NADP(+); Xref=Rhea:RHEA:39151,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:71407, ChEBI:CHEBI:76374;
CC Evidence={ECO:0000269|PubMed:12087109, ECO:0000269|PubMed:25003994,
CC ECO:0000305|PubMed:17719544};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39152;
CC Evidence={ECO:0000305|PubMed:12087109, ECO:0000305|PubMed:17719544,
CC ECO:0000305|PubMed:25003994};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxoeicosanoyl-CoA + H(+) + NADPH = (3R)-hydroxyeicosanoyl-
CC CoA + NADP(+); Xref=Rhea:RHEA:39171, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:65115,
CC ChEBI:CHEBI:76373; Evidence={ECO:0000269|PubMed:12087109,
CC ECO:0000305|PubMed:17719544};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39172;
CC Evidence={ECO:0000305|PubMed:12087109, ECO:0000305|PubMed:17719544};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxodocosanoyl-CoA + H(+) + NADPH = (3R)-hydroxydocosanoyl-
CC CoA + NADP(+); Xref=Rhea:RHEA:39183, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:71451,
CC ChEBI:CHEBI:76375; Evidence={ECO:0000305|PubMed:17719544};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39184;
CC Evidence={ECO:0000305|PubMed:17719544};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxotetracosanoyl-CoA + H(+) + NADPH = (3R)-
CC hydroxytetracosanoyl-CoA + NADP(+); Xref=Rhea:RHEA:39195,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:73977, ChEBI:CHEBI:76377;
CC Evidence={ECO:0000305|PubMed:17719544};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39196;
CC Evidence={ECO:0000305|PubMed:17719544};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxohexacosanoyl-CoA + H(+) + NADPH = (3R)-
CC hydroxyhexacosanoyl-CoA + NADP(+); Xref=Rhea:RHEA:39207,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:73980, ChEBI:CHEBI:76378;
CC Evidence={ECO:0000305|PubMed:17719544};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39208;
CC Evidence={ECO:0000305|PubMed:17719544};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000269|PubMed:12087109}.
CC -!- SUBUNIT: Interacts with the fatty acid elongation system components
CC ELO3 and TSC13. {ECO:0000255|HAMAP-Rule:MF_03107,
CC ECO:0000269|PubMed:12087109}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000255|HAMAP-Rule:MF_03107, ECO:0000269|PubMed:23263984}; Single-
CC pass membrane protein {ECO:0000255|HAMAP-Rule:MF_03107}.
CC -!- MISCELLANEOUS: Present with 41900 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000255|HAMAP-Rule:MF_03107}.
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DR EMBL; Z36028; CAA85118.1; -; Genomic_DNA.
DR EMBL; AY557868; AAS56194.1; -; Genomic_DNA.
DR EMBL; BK006936; DAA07274.1; -; Genomic_DNA.
DR PIR; S46030; S46030.
DR RefSeq; NP_009717.1; NM_001178507.1.
DR AlphaFoldDB; P38286; -.
DR SMR; P38286; -.
DR BioGRID; 32858; 161.
DR DIP; DIP-8128N; -.
DR IntAct; P38286; 68.
DR MINT; P38286; -.
DR STRING; 4932.YBR159W; -.
DR SwissLipids; SLP:000000502; -.
DR iPTMnet; P38286; -.
DR MaxQB; P38286; -.
DR PaxDb; P38286; -.
DR PRIDE; P38286; -.
DR EnsemblFungi; YBR159W_mRNA; YBR159W; YBR159W.
DR GeneID; 852456; -.
DR KEGG; sce:YBR159W; -.
DR SGD; S000000363; IFA38.
DR VEuPathDB; FungiDB:YBR159W; -.
DR eggNOG; KOG1014; Eukaryota.
DR HOGENOM; CLU_010194_38_0_1; -.
DR InParanoid; P38286; -.
DR OMA; FLQHWSS; -.
DR BioCyc; MetaCyc:MON3O-79; -.
DR BioCyc; YEAST:MON3O-79; -.
DR BRENDA; 1.1.1.330; 984.
DR UniPathway; UPA00094; -.
DR PRO; PR:P38286; -.
DR Proteomes; UP000002311; Chromosome II.
DR RNAct; P38286; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:SGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:SGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0102339; F:3-oxo-arachidoyl-CoA reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0102340; F:3-oxo-behenoyl-CoA reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0102342; F:3-oxo-cerotoyl-CoA reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0102341; F:3-oxo-lignoceroyl-CoA reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0045703; F:ketoreductase activity; IMP:SGD.
DR GO; GO:0030497; P:fatty acid elongation; 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 HAMAP; MF_03107; 3_ketoreductase; 1.
DR InterPro; IPR027533; 3_ketoreductase_fungal.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Fatty acid biosynthesis; Fatty acid metabolism;
KW Lipid biosynthesis; Lipid metabolism; Membrane; NADP; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..347
FT /note="Very-long-chain 3-oxoacyl-CoA reductase"
FT /id="PRO_0000054868"
FT TRANSMEM 20..40
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03107"
FT ACT_SITE 223
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03107"
FT BINDING 210
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03107"
SQ SEQUENCE 347 AA; 38708 MW; E19044E8C89B8A6F CRC64;
MTFMQQLQEA GERFRCINGL LWVVFGLGVL KCTTLSLRFL ALIFDLFLLP AVNFDKYGAK
TGKYCAITGA SDGIGKEFAR QMAKRGFNLV LISRTQSKLE ALQKELEDQH HVVVKILAID
IAEDKESNYE SIKELCAQLP ITVLVNNVGQ SHSIPVPFLE TEEKELRNII TINNTATLLI
TQIIAPKIVE TVKAENKKSG TRGLILTMGS FGGLIPTPLL ATYSGSKSFL QGWSNSLAGE
LSKDAIDVEL IISYLVTSSM SKIRRSSLMI PNPQQFVKST LRSVGRRCGS QERYATMTPY
WAHAVYQFVI TETFGVYSKI VNSINYSFHK SIRIRALKKA ARQVKKE
