HMGA_ASPFU
ID HMGA_ASPFU Reviewed; 449 AA.
AC Q4WHT9;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=Homogentisate 1,2-dioxygenase hmgA {ECO:0000303|PubMed:19028908};
DE EC=1.13.11.5 {ECO:0000269|PubMed:19715768, ECO:0000269|PubMed:22046314};
DE AltName: Full=Homogentisate oxygenase hmgA {ECO:0000305};
DE AltName: Full=Homogentisic acid oxidase hmgA {ECO:0000305};
DE AltName: Full=Homogentisicase hmgA {ECO:0000305};
DE AltName: Full=L-tyrosine degradation gene cluster protein hmgA {ECO:0000303|PubMed:22046314};
DE AltName: Full=Pyomelanin biosynthesis cluster protein hmgA {ECO:0000303|PubMed:22046314};
GN Name=hmgA {ECO:0000303|PubMed:19028908}; ORFNames=AFUA_2G04220;
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 FUNCTION, DISRUPTION PHENOTYPE, INDUCTION, AND PATHWAY.
RX PubMed=19028908; DOI=10.1128/aem.02077-08;
RA Schmaler-Ripcke J., Sugareva V., Gebhardt P., Winkler R., Kniemeyer O.,
RA Heinekamp T., Brakhage A.A.;
RT "Production of pyomelanin, a second type of melanin, via the tyrosine
RT degradation pathway in Aspergillus fumigatus.";
RL Appl. Environ. Microbiol. 75:493-503(2009).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, DISRUPTION PHENOTYPE,
RP AND PATHWAY.
RX PubMed=19715768; DOI=10.1016/j.fgb.2009.08.005;
RA Valiante V., Jain R., Heinekamp T., Brakhage A.A.;
RT "The MpkA MAP kinase module regulates cell wall integrity signaling and
RT pyomelanin formation in Aspergillus fumigatus.";
RL Fungal Genet. Biol. 46:909-918(2009).
RN [4]
RP FUNCTION, INDUCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=22046314; DOI=10.1371/journal.pone.0026604;
RA Keller S., Macheleidt J., Scherlach K., Schmaler-Ripcke J., Jacobsen I.D.,
RA Heinekamp T., Brakhage A.A.;
RT "Pyomelanin formation in Aspergillus fumigatus requires HmgX and the
RT transcriptional activator HmgR but is dispensable for virulence.";
RL PLoS ONE 6:e26604-e26604(2011).
CC -!- FUNCTION: Homogentisate 1,2-dioxygenase; part of the L-tyrosine
CC degradation gene cluster that mediates the biosynthesis of the brownish
CC pigment pyomelanin as an alternative melanin (PubMed:19028908,
CC PubMed:19715768, PubMed:22046314). The 4-hydroxyphenylpyruvate
CC dioxygenase hppD catalyzes the conversion of 4-hydroxyphenylpyruvate to
CC homogentisic acid (HGA) (PubMed:19028908, PubMed:22046314). The protein
CC hmgX is crucial for this conversion and thus, probably functions as an
CC accessory factor to mediate specific activity of hppD
CC (PubMed:22046314). The homogentisate 1,2-dioxygenase hmgA is then
CC involved in the cleavage of the aromatic ring of HGA and its conversion
CC to 4-maleylacetoacetate (PubMed:19028908, PubMed:19715768). When hmgA
CC activity is lowered by the cell wall integrity (CWI) signaling pathway,
CC HGA accumulates and leads to the production of pyomelanin through
CC benzoquinone acetic acid after oxidation and polymerization
CC (PubMed:19715768). On the opposite, in non-stress conditions, both hppD
CC and hmgA activities are balanced and HGA is degraded into 4-
CC maleylacetoacetate (PubMed:19715768). 4-maleylacetoacetate is further
CC converted to 4-fumarylacetoacetate by the maleylacetoacetate isomerase
CC maiA, which is degraded into fumarate and acetoacetate by the
CC fumarylacetoacetase fahA (Probable). {ECO:0000269|PubMed:19028908,
CC ECO:0000269|PubMed:19715768, ECO:0000269|PubMed:22046314,
CC ECO:0000305|PubMed:19028908}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=homogentisate + O2 = 4-maleylacetoacetate + H(+);
CC Xref=Rhea:RHEA:15449, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16169, ChEBI:CHEBI:17105; EC=1.13.11.5;
CC Evidence={ECO:0000269|PubMed:19715768, ECO:0000269|PubMed:22046314};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15450;
CC Evidence={ECO:0000269|PubMed:19715768, ECO:0000269|PubMed:22046314};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:Q93099};
CC -!- ACTIVITY REGULATION: Growth under standard conditions leads to moderate
CC phosphorylation of mpkA and hppD and hmgA activities are balanced
CC leading further to degradation of HGA and formation of 4-
CC maleylacetoacetate (PubMed:19715768). Cell wall stress, resulting in
CC disturbance of balanced hppD and hmgA enzyme activity, (with reduced
CC hmgA activity), leads to HGA accumulation that polymerizes to
CC pyomelanin (PubMed:19715768). {ECO:0000269|PubMed:19715768}.
