Q54XS1 (PH4H_DICDI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phenylalanine-4-hydroxylase
Short name=PAH
EC=1.14.16.1
EC=1.14.16.4

Alternative name(s):
Phe-4-monooxygenase
Tryptophan 5-hydroxylase
Short name=TRH
Tryptophan 5-monooxygenase

Gene names

Name:	pah
ORF Names:	DDB_G0278781

Organism

Dictyostelium discoideum (Slime mold)

Taxonomic identifier

44689 [NCBI]

Taxonomic lineage

Eukaryota › Amoebozoa › Mycetozoa › Dictyosteliida › Dictyostelium

Protein attributes

Sequence length	441 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Hydroxylates L-tryptophan to 5-hydroxy-L-tryptophan but does not hydroxylate L-tyrosine to L-DOPA. It uses D-threo-tetrahydrodictyopterin (DH4), also known as dictyoperin, as a cofactor. Ref.2
Catalytic activity	L-phenylalanine + tetrahydrobiopterin + O2 = L-tyrosine + 4a-hydroxytetrahydrobiopterin. L-tryptophan + tetrahydrobiopterin + O2 = 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin.
Cofactor	Binds 1 Fe2+ ion By similarity.
Pathway	Amino-acid degradation; L-phenylalanine degradation; acetoacetate and fumarate from L-phenylalanine: step 1/6.
Subunit structure	Homoetramer. Ref.2
Miscellaneous	This enzyme uses tetrahydrodictyopterin (DH4), a D-threo isomer of biopterin, and not tetrahydrobiopterin (TH4) for it's catalytic activity.
Sequence similarities	Belongs to the biopterin-dependent aromatic amino acid hydroxylase family. Contains 1 ACT domain.
Biophysicochemical properties	Kinetic parameters: KM=620 µM for for L-Phe with BH4 as cofactor Ref.2 KM=90 µM for for L-Phe with DH4 as cofactor KM=49 µM for for BH4 KM=39 µM for for DH4 Vmax=660 nmol/min/mg enzyme with BH4 as cofactor (preincubated with L-Phe) Vmax=840 nmol/min/mg enzyme with DH4 as cofactor (preincubated with L-Phe) Vmax=1620 nmol/min/mg enzyme with BH4 as cofactor (preincubated with BH4) Vmax=1890 nmol/min/mg enzyme with DH4 as cofactor (preincubated with DH4) Temperature dependence: Optimum temperature is 40 degrees Celsius.

Ontologies

Keywords
Biological process	Phenylalanine catabolism
Ligand	Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	L-phenylalanine biosynthetic process Inferred from electronic annotation. Source: InterPro L-phenylalanine catabolic process Inferred from direct assay Ref.2. Source: dictyBase protein tetramerization Inferred from direct assay Ref.2. Source: dictyBase tyrosine biosynthetic process Inferred from direct assay Ref.2. Source: dictyBase
Molecular function	iron ion binding Inferred from electronic annotation. Source: InterPro phenylalanine 4-monooxygenase activity Inferred from direct assay Ref.2. Source: dictyBase prephenate dehydratase activity Inferred from electronic annotation. Source: InterPro tetrahydrobiopterin binding Inferred from direct assay Ref.2. Source: dictyBase tryptophan 5-monooxygenase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 441	441	Phenylalanine-4-hydroxylase		PRO_0000328336
Regions
	Domain	23 – 89	67	ACT
Sites
	Metal binding	273	1	Iron By similarity
	Metal binding	278	1	Iron By similarity
	Metal binding	318	1	Iron By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q54XS1 [UniParc]. Last modified May 24, 2005. Version 1. Checksum: D02E03F28A873D1C	FASTA	441	50,415
	10 20 30 40 50 60 MESNTNSQGQ GIIPQSYHSS IFFSISKGSD KIGGLLEYLE IIKKHNINIT RIESRPSKTE 70 80 90 100 110 120 KKDYDFFLDL EYPTENNKEV EKVIKDLEEK GVKATTLQES SNQTYAPWFP RKISDLDLFA 130 140 150 160 170 180 NKVLEMGSDL TSDHPGASDP VYRERRREIA KIASTYKHGD EIPRIDYTEE EIKTWGVVYN 190 200 210 220 230 240 RLKELFPTNA CHQHAYIFPL LEQNCGYSPD NIPQLQDISN FLQECTGWRI RPVQGLLSAR 250 260 270 280 290 300 DFLNGLAFRV FHATQYIRHP SVPLYTPEPD CCHELLGHVP LLADPDFADF SQEIGLASIG 310 320 330 340 350 360 ASDEDIQLLS TCYWFTVEFG LCKEGDTIRA YGAGILSSTG EMEHFLTDKA KKLPFNPFDA 370 380 390 400 410 420 CNTEYPITTF QPLYYVAESF QKAKEQMRQF ADSFKKPFSI RYNPYTQSIE ILDNKDKLLN 430 440 ICNDIRNQSE ILADAISKLK A

