PH4H_BOVIN
ID PH4H_BOVIN Reviewed; 451 AA.
AC Q2KIH7; A5D9G6;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Phenylalanine-4-hydroxylase;
DE Short=PAH;
DE EC=1.14.16.1 {ECO:0000250|UniProtKB:P00439};
DE AltName: Full=Phe-4-monooxygenase;
GN Name=PAH;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Testis;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes the hydroxylation of L-phenylalanine to L-tyrosine.
CC {ECO:0000250|UniProtKB:P00439}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-phenylalanine +
CC O2 = (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin + L-
CC tyrosine; Xref=Rhea:RHEA:20273, ChEBI:CHEBI:15379, ChEBI:CHEBI:15642,
CC ChEBI:CHEBI:58095, ChEBI:CHEBI:58315, ChEBI:CHEBI:59560;
CC EC=1.14.16.1; Evidence={ECO:0000250|UniProtKB:P00439};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:P04176};
CC -!- ACTIVITY REGULATION: N-terminal region of PAH is thought to contain
CC allosteric binding sites for phenylalanine and to constitute an
CC 'inhibitory' domain that regulates the activity of a catalytic domain
CC in the C-terminal portion of the molecule.
CC {ECO:0000250|UniProtKB:P00439}.
CC -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation;
CC acetoacetate and fumarate from L-phenylalanine: step 1/6.
CC -!- SUBUNIT: Homodimer and homotetramer. {ECO:0000250|UniProtKB:P00439}.
CC -!- PTM: Phosphorylation at Ser-16 increases basal activity and facilitates
CC activation by the substrate phenylalanine.
CC {ECO:0000250|UniProtKB:P00439}.
CC -!- SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid
CC hydroxylase family. {ECO:0000305}.
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DR EMBL; BT030585; ABQ13025.1; -; mRNA.
DR EMBL; BC112633; AAI12634.1; -; mRNA.
DR RefSeq; NP_001039523.1; NM_001046058.2.
DR AlphaFoldDB; Q2KIH7; -.
DR SMR; Q2KIH7; -.
DR STRING; 9913.ENSBTAP00000016999; -.
DR PaxDb; Q2KIH7; -.
DR Ensembl; ENSBTAT00000076031; ENSBTAP00000065971; ENSBTAG00000012794.
DR GeneID; 510583; -.
DR KEGG; bta:510583; -.
DR CTD; 5053; -.
DR VEuPathDB; HostDB:ENSBTAG00000012794; -.
DR VGNC; VGNC:32554; PAH.
DR eggNOG; KOG3820; Eukaryota.
DR GeneTree; ENSGT00950000182885; -.
DR HOGENOM; CLU_023198_0_1_1; -.
DR InParanoid; Q2KIH7; -.
DR OMA; HAAQPLY; -.
DR OrthoDB; 614557at2759; -.
DR TreeFam; TF313327; -.
DR UniPathway; UPA00139; UER00337.
DR Proteomes; UP000009136; Chromosome 5.
DR Bgee; ENSBTAG00000012794; Expressed in liver and 65 other tissues.
DR ExpressionAtlas; Q2KIH7; baseline.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004505; F:phenylalanine 4-monooxygenase activity; IBA:GO_Central.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006571; P:tyrosine biosynthetic process; IBA:GO_Central.
DR CDD; cd03347; eu_PheOH; 1.
DR Gene3D; 1.10.800.10; -; 1.
DR InterPro; IPR045865; ACT-like_dom_sf.
DR InterPro; IPR002912; ACT_dom.
DR InterPro; IPR001273; ArAA_hydroxylase.
DR InterPro; IPR018301; ArAA_hydroxylase_Fe/CU_BS.
DR InterPro; IPR036951; ArAA_hydroxylase_sf.
DR InterPro; IPR036329; Aro-AA_hydroxylase_C_sf.
DR InterPro; IPR019774; Aromatic-AA_hydroxylase_C.
DR InterPro; IPR041912; Euk_PheOH_cat.
DR InterPro; IPR005961; Phe-4-hydroxylase_tetra.
DR InterPro; IPR019773; Tyrosine_3-monooxygenase-like.
DR PANTHER; PTHR11473; PTHR11473; 1.
DR Pfam; PF01842; ACT; 1.
DR Pfam; PF00351; Biopterin_H; 1.
DR PIRSF; PIRSF000336; TH; 1.
DR PRINTS; PR00372; FYWHYDRXLASE.
DR SUPFAM; SSF55021; SSF55021; 1.
DR SUPFAM; SSF56534; SSF56534; 1.
DR TIGRFAMs; TIGR01268; Phe4hydrox_tetr; 1.
DR PROSITE; PS51671; ACT; 1.
DR PROSITE; PS00367; BH4_AAA_HYDROXYL_1; 1.
DR PROSITE; PS51410; BH4_AAA_HYDROXYL_2; 1.
PE 2: Evidence at transcript level;
KW Allosteric enzyme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Phenylalanine catabolism; Phosphoprotein; Reference proteome.
FT CHAIN 1..451
FT /note="Phenylalanine-4-hydroxylase"
FT /id="PRO_0000281913"
FT DOMAIN 35..113
FT /note="ACT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01007"
FT BINDING 284
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P04176"
FT BINDING 289
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P04176"
FT BINDING 329
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:P04176"
FT MOD_RES 16
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P00439"
SQ SEQUENCE 451 AA; 51727 MW; 2D2791910652BD2E CRC64;
MSALVLESRA LGRKLSDFGQ ETSYIEGNSD QNAVSLIFSL KEEVGALARV LRLFEENDIN
LTHIESRPSR LRKDEYEFFT NLDQRSVPAL ANIIKILRHD IGATVHELSR DKKKDTVPWF
PRTIQELDNF ANQVLSYGAE LDADHPGFKD PVYRARRKQF ADIAYNYRHG QPIPRVEYTE
EEKKTWGTVF RTLKSLYKTH ACYEHNHIFP LLEKYCGFRE DNIPQLEEVS QFLQSCTGFR
LRPVAGLLSS RDFLGGLAFR VFHCTQYIRH GSKPMYTPEP DICHELLGHV PLFSDRSFAQ
FSQEIGLASL GAPDEYIEKL ATIYWFTVEF GLCKQGDSIK AYGAGLLSSF GELQYCLSDK
PKLLPLELEK TAVQEYTITE FQPLYYVAES FNDAKEKVRN FAATIPRPFS VHYDPYTQRI
EVLDNTQQLK ILADSISSEV EILCSALQKL K
