PH4H_DICDI
ID PH4H_DICDI Reviewed; 441 AA.
AC Q54XS1;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Phenylalanine-4-hydroxylase;
DE Short=PAH {ECO:0000303|PubMed:18835579};
DE EC=1.14.16.1 {ECO:0000269|PubMed:18835579};
DE AltName: Full=Phe-4-monooxygenase;
DE AltName: Full=Tryptophan 5-hydroxylase;
DE Short=TRH;
DE EC=1.14.16.4 {ECO:0000269|PubMed:18835579};
DE AltName: Full=Tryptophan 5-monooxygenase;
GN Name=pah; ORFNames=DDB_G0278781;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=18835579; DOI=10.1016/j.gene.2008.09.005;
RA Siltberg-Liberles J., Steen I.H., Svebak R.M., Martinez A.;
RT "The phylogeny of the aromatic amino acid hydroxylases revisited by
RT characterizing phenylalanine hydroxylase from Dictyostelium discoideum.";
RL Gene 427:86-92(2008).
CC -!- FUNCTION: Catalyzes the hydroxylation of L-phenylalanine
CC (PubMed:18835579). Hydroxylates L-tryptophan to 5-hydroxy-L-tryptophan
CC but does not hydroxylate L-tyrosine to L-DOPA (PubMed:18835579). It
CC uses D-threo-tetrahydrodictyopterin (DH4), also known as dictyoperin,
CC as a cofactor. {ECO:0000269|PubMed:18835579}.
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:0000269|PubMed:18835579};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20274;
CC Evidence={ECO:0000269|PubMed:18835579};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tryptophan + O2
CC = (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin + 5-
CC hydroxy-L-tryptophan; Xref=Rhea:RHEA:16709, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15642, ChEBI:CHEBI:57912, ChEBI:CHEBI:58266,
CC ChEBI:CHEBI:59560; EC=1.14.16.4;
CC Evidence={ECO:0000269|PubMed:18835579};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16710;
CC Evidence={ECO:0000269|PubMed:18835579};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000250};
CC Note=Binds 1 Fe(2+) ion. {ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=620 uM for L-Phe with BH(4) as cofactor
CC {ECO:0000269|PubMed:18835579};
CC KM=90 uM for L-Phe with DH(4) as cofactor
CC {ECO:0000269|PubMed:18835579};
CC KM=49 uM for BH(4) {ECO:0000269|PubMed:18835579};
CC KM=39 uM for DH(4) {ECO:0000269|PubMed:18835579};
CC Vmax=660 nmol/min/mg enzyme with BH(4) as cofactor (preincubated with
CC L-Phe) {ECO:0000269|PubMed:18835579};
CC Vmax=840 nmol/min/mg enzyme with DH(4) as cofactor (preincubated with
CC L-Phe) {ECO:0000269|PubMed:18835579};
CC Vmax=1620 nmol/min/mg enzyme with BH(4) as cofactor (preincubated
CC with BH(4)) {ECO:0000269|PubMed:18835579};
CC Vmax=1890 nmol/min/mg enzyme with DH(4) as cofactor (preincubated
CC with DH(4)) {ECO:0000269|PubMed:18835579};
CC Temperature dependence:
CC Optimum temperature is 40 degrees Celsius.
CC {ECO:0000269|PubMed:18835579};
CC -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation;
CC acetoacetate and fumarate from L-phenylalanine: step 1/6.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:18835579}.
CC -!- INTERACTION:
CC Q54XS1; Q54XS1: pah; NbExp=4; IntAct=EBI-8067766, EBI-8067766;
CC -!- MISCELLANEOUS: This enzyme uses tetrahydrodictyopterin (DH4), a D-threo
CC isomer of biopterin, and not tetrahydrobiopterin (TH4) for it's
CC catalytic activity.
CC -!- SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid
CC hydroxylase family. {ECO:0000305}.
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DR EMBL; AAFI02000024; EAL67992.1; -; Genomic_DNA.
DR RefSeq; XP_641959.1; XM_636867.1.
DR PDB; 5JK5; X-ray; 2.07 A; A/B=1-415.
DR PDB; 5JK6; X-ray; 2.07 A; A/B=1-415.
DR PDB; 5JK8; X-ray; 2.39 A; A/B=1-415.
DR PDBsum; 5JK5; -.
DR PDBsum; 5JK6; -.
DR PDBsum; 5JK8; -.
DR AlphaFoldDB; Q54XS1; -.
DR SMR; Q54XS1; -.
DR MINT; Q54XS1; -.
DR STRING; 44689.DDB0231664; -.
DR PaxDb; Q54XS1; -.
DR PRIDE; Q54XS1; -.
DR EnsemblProtists; EAL67992; EAL67992; DDB_G0278781.
DR GeneID; 8621691; -.
DR KEGG; ddi:DDB_G0278781; -.
DR dictyBase; DDB_G0278781; pah.
DR eggNOG; KOG3820; Eukaryota.
DR HOGENOM; CLU_023198_0_1_1; -.
DR InParanoid; Q54XS1; -.
DR OMA; HAAQPLY; -.
DR PhylomeDB; Q54XS1; -.
DR Reactome; R-DDI-209905; Catecholamine biosynthesis.
DR Reactome; R-DDI-209931; Serotonin and melatonin biosynthesis.
DR Reactome; R-DDI-8964208; Phenylalanine metabolism.
DR SABIO-RK; Q54XS1; -.
DR UniPathway; UPA00139; UER00337.
DR PRO; PR:Q54XS1; -.
DR Proteomes; UP000002195; Chromosome 3.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004505; F:phenylalanine 4-monooxygenase activity; IDA:dictyBase.
DR GO; GO:0004664; F:prephenate dehydratase activity; IEA:InterPro.
