PHHA_ASPNC
ID PHHA_ASPNC Reviewed; 636 AA.
AC A2QGH7;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=p-hydroxybenzoate-m-hydroxylase A {ECO:0000303|Ref.2};
DE EC=1.14.13.33 {ECO:0000269|Ref.2};
DE AltName: Full=4-hydroxybenzoate-3-monooxygenase phhA {ECO:0000303|Ref.2};
DE AltName: Full=FAD-dependent monooxygenase phhA {ECO:0000305};
GN Name=phhA {ECO:0000303|Ref.2}; ORFNames=An03g03330;
OS Aspergillus niger (strain CBS 513.88 / FGSC A1513).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=425011;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CBS 513.88 / FGSC A1513 / ATCC MYA-4892;
RX PubMed=17259976; DOI=10.1038/nbt1282;
RA Pel H.J., de Winde J.H., Archer D.B., Dyer P.S., Hofmann G., Schaap P.J.,
RA Turner G., de Vries R.P., Albang R., Albermann K., Andersen M.R.,
RA Bendtsen J.D., Benen J.A.E., van den Berg M., Breestraat S., Caddick M.X.,
RA Contreras R., Cornell M., Coutinho P.M., Danchin E.G.J., Debets A.J.M.,
RA Dekker P., van Dijck P.W.M., van Dijk A., Dijkhuizen L., Driessen A.J.M.,
RA d'Enfert C., Geysens S., Goosen C., Groot G.S.P., de Groot P.W.J.,
RA Guillemette T., Henrissat B., Herweijer M., van den Hombergh J.P.T.W.,
RA van den Hondel C.A.M.J.J., van der Heijden R.T.J.M., van der Kaaij R.M.,
RA Klis F.M., Kools H.J., Kubicek C.P., van Kuyk P.A., Lauber J., Lu X.,
RA van der Maarel M.J.E.C., Meulenberg R., Menke H., Mortimer M.A.,
RA Nielsen J., Oliver S.G., Olsthoorn M., Pal K., van Peij N.N.M.E.,
RA Ram A.F.J., Rinas U., Roubos J.A., Sagt C.M.J., Schmoll M., Sun J.,
RA Ussery D., Varga J., Vervecken W., van de Vondervoort P.J.J., Wedler H.,
RA Woesten H.A.B., Zeng A.-P., van Ooyen A.J.J., Visser J., Stam H.;
RT "Genome sequencing and analysis of the versatile cell factory Aspergillus
RT niger CBS 513.88.";
RL Nat. Biotechnol. 25:221-231(2007).
RN [2]
RP INDUCTION, FUNCTION, DISRUPTION PHENOTYPE, AND CATALYTIC ACTIVITY.
RX DOI=10.1021/acssuschemeng.9b04918;
RA Lubbers R.J.M., Dilokpimol A., Peng M., Visser J., Makela M.R.,
RA Hilden K.S., de Vries R.P.;
RT "Discovery of novel p-hydroxybenzoate-m-hydroxylase, protocatechuate 3,4
RT ring-cleavage dioxygenase, and hydroxyquinol 1,2 ring-cleavage dioxygenase
RT from the filamentous fungus Aspergillus niger.";
RL ACS Sustain. Chem. Eng. 7:19081-19089(2019).
CC -!- FUNCTION: FAD-dependent monooxygenase; part of the benzoic acid
CC degradation pathway also known as the protocatechuic acid pathway
CC (Ref.2). Benzoic acid debradation begins with the conversion of benzoic
CC acid into 4-hydroxybenzoic acid through hydroxylation by the benzoate-
CC 4-monooxygenase bphA, and its partner NADPH-cytochrome P450 reductase
CC cprA which act as a mediator in electron donation from NADPH (By
CC similarity). 4-Hydroxybenzoic acid is then converted into 3,4-
CC dihydroxybenzoic acid (also called protocatechuic acid) by the p-
CC hydroxybenzoate-m-hydroxylase phhA (Ref.2). Protocatechuic acid is
CC converted into 3-carboxy-cis,cis-muconic acid by the intradiol ring-
CC cleavage dioxygenase prcA, which is further metabolized through the 3-
CC oxoadipate pathway to finally enter the tricarboxylic acid cycle (TCA)
CC (Ref.2). {ECO:0000250|UniProtKB:A2QTW5, ECO:0000269|Ref.2}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-hydroxybenzoate + H(+) + NADH + O2 = 3,4-dihydroxybenzoate +
CC H2O + NAD(+); Xref=Rhea:RHEA:19473, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17879,
CC ChEBI:CHEBI:36241, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC EC=1.14.13.33; Evidence={ECO:0000269|Ref.2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19474;
CC Evidence={ECO:0000269|Ref.2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-hydroxybenzoate + H(+) + NADPH + O2 = 3,4-dihydroxybenzoate
CC + H2O + NADP(+); Xref=Rhea:RHEA:19477, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17879,
CC ChEBI:CHEBI:36241, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.14.13.33; Evidence={ECO:0000269|Ref.2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19478;
CC Evidence={ECO:0000269|Ref.2};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q6SSJ6};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:Q6SSJ6};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is induced in the presence of caffeic acid, p-
CC coumaric acid, p-hydroxybenzoic acid, protocatechuic acid, and benzoic
CC acid. {ECO:0000269|Ref.2}.