CC -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation;
CC acetoacetate and fumarate from L-phenylalanine: step 4/6.
CC {ECO:0000269|PubMed:19028908, ECO:0000269|PubMed:19715768,
CC ECO:0000269|PubMed:22046314}.
CC -!- INDUCTION: Expression is induced by L-tyrosine (PubMed:19028908).
CC Expression is positively regulated by the cluster-specific
CC transcription factor hmgR (PubMed:22046314).
CC {ECO:0000269|PubMed:19028908, ECO:0000269|PubMed:22046314}.
CC -!- DISRUPTION PHENOTYPE: Impairs growth on L-tyrosine as the sole carbon
CC (PubMed:19028908). Leads to the accumulation of homogentisic acid (HGA)
CC and its subsequent polymerization to pyomelanin (PubMed:19028908).
CC {ECO:0000269|PubMed:19028908}.
CC -!- SIMILARITY: Belongs to the homogentisate dioxygenase family.
CC {ECO:0000305}.
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DR EMBL; AAHF01000008; EAL87516.1; -; Genomic_DNA.
DR RefSeq; XP_749554.1; XM_744461.1.
DR SMR; Q4WHT9; -.
DR STRING; 746128.CADAFUBP00002078; -.
DR EnsemblFungi; EAL87516; EAL87516; AFUA_2G04220.
DR GeneID; 3507122; -.
DR KEGG; afm:AFUA_2G04220; -.
DR VEuPathDB; FungiDB:Afu2g04220; -.
DR eggNOG; KOG1417; Eukaryota.
DR HOGENOM; CLU_027174_0_0_1; -.
DR InParanoid; Q4WHT9; -.
DR OMA; FMFETRW; -.
DR OrthoDB; 795654at2759; -.
DR UniPathway; UPA00139; UER00339.
DR Proteomes; UP000002530; Chromosome 2.
DR GO; GO:0004411; F:homogentisate 1,2-dioxygenase activity; IDA:AspGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IBA:GO_Central.
DR GO; GO:0006572; P:tyrosine catabolic process; IMP:AspGD.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR005708; Homogentis_dOase.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR InterPro; IPR011051; RmlC_Cupin_sf.
DR PANTHER; PTHR11056; PTHR11056; 1.
DR Pfam; PF04209; HgmA; 1.
DR SUPFAM; SSF51182; SSF51182; 1.
DR TIGRFAMs; TIGR01015; hmgA; 1.
PE 1: Evidence at protein level;
KW Dioxygenase; Iron; Metal-binding; Oxidoreductase; Phenylalanine catabolism;
KW Reference proteome; Tyrosine catabolism.
FT CHAIN 1..449
FT /note="Homogentisate 1,2-dioxygenase hmgA"
FT /id="PRO_0000453192"
FT BINDING 342
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q93099"
FT BINDING 348
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q93099"
FT BINDING 379
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q93099"
SQ SEQUENCE 449 AA; 50255 MW; 7DAC49D0004CA90C CRC64;
MPVTQFSHPD PYSYQTGFDS YHETEAVKGA LPVGQNSPQK APYGLYAEKL SGTAFTAPRH
ENKQTWVYRI LPAAAHENFK AEDADSYHTS MTTETHKLHH IPNQLRWDPF DLDETVDWVH
GLHLVAGAGD PTLKHGLGII LYAAGKDMGK EAFYSADGDF LIVPQHGVLD IQTELGRLMV
RPNEICVIPR GVRYRVTLPA GPVRGYICEL YQGHYQLPEL GPIGSNCLAN ARDFQAPVAS
FEDEEEPTEW RLYSKFNNTL FSARQDHTPF DIVAWHGNYY PYKYDLGRFN TIGSISFDHP
DPSIFTVLTG PSDHAGTAIA DFVIFPPRWL VAENTFRPPW YHRNTMSEFM GLICGNYDAK
TGGGFQPAGA SLHNVMSAHG PDADAFEGAS NAELKPQKVG DGSMAFMFES CLMVGVSEWG
LKTCQKVQEQ YNEHSWRPLK RHFKNPNKA
