ERG13_GANLU
ID ERG13_GANLU Reviewed; 470 AA.
AC K7PL94;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2013, sequence version 1.
DT 03-AUG-2022, entry version 24.
DE RecName: Full=Hydroxymethylglutaryl-CoA synthase {ECO:0000303|PubMed:23138457};
DE Short=HMG-CoA synthase {ECO:0000303|PubMed:23138457};
DE EC=2.3.3.10 {ECO:0000305|PubMed:23138457};
DE AltName: Full=3-hydroxy-3-methylglutaryl coenzyme A synthase {ECO:0000250|UniProtKB:P54839};
GN Name=HMGS {ECO:0000303|PubMed:23138457};
OS Ganoderma lucidum (Ling zhi medicinal fungus) (Bracket fungus).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Polyporales; Polyporaceae; Ganoderma.
OX NCBI_TaxID=5315;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, AND INDUCTION.
RC STRAIN=HG;
RX PubMed=23138457; DOI=10.1007/s11274-012-1206-z;
RA Ren A., Ouyang X., Shi L., Jiang A.L., Mu D.S., Li M.J., Han Q., Zhao M.W.;
RT "Molecular characterization and expression analysis of GlHMGS, a gene
RT encoding hydroxymethylglutaryl-CoA synthase from Ganoderma lucidum (Ling-
RT zhi) in ganoderic acid biosynthesis pathway.";
RL World J. Microbiol. Biotechnol. 29:523-531(2013).
RN [2]
RP FUNCTION.
RX PubMed=18460810; DOI=10.1271/bbb.80011;
RA Shang C.H., Zhu F., Li N., Ou-Yang X., Shi L., Zhao M.W., Li Y.X.;
RT "Cloning and characterization of a gene encoding HMG-CoA reductase from
RT Ganoderma lucidum and its functional identification in yeast.";
RL Biosci. Biotechnol. Biochem. 72:1333-1339(2008).
RN [3]
RP FUNCTION.
RX PubMed=29476632; DOI=10.1002/bit.26583;
RA Wang W.F., Xiao H., Zhong J.J.;
RT "Biosynthesis of a ganoderic acid in Saccharomyces cerevisiae by expressing
RT a cytochrome P450 gene from Ganoderma lucidum.";
RL Biotechnol. Bioeng. 115:1842-1854(2018).
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:23138457). This module also plays a key role in the
CC biosynthesis of triterpenes such as ganoderic acids (GA), a group of
CC highly oxygenated lanostane-type triterpenoids which are well
CC recognized as a main group of unique bioactive compounds in the
CC medicinal mushroom Ganoderma lucidum (PubMed:23138457) (Probable). In
CC this module, the acetyl-CoA acetyltransferase catalyzes the formation
CC of acetoacetyl-CoA (By similarity). The hydroxymethylglutaryl-CoA
CC synthase HMGS then condenses acetyl-CoA with acetoacetyl-CoA to form
CC HMG-CoA (PubMed:23138457). The rate-limiting step of the early module
CC is the reduction to mevalonate by the 3-hydroxy-3-methylglutaryl-
CC coenzyme A (HMG-CoA) reductase (PubMed:18460810).
CC {ECO:0000250|UniProtKB:P54839, ECO:0000269|PubMed:18460810,
CC ECO:0000269|PubMed:23138457, ECO:0000305|PubMed:29476632}.
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: Expression is up-regulated by salicylic acid, abscisic acid
CC and methyl jasmonate. {ECO:0000269|PubMed:23138457}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. HMG-CoA synthase
CC 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; JN391468; AFM91095.1; -; mRNA.
DR EMBL; JN391469; AFM91096.1; -; Genomic_DNA.
DR UniPathway; UPA00058; UER00102.
DR GO; GO:0004421; F:hydroxymethylglutaryl-CoA synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0006084; P:acetyl-CoA metabolic process; IEA:InterPro.
DR GO; GO:0010142; P:farnesyl diphosphate biosynthetic process, mevalonate pathway; IEA:InterPro.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 3.40.47.10; -; 1.
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.
PE 2: Evidence at transcript level;
KW Lipid biosynthesis; Lipid metabolism; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase.
FT CHAIN 1..470
FT /note="Hydroxymethylglutaryl-CoA synthase"
FT /id="PRO_0000454390"
FT ACT_SITE 100
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT ACT_SITE 134
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT ACT_SITE 269
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
SQ SEQUENCE 470 AA; 51206 MW; D3A8E73440E09E2B CRC64;
MTVPINASTS QDVEAPPRPK DVGILAIEMY FPKRCISEEE LEAFDSVSKG KYTIGLGQKF
MACCDDREDI NTFALTAMTS LIEKYNVDPK SIGRIDVGTE TIIDKSKSTK THLMDYFAEA
GNTDVEGVDS KNACYGSTAA LFNAVNWIES SSWDGRNAIV VGGDIAIYAE GSGRPTGGAG
AVAMLIGPNA PLVLEPIHGT HMANTYDFYK PKLDSEYPEV DGQLSITTYI SAIDASYAAY
RAKHAKAKKA AGLGGPAFSL ADVDYPVFHS PYGKMVQKAH ARLVYNDFLA NPDAPRYAQV
PERAAWLAQP YKASLTDKTL EKTFMGVAKA QFDGTVEKGM RCARRCGNMY TASLYGGLAS
LLASVEPAEI RGKRISMFAF GSGLASSFFT IKVKGDTTEV QEKLDLIRRL ESMDVVPCQA
YVDSLALREK NHNAGSYVPE GSIDNIWPGG YYLESIDSKY RRKYIRAPKA
