ER13A_ASPFU
ID ER13A_ASPFU Reviewed; 467 AA.
AC Q4WBQ3;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 2.
DT 25-MAY-2022, entry version 86.
DE RecName: Full=Hydroxymethylglutaryl-CoA synthase erg13A {ECO:0000303|PubMed:16110826};
DE Short=HMG-CoA synthase {ECO:0000303|PubMed:16110826};
DE EC=2.3.3.10 {ECO:0000250|UniProtKB:P41338};
DE AltName: Full=3-hydroxy-3-methylglutaryl coenzyme A synthase erg13A {ECO:0000303|PubMed:16110826};
DE AltName: Full=Ergosterol biosynthesis protein 13A {ECO:0000303|PubMed:16110826};
GN Name=erg13A {ECO:0000303|PubMed:16110826}; ORFNames=AFUA_8G07210;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP IDENTIFICATION, AND FUNCTION.
RX PubMed=16110826; DOI=10.1080/13693780400029114;
RA Ferreira M.E., Colombo A.L., Paulsen I., Ren Q., Wortman J., Huang J.,
RA Goldman M.H., Goldman G.H.;
RT "The ergosterol biosynthesis pathway, transporter genes, and azole
RT resistance in Aspergillus fumigatus.";
RL Med. Mycol. 43:S313-S319(2005).
RN [3]
RP FUNCTION.
RX PubMed=22106303; DOI=10.1073/pnas.1106399108;
RA Yasmin S., Alcazar-Fuoli L., Gruendlinger M., Puempel T., Cairns T.,
RA Blatzer M., Lopez J.F., Grimalt J.O., Bignell E., Haas H.;
RT "Mevalonate governs interdependency of ergosterol and siderophore
RT biosyntheses in the fungal pathogen Aspergillus fumigatus.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:E497-E504(2012).
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) (By
CC similarity). Erg13A and erg13B condense acetyl-CoA with acetoacetyl-CoA
CC to form hydroxymethylglutaryl-CoA (HMG-CoA) (By similarity). The first
CC 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 erg13A and erg13B then
CC condense acetyl-CoA with acetoacetyl-CoA to form HMG-CoA. The rate-
CC limiting step of the early module is the reduction to mevalonate by the
CC 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductases hmg1 and
CC hmg2. Mevalonate is also a precursor for the extracellular siderophore
CC triacetylfusarinine C (TAFC) (PubMed:16110826, PubMed:22106303)
CC (Probable). {ECO:0000250|UniProtKB:P41338, ECO:0000305|PubMed:16110826,
CC ECO:0000305|PubMed:22106303}.
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:P41338, ECO:0000255|PROSITE-
CC ProRule:PRU10116};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10189;
CC Evidence={ECO:0000250|UniProtKB:P41338};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 2/3.
CC {ECO:0000250|UniProtKB:P41338}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. HMG-CoA synthase
CC family. {ECO:0000305}.
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DR EMBL; AAHF01000013; EAL85481.2; -; Genomic_DNA.
DR RefSeq; XP_747519.2; XM_742426.2.
DR STRING; 746128.CADAFUBP00007846; -.
DR EnsemblFungi; EAL85481; EAL85481; AFUA_8G07210.
DR GeneID; 3504812; -.
DR KEGG; afm:AFUA_8G07210; -.
DR VEuPathDB; FungiDB:Afu8g07210; -.
DR eggNOG; KOG1393; Eukaryota.
DR HOGENOM; CLU_008065_0_1_1; -.
DR InParanoid; Q4WBQ3; -.
DR OMA; YFAFHAP; -.
DR OrthoDB; 495111at2759; -.
DR UniPathway; UPA00058; UER00102.
DR Proteomes; UP000002530; Chromosome 8.
DR GO; GO:0004421; F:hydroxymethylglutaryl-CoA synthase activity; IBA:GO_Central.
DR GO; GO:0006084; P:acetyl-CoA metabolic process; IBA:GO_Central.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IBA:GO_Central.
DR GO; GO:0010142; P:farnesyl diphosphate biosynthetic process, mevalonate pathway; IBA:GO_Central.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR000590; HMG_CoA_synt_AS.
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.
DR PROSITE; PS01226; HMG_COA_SYNTHASE; 1.
PE 3: Inferred from homology;
KW Acyltransferase; Lipid biosynthesis; Lipid metabolism; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transferase.
FT CHAIN 1..467
FT /note="Hydroxymethylglutaryl-CoA synthase erg13A"
FT /id="PRO_0000454148"
FT ACT_SITE 86
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT ACT_SITE 118
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT ACT_SITE 259
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
SQ SEQUENCE 467 AA; 51636 MW; D31F5012118E43DC CRC64;
MPSSAQNVGI KALEIYFPSR YVPQTELETF LGASAGKYTI GLGQQNMSFC DDREDLYSLA
LTAVSSLLRK YAIDPNTIGR LEVGTETLLD KAKSCKTVLM QLFGDNTDIE GVDTYNACYG
GTNALFNAVN WIESSSWDGR DAIVVAGDIA LYETPAARPT GGAGCVAMLI GPDAPLVLEP
VRGSCMKHVY DFYKAYFKSE YPLVDGQFSN TCYLGALDAC YQRYQAKQRA RQAAKTNGTA
ISNGHQGSFL DTFDYFAFHA PNCKLVAKGY GRLLFNDFKL ESGSFDEVPA QVREADFAAS
LTDKALEKLC VSLTKERFVQ RVEPSLTAPT NCGNMYTASV YAGLISLISN VPSDRLQDKR
IGMFSYGSGL ASTLFSFRVK GDTTEMARKI GLQDRLSART AVSPEFYDQM CKLREKAYQQ
RNYTPEGSVE SLAPGTYFLV HVDDAYRRKY DMKPYLSMCE DRHEQAV
