PBCC_EMENI
ID PBCC_EMENI Reviewed; 416 AA.
AC C8VN86; Q5BCY7;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 1.
DT 25-MAY-2022, entry version 78.
DE RecName: Full=3-hydroxy-3-methylglutaryl coenzyme A reductase AN1593 {ECO:0000303|PubMed:22506079};
DE Short=HMG-CoA reductase {ECO:0000303|PubMed:22506079};
DE EC=1.1.1.34 {ECO:0000255|RuleBase:RU361219};
DE AltName: Full=Pimaradiene biosynthesis cluster protein AN1593 {ECO:0000303|PubMed:22506079};
GN ORFNames=AN1593, ANIA_01593;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
RN [3]
RP FUNCTION, INDUCTION, AND PATHWAY.
RX PubMed=22506079; DOI=10.1371/journal.pone.0035450;
RA Bromann K., Toivari M., Viljanen K., Vuoristo A., Ruohonen L.,
RA Nakari-Setaelae T.;
RT "Identification and characterization of a novel diterpene gene cluster in
RT Aspergillus nidulans.";
RL PLoS ONE 7:e35450-e35450(2012).
RN [4]
RP FUNCTION.
RX PubMed=27098256; DOI=10.1007/s00253-016-7517-5;
RA Bromann K., Toivari M., Viljanen K., Ruohonen L., Nakari-Setaelae T.;
RT "Engineering Aspergillus nidulans for heterologous ent-kaurene and gamma-
RT terpinene production.";
RL Appl. Microbiol. Biotechnol. 100:6345-6359(2016).
CC -!- FUNCTION: 3-hydroxy-3-methylglutaryl coenzyme A reductase; part of the
CC gene cluster that mediates the biosynthesis of the diterpene ent-
CC pimara-8(14),15-diene (PD) (PubMed:22506079, PubMed:27098256). Within
CC the cluster, the HMG-CoA reductase AN1593 functions in the mevalonate
CC pathway, which produces isoprenoid precursors (PubMed:22506079,
CC PubMed:27098256). The geranylgeranyl pyrophosphate (GGPP) synthase
CC AN1592 is needed in the formation of GGPP, the precursor for diterpenes
CC (PubMed:22506079, PubMed:27098256). Lastly, the pimaradiene synthase
CC pbcA performs the 2 cyclization steps that convert GGPP to ent-pimara-
CC 8(14),15-diene (PubMed:22506079, PubMed:27098256). The putative roles
CC of the remaining cluster enzymes in ent-pimara-8(14),15-diene
CC biosynthesis is unclear (Probable). The cytochrome P450 monooxygenase
CC AN1598, the glutathione S-transferase AN1595, the oxidoreductases
CC AN1596 and AN1597 probably function as decorative enzymes (Probable).
CC It is possible that in biological conditions the compound is oxidized
CC to ent-pimara-8(14),15-dien-19-oic acid, which is a bioactive diterpene
CC compound predominant in many plant extracts (Probable).
CC {ECO:0000269|PubMed:22506079, ECO:0000269|PubMed:27098256,
CC ECO:0000305|PubMed:22506079}.
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|RuleBase:RU361219};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC {ECO:0000255|RuleBase:RU361219}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is positively regulated by the cluster-specific
CC transcription factor pbcR. {ECO:0000269|PubMed:22506079}.
CC -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAA64300.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AACD01000025; EAA64300.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BN001307; CBF85179.1; -; Genomic_DNA.
DR RefSeq; XP_659197.1; XM_654105.1.
DR AlphaFoldDB; C8VN86; -.
DR SMR; C8VN86; -.
DR STRING; 162425.CADANIAP00008226; -.
DR EnsemblFungi; CBF85179; CBF85179; ANIA_01593.
DR EnsemblFungi; EAA64300; EAA64300; AN1593.2.
DR GeneID; 2875220; -.
DR KEGG; ani:AN1593.2; -.
DR VEuPathDB; FungiDB:AN1593; -.
DR eggNOG; KOG2480; Eukaryota.
DR HOGENOM; CLU_455668_0_0_1; -.
DR InParanoid; C8VN86; -.
DR OMA; DDKMTRA; -.
DR OrthoDB; 907394at2759; -.
DR UniPathway; UPA00058; UER00103.
DR Proteomes; UP000000560; Chromosome VII.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005778; C:peroxisomal membrane; IBA:GO_Central.
DR GO; GO:0004420; F:hydroxymethylglutaryl-CoA reductase (NADPH) activity; IBA:GO_Central.
DR GO; GO:0015936; P:coenzyme A metabolic process; IEA:InterPro.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IBA:GO_Central.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IBA:GO_Central.
DR GO; GO:0019748; P:secondary metabolic process; IEP:AspGD.
DR GO; GO:0016126; P:sterol biosynthetic process; IBA:GO_Central.
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 PANTHER; PTHR10572; PTHR10572; 1.
DR Pfam; PF00368; HMG-CoA_red; 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.
PE 2: Evidence at transcript level;
KW Glycoprotein; Lipid biosynthesis; Lipid metabolism; Membrane; NADP;
KW Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..416
FT /note="3-hydroxy-3-methylglutaryl coenzyme A reductase
FT AN1593"
FT /id="PRO_0000450841"
FT TRANSMEM 380..400
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 103
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 236
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 312
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 408
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 277
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 416 AA; 43383 MW; 629C54724C315050 CRC64;
MPESQIIELG TLGQIPLYSL ERALQDPLRA VKLRRQIVSQ HQATGNIDFT TDGSALPYEG
YDYKAVLGAC CENVIGYMPI PVGVAGPIKI NGKMVFLPMS TTEGALVAST NRGCMAINAG
GGVTALVLGD GMTRAPIVRF PSLEEAGAAK QWLGSDAGFL IIEDAFNASS RFARLQNIKA
TAVGSDLYIR FTASTGDAMG MNMISKGVEQ ALEAMQKHGF ESMDVVSLSG NFCADKKPAA
VNWIEGRGKT VTAQATIPEH AVRETLKTSV EALVELNVSK NLVGSAVAGA LGGFNAHAAN
VVTAIYLATG QDPAQNVQSS NTLTVMKNVN GDLQISVFMP SIEVGTVGGG TVLGPQKAML
HMMGVQGADP EQPGRNAQEL ALLVAAGVLA GELSLCSALS AGSLVKSHLT HNRKKG
