HMDH1_GIBZE
ID HMDH1_GIBZE Reviewed; 1181 AA.
AC I1RXX1;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2012, sequence version 1.
DT 03-AUG-2022, entry version 64.
DE RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase 1 {ECO:0000303|PubMed:30874562};
DE Short=HMG-CoA reductase 1 {ECO:0000303|PubMed:30874562};
DE EC=1.1.1.34 {ECO:0000305|PubMed:30874562};
DE AltName: Full=Ergosterol biosynthesis protein HMG1 {ECO:0000303|PubMed:30874562};
GN Name=HMG1 {ECO:0000303|PubMed:30874562}; ORFNames=FGRAMPH1_01T27691;
OS Gibberella zeae (strain ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084
OS / PH-1) (Wheat head blight fungus) (Fusarium graminearum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium.
OX NCBI_TaxID=229533;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RX PubMed=17823352; DOI=10.1126/science.1143708;
RA Cuomo C.A., Gueldener U., Xu J.-R., Trail F., Turgeon B.G., Di Pietro A.,
RA Walton J.D., Ma L.-J., Baker S.E., Rep M., Adam G., Antoniw J., Baldwin T.,
RA Calvo S.E., Chang Y.-L., DeCaprio D., Gale L.R., Gnerre S., Goswami R.S.,
RA Hammond-Kosack K., Harris L.J., Hilburn K., Kennell J.C., Kroken S.,
RA Magnuson J.K., Mannhaupt G., Mauceli E.W., Mewes H.-W., Mitterbauer R.,
RA Muehlbauer G., Muensterkoetter M., Nelson D., O'Donnell K., Ouellet T.,
RA Qi W., Quesneville H., Roncero M.I.G., Seong K.-Y., Tetko I.V., Urban M.,
RA Waalwijk C., Ward T.J., Yao J., Birren B.W., Kistler H.C.;
RT "The Fusarium graminearum genome reveals a link between localized
RT polymorphism and pathogen specialization.";
RL Science 317:1400-1402(2007).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RX PubMed=20237561; DOI=10.1038/nature08850;
RA Ma L.-J., van der Does H.C., Borkovich K.A., Coleman J.J., Daboussi M.-J.,
RA Di Pietro A., Dufresne M., Freitag M., Grabherr M., Henrissat B.,
RA Houterman P.M., Kang S., Shim W.-B., Woloshuk C., Xie X., Xu J.-R.,
RA Antoniw J., Baker S.E., Bluhm B.H., Breakspear A., Brown D.W.,
RA Butchko R.A.E., Chapman S., Coulson R., Coutinho P.M., Danchin E.G.J.,
RA Diener A., Gale L.R., Gardiner D.M., Goff S., Hammond-Kosack K.E.,
RA Hilburn K., Hua-Van A., Jonkers W., Kazan K., Kodira C.D., Koehrsen M.,
RA Kumar L., Lee Y.-H., Li L., Manners J.M., Miranda-Saavedra D.,
RA Mukherjee M., Park G., Park J., Park S.-Y., Proctor R.H., Regev A.,
RA Ruiz-Roldan M.C., Sain D., Sakthikumar S., Sykes S., Schwartz D.C.,
RA Turgeon B.G., Wapinski I., Yoder O., Young S., Zeng Q., Zhou S.,
RA Galagan J., Cuomo C.A., Kistler H.C., Rep M.;
RT "Comparative genomics reveals mobile pathogenicity chromosomes in
RT Fusarium.";
RL Nature 464:367-373(2010).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4620 / CBS 123657 / FGSC 9075 / NRRL 31084 / PH-1;
RX PubMed=26198851; DOI=10.1186/s12864-015-1756-1;
RA King R., Urban M., Hammond-Kosack M.C.U., Hassani-Pak K.,
RA Hammond-Kosack K.E.;
RT "The completed genome sequence of the pathogenic ascomycete fungus Fusarium
RT graminearum.";
RL BMC Genomics 16:544-544(2015).
RN [4]
RP FUNCTION, AND INDUCTION.
RX PubMed=30874562; DOI=10.1038/s41467-019-09145-6;
RA Liu Z., Jian Y., Chen Y., Kistler H.C., He P., Ma Z., Yin Y.;
RT "A phosphorylated transcription factor regulates sterol biosynthesis in
RT Fusarium graminearum.";
RL Nat. Commun. 10:1228-1228(2019).
CC -!- FUNCTION: 3-hydroxy-3-methylglutaryl-coenzyme A reductase; part of the
CC first module of ergosterol biosynthesis pathway that includes the early
CC steps of the pathway, conserved across all eukaryotes, and which
CC results in the formation of mevalonate from acetyl-coenzyme A (acetyl-
CC CoA) (By similarity). HMG1 catalyzes the reduction of
CC hydroxymethylglutaryl-CoA (HMG-CoA) to mevalonate (By similarity). The
CC first module starts with the action of the cytosolic acetyl-CoA
CC acetyltransferase ERG10B that catalyzes the formation of acetoacetyl-
CC CoA. The hydroxymethylglutaryl-CoA synthases 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 (Probable).
