ID   HCS1_USTMA              Reviewed;         462 AA.
AC   Q4P3F1; D4G7A2;
DT   25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2005, sequence version 1.
DT   03-AUG-2022, entry version 97.
DE   RecName: Full=Hydroxymethylglutaryl-CoA synthase {ECO:0000303|PubMed:20070524};
DE            Short=HMG-CoA synthase {ECO:0000303|PubMed:20070524};
DE            EC=2.3.3.10 {ECO:0000269|PubMed:20070524};
DE   AltName: Full=3-hydroxy-3-methylglutaryl coenzyme A synthase {ECO:0000255|RuleBase:RU364071};
GN   Name=hcs1 {ECO:0000303|PubMed:20070524}; ORFNames=UMAG_05362;
OS   Ustilago maydis (strain 521 / FGSC 9021) (Corn smut fungus).
OC   Eukaryota; Fungi; Dikarya; Basidiomycota; Ustilaginomycotina;
OC   Ustilaginomycetes; Ustilaginales; Ustilaginaceae; Ustilago.
OX   NCBI_TaxID=237631;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=521 / FGSC 9021;
RX   PubMed=17080091; DOI=10.1038/nature05248;
RA   Kaemper J., Kahmann R., Boelker M., Ma L.-J., Brefort T., Saville B.J.,
RA   Banuett F., Kronstad J.W., Gold S.E., Mueller O., Perlin M.H.,
RA   Woesten H.A.B., de Vries R., Ruiz-Herrera J., Reynaga-Pena C.G.,
RA   Snetselaar K., McCann M., Perez-Martin J., Feldbruegge M., Basse C.W.,
RA   Steinberg G., Ibeas J.I., Holloman W., Guzman P., Farman M.L.,
RA   Stajich J.E., Sentandreu R., Gonzalez-Prieto J.M., Kennell J.C., Molina L.,
RA   Schirawski J., Mendoza-Mendoza A., Greilinger D., Muench K., Roessel N.,
RA   Scherer M., Vranes M., Ladendorf O., Vincon V., Fuchs U., Sandrock B.,
RA   Meng S., Ho E.C.H., Cahill M.J., Boyce K.J., Klose J., Klosterman S.J.,
RA   Deelstra H.J., Ortiz-Castellanos L., Li W., Sanchez-Alonso P.,
RA   Schreier P.H., Haeuser-Hahn I., Vaupel M., Koopmann E., Friedrich G.,
RA   Voss H., Schlueter T., Margolis J., Platt D., Swimmer C., Gnirke A.,
RA   Chen F., Vysotskaia V., Mannhaupt G., Gueldener U., Muensterkoetter M.,
RA   Haase D., Oesterheld M., Mewes H.-W., Mauceli E.W., DeCaprio D., Wade C.M.,
RA   Butler J., Young S.K., Jaffe D.B., Calvo S.E., Nusbaum C., Galagan J.E.,
RA   Birren B.W.;
RT   "Insights from the genome of the biotrophic fungal plant pathogen Ustilago
RT   maydis.";
RL   Nature 444:97-101(2006).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=521 / FGSC 9021;
RA   Gueldener U., Muensterkoetter M., Walter M.C., Mannhaupt G., Kahmann R.;
RL   Submitted (SEP-2014) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND CATALYTIC ACTIVITY.
RC   STRAIN=521 / FGSC 9021;
RX   PubMed=20070524; DOI=10.1111/j.1365-2958.2010.07048.x;
RA   Winterberg B., Uhlmann S., Linne U., Lessing F., Marahiel M.A.,
RA   Eichhorn H., Kahmann R., Schirawski J.;
RT   "Elucidation of the complete ferrichrome A biosynthetic pathway in Ustilago
RT   maydis.";
RL   Mol. Microbiol. 75:1260-1271(2010).
