HPPD1_ASPFU
ID HPPD1_ASPFU Reviewed; 403 AA.
AC Q4WHU1;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=4-hydroxyphenylpyruvate dioxygenase {ECO:0000303|PubMed:19028908};
DE Short=4HPPD {ECO:0000305};
DE Short=HPD {ECO:0000305};
DE Short=HPPDase {ECO:0000305};
DE EC=1.13.11.27 {ECO:0000269|PubMed:22046314};
DE AltName: Full=L-tyrosine degradation gene cluster protein hppD {ECO:0000303|PubMed:22046314};
DE AltName: Full=Pyomelanin biosynthesis cluster protein hppD {ECO:0000303|PubMed:22046314};
GN Name=hppD {ECO:0000303|PubMed:19028908}; ORFNames=AFUA_2G04200;
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, AND DISRUPTION PHENOTYPE.
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: 4-hydroxyphenylpyruvate 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: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=3-(4-hydroxyphenyl)pyruvate + O2 = CO2 + homogentisate;
CC Xref=Rhea:RHEA:16189, ChEBI:CHEBI:15379, ChEBI:CHEBI:16169,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:36242; EC=1.13.11.27;
CC Evidence={ECO:0000269|PubMed:22046314};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16190;
CC Evidence={ECO:0000269|PubMed:22046314};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:P93836};
CC Note=Binds 1 Fe cation per subunit. {ECO:0000250|UniProtKB:P93836};
CC -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation;
CC acetoacetate and fumarate from L-phenylalanine: step 3/6.
CC {ECO:0000305|PubMed:19028908}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P93836}.
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 source and affects homogentisic acid and pyomelanin formation
CC (PubMed:19028908, PubMed:19715768). Leads to increased sensitivity to
CC reactive oxygen intermediates (PubMed:19028908).
CC {ECO:0000269|PubMed:19028908, ECO:0000269|PubMed:19715768}.
CC -!- SIMILARITY: Belongs to the 4HPPD family. {ECO:0000305}.
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DR EMBL; AAHF01000008; EAL87514.1; -; Genomic_DNA.
DR RefSeq; XP_749552.1; XM_744459.1.
DR AlphaFoldDB; Q4WHU1; -.
DR SMR; Q4WHU1; -.
DR STRING; 746128.CADAFUBP00002076; -.
DR PRIDE; Q4WHU1; -.
DR EnsemblFungi; EAL87514; EAL87514; AFUA_2G04200.
DR GeneID; 3507145; -.
DR KEGG; afm:AFUA_2G04200; -.
DR VEuPathDB; FungiDB:Afu2g04200; -.
DR eggNOG; KOG0638; Eukaryota.
DR HOGENOM; CLU_034004_3_1_1; -.
DR InParanoid; Q4WHU1; -.
DR OMA; DPFPVKG; -.
DR OrthoDB; 1087836at2759; -.
DR UniPathway; UPA00139; UER00362.
DR Proteomes; UP000002530; Chromosome 2.
DR GO; GO:0003868; F:4-hydroxyphenylpyruvate dioxygenase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0042438; P:melanin biosynthetic process; IMP:AspGD.
DR GO; GO:0006572; P:tyrosine catabolic process; IMP:AspGD.
DR CDD; cd07250; HPPD_C_like; 1.
DR CDD; cd08342; HPPD_N_like; 1.
DR Gene3D; 3.10.180.10; -; 2.
DR InterPro; IPR005956; 4OHPhenylPyrv_dOase.
DR InterPro; IPR041735; 4OHPhenylPyrv_dOase_C.
DR InterPro; IPR041736; 4OHPhenylPyrv_dOase_N.
DR InterPro; IPR029068; Glyas_Bleomycin-R_OHBP_Dase.
DR InterPro; IPR004360; Glyas_Fos-R_dOase_dom.
DR InterPro; IPR037523; VOC.
DR PANTHER; PTHR11959; PTHR11959; 1.
DR Pfam; PF00903; Glyoxalase; 1.
DR PIRSF; PIRSF009283; HPP_dOase; 1.
DR SUPFAM; SSF54593; SSF54593; 1.
DR TIGRFAMs; TIGR01263; 4HPPD; 1.
DR PROSITE; PS51819; VOC; 2.
PE 1: Evidence at protein level;
KW Dioxygenase; Iron; Metal-binding; Oxidoreductase; Phenylalanine catabolism;
KW Reference proteome; Repeat; Tyrosine catabolism.
FT CHAIN 1..403
FT /note="4-hydroxyphenylpyruvate dioxygenase"
FT /id="PRO_0000088401"
FT DOMAIN 25..169
FT /note="VOC 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT DOMAIN 201..359
FT /note="VOC 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01163"
FT BINDING 204
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P93836"
FT BINDING 287
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P93836"
FT BINDING 370
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P93836"
SQ SEQUENCE 403 AA; 45534 MW; 849FED016DA354AC CRC64;
MAPSAISTSP PPTDRVSSSL ASYKGYDHVH WYVGNAKQAA SYYITRMGFK RIAYRGLETG
CRSVCSHVVR NGDITFILTS PLRSLDQVDR FPPEEQELLK EIHAHLEKHG DGVKDVAFEV
DSVDSVFYAA TNNGAKIVSQ PRTLEDDNGQ VRVATIQTYG ETTHTLVERG SYHGAFLPGY
RMETGVEDPI SQLLPGVHLN RIDHCVGNQD WDEMDKVCEY YEKALGFHRF WSVDDKQICT
EYSALKSIVM ASPNEVVKMP INEPAKGKKQ SQIEEYVDFY NGAGVQHIAL LTDDIIRDIT
NLKARGVEFI KVPDTYYEDI KVRLKKAGLT LHEDFETIRS LDILIDFDEG GYLLQLFTKH
LMDRPTVFIE IIQRHNFSGF GAGNFKSLFE AIEREQALRG NLV