ID   ERG13_YEAST             Reviewed;         491 AA.
AC   P54839; D6W0F9;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   03-AUG-2022, entry version 184.
DE   RecName: Full=Hydroxymethylglutaryl-CoA synthase {ECO:0000303|PubMed:12702274};
DE            Short=HMG-CoA synthase {ECO:0000303|PubMed:12702274};
DE            EC=2.3.3.10 {ECO:0000305|PubMed:12702274};
DE   AltName: Full=3-hydroxy-3-methylglutaryl coenzyme A synthase {ECO:0000303|PubMed:12702274};
GN   Name=ERG13 {ECO:0000303|PubMed:12702274}; Synonyms=HMGS;
GN   OrderedLocusNames=YML126C; ORFNames=YM4987.09C;
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 28383 / FL100 / VTT C-80102;
RA   Kribii R., Cordier H., Karst F.;
RL   Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169872;
RA   Bowman S., Churcher C.M., Badcock K., Brown D., Chillingworth T.,
RA   Connor R., Dedman K., Devlin K., Gentles S., Hamlin N., Hunt S., Jagels K.,
RA   Lye G., Moule S., Odell C., Pearson D., Rajandream M.A., Rice P.,
RA   Skelton J., Walsh S.V., Whitehead S., Barrell B.G.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII.";
RL   Nature 387:90-93(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   FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX   PubMed=12702274; DOI=10.1111/j.1567-1364.2002.tb00093.x;
RA   Grabinska K., Palamarczyk G.;
RT   "Dolichol biosynthesis in the yeast Saccharomyces cerevisiae: an insight
RT   into the regulatory role of farnesyl diphosphate synthase.";
RL   FEMS Yeast Res. 2:259-265(2002).
RN   [5]
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   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-276, AND IDENTIFICATION BY
RP   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   [7]
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).
CC   -!- FUNCTION: Hydroxymethylglutaryl-CoA synthase; part of the first module
CC       of 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:12702274). ERG13 condenses acetyl-CoA with acetoacetyl-CoA to
CC       form hydroxymethylglutaryl-CoA (HMG-CoA) (PubMed:12702274). The first
CC       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:12702274,
CC       ECO:0000303|PubMed:32679672}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=acetoacetyl-CoA + acetyl-CoA + H2O = (3S)-hydroxy-3-
CC         methylglutaryl-CoA + CoA + H(+); Xref=Rhea:RHEA:10188,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43074,
CC         ChEBI:CHEBI:57286, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288; EC=2.3.3.10;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU10116,
CC         ECO:0000305|PubMed:12702274};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10189;
CC         Evidence={ECO:0000305|PubMed:12702274};
CC   -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC       biosynthesis; (R)-mevalonate from acetyl-CoA: step 2/3.
CC       {ECO:0000305|PubMed:12702274}.
CC   -!- DISRUPTION PHENOTYPE: Drastically increases HMG2 half-life.
CC       {ECO:0000269|PubMed:12702274}.
CC   -!- MISCELLANEOUS: Present with 34800 molecules/cell in log phase SD
CC       medium. {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the thiolase-like superfamily. HMG-CoA synthase
CC       family. {ECO:0000305}.
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DR   EMBL; X96617; CAA65437.1; -; Genomic_DNA.
DR   EMBL; Z50178; CAA90557.1; -; Genomic_DNA.
DR   EMBL; BK006946; DAA09773.1; -; Genomic_DNA.
DR   PIR; S58202; S58202.
DR   RefSeq; NP_013580.1; NM_001182489.1.
DR   AlphaFoldDB; P54839; -.
DR   SMR; P54839; -.
DR   BioGRID; 35079; 282.
DR   DIP; DIP-5071N; -.
DR   IntAct; P54839; 36.
DR   MINT; P54839; -.
DR   STRING; 4932.YML126C; -.
DR   iPTMnet; P54839; -.
DR   MaxQB; P54839; -.
DR   PaxDb; P54839; -.
DR   PRIDE; P54839; -.
DR   EnsemblFungi; YML126C_mRNA; YML126C; YML126C.
DR   GeneID; 854913; -.
DR   KEGG; sce:YML126C; -.
