ERG10_YEAST
ID ERG10_YEAST Reviewed; 398 AA.
AC P41338; D6W3Y5;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Acetyl-CoA acetyltransferase {ECO:0000303|PubMed:7989303};
DE EC=2.3.1.9 {ECO:0000269|PubMed:5571829, ECO:0000269|PubMed:7989303};
DE AltName: Full=Acetoacetyl-CoA thiolase {ECO:0000303|PubMed:7989303};
DE AltName: Full=Ergosterol biosynthesis protein 10 {ECO:0000303|PubMed:7989303};
GN Name=ERG10 {ECO:0000303|PubMed:7989303}; OrderedLocusNames=YPL028W;
GN ORFNames=LPB3;
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], FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RX PubMed=7989303; DOI=10.1016/s0021-9258(18)31705-8;
RA Hiser L.M., Basson M.E., Rine J.;
RT "ERG10 from Saccharomyces cerevisiae encodes acetoacetyl-CoA thiolase.";
RL J. Biol. Chem. 269:31383-31389(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169875;
RA Bussey H., Storms R.K., Ahmed A., Albermann K., Allen E., Ansorge W.,
RA Araujo R., Aparicio A., Barrell B.G., Badcock K., Benes V., Botstein D.,
RA Bowman S., Brueckner M., Carpenter J., Cherry J.M., Chung E.,
RA Churcher C.M., Coster F., Davis K., Davis R.W., Dietrich F.S., Delius H.,
RA DiPaolo T., Dubois E., Duesterhoeft A., Duncan M., Floeth M., Fortin N.,
RA Friesen J.D., Fritz C., Goffeau A., Hall J., Hebling U., Heumann K.,
RA Hilbert H., Hillier L.W., Hunicke-Smith S., Hyman R.W., Johnston M.,
RA Kalman S., Kleine K., Komp C., Kurdi O., Lashkari D., Lew H., Lin A.,
RA Lin D., Louis E.J., Marathe R., Messenguy F., Mewes H.-W., Mirtipati S.,
RA Moestl D., Mueller-Auer S., Namath A., Nentwich U., Oefner P., Pearson D.,
RA Petel F.X., Pohl T.M., Purnelle B., Rajandream M.A., Rechmann S.,
RA Rieger M., Riles L., Roberts D., Schaefer M., Scharfe M., Scherens B.,
RA Schramm S., Schroeder M., Sdicu A.-M., Tettelin H., Urrestarazu L.A.,
RA Ushinsky S., Vierendeels F., Vissers S., Voss H., Walsh S.V., Wambutt R.,
RA Wang Y., Wedler E., Wedler H., Winnett E., Zhong W.-W., Zollner A.,
RA Vo D.H., Hani J.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI.";
RL Nature 387:103-105(1997).
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 PROTEIN SEQUENCE OF 2-36 AND 137-148, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RA Bienvenut W.V., Peters C.;
RL Submitted (JUN-2005) to UniProtKB.
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=5571829; DOI=10.1016/s0021-9258(18)62028-9;
RA Kornblatt J.A., Rudney H.;
RT "Two forms of acetoacetyl coenzyme A thiolase in yeast. I. Separation and
RT properties.";
RL J. Biol. Chem. 246:4417-4423(1971).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=5571830; DOI=10.1016/s0021-9258(18)62029-0;
RA Kornblatt J.A., Rudney H.;
RT "Two forms of acetoacetyl coenzyme A thiolase in yeast. II. Intracellular
RT location and relationship to growth.";
RL J. Biol. Chem. 246:4424-4430(1971).
RN [7]
RP INDUCTION.
RX PubMed=8754796; DOI=10.1128/mcb.16.8.3981;
RA Dimster-Denk D., Rine J.;
RT "Transcriptional regulation of a sterol-biosynthetic enzyme by sterol
RT levels in Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 16:3981-3989(1996).
RN [8]
RP INDUCTION, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12039763; DOI=10.1128/aem.68.6.3024-3030.2002;
RA Rodriguez-Vargas S., Estruch F., Randez-Gil F.;
RT "Gene expression analysis of cold and freeze stress in Baker's yeast.";
RL Appl. Environ. Microbiol. 68:3024-3030(2002).
RN [9]
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 [10]
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).
RN [11]
RP REVIEW ON ERGOSTEROL BIOSYNTHESIS.
RX PubMed=32679672; DOI=10.3390/genes11070795;
RA Jorda T., Puig S.;
RT "Regulation of ergosterol biosynthesis in Saccharomyces cerevisiae.";
RL Genes (Basel) 11:0-0(2020).
RN [12] {ECO:0007744|PDB:5XYJ, ECO:0007744|PDB:5XZ5}
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS), AND SUBUNIT.
RX PubMed=29372902; DOI=10.1107/s2053230x17016971;
RA Zhou P., Zhu Z., Hidayatullah Khan M., Zheng P., Teng M., Niu L.;
RT "Crystal structure of cytoplasmic acetoacetyl-CoA thiolase from
RT Saccharomyces cerevisiae.";
RL Acta Crystallogr. F Struct. Biol. Commun. 74:6-13(2018).
