HMDH_GANLU
ID HMDH_GANLU Reviewed; 1226 AA.
AC B2KX91;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 1.
DT 03-AUG-2022, entry version 57.
DE RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase {ECO:0000303|PubMed:18460810};
DE Short=HMG-CoA reductase {ECO:0000303|PubMed:18460810};
DE EC=1.1.1.34 {ECO:0000305|PubMed:18460810};
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 DEVELOPMENTAL
RP STAGE.
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 [2]
RP FUNCTION.
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 [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).
RN [4]
RP INDUCTION.
RX PubMed=30821132; DOI=10.1111/1751-7915.13381;
RA Xu J.W., Yue T.H., Yu X., Zhao P., Li T., Li N.;
RT "Enhanced production of individual ganoderic acids by integrating
RT Vitreoscilla haemoglobin expression and calcium ion induction in liquid
RT static cultures of Ganoderma lingzhi.";
RL Microb. Biotechnol. 12:1180-1187(2019).
CC -!- FUNCTION: HMG-CoA reductase; part of the first module of ergosterol
CC biosynthesis pathway that includes the early steps of the pathway,
CC conserved across all eukaryotes, and which results in the formation of
CC mevalonate from acetyl-coenzyme A (acetyl-CoA) (PubMed:18460810). This
CC module also plays a key role in the biosynthesis of triterpenes such as
CC ganoderic acids (GA), a group of highly oxygenated lanostane-type
CC triterpenoids which are well recognized as a main group of unique
CC bioactive compounds in the medicinal mushroom Ganoderma lucidum
CC (PubMed:23138457) (Probable). In this module, the acetyl-CoA
CC acetyltransferase catalyzes the formation of acetoacetyl-CoA (By
CC similarity). The hydroxymethylglutaryl-CoA synthase HMGS then condenses
CC acetyl-CoA with acetoacetyl-CoA to form HMG-CoA (PubMed:23138457). The
CC rate-limiting step of the early module is the reduction to mevalonate
CC by the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase
CC (PubMed:18460810). {ECO:0000250|UniProtKB:P12683,
CC ECO:0000269|PubMed:18460810, ECO:0000269|PubMed:23138457,
CC ECO:0000305|PubMed:29476632}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-mevalonate + CoA + 2 NADP(+) = (3S)-hydroxy-3-
CC methylglutaryl-CoA + 2 H(+) + 2 NADPH; Xref=Rhea:RHEA:15989,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:36464, ChEBI:CHEBI:43074,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.34;
CC Evidence={ECO:0000305|PubMed:18460810};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P12683}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- DEVELOPMENTAL STAGE: Expression is relatively low in mycelia and
CC reaches the highest level in the primordia.
CC {ECO:0000269|PubMed:18460810}.
CC -!- INDUCTION: Expression is induced in ganoderic acid (GA) producing
CC conditions. {ECO:0000269|PubMed:30821132}.
CC -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
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DR EMBL; EU263989; ABY84848.1; -; mRNA.
DR EMBL; EU263990; ABY84849.1; -; Genomic_DNA.
DR SMR; B2KX91; -.
DR BRENDA; 1.1.1.34; 2399.
DR UniPathway; UPA00058; UER00103.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004420; F:hydroxymethylglutaryl-CoA reductase (NADPH) activity; IEA:UniProtKB-EC.
DR GO; GO:0015936; P:coenzyme A metabolic process; IEA:InterPro.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:InterPro.
DR GO; GO:0016126; P:sterol biosynthetic process; IEA:UniProtKB-KW.
DR CDD; cd00643; HMG-CoA_reductase_classI; 1.
DR Gene3D; 1.10.3270.10; -; 1.
DR Gene3D; 3.30.70.420; -; 1.
DR Gene3D; 3.90.770.10; -; 1.
DR InterPro; IPR002202; HMG_CoA_Rdtase.
DR InterPro; IPR023074; HMG_CoA_Rdtase_cat_sf.
DR InterPro; IPR023076; HMG_CoA_Rdtase_CS.
DR InterPro; IPR004554; HMG_CoA_Rdtase_eu_arc.
DR InterPro; IPR023282; HMG_CoA_Rdtase_N.
DR InterPro; IPR009023; HMG_CoA_Rdtase_NAD(P)-bd_sf.
DR InterPro; IPR009029; HMG_CoA_Rdtase_sub-bd_dom_sf.
DR InterPro; IPR000731; SSD.