CC {ECO:0000250|UniProtKB:Q4WHZ1, ECO:0000305|PubMed:30874562}.
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:0000255|PROSITE-ProRule:PRU10003,
CC ECO:0000305|PubMed:30874562};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15991;
CC Evidence={ECO:0000305|PubMed:30874562};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC {ECO:0000305|PubMed:30874562}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- INDUCTION: Expression is regulated by the Zn(2)-C6 fungal-type
CC transcription factor FgSR which binds directly to the promoter.
CC {ECO:0000269|PubMed:30874562}.
CC -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
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DR EMBL; HG970335; CEF84192.1; -; Genomic_DNA.
DR RefSeq; XP_011328582.1; XM_011330280.1.
DR STRING; 5518.FGSG_09197P0; -.
DR GeneID; 23556160; -.
DR KEGG; fgr:FGSG_09197; -.
DR VEuPathDB; FungiDB:FGRAMPH1_01G27691; -.
DR eggNOG; KOG2480; Eukaryota.
DR HOGENOM; CLU_001734_0_0_1; -.
DR InParanoid; I1RXX1; -.
DR UniPathway; UPA00058; UER00103.
DR PHI-base; PHI:1006; -.
DR Proteomes; UP000070720; Chromosome 4.
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; IPR025583; HMG-CoA_N_dom.
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; PF13323; HPIH; 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; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1181
FT /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase 1"
FT /id="PRO_0000454672"
FT TRANSMEM 244..264
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 272..292
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 298..318
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 376..396
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 400..420
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 480..500
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 243..423
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT REGION 664..687
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1136..1181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1138..1181
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1181 AA; 127575 MW; 275D502F98549F72 CRC64;
MASILLPKRF RGETAPAEKT TPSWASKRLT PIAQFISRLA CSHPIHTVVL VAVLASTSYV
GLLQESFFST DLPTVGKADW SSLVEGSRVL RAGPETAWNW KAIEQDSIQH AGADADHLAL
LTLVFPDTHS AESSSTAPRS SHVPVPQNLS ITPLPSTKNS FTAYSQDSIL AYSLPYAEGP
EFLAATQEIP SEDAVETETQ HGREKKTWIM KAAKVNTQNS VVQWANNAWT EFLDLLKNAE
TLDIVIMFLG YIAMHLTFVS LFLSMRKLGS KFWLGICTLF SSVFAFLFGL IVTTKLGVPI
SVILLSEGLP FLVVTIGFEK NIVLTRAVMS HAIEHRRQIQ NSKSGKGSPE RSMQNVIQYA
VQSAIKEKGF EIMRDYAIEI VILALGAASG VQGGLQHFCF LAAWTLFFDF ILLFTFYTAI
LSIKLEINRI KRHVDMRMAL EDDGVSRRVA ENVAKSDGDW TRVKGDSSLF GRKSSSVPTF
KVLMILGFIF VNIVNICSIP FRNPRSLSTI RTWASSLGGV VAPLSVDPFK VASNGLDAIL
AAAKSNNRPT LVTVLTPIKY ELEYPSIHYA LGSAINGNNA EYTDAFHHHF QGYGVGGRMV
GGILKSLEDP VLSKWIVIAL ALSVALNGYL FNVARWGIKD PNVPEHNIDR NELARAQQFN
DTGSATLPLG EYVPPTPMRT EPSTPAITDD EAEGLQMTKA RSDKLPNRPN EELEKLLAEK
RVKEMSDEEL VSLSMRGKIP GYALEKTLGD FTRAVKIRRS IIARNRATSD LTHSLERSKL
PFEKYNWERV FGACCENVIG YMPLPVGVAG PLVIDGQSYF IPMATTEGVL VASASRGCKA
INAGGGAVTV LTADGMTRGP CVAFETLERA GAAKLWLDSE AGSDIMKKAF NSTSRFARLQ
SMKTALAGTN LYIRFKTTTG DAMGMNMISK GVEHALSVMS NEAGFDDMQI VSVSGNYCTD
KKAAALNWID GRGKGVVAEA IIPGDVVRSV LKSDVDALVE LNISKNLIGS AMAGSVGGFN
AHAANIVAAI FLATGQDPAQ VVESANCITI MKNLRGALQI SVSMPSLEVG TLGGGTILEP
QSAMLDLLGV RGSHPTNPGD NSRRLARIIG ASVLAGELSL CSALAAGHLV RAHMQHNRSA
APSRSTTPAP MTPVSFAMTN GPERSASTTS MSAAAIQRSK R