CC -!- FUNCTION: Acetyl-CoA acetyltransferase; part of the first module of
CC ergosterol biosynthesis pathway that includes the early steps of the
CC pathway, conserved across all eukaryotes, and which results in the
CC formation of mevalonate from acetyl-coenzyme A (acetyl-CoA)
CC (PubMed:7989303, PubMed:5571829). ERG10 catalyzes the formation of
CC acetoacetyl-CoA from acetyl-CoA (PubMed:7989303, PubMed:5571829). The
CC first module starts with the action of the cytosolic acetyl-CoA
CC acetyltransferase ERG10 that catalyzes the formation of acetoacetyl-
CC CoA. The hydroxymethylglutaryl-CoA synthase ERG13 then condenses
CC acetyl-CoA with acetoacetyl-CoA to form HMG-CoA. The rate-limiting step
CC of the early module is the reduction to mevalonate by the 3-hydroxy-3-
CC methylglutaryl-coenzyme A (HMG-CoA) reductases HMG1 and HMG2 which are
CC derived from a single ancestral HMGR gene by gene duplication
CC (PubMed:32679672). {ECO:0000269|PubMed:5571829,
CC ECO:0000269|PubMed:7989303, ECO:0000303|PubMed:32679672}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 acetyl-CoA = acetoacetyl-CoA + CoA; Xref=Rhea:RHEA:21036,
CC ChEBI:CHEBI:57286, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288; EC=2.3.1.9;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10020,
CC ECO:0000269|PubMed:5571829, ECO:0000269|PubMed:7989303};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21037;
CC Evidence={ECO:0000269|PubMed:5571829, ECO:0000269|PubMed:7989303};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.16 mM for CoA {ECO:0000269|PubMed:5571829};
CC KM=0.35 mM for acetoacetyl-CoA {ECO:0000269|PubMed:5571829};
CC pH dependence:
CC Optimum pH is 8.8. {ECO:0000269|PubMed:5571829};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 1/3.
CC {ECO:0000269|PubMed:5571829, ECO:0000269|PubMed:7989303}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:29372902}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:5571830}.
CC -!- INDUCTION: Induced by low intracellular sterol levels (PubMed:8754796).
CC Also highly induced by cold conditions (PubMed:12039763).
CC {ECO:0000269|PubMed:12039763, ECO:0000269|PubMed:8754796}.
CC -!- DISRUPTION PHENOTYPE: Leads to cold and freeze sensitivity.
CC {ECO:0000269|PubMed:12039763}.
CC -!- MISCELLANEOUS: Present with 60895 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Thiolase family.
CC {ECO:0000305}.
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DR EMBL; L20428; AAA62378.1; -; Genomic_DNA.
DR EMBL; U36624; AAB68159.1; -; Genomic_DNA.
DR EMBL; BK006949; DAA11401.1; -; Genomic_DNA.
DR PIR; A55654; A55654.
DR RefSeq; NP_015297.1; NM_001183842.1.
DR PDB; 5XYJ; X-ray; 1.93 A; A/B=1-398.
DR PDB; 5XZ5; X-ray; 2.20 A; A/B=1-398.
DR PDBsum; 5XYJ; -.
DR PDBsum; 5XZ5; -.
DR AlphaFoldDB; P41338; -.
DR SMR; P41338; -.
DR BioGRID; 36150; 268.
DR DIP; DIP-6396N; -.
DR IntAct; P41338; 9.
DR MINT; P41338; -.
DR STRING; 4932.YPL028W; -.
DR iPTMnet; P41338; -.
DR MaxQB; P41338; -.
DR PaxDb; P41338; -.
DR PRIDE; P41338; -.
DR EnsemblFungi; YPL028W_mRNA; YPL028W; YPL028W.
DR GeneID; 856079; -.
DR KEGG; sce:YPL028W; -.
DR SGD; S000005949; ERG10.
DR VEuPathDB; FungiDB:YPL028W; -.
DR eggNOG; KOG1390; Eukaryota.
DR GeneTree; ENSGT01030000234626; -.
DR HOGENOM; CLU_031026_0_1_1; -.
DR InParanoid; P41338; -.
DR OMA; ICPSIAI; -.
DR BioCyc; MetaCyc:YPL028W-MON; -.
DR BioCyc; YEAST:YPL028W-MON; -.
DR BRENDA; 2.3.1.9; 984.
DR UniPathway; UPA00058; UER00101.
DR PRO; PR:P41338; -.
DR Proteomes; UP000002311; Chromosome XVI.
DR RNAct; P41338; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; HDA:SGD.
DR GO; GO:0003985; F:acetyl-CoA C-acetyltransferase activity; IDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IMP:SGD.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IBA:GO_Central.
DR CDD; cd00751; thiolase; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR002155; Thiolase.
DR InterPro; IPR016039; Thiolase-like.
DR InterPro; IPR020615; Thiolase_acyl_enz_int_AS.
DR InterPro; IPR020610; Thiolase_AS.
DR InterPro; IPR020617; Thiolase_C.
DR InterPro; IPR020613; Thiolase_CS.
DR InterPro; IPR020616; Thiolase_N.
