[1]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Liver; DOI=10.1021/bi00324a002; PubMed=2986678 [NCBI, ExPASy, EBI, Israel, Japan] Kwok S.C.M., Ledley F.D., Dilella A.G., Robson K.J.H., Woo S.L.C.; "Nucleotide sequence of a full-length complementary DNA clone and amino acid sequence of human phenylalanine hydroxylase."; Biochemistry 24:556-561(1985).
[2]	NUCLEOTIDE SEQUENCE [MRNA]. Scriver C.R., Nowacki P.M., Byck S., Prevost L.; Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
[3]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. TISSUE=Liver; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[4]	PROTEIN SEQUENCE OF 131-144. PubMed=2461704 [NCBI, ExPASy, EBI, Israel, Japan] Cotton R.G., McAdam W., Jennings I., Morgan F.J.; "A monoclonal antibody to aromatic amino acid hydroxylases. Identification of the epitope."; Biochem. J. 255:193-196(1988).
[5]	X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 117-424. DOI=10.1038/nsb1297-995; PubMed=9406548 [NCBI, ExPASy, EBI, Israel, Japan] Erlandsen H., Fusetti F., Martinez A., Hough E., Flatmark T., Stevens R.C.; "Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria."; Nat. Struct. Biol. 4:995-1000(1997).
[6]	X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 117-424. DOI=10.1021/bi9815290; PubMed=9843368 [NCBI, ExPASy, EBI, Israel, Japan] Erlandsen H., Flatmark T., Stevens R.C., Hough E.; "Crystallographic analysis of the human phenylalanine hydroxylase catalytic domain with bound catechol inhibitors at 2.0-A resolution."; Biochemistry 37:15638-15646(1998).
[7]	X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 117-452. DOI=10.1074/jbc.273.27.16962; PubMed=9642259 [NCBI, ExPASy, EBI, Israel, Japan] Fusetti F., Erlandsen H., Flatmark T., Stevens R.C.; "Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria."; J. Biol. Chem. 273:16962-16967(1998).
[8]	X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 118-424. DOI=10.1021/bi992531+; PubMed=10694386 [NCBI, ExPASy, EBI, Israel, Japan] Erlandsen H., Bjorgo E., Flatmark T., Stevens R.C.; "Crystal structure and site-specific mutagenesis of pterin-bound human phenylalanine hydroxylase."; Biochemistry 39:2208-2217(2000).
[9]	X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 103-427. DOI=10.1006/jmbi.2001.5061; PubMed=11718561 [NCBI, ExPASy, EBI, Israel, Japan] Andersen O.A., Flatmark T., Hough E.; "High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin."; J. Mol. Biol. 314:279-291(2001).
[10]	REVIEW ON PKU VARIANTS. PubMed=1679029 [NCBI, ExPASy, EBI, Israel, Japan] Konecki D.S., Lichter-Konecki U.; "The phenylketonuria locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations."; Hum. Genet. 87:377-388(1991).
[11]	REVIEW ON PKU VARIANTS. DOI=10.1007/BF01799577; PubMed=2246858 [NCBI, ExPASy, EBI, Israel, Japan] Cotton R.G.; "Heterogeneity of phenylketonuria at the clinical, protein and DNA levels."; J. Inherit. Metab. Dis. 13:739-750(1990).
[12]	REVIEW ON PKU VARIANTS. PubMed=1301187 [NCBI, ExPASy, EBI, Israel, Japan] Eisensmith R.C., Woo S.L.C.; "Molecular basis of phenylketonuria and related hyperphenylalaninemias: mutations and polymorphisms in the human phenylalanine hydroxylase gene."; Hum. Mutat. 1:13-22(1992).
[13]	DATABASE OF PKU VARIANTS. DOI=10.1093/nar/24.1.127; PubMed=8594560 [NCBI, ExPASy, EBI, Israel, Japan] Hoang L., Byck S., Prevost L., Scriver C.R.; "PAH Mutation Analysis Consortium Database: a database for disease-producing and other allelic variation at the human PAH locus."; Nucleic Acids Res. 24:127-131(1996).
[14]	VARIANT PKU PRO-311. DOI=10.1021/bi00408a032; PubMed=2840952 [NCBI, ExPASy, EBI, Israel, Japan] Lichter-Konecki U., Konecki D.S., Dilella A.G., Brayton K., Marvit J., Hahn T.M., Trefz F.K., Woo S.L.C.; "Phenylalanine hydroxylase deficiency caused by a single base substitution in an exon of the human phenylalanine hydroxylase gene."; Biochemistry 27:2881-2885(1988).