DR GO; GO:0034617; F:tetrahydrobiopterin binding; IDA:dictyBase.
DR GO; GO:0004510; F:tryptophan 5-monooxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0019954; P:asexual reproduction; IMP:dictyBase.
DR GO; GO:0009094; P:L-phenylalanine biosynthetic process; IEA:InterPro.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IDA:dictyBase.
DR GO; GO:0006571; P:tyrosine biosynthetic process; IDA:dictyBase.
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; IPR018528; Preph_deHydtase_CS.
DR InterPro; IPR019773; Tyrosine_3-monooxygenase-like.
DR PANTHER; PTHR11473; PTHR11473; 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 PROSITE; PS51671; ACT; 1.
DR PROSITE; PS00367; BH4_AAA_HYDROXYL_1; 1.
DR PROSITE; PS51410; BH4_AAA_HYDROXYL_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Phenylalanine catabolism; Reference proteome.
FT CHAIN 1..441
FT /note="Phenylalanine-4-hydroxylase"
FT /id="PRO_0000328336"
FT DOMAIN 23..102
FT /note="ACT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01007"
FT BINDING 273
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT BINDING 278
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT BINDING 318
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT STRAND 17..26
FT /evidence="ECO:0007829|PDB:5JK5"
FT HELIX 32..45
FT /evidence="ECO:0007829|PDB:5JK5"
FT STRAND 49..56
FT /evidence="ECO:0007829|PDB:5JK5"
FT STRAND 63..74
FT /evidence="ECO:0007829|PDB:5JK5"
FT HELIX 79..88
FT /evidence="ECO:0007829|PDB:5JK5"
FT TURN 89..91
FT /evidence="ECO:0007829|PDB:5JK5"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:5JK5"
FT STRAND 104..107
FT /evidence="ECO:0007829|PDB:5JK5"
FT HELIX 113..119
FT /evidence="ECO:0007829|PDB:5JK5"
FT STRAND 125..129
FT /evidence="ECO:0007829|PDB:5JK5"
FT TURN 135..138
FT /evidence="ECO:0007829|PDB:5JK5"
FT HELIX 140..155
FT /evidence="ECO:0007829|PDB:5JK5"
FT HELIX 169..183
FT /evidence="ECO:0007829|PDB:5JK5"
FT HELIX 186..189
FT /evidence="ECO:0007829|PDB:5JK5"
FT HELIX 192..204
FT /evidence="ECO:0007829|PDB:5JK5"
FT HELIX 215..226
FT /evidence="ECO:0007829|PDB:5JK5"
FT STRAND 229..232
FT /evidence="ECO:0007829|PDB:5JK5"
FT STRAND 234..236
FT /evidence="ECO:0007829|PDB:5JK6"
FT HELIX 239..246
FT /evidence="ECO:0007829|PDB:5JK5"
FT TURN 247..249
FT /evidence="ECO:0007829|PDB:5JK5"
FT STRAND 250..253
FT /evidence="ECO:0007829|PDB:5JK5"
FT HELIX 271..277
FT /evidence="ECO:0007829|PDB:5JK5"
FT HELIX 279..282
FT /evidence="ECO:0007829|PDB:5JK5"
FT HELIX 285..298
FT /evidence="ECO:0007829|PDB:5JK5"
FT HELIX 303..314
FT /evidence="ECO:0007829|PDB:5JK5"
FT TURN 315..319
FT /evidence="ECO:0007829|PDB:5JK5"
FT STRAND 321..324
FT /evidence="ECO:0007829|PDB:5JK5"
FT STRAND 327..330
FT /evidence="ECO:0007829|PDB:5JK5"
FT HELIX 333..336
FT /evidence="ECO:0007829|PDB:5JK5"
FT HELIX 339..345
FT /evidence="ECO:0007829|PDB:5JK5"
FT STRAND 350..354
FT /evidence="ECO:0007829|PDB:5JK5"
FT HELIX 357..360
FT /evidence="ECO:0007829|PDB:5JK5"
FT STRAND 367..369
FT /evidence="ECO:0007829|PDB:5JK5"
FT STRAND 372..378
FT /evidence="ECO:0007829|PDB:5JK5"
FT HELIX 380..393
FT /evidence="ECO:0007829|PDB:5JK5"
FT STRAND 397..403
FT /evidence="ECO:0007829|PDB:5JK5"
FT TURN 404..407
FT /evidence="ECO:0007829|PDB:5JK5"
FT STRAND 408..413
FT /evidence="ECO:0007829|PDB:5JK5"
SQ SEQUENCE 441 AA; 50415 MW; D02E03F28A873D1C CRC64;
MESNTNSQGQ GIIPQSYHSS IFFSISKGSD KIGGLLEYLE IIKKHNINIT RIESRPSKTE
KKDYDFFLDL EYPTENNKEV EKVIKDLEEK GVKATTLQES SNQTYAPWFP RKISDLDLFA
NKVLEMGSDL TSDHPGASDP VYRERRREIA KIASTYKHGD EIPRIDYTEE EIKTWGVVYN
RLKELFPTNA CHQHAYIFPL LEQNCGYSPD NIPQLQDISN FLQECTGWRI RPVQGLLSAR
DFLNGLAFRV FHATQYIRHP SVPLYTPEPD CCHELLGHVP LLADPDFADF SQEIGLASIG
ASDEDIQLLS TCYWFTVEFG LCKEGDTIRA YGAGILSSTG EMEHFLTDKA KKLPFNPFDA
CNTEYPITTF QPLYYVAESF QKAKEQMRQF ADSFKKPFSI RYNPYTQSIE ILDNKDKLLN
ICNDIRNQSE ILADAISKLK A