DR Pfam; PF02803; Thiolase_C; 1.
DR Pfam; PF00108; Thiolase_N; 1.
DR PIRSF; PIRSF000429; Ac-CoA_Ac_transf; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
DR TIGRFAMs; TIGR01930; AcCoA-C-Actrans; 1.
DR PROSITE; PS00098; THIOLASE_1; 1.
DR PROSITE; PS00737; THIOLASE_2; 1.
DR PROSITE; PS00099; THIOLASE_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Acyltransferase; Cytoplasm;
KW Direct protein sequencing; Metal-binding; Potassium; Reference proteome;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PubMed:22814378"
FT CHAIN 2..398
FT /note="Acetyl-CoA acetyltransferase"
FT /id="PRO_0000206416"
FT ACT_SITE 91
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT ACT_SITE 354
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10020"
FT ACT_SITE 384
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10020"
FT BINDING 186
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 186
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 231
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 248
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 249
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 251
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 252
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT BINDING 350
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P24752"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|Ref.4, ECO:0007744|PubMed:22814378"
FT STRAND 5..12
FT /evidence="ECO:0007829|PDB:5XYJ"
FT TURN 21..24
FT /evidence="ECO:0007829|PDB:5XYJ"
FT HELIX 27..40
FT /evidence="ECO:0007829|PDB:5XYJ"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:5XYJ"
FT STRAND 53..57
FT /evidence="ECO:0007829|PDB:5XYJ"
FT HELIX 68..75
FT /evidence="ECO:0007829|PDB:5XYJ"
FT STRAND 83..87
FT /evidence="ECO:0007829|PDB:5XYJ"
FT HELIX 90..92
FT /evidence="ECO:0007829|PDB:5XYJ"
FT HELIX 93..106
FT /evidence="ECO:0007829|PDB:5XYJ"
FT STRAND 111..121
FT /evidence="ECO:0007829|PDB:5XYJ"
FT TURN 129..133
FT /evidence="ECO:0007829|PDB:5XYJ"
FT HELIX 145..149
FT /evidence="ECO:0007829|PDB:5XYJ"
FT TURN 154..156
FT /evidence="ECO:0007829|PDB:5XYJ"
FT HELIX 160..170
FT /evidence="ECO:0007829|PDB:5XYJ"
FT HELIX 175..195
FT /evidence="ECO:0007829|PDB:5XYJ"
FT TURN 196..201
FT /evidence="ECO:0007829|PDB:5XYJ"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:5XYJ"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:5XYJ"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:5XYJ"
FT HELIX 229..233
FT /evidence="ECO:0007829|PDB:5XYJ"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:5XYJ"
FT STRAND 241..243
FT /evidence="ECO:0007829|PDB:5XYJ"
FT TURN 248..250
FT /evidence="ECO:0007829|PDB:5XYJ"
FT STRAND 255..265
FT /evidence="ECO:0007829|PDB:5XYJ"
FT HELIX 266..271
FT /evidence="ECO:0007829|PDB:5XYJ"
FT STRAND 278..287
FT /evidence="ECO:0007829|PDB:5XYJ"
FT HELIX 290..296
FT /evidence="ECO:0007829|PDB:5XYJ"
FT HELIX 297..307
FT /evidence="ECO:0007829|PDB:5XYJ"
FT HELIX 313..315
FT /evidence="ECO:0007829|PDB:5XYJ"
FT STRAND 318..321
FT /evidence="ECO:0007829|PDB:5XYJ"
FT HELIX 326..336
FT /evidence="ECO:0007829|PDB:5XYJ"
FT HELIX 340..342
FT /evidence="ECO:0007829|PDB:5XYJ"
FT HELIX 349..352
FT /evidence="ECO:0007829|PDB:5XYJ"
FT HELIX 356..374
FT /evidence="ECO:0007829|PDB:5XYJ"
FT STRAND 378..385
FT /evidence="ECO:0007829|PDB:5XYJ"
FT TURN 386..388
FT /evidence="ECO:0007829|PDB:5XYJ"
FT STRAND 389..397
FT /evidence="ECO:0007829|PDB:5XYJ"
SQ SEQUENCE 398 AA; 41729 MW; E835A8E040629A5C CRC64;
MSQNVYIVST ARTPIGSFQG SLSSKTAVEL GAVALKGALA KVPELDASKD FDEIIFGNVL
SANLGQAPAR QVALAAGLSN HIVASTVNKV CASAMKAIIL GAQSIKCGNA DVVVAGGCES
MTNAPYYMPA ARAGAKFGQT VLVDGVERDG LNDAYDGLAM GVHAEKCARD WDITREQQDN
FAIESYQKSQ KSQKEGKFDN EIVPVTIKGF RGKPDTQVTK DEEPARLHVE KLRSARTVFQ
KENGTVTAAN ASPINDGAAA VILVSEKVLK EKNLKPLAII KGWGEAAHQP ADFTWAPSLA
VPKALKHAGI EDINSVDYFE FNEAFSVVGL VNTKILKLDP SKVNVYGGAV ALGHPLGCSG
ARVVVTLLSI LQQEGGKIGV AAICNGGGGA SSIVIEKI
