HMDH_GIBF5
ID HMDH_GIBF5 Reviewed; 1183 AA.
AC S0DQM8; Q12577; Q12615;
DT 11-DEC-2013, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2013, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase {ECO:0000303|Ref.2};
DE Short=HMG-CoA reductase {ECO:0000303|Ref.2};
DE EC=1.1.1.34 {ECO:0000250|UniProtKB:Q4WHZ1};
GN Name=HMGR; Synonyms=HMGA {ECO:0000303|Ref.2}; ORFNames=FFUJ_04000;
OS Gibberella fujikuroi (strain CBS 195.34 / IMI 58289 / NRRL A-6831) (Bakanae
OS and foot rot disease fungus) (Fusarium fujikuroi).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium;
OC Fusarium fujikuroi species complex.
OX NCBI_TaxID=1279085;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CBS 195.34 / IMI 58289 / NRRL A-6831;
RX PubMed=23825955; DOI=10.1371/journal.ppat.1003475;
RA Wiemann P., Sieber C.M.K., von Bargen K.W., Studt L., Niehaus E.-M.,
RA Espino J.J., Huss K., Michielse C.B., Albermann S., Wagner D.,
RA Bergner S.V., Connolly L.R., Fischer A., Reuter G., Kleigrewe K., Bald T.,
RA Wingfield B.D., Ophir R., Freeman S., Hippler M., Smith K.M., Brown D.W.,
RA Proctor R.H., Muensterkoetter M., Freitag M., Humpf H.-U., Gueldener U.,
RA Tudzynski B.;
RT "Deciphering the cryptic genome: genome-wide analyses of the rice pathogen
RT Fusarium fujikuroi reveal complex regulation of secondary metabolism and
RT novel metabolites.";
RL PLoS Pathog. 9:E1003475-E1003475(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 823-928.
RC STRAIN=CBS 195.34 / IMI 58289 / NRRL A-6831;
RX DOI=10.1016/0147-5975(92)90024-L;
RA Corrochano L.M., Avalos J.;
RT "Cloning a segment of the gene encoding 3-hydroxy-3-methyglutaryl coenzyme
RT A reductase in Phycomyces blakesleeanus and Gibberella fujikuroi by the
RT polymerase chain reaction.";
RL Exp. Mycol. 16:167-171(1992).
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) (By similarity). In this
CC module, the cytosolic acetyl-CoA acetyltransferase catalyzes the
CC formation of acetoacetyl-CoA (By similarity). The
CC hydroxymethylglutaryl-CoA synthase then condenses acetyl-CoA with
CC acetoacetyl-CoA to form HMG-CoA (By similarity). 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) reductase HMGR (By similarity).
CC {ECO:0000250|UniProtKB:Q4WHZ1}.
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 -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC {ECO:0000250|UniProtKB:Q4WHZ1}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
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DR EMBL; HF679024; CCT64750.1; -; Genomic_DNA.
DR EMBL; X58370; CAA41261.1; -; Genomic_DNA.
DR PIR; S17343; S17343.
DR AlphaFoldDB; S0DQM8; -.
DR SMR; S0DQM8; -.
DR STRING; 1279085.S0DQM8; -.
DR PRIDE; S0DQM8; -.
DR EnsemblFungi; CCT64750; CCT64750; FFUJ_04000.
DR VEuPathDB; FungiDB:FFUJ_04000; -.
DR HOGENOM; CLU_001734_0_0_1; -.
DR UniPathway; UPA00058; UER00103.
DR Proteomes; UP000016800; Chromosome 2.
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 3: Inferred from homology;
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..1183
FT /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT /id="PRO_0000424592"
FT TOPO_DOM 1..245
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 246..266
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 267..273
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 274..294
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 295..299
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 300..320
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 321..378
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 379..399
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 400..402
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 403..423
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 424..482
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT TRANSMEM 483..503
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 504..1183
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P12684"
FT DOMAIN 245..426
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT REGION 1136..1183
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1139..1183
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 828
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 962
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 1038
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 1134
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT BINDING 834..840
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 895..897
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 922..930
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 991..993
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 1133..1134
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 1138..1139
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT CONFLICT 896
FT /note="R -> S (in Ref. 2; CAA41261)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1183 AA; 127666 MW; EAA372D9039EA03D CRC64;
MAAILLPQRF RGEAPVTEKT TPSWASKRLT PIAQFLSRLA CSHPIHTVVV VAVLASTSYV
GLLQESLFNT DVESATLGKA DWSTLVEGSR VLRAGPETAW NWKAVEQDVV ADAGSDADHL
ALLTLVFPDS LSAESSSTAP RSHHVPIPQN LSITSLPSTE NPFTAYSQDS ILAYALPYSE
GPEFLAAAQE IPNEDAVEIE TKHGREKKTW IMKAAKVNTR NSVVQWVSNA WSEFLDLLKN
AETLDIVIML LGYIAMHLTF VSLFLSMRKM GSKFWLGICT LFSSVFAFLF GLVVTTKLGV
PISVILLSEG LPFLVVTIGF EKNIVLTRAV MSHAIEHRRI QAQNSKSGKR SPERSTQNMI
QYAVQAAIKE KGFEIIRDYA IEIVILVIGA ASGVQGGLQQ FCFLAAWTLF FDFILLFTFY
TAILSIKLEI NRIKRHVDMR MALEDDGVSR RVAENVAKGD DELNRVRGDA PLFGRKSSSI
PKFKVLMILG FIFVNIVNIC SIPFRNPSSM STIRTWASSL GGVIAPLSVD PFKVASNGLD
AILATAKSNN RPTLVTVLTP IKYELEYPSI HYALGSAASN PAYNDAFHHH FQGYGVGGRM
VGGILKSLED PVLSKWIVIA LALSVALNGY LFNVARWGIK DPNVPEHNID RNELARAQQF
NDTGSATLPL GEYVPPTPMR TQPSTPAITD DEAEGLHMTK ARPANLPNRS NEELEKLLSE
KRVREMTDEE VISLSMRGKI PGYALEKTLG DFTRAVKIRR SIIARNKATT DITHSLDRSK
LPYENYNWER VFGACCENVI GYMPLPVGVA GPLVIDGQSY FIPMATTEGV LVASASRGCK
AINSGGGAIT VLTADGMTRG PCVAFETLER AGAAKLWLDS EAGQDMMKKA FNSTSRFARL
QSMKTALAGT NLYIRFKTTT GDAMGMNMIS KGVEHALSVM ANDGGFDDMQ IISVSGNYCT
DKKAAALNWI DGRGKGVVAE AIIPGEVVRS VLKSDVDSLV ELNVAKNLIG SAMAGSVGGF
NAHAANIVAA IFLATGQDPA QVVESANCIT IMKNLNGALQ ISVSMPSLEV GTLGGGTILE
PQGAMLDILG VRGSHPTNPG DNARRLARII GAAVLAGELS LCSALAAGHL VRAHMQHNRS
AAPSRSTTPA PPMTPVSLAM TSAQERSAST TSMSAAAIQR SKR
