FAHA_ASPFU
ID FAHA_ASPFU Reviewed; 431 AA.
AC Q4WHT8;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=Fumarylacetoacetase fahA {ECO:0000303|PubMed:19028908};
DE EC=3.7.1.2 {ECO:0000305|PubMed:19028908};
DE AltName: Full=Fumarylacetoacetate hydrolase fahA {ECO:0000303|PubMed:19028908};
DE AltName: Full=L-tyrosine degradation gene cluster protein fahA {ECO:0000303|PubMed:19028908};
DE AltName: Full=Pyomelanin biosynthesis cluster protein fahA {ECO:0000303|PubMed:19028908};
GN Name=fahA {ECO:0000303|PubMed:19028908}; ORFNames=AFUA_2G04230;
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, 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.
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, 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: Fumarylacetoacetase; part of the L-tyrosine degradation gene
CC cluster that mediates the biosynthesis of the brownish pigment
CC pyomelanin as an alternative melanin (PubMed:19028908,
CC PubMed:22046314). The 4-hydroxyphenylpyruvate dioxygenase hppD
CC catalyzes the conversion of 4-hydroxyphenylpyruvate to homogentisic
CC acid (HGA) (PubMed:19028908, PubMed:22046314). The protein hmgX is
CC 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=4-fumarylacetoacetate + H2O = acetoacetate + fumarate + H(+);
CC Xref=Rhea:RHEA:10244, ChEBI:CHEBI:13705, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:18034, ChEBI:CHEBI:29806; EC=3.7.1.2;
CC Evidence={ECO:0000305|PubMed:19028908};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10245;
CC Evidence={ECO:0000305|PubMed:19028908};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:P35505};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P35505};
CC -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation;
CC acetoacetate and fumarate from L-phenylalanine: step 6/6.
CC {ECO:0000305|PubMed:19028908}.
CC -!- INDUCTION: Expression is positively regulated by the cluster-specific
CC transcription factor hmgR. {ECO:0000269|PubMed:22046314}.
CC -!- SIMILARITY: Belongs to the FAH family. {ECO:0000305}.
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DR EMBL; AAHF01000008; EAL87517.1; -; Genomic_DNA.
DR RefSeq; XP_749555.1; XM_744462.1.
DR SMR; Q4WHT8; -.
DR STRING; 746128.CADAFUBP00002079; -.
DR EnsemblFungi; EAL87517; EAL87517; AFUA_2G04230.
DR GeneID; 3507123; -.
DR KEGG; afm:AFUA_2G04230; -.
DR VEuPathDB; FungiDB:Afu2g04230; -.
DR eggNOG; KOG2843; Eukaryota.
DR HOGENOM; CLU_026207_2_0_1; -.
DR InParanoid; Q4WHT8; -.
DR OMA; YWTAAQQ; -.
DR OrthoDB; 980065at2759; -.
DR UniPathway; UPA00139; UER00341.
DR Proteomes; UP000002530; Chromosome 2.
DR GO; GO:0004334; F:fumarylacetoacetase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1902000; P:homogentisate catabolic process; IBA:GO_Central.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IBA:GO_Central.
DR GO; GO:0006572; P:tyrosine catabolic process; IBA:GO_Central.
DR Gene3D; 2.30.30.230; -; 1.
DR Gene3D; 3.90.850.10; -; 1.
DR InterPro; IPR005959; Fumarylacetoacetase.
DR InterPro; IPR011234; Fumarylacetoacetase-like_C.
DR InterPro; IPR036663; Fumarylacetoacetase_C_sf.
DR InterPro; IPR015377; Fumarylacetoacetase_N.
DR InterPro; IPR036462; Fumarylacetoacetase_N_sf.
DR PANTHER; PTHR43069; PTHR43069; 1.
DR Pfam; PF01557; FAA_hydrolase; 1.
DR Pfam; PF09298; FAA_hydrolase_N; 1.
DR SUPFAM; SSF56529; SSF56529; 1.
DR SUPFAM; SSF63433; SSF63433; 1.
DR TIGRFAMs; TIGR01266; fum_ac_acetase; 1.
PE 2: Evidence at transcript level;
KW Calcium; Hydrolase; Magnesium; Metal-binding; Phenylalanine catabolism;
KW Reference proteome; Tyrosine catabolism.
FT CHAIN 1..431
FT /note="Fumarylacetoacetase fahA"
FT /id="PRO_0000453191"
FT REGION 362..382
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 140
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q00770"
FT BINDING 133
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 135
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 149
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 209
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 211
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 243
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 243
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 250
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 254
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 263
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 267
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P35505"
FT BINDING 362
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P35505"
SQ SEQUENCE 431 AA; 46817 MW; FDA6448FC4EAB32D CRC64;
MASWLQIPKN SPFSLANIPF GIISSAKITS PVAAVAVGDY ALNLSIFASS GGFSQLPVIQ
PHLGVFSQPT LNAFAALGRP VHRQVREYIQ SVFRADTPFP QILKDNSTLQ KEALLPLSEV
TNHLPMHIGD YTDFYAGLNH AYNVGVLFRG PENALQPNYK HLPVGYHGRA SSVVTSGTPI
RRPNGQILAN PAANPKVPTF SPCKRLDIEL ELAAFVSKSN ELGKPVSIDE AEDHIFGVVL
MNDWSARDIQ AWEYVPLGPF NAKNFATTIT PWVVLLDALE PFRTAGLEPG NRESLLPYLR
EKRELNAYDI PLEVEITNAG GKPTLISRTN AKNLLYSFPQ MLAHHTITGC NMNTGDLLGS
GTISGKENQT QGSLLEQTNG KNPLKLADGS ERLFLEDGDT VVLRGMAGTE GNYVGFGDCV
GTILPALKLE F
