Reviewed, UniProtKB/Swiss-Prot P04176 (PH4H_RAT)

Names and origin

Protein names

Recommended name:
    Phenylalanine-4-hydroxylase
      Short name=PAH
    EC=1.14.16.1
Alternative name(s):
    Phe-4-monooxygenase

Gene names

Name:

Pah

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	453 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Catalytic activity	L-phenylalanine + tetrahydrobiopterin + O2 = L-tyrosine + 4a-hydroxytetrahydrobiopterin.
Cofactor	Fe2+ ion.
Enzyme regulation	N-terminal region of PAH is thought to contain allosteric binding sites for phenylalanine and to constitute an "inhibitory" domain that regulates the activity of a catalytic domain in the C-terminal portion of the molecule.
Pathway	Amino-acid degradation; L-phenylalanine degradation; acetoacetic acid and fumarate from L-phenylalanine: step 1/6.
Subunit structure	Homodimer.
Sequence similarities	Belongs to the biopterin-dependent aromatic amino acid hydroxylase family. Contains 1 ACT domain.

Ontologies

Keywords
Biological process	Phenylalanine catabolism
Ligand	Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Allosteric enzyme Direct protein sequencing
Gene Ontology (GO)
Biological process	L-phenylalanine catabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW protein amino acid hydroxylation Inferred from direct assay. Source: RGD tetrahydrobiopterin metabolic process Inferred from direct assay. Source: RGD tyrosine biosynthetic process Inferred from direct assay. Source: RGD
Molecular function	amino acid binding Inferred from direct assay. Source: RGD cofactor binding Inferred from direct assay. Source: RGD iron ion binding Ref.4 Inferred from direct assay. Source: RGD phenylalanine 4-monooxygenase activity Inferred from direct assay. Source: RGD protein homodimerization activity Ref.4 Inferred from direct assay. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 453

452

Phenylalanine-4-hydroxylase

PRO_0000205550

Regions

Domain

36 – 111

76

ACT

Sites

Metal binding

285

1

Iron

Metal binding

290

1

Iron

Metal binding

330

1

Iron

Amino acid modifications

Modified residue

2

1

N-acetylalanine By similarity

Modified residue

16

1

Phosphoserine; by PKA Ref.2

Secondary structure

1

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453

Helix Strand Turn

Details...

Beta strand

35 – 42

8

Helix

47 – 56

10

Turn

57 – 59

3

Beta strand

64 – 69

6

Beta strand

76 – 81

6

Helix

85 – 87

3

Helix

88 – 100

13

Beta strand

106 – 110

5

Helix

125 – 129

5

Turn

130 – 133

4

Turn

147 – 150

4

Helix

152 – 166

15

Helix

181 – 201

21

Helix

204 – 216

13

Helix

227 – 238

12

Beta strand

241 – 244

4

Helix

251 – 258

8

Turn

259 – 261

3

Beta strand

262 – 265

4

Helix

283 – 289

7

Helix

291 – 294

4

Helix

297 – 310

14

Helix

315 – 326

12

Turn

327 – 331

5

Beta strand

333 – 336

4

Beta strand

339 – 342

4

Helix

345 – 348

4

Helix

351 – 357

7

Beta strand

359 – 366

8

Helix

369 – 372

4

Beta strand

379 – 382

4

Beta strand

384 – 390

7

Helix

392 – 403

12

Beta strand

409 – 415

7

Turn

416 – 419

4

Beta strand

420 – 424

5

Sequences

	Sequence		Length	Mass (Da)
	P04176-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 365D9E8A7E498D52	FASTA	453	51,822
	10 20 30 40 50 60 MAAVVLENGV LSRKLSDFGQ ETSYIEDNSN QNGAISLIFS LKEEVGALAK VLRLFEENDI 70 80 90 100 110 120 NLTHIESRPS RLNKDEYEFF TYLDKRTKPV LGSIIKSLRN DIGATVHELS RDKEKNTVPW 130 140 150 160 170 180 FPRTIQELDR FANQILSYGA ELDADHPGFK DPVYRARRKQ FADIAYNYRH GQPIPRVEYT 190 200 210 220 230 240 EEEKQTWGTV FRTLKALYKT HACYEHNHIF PLLEKYCGFR EDNIPQLEDV SQFLQTCTGF 250 260 270 280 290 300 RLRPVAGLLS SRDFLGGLAF RVFHCTQYIR HGSKPMYTPE PDICHELLGH VPLFSDRSFA 310 320 330 340 350 360 QFSQEIGLAS LGAPDEYIEK LATIYWFTVE FGLCKEGDSI KAYGAGLLSS FGELQYCLSD 370 380 390 400 410 420 KPKLLPLELE KTACQEYSVT EFQPLYYVAE SFSDAKEKVR TFAATIPRPF SVRYDPYTQR 430 440 450 VEVLDNTQQL KILADSINSE VGILCNALQK IKS