DR   SGD; S000004595; ERG13.
DR   VEuPathDB; FungiDB:YML126C; -.
DR   eggNOG; KOG1393; Eukaryota.
DR   GeneTree; ENSGT00390000006096; -.
DR   HOGENOM; CLU_008065_0_1_1; -.
DR   InParanoid; P54839; -.
DR   OMA; DDAYNWI; -.
DR   BioCyc; MetaCyc:YML126C-MON; -.
DR   BioCyc; YEAST:YML126C-MON; -.
DR   BRENDA; 2.3.3.10; 984.
DR   Reactome; R-SCE-191273; Cholesterol biosynthesis.
DR   Reactome; R-SCE-77111; Synthesis of Ketone Bodies.
DR   UniPathway; UPA00058; UER00102.
DR   PRO; PR:P54839; -.
DR   Proteomes; UP000002311; Chromosome XIII.
DR   RNAct; P54839; protein.
DR   GO; GO:0005634; C:nucleus; HDA:SGD.
DR   GO; GO:0004421; F:hydroxymethylglutaryl-CoA synthase activity; IMP:SGD.
DR   GO; GO:0006084; P:acetyl-CoA metabolic process; IBA:GO_Central.
DR   GO; GO:0006696; P:ergosterol biosynthetic process; IMP:SGD.
DR   GO; GO:0010142; P:farnesyl diphosphate biosynthetic process, mevalonate pathway; IBA:GO_Central.
DR   Gene3D; 3.40.47.10; -; 1.
DR   InterPro; IPR000590; HMG_CoA_synt_AS.
DR   InterPro; IPR013746; HMG_CoA_synt_C_dom.
DR   InterPro; IPR013528; HMG_CoA_synth_N.
DR   InterPro; IPR010122; HMG_CoA_synthase_euk.
DR   InterPro; IPR016039; Thiolase-like.
DR   Pfam; PF08540; HMG_CoA_synt_C; 1.
DR   Pfam; PF01154; HMG_CoA_synt_N; 1.
DR   SUPFAM; SSF53901; SSF53901; 2.
DR   TIGRFAMs; TIGR01833; HMG-CoA-S_euk; 1.
DR   PROSITE; PS01226; HMG_COA_SYNTHASE; 1.
PE   1: Evidence at protein level;
KW   Lipid biosynthesis; Lipid metabolism; Phosphoprotein; Reference proteome;
KW   Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW   Sterol metabolism; Transferase.
FT   CHAIN           1..491
FT                   /note="Hydroxymethylglutaryl-CoA synthase"
FT                   /id="PRO_0000213758"
FT   ACT_SITE        127
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT   ACT_SITE        159
FT                   /note="Acyl-thioester intermediate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT   ACT_SITE        296
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT   MOD_RES         276
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956"
SQ   SEQUENCE   491 AA;  55014 MW;  44DFF3C0B0356D9E CRC64;
     MKLSTKLCWC GIKGRLRPQK QQQLHNTNLQ MTELKKQKTA EQKTRPQNVG IKGIQIYIPT
     QCVNQSELEK FDGVSQGKYT IGLGQTNMSF VNDREDIYSM SLTVLSKLIK SYNIDTNKIG
     RLEVGTETLI DKSKSVKSVL MQLFGENTDV EGIDTLNACY GGTNALFNSL NWIESNAWDG
     RDAIVVCGDI AIYDKGAARP TGGAGTVAMW IGPDAPIVFD SVRASYMEHA YDFYKPDFTS
     EYPYVDGHFS LTCYVKALDQ VYKSYSKKAI SKGLVSDPAG SDALNVLKYF DYNVFHVPTC
     KLVTKSYGRL LYNDFRANPQ LFPEVDAELA TRDYDESLTD KNIEKTFVNV AKPFHKERVA
     QSLIVPTNTG NMYTASVYAA FASLLNYVGS DDLQGKRVGL FSYGSGLAAS LYSCKIVGDV
     QHIIKELDIT NKLAKRITET PKDYEAAIEL RENAHLKKNF KPQGSIEHLQ SGVYYLTNID
     DKFRRSYDVK K