ERG13_CANAL
ID ERG13_CANAL Reviewed; 451 AA.
AC A0A1D8PTW6;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 18-JAN-2017, sequence version 1.
DT 25-MAY-2022, entry version 26.
DE RecName: Full=Hydroxymethylglutaryl-CoA synthase {ECO:0000250|UniProtKB:P54839};
DE Short=HMG-CoA synthase {ECO:0000250|UniProtKB:P54839};
DE EC=2.3.3.10 {ECO:0000250|UniProtKB:P54839};
DE AltName: Full=3-hydroxy-3-methylglutaryl coenzyme A synthase {ECO:0000250|UniProtKB:P54839};
GN Name=ERG13; OrderedLocusNames=CAALFM_CR09160CA, orf19.7312;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4]
RP FUNCTION.
RX PubMed=14653518; DOI=10.1080/1369378031000137233;
RA Song J.L., Lyons C.N., Holleman S., Oliver B.G., White T.C.;
RT "Antifungal activity of fluconazole in combination with lovastatin and
RT their effects on gene expression in the ergosterol and prenylation pathways
RT in Candida albicans.";
RL Med. Mycol. 41:417-425(2003).
RN [5]
RP INDUCTION.
RX PubMed=15917516; DOI=10.1128/aac.49.6.2226-2236.2005;
RA Liu T.T., Lee R.E., Barker K.S., Lee R.E., Wei L., Homayouni R.,
RA Rogers P.D.;
RT "Genome-wide expression profiling of the response to azole, polyene,
RT echinocandin, and pyrimidine antifungal agents in Candida albicans.";
RL Antimicrob. Agents Chemother. 49:2226-2236(2005).
RN [6]
RP INDUCTION.
RX PubMed=17588813; DOI=10.1016/j.ijmm.2007.03.020;
RA Kusch H., Engelmann S., Bode R., Albrecht D., Morschhauser J., Hecker M.;
RT "A proteomic view of Candida albicans yeast cell metabolism in exponential
RT and stationary growth phases.";
RL Int. J. Med. Microbiol. 298:291-318(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUMOYLATION.
RX PubMed=21209325; DOI=10.1091/mbc.e10-07-0632;
RA Leach M.D., Stead D.A., Argo E., Brown A.J.;
RT "Identification of sumoylation targets, combined with inactivation of SMT3,
RT reveals the impact of sumoylation upon growth, morphology, and stress
RT resistance in the pathogen Candida albicans.";
RL Mol. Biol. Cell 22:687-702(2011).
RN [8]
RP INDUCTION.
RX PubMed=22265407; DOI=10.1016/j.cell.2011.10.048;
RA Nobile C.J., Fox E.P., Nett J.E., Sorrells T.R., Mitrovich Q.M.,
RA Hernday A.D., Tuch B.B., Andes D.R., Johnson A.D.;
RT "A recently evolved transcriptional network controls biofilm development in
RT Candida albicans.";
RL Cell 148:126-138(2012).
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) (By
CC similarity). ERG13 condenses acetyl-CoA with acetoacetyl-CoA to form
CC hydroxymethylglutaryl-CoA (HMG-CoA) (By similarity). The first module
CC starts with the action of the cytosolic acetyl-CoA acetyltransferase
CC ERG10 that catalyzes the formation of acetoacetyl-CoA. The
CC hydroxymethylglutaryl-CoA synthase ERG13 then condenses acetyl-CoA with
CC acetoacetyl-CoA to form HMG-CoA. The 3-hydroxy-3-methylglutaryl-
CC coenzyme A (HMG-CoA) reductase HMG1 finally reduces HMG-CoA to produce
CC mevalonate (Probable). {ECO:0000250|UniProtKB:P54839,
CC ECO:0000305|PubMed:14653518}.
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:0000250|UniProtKB:P54839};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10189;
CC Evidence={ECO:0000250|UniProtKB:P54839};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 2/3.
CC {ECO:0000250|UniProtKB:P54839}.
CC -!- INDUCTION: Expressed during exponential and stationary growth phase
CC (PubMed:17588813). Expression is repressed by amphotericin B and
CC caspofungin (PubMed:15917516). Expression is also repressed during
CC biofilm formation (PubMed:22265407). {ECO:0000269|PubMed:15917516,
CC ECO:0000269|PubMed:17588813, ECO:0000269|PubMed:22265407}.
CC -!- PTM: Is a probable target for sumoylation.
CC {ECO:0000269|PubMed:21209325}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. HMG-CoA synthase
CC family. {ECO:0000305}.
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DR EMBL; CP017630; AOW31581.1; -; Genomic_DNA.
DR RefSeq; XP_716446.1; XM_711353.1.
DR AlphaFoldDB; A0A1D8PTW6; -.
DR SMR; A0A1D8PTW6; -.
DR STRING; 237561.A0A1D8PTW6; -.
DR GeneID; 3641881; -.
DR KEGG; cal:CAALFM_CR09160CA; -.
DR CGD; CAL0000197068; ERG13.
DR VEuPathDB; FungiDB:CR_09160C_A; -.
DR eggNOG; KOG1393; Eukaryota.
DR OMA; DDAYNWI; -.
DR OrthoDB; 495111at2759; -.
DR UniPathway; UPA00058; UER00102.
DR Proteomes; UP000000559; Chromosome R.
DR GO; GO:0004421; F:hydroxymethylglutaryl-CoA synthase activity; IBA:GO_Central.
DR GO; GO:0006084; P:acetyl-CoA metabolic process; IBA:GO_Central.
DR GO; GO:0009267; P:cellular response to starvation; IMP:CGD.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IBA:GO_Central.
DR GO; GO:0010142; P:farnesyl diphosphate biosynthetic process, mevalonate pathway; IBA:GO_Central.
DR GO; GO:0030447; P:filamentous growth; IMP:CGD.
DR GO; GO:0036180; P:filamentous growth of a population of unicellular organisms in response to biotic stimulus; IMP:CGD.
DR GO; GO:0036170; P:filamentous growth of a population of unicellular organisms in response to starvation; IMP:CGD.
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; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transferase; Ubl conjugation.
FT CHAIN 1..451
FT /note="Hydroxymethylglutaryl-CoA synthase"
FT /id="PRO_0000454164"
FT ACT_SITE 88
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT ACT_SITE 120
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT ACT_SITE 250
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
SQ SEQUENCE 451 AA; 49755 MW; 5877580E750709D3 CRC64;
MVMTNSPQNI GIKGIEVYIP GQAVNQSDLE KFDGIPQGKY TIGLGQTNMA FVNDREDIYS
ISLTVLSRLI KNYSIDTNKI GRLEVGTETL LDKSKSVKSV LMQLFPGNND IEGIDTVNAC
YGGTSSVINA INWIESSSWD GRDAIVVAGD IAIYDKGAAR PTGGVGAIAL LIGPDAPIVF
DSIRGSFMEH AYDFYKPDFT SEYPVVDGHF SLSCYVKAVD NCYKNYSKKI TGDANKTVGV
YDHFDFSAFH VPTCKLVTKS YARLLYNDYV SNPSKFADLI DETTRKHIDG LTYDESLTDK
ILEKTFVGLA KDETKKRVQP ALQVPTNTGN MYTASAWVSL ASLLYYVGSD NLKNKRISIF
SYGSGLASTL LSVTVKGDVS AITKVLDFDY KLGDGRKIQS PEDYLAAIEL REKAHLQKSF
KPQGSTDNLS QGTYYLTEID DKFRRAYAIK E