DR PANTHER; PTHR10572; PTHR10572; 1.
DR Pfam; PF00368; HMG-CoA_red; 1.
DR Pfam; PF12349; Sterol-sensing; 1.
DR PRINTS; PR00071; HMGCOARDTASE.
DR SUPFAM; SSF55035; SSF55035; 1.
DR SUPFAM; SSF56542; SSF56542; 1.
DR TIGRFAMs; TIGR00533; HMG_CoA_R_NADP; 1.
DR PROSITE; PS00066; HMG_COA_REDUCTASE_1; 1.
DR PROSITE; PS00318; HMG_COA_REDUCTASE_2; 1.
DR PROSITE; PS01192; HMG_COA_REDUCTASE_3; 1.
DR PROSITE; PS50065; HMG_COA_REDUCTASE_4; 1.
DR PROSITE; PS50156; SSD; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Membrane;
KW NADP; Oxidoreductase; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..1226
FT /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT /id="PRO_0000454391"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 224..244
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 252..272
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 337..357
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 373..393
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 481..501
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 1150..1170
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 223..391
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT REGION 428..449
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 683..702
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 722..742
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1182..1226
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1200..1214
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 869
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 1001
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 1077
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 1175
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT BINDING 875..881
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 936..938
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 963..971
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 1030..1032
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 1174..1175
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 1179..1180
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
SQ SEQUENCE 1226 AA; 131175 MW; 732B5BE6696C39C8 CRC64;
MRAVLRLLST HTVFSPIETI VSVFVLATLA YFHILSGIKH SSFFASSHPP AIRPAFAHLT
NGEWVAVSQH DWTEAWKHPG GSLDALELQQ VVFTLDDKTQ PSAVLDASAI SQHLVSNVPA
LSGKAYSSLC HHPNVSGTSC FTSVSGPGAS PILTLSFKPG TRDDWLGSLR KEKTITLDGV
KYDVGAGKRQ ESIGDMESSK WVAYALSALV LRFWELTKAD SLDILVVLTG YILMHVTFMR
LFLASRALGS NFWLSAGIFS SATISFLFTL PMCRSMDIPL DPIALTEALP FLVCTVGFDK
PLRLARAVMA HPNILKPQDD GRMKAAGDVI LEALDRVGNM ILRDYALEIA VLFVGVNSRV
GGLKEFCAVA AALLAMDRLM TFTLYTAVLT IMVEVRRIKK VRDMTKARSR SSSITAVTAN
GTAIRGVLSR KSSKQSVTEP ETTKNLRQRA TDSAIGVKGS LLKDGGRLQE AEENPMARLK
LLLIASFLTL HILNFCTTLT SATANARHQR HPFRTVQEVV PIPRVDITTP AIANILSHLA
VAQEPMFTVV GSEPIELLVK VAAPVYVHAL PLAPALRASN TNTGEAIENF MSSWSSLVGD
PVVSKWIVAL LAVSVALNGY LLKGIAAGSG LAAMRAVRSQ GVRFRSRARS IVKISDEPEP
EPEHSIDPAP VVFFASAAPA VEAPAPAPAP EPEPPVNRPP PLTIFSRPLN LETVDKKLQD
ALPIRSPPPV EPITPESREV EPTQVEVRSL AECVDVFENG PRPVSVALKT LNDEEVILLC
QTGKIAPYAL VKMLADFDRA VRVRRALISR ASRTKTLENS LVPMKDYDYA RVMGACCENV
IGYMPLPLGI AGPLKIDGLM YPIPMATAEG TLVASTSRGC KALNAGGGVT TVLTADGMTR
GPAIDFPSIV RAAEAKAFIE SEDGYATIRE AFESTSRFAK LQKIKCALAG RTLFVRFATR
TGDAMGMNMI SKATEKALDV LSHEFPEMVV LALSGNYCTD KKPAAISWIE GRGKSIVAEA
VIPGKVVKSV LKTTVESLCN VNTKKNLIGS AMAGSVGGFN AHAANILTAV FLATGQDPAQ
NVESSNCMTL MEPTNGGEDL LMTISMPCIE VGTVGGGTIL EPQGAVLDLL GVRGAHPTNP
GQNAQQLARI IASAVMAGEL SLISALAAGH LVRAHLAHNR SQLNTPMPSR PHTPGPEDVS
HVQQLPTPSA SDDKGVTAQG YVVEAK