CC   -!- FUNCTION: Hydroxymethylglutaryl-CoA synthase involved in the
CC       biosynthesis of siderophore ferrichrome A which is contributing to
CC       organismal virulence (PubMed:20070524). The first step of ferrichrome A
CC       biosynthesis is performed by the HMG-CoA synthase hcs1 which catalyzes
CC       the generation of HMG-CoA and CoA using acetoacetyl-CoA and acetyl-CoA
CC       as substrates (PubMed:20070524). The enoyl-CoA isomerase/hydratase fer4
CC       then catalyzes the conversion of hcs1-produced HMG-CoA to
CC       methylglutaconyl-CoA (PubMed:20070524). The acyltransferase fer5 then
CC       fuses the fer4-generated methylglutaconyl-CoA with sid1-generated
CC       hydroxyornithine to yield methylglutaconyl hydroxyornithine
CC       (PubMed:20070524). Methylglutaconyl hydroxyornithine is then available
CC       for use by the NRPS fer3 to generate ferrichrome A (PubMed:20070524).
CC       {ECO:0000269|PubMed:20070524}.
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:0000269|PubMed:20070524};
CC   -!- PATHWAY: Siderophore biosynthesis. {ECO:0000269|PubMed:20070524}.
CC   -!- DISRUPTION PHENOTYPE: Leads to a swollen morphology and a cytokinesis
CC       defect preceding lysis of cells (PubMed:20070524).
CC       {ECO:0000269|PubMed:20070524}.
CC   -!- SIMILARITY: Belongs to the thiolase-like superfamily. HMG-CoA synthase
CC       family. {ECO:0000305}.
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DR   EMBL; CM003158; KIS66367.1; -; Genomic_DNA.
DR   EMBL; BN001277; CAR97787.1; -; Genomic_DNA.
DR   RefSeq; XP_011392062.1; XM_011393760.1.
DR   AlphaFoldDB; Q4P3F1; -.
DR   SMR; Q4P3F1; -.
DR   STRING; 5270.UM05362P0; -.
DR   EnsemblFungi; KIS66367; KIS66367; UMAG_05362.
DR   GeneID; 23565277; -.
DR   KEGG; uma:UMAG_05362; -.
DR   VEuPathDB; FungiDB:UMAG_05362; -.
DR   eggNOG; KOG1393; Eukaryota.
DR   HOGENOM; CLU_008065_0_1_1; -.
DR   InParanoid; Q4P3F1; -.
DR   OMA; DDAYNWI; -.
DR   OrthoDB; 495111at2759; -.
DR   BioCyc; MetaCyc:MON-18963; -.
DR   Proteomes; UP000000561; Chromosome 19.
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   1: Evidence at protein level;
KW   Reference proteome; Transferase; Virulence.
FT   CHAIN           1..462
FT                   /note="Hydroxymethylglutaryl-CoA synthase"
FT                   /id="PRO_0000441965"
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        261
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10116"
SQ   SEQUENCE   462 AA;  50701 MW;  EB83795F497CBAC5 CRC64;
     MSARPQNVGI KAIEIYFPRR CISEDELEDF DGVAKGKYTI GFGQKYMACT DDREDINSFA
     LSVVSGLLEK NNIDPRSIGR LDVGTETIID KSKSVKTVLM DLFAPSGNMN IEGIDSKNAC
     YGGTAALFNA INWVESSSWD GRDAIVVAGD IAIYAEGSAR PVGGAGSVAM LIGPDAPLVF
     EPAHGTHMSN YWDFYKPNLS SEYPEVDGPE TIQTYLGCLD KAYDAYRLRA AKLKSGAANG
     HSDASSLASI KVDDFDYTLF HSPYSKLVQK GFGRLLYNDF FSDPKNEKYA SIPANFAELD
     RKSTITNKDV EKAFAAFGKE AQQTKLEPGM NTVRRCGNMY TASLYGGLVS LLSNIPSQEI
     QGKRILLYSF GSGAAASMFA IRINGSTEQI VKAVDLKNRL DSMKVVPCQT YVEALKTREA
     THNAVNHKPV GQLENLWPGA YYLENVDHMY RRTYGRIPTN AN