CC -!- DISRUPTION PHENOTYPE: Abolishes growth on benzoic acid, benzaldehyde,
CC benzyl alcohol, p-anisic acid, p-anisyl alcohol, and p-hydroxybenzoic
CC acid; and reduces growth on p-coumaric acid and cinnamic acid.
CC {ECO:0000269|Ref.2}.
CC -!- SIMILARITY: Belongs to the PheA/TfdB FAD monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; AM270053; CAK47774.1; -; Genomic_DNA.
DR RefSeq; XP_001390216.1; XM_001390179.1.
DR SMR; A2QGH7; -.
DR PaxDb; A2QGH7; -.
DR EnsemblFungi; CAK47774; CAK47774; An03g03330.
DR GeneID; 4980323; -.
DR KEGG; ang:ANI_1_382034; -.
DR VEuPathDB; FungiDB:An03g03330; -.
DR HOGENOM; CLU_009665_9_3_1; -.
DR Proteomes; UP000006706; Chromosome 6R.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0106355; F:4-hydroxybenzoate 3-monooxygenase [NADH] activity; IEA:RHEA.
DR GO; GO:0106356; F:4-hydroxybenzoate 3-monooxygenase [NADPH] activity; IEA:RHEA.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0018662; F:phenol 2-monooxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 3.40.30.20; -; 1.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR012941; Phe_hydrox_C_dim_dom.
DR InterPro; IPR038220; PHOX_C_sf.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR Pfam; PF07976; Phe_hydrox_dim; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Membrane; Oxidoreductase; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..636
FT /note="p-hydroxybenzoate-m-hydroxylase A"
FT /id="PRO_0000453616"
FT TRANSMEM 11..28
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 10..39
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q6SSJ6"
FT BINDING 241..243
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q6SSJ6"
FT BINDING 289
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q6SSJ6"
FT BINDING 310
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q6SSJ6"
SQ SEQUENCE 636 AA; 70898 MW; 9E8848DAEA26B321 CRC64;
MAPSQQEKYD IVIVGAGPVG IVLSLCMSRW GYKVKHIDNR PVPTATGRAD GIQPRSTEIL
RNLGLKRQIM AFKPAKVYDV AFWDPLPGGQ GIHRTGSWPS CPRFIDTRYP FTTLVHQGKI
ERVFLDEIQK AGTTVERPWT IVGFKNDGLD ETYPVEVQLK SIDTNVIETV RTKYLFSGEG
ARSFIRQQLG IQIQYKDPIS YVWGVMDGVV RTNFPDIETK CTIHSDAGSI MVIPREDNMV
RLYVQIASSD DPDFDPRKTA TAEDVQATAR KILQPYWVEW DRVEWYSVYP IGQGISEKYT
LDERVFMGGD ACHTHSPKAG QGMNTAFHDA LNMAWKLHAV ESGLAKRSIL STYETERKDI
AETLLSFDNK YAALFSKRRP TAGEVGEASH TTAAAGGEED EFVKTFKSSC EFTSGYGVAY
KPNVFTWDAT HPAQSPLFDV PGVRLTPGRA FTPTTVTRLA DSNHVHLEQE IPANGAFRIF
IFAGKQDKTS KAITDLAANL EKERSFLSVY RRADIADVSF FENHLPHSKL FSICLVYAGE
KNQIDVDSIP KILRDYHHHL YADNIPDVRV PQATYAAHEK LGFDVEKGGV VVTRPDSHVA
CTVQLSEGSG TVDALNAFFG SFATKPLGQD SQQSRL