References

[1]	"Isolation and sequence of a cDNA clone which contains the complete coding region of rat phenylalanine hydroxylase. Structural homology with tyrosine hydroxylase, glucocorticoid regulation, and use of alternate polyadenylation sites." Dahl H.-H.M., Mercer J.F.B. J. Biol. Chem. 261:4148-4153(1986) [PubMed: 2869038] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Amino acid sequence at the phosphorylated site of rat liver phenylalanine hydroxylase and phosphorylation of a corresponding synthetic peptide." Wretborn M., Humble E., Ragnarsson U., Engstrom L. Biochem. Biophys. Res. Commun. 93:403-408(1980) [PubMed: 7387651] [Abstract] Cited for: PROTEIN SEQUENCE OF 12-21, PHOSPHORYLATION AT SER-16. Tissue: Liver.
[3]	"Sequence comparison of rat liver phenylalanine hydroxylase and its cDNA clones." Robson K.J.H., Beattie W., James R.J., Cotton R.C.H., Morgan F.J., Woo S.L.C. Biochemistry 23:5671-5675(1984) [PubMed: 6098294] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 208-453.
[4]	"Structural basis of autoregulation of phenylalanine hydroxylase." Kobe B., Jennings I.G., House C.M., Michell B.J., Goodwill K.E., Santarsiero B.D., Stevens R.C., Cotton R.G., Kemp B.E. Nat. Struct. Biol. 6:442-448(1999) [PubMed: 10331871] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).

Cross-references

Sequence databases

EMBLGenBankDDBJ

M12337 mRNA. Translation: AAA41843.1.
K02599 mRNA. Translation: AAA41794.1.

IPI

IPI00193258.

PIR

WHRTF. A25321.

UniGene

Rn.1652

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PHZ	X-ray	2.20	A	1-429	[»]
2PHM	X-ray	2.60	A	1-429	[»]

ModBase

Search...

PTM databases

PhosphoSite

P04176.

Proteomic databases

PRIDE

P04176.

Genome annotation databases

Ensembl

ENSRNOG00000004302. Rattus norvegicus. [Contig view]

Organism-specific databases

RGD

3248. Pah.

Phylogenomic databases

HOVERGEN

P04176.

Enzyme and pathway databases

BRENDA

1.14.16.1. 248.

Gene expression databases

ArrayExpress

P04176.

GermOnline

ENSRNOG00000004302. Rattus norvegicus.

Family and domain databases

InterPro

IPR002912. ACT_bd.
IPR001273. ArAA_hydroxylase.
IPR018301. ArAA_hydroxylase_Fe/CU_BS.
IPR019774. Aromatic-AA_hydroxylase_C.
IPR005961. Phe-4-hydroxylase_tetra.
IPR019773. Tyrosine_3-monooxygenase-like.
[Graphical view]

Gene3D

G3DSA:1.10.800.10. Aaa_hydroxylase. 1 hit.

PANTHER

PTHR11473. Aaa_hydroxylase. 1 hit.

Pfam

PF01842. ACT. 1 hit.
PF00351. Biopterin_H. 1 hit.
[Graphical view]

PIRSF

PIRSF000336. TH. 1 hit.

PRINTS

PR00372. FYWHYDRXLASE.

ProDom

PD002559. Aaa_hydroxylase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

TIGRFAMs

TIGR01268. Phe4hydrox_tetr. 1 hit.

PROSITE

PS00367. BIOPTERIN_HYDROXYL. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

PH4H_RAT

Accession

Primary (citable) accession number: P04176

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 1987
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 97 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)