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The genome of the social amoeba Dictyostelium discoideum." Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R., Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B., Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T., Lehmann R., Hamlin N. , Davies R., Gaudet P., Fey P., Pilcher K., Chen G., Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N., Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E., Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N., Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D., Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T., Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D., Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A., Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M., Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A., Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y., Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C., Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R., Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A. Nature 435:43-57(2005) [PubMed: 15875012] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: AX4.
[2]	"The phylogeny of the aromatic amino acid hydroxylases revisited by characterizing phenylalanine hydroxylase from Dictyostelium discoideum." Siltberg-Liberles J., Steen I.H., Svebak R.M., Martinez A. Gene 427:86-92(2008) [PubMed: 18835579] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AAFI02000024 Genomic DNA. Translation: EAL67992.1.
RefSeq	XP_641959.1. XM_636867.1.
3D structure databases
HSSP	HSSP built from PDB template 1TOH based on UniProtKB P04177.
ProteinModelPortal	Q54XS1.
SMR	Q54XS1. Positions 107-440.
ModBase	Search...
Protein-protein interaction databases
STRING	Q54XS1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblProtists	DDB0231664; DDB0231664; DDB_G0278781.
GeneID	8621691.
GenomeReviews	Gene locus pah in contig CM000152_GR.
KEGG	ddi:DDB_G0278781.
Organism-specific databases
dictyBase	DDB_G0278781. pah.
Phylogenomic databases
eggNOG	KOG3820.
GeneTree	EPrGT00050000005952.
HOGENOM	HBG484724.
OMA	PRAYENK.
PhylomeDB	Q54XS1.
ProtClustDB	CLSZ2729099.
Family and domain databases
InterPro	IPR001273. ArAA_hydroxylase. IPR018301. ArAA_hydroxylase_Fe/CU_BS. IPR019774. Aromatic-AA_hydroxylase_C. IPR018528. Preph_deHydtase_CS. IPR019773. Tyrosine_3-monooxygenase-like. [Graphical view]
Gene3D	G3DSA:1.10.800.10. Aaa_hydroxylase. 1 hit.
KO	K00500.
PANTHER	PTHR11473. Aaa_hydroxylase. 1 hit.
Pfam	PF00351. Biopterin_H. 1 hit. [Graphical view]
PIRSF	PIRSF000336. TH. 1 hit.
PRINTS	PR00372. FYWHYDRXLASE.
SUPFAM	SSF56534. Aaa_hydroxylase. 1 hit.
PROSITE	PS00367. BH4_AAA_HYDROXYL_1. 1 hit. PS51410. BH4_AAA_HYDROXYL_2. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

PH4H_DICDI

Accession

Primary (citable) accession number: Q54XS1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 8, 2008
Last sequence update:	May 24, 2005
Last modified:	November 16, 2011
This is version 53 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)