ER13B_ASPFU
ID ER13B_ASPFU Reviewed; 460 AA.
AC Q4WXT8;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 25-MAY-2022, entry version 92.
DE RecName: Full=Hydroxymethylglutaryl-CoA synthase erg13B {ECO:0000250|UniProtKB:P41338};
DE Short=HMG-CoA synthase {ECO:0000250|UniProtKB:P41338};
DE EC=2.3.3.10 {ECO:0000250|UniProtKB:P41338};
DE AltName: Full=3-hydroxy-3-methylglutaryl coenzyme A synthase erg13B {ECO:0000250|UniProtKB:P41338};
DE AltName: Full=Ergosterol biosynthesis protein 13B {ECO:0000303|PubMed:16110826};
GN Name=erg13B {ECO:0000303|PubMed:16110826}; ORFNames=AFUA_3G10660;
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; AAHF01000002; EAL92515.1; -; Genomic_DNA.
DR RefSeq; XP_754553.1; XM_749460.1.
DR SMR; Q4WXT8; -.
DR STRING; 746128.CADAFUBP00003769; -.
DR EnsemblFungi; EAL92515; EAL92515; AFUA_3G10660.
DR GeneID; 3512339; -.
DR KEGG; afm:AFUA_3G10660; -.
DR VEuPathDB; FungiDB:Afu3g10660; -.
DR eggNOG; KOG1393; Eukaryota.
DR HOGENOM; CLU_008065_0_1_1; -.
DR InParanoid; Q4WXT8; -.
DR OMA; DDAYNWI; -.
DR OrthoDB; 495111at2759; -.
DR UniPathway; UPA00058; UER00102.
DR Proteomes; UP000002530; Chromosome 3.
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..460
FT /note="Hydroxymethylglutaryl-CoA synthase erg13B"
FT /id="PRO_0000454149"
FT ACT_SITE 86
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT ACT_SITE 120
FT /note="Acyl-thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
FT ACT_SITE 263
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
SQ SEQUENCE 460 AA; 50797 MW; BBDE03FC2362AF1B CRC64;
MSARPQNVGI KAIEVYFPSQ CVDQAELEKF DGVSEGKYTI GLGQTKMSFC DDREDIYSIA
LTTCSSLLRK YNIDPKSIGR LEVGTETLLD KSKSVKSVLM QLFAPHGNTN IEGVDTVNAC
YGGTNAVFNS INWVESSAWD GRDAIVVCGD IALYAKGAAR PTGGAGAVAM LIGPDAPIVF
EPGLRGSYVT HAYDFFKPDL TSEYPVVDGH FSLKCYTEAV DACYKAYAAR EKVLKAKVQN
GTNGVENDET KTPLDRFDYV LFHAPTCKLV QKSYGRMLYN DYLANPSHPA FAEVPSELRD
LDYEKSFTDK TVEKTFMGLT KKTFAERVRP GLDVATLCGN MYTATVYAGL ASLLSNVTFD
PSQPKRVALF SYGSGLASSM FSVKIVGDVS GMVEKLDLHK RLNARTVLPP QTYDEMCILR
EHAHLKKNFK PTGNPDTLFP GTYYLTEIDD MFRRKYEIKA