[15]	VARIANT PKU LYS-280. PubMed=2564729 [NCBI, ExPASy, EBI, Israel, Japan] Lyonnet S., Caillaud C., Rey F., Berthelon M., Frezal J., Rey J., Munnich A.; "Molecular genetics of phenylketonuria in Mediterranean countries: a mutation associated with partial phenylalanine hydroxylase deficiency."; Am. J. Hum. Genet. 44:511-517(1989).
[16]	VARIANT PKU PRO-311. PubMed=2615649 [NCBI, ExPASy, EBI, Israel, Japan] Hofman K.J., Antonarakis S.E., Missiou-Tsangaraki S., Boehm C.D., Valle D.; "Phenylketonuria in the Greek population. Haplotype analysis of the phenylalanine hydroxylase gene and identification of a PKU mutation."; Mol. Biol. Med. 6:245-250(1989).
[17]	VARIANT PKU LEU-364 DEL. DOI=10.1007/BF00206750; PubMed=1975559 [NCBI, ExPASy, EBI, Israel, Japan] Svensson E., Andersson B., Hagenfeldt L.; "Two mutations within the coding sequence of the phenylalanine hydroxylase gene."; Hum. Genet. 85:300-304(1990).
[18]	VARIANT PKU GLN-261. PubMed=1671810 [NCBI, ExPASy, EBI, Israel, Japan] Dianzani I., Forrest S.M., Camaschella C., Saglio G., Ponzone A., Cotton R.G.; "Screening for mutations in the phenylalanine hydroxylase gene from Italian patients with phenylketonuria by using the chemical cleavage method: a new splice mutation."; Am. J. Hum. Genet. 48:631-635(1991).
[19]	VARIANT PKU SER-255. PubMed=2014802 [NCBI, ExPASy, EBI, Israel, Japan] Hofman K.J., Steel G., Kazazian H.H. Jr., Valle D.; "Phenylketonuria in U.S. blacks: molecular analysis of the phenylalanine hydroxylase gene."; Am. J. Hum. Genet. 48:791-798(1991).
[20]	VARIANTS PKU TRP-252 AND LEU-281. DOI=10.1016/0888-7543(91)90225-4; PubMed=1672294 [NCBI, ExPASy, EBI, Israel, Japan] Okano Y., Wang T., Eisensmith R.C., Longhi R., Riva E., Giovannini M., Cerone R., Romano C., Woo S.L.C.; "Phenylketonuria missense mutations in the Mediterranean."; Genomics 9:96-103(1991).
[21]	VARIANT PKU LEU-281. DOI=10.1016/0888-7543(91)90238-A; PubMed=1672290 [NCBI, ExPASy, EBI, Israel, Japan] Dworniczak B., Grudda K., Stumper J., Bartholome K., Aulehla-Scholz C., Horst J.; "Phenylalanine hydroxylase gene: novel missense mutation in exon 7 causing severe phenylketonuria."; Genomics 9:193-199(1991).
[22]	VARIANTS PKU SER-48 AND GLY-221. PubMed=1679030 [NCBI, ExPASy, EBI, Israel, Japan] Konecki D.S., Schlotter M., Trefz F.K., Lichter-Konecki U.; "The identification of two mis-sense mutations at the PAH gene locus in a Turkish patient with phenylketonuria."; Hum. Genet. 87:389-393(1991).
[23]	VARIANT PKU ILE-94 DEL. PubMed=1709636 [NCBI, ExPASy, EBI, Israel, Japan] Caillaud C., Lyonnet S., Rey F., Melle D., Frebourg T., Berthelon M., Vilarinho L., Vaz Osorio R., Rey J., Munnich A.; "A 3-base pair in-frame deletion of the phenylalanine hydroxylase gene results in a kinetic variant of phenylketonuria."; J. Biol. Chem. 266:9351-9354(1991).
[24]	VARIANTS NON-PKU HPA VAL-306 AND ASN-415. DOI=10.1016/S0888-7543(05)80274-5; PubMed=1358789 [NCBI, ExPASy, EBI, Israel, Japan] Economou-Petersen E., Henriksen K.F., Guldberg P., Guettler F.; "Molecular basis for nonphenylketonuria hyperphenylalaninemia."; Genomics 14:1-5(1992).
[25]	VARIANTS PKU GLN-408 AND TRP-408. DOI=10.1007/BF00221944; PubMed=1355066 [NCBI, ExPASy, EBI, Israel, Japan] Lin C.H., Hsiao K.J., Tsai T.F., Chao H.K., Su T.S.; "Identification of a missense phenylketonuria mutation at codon 408 in Chinese."; Hum. Genet. 89:593-596(1992).
[26]	VARIANT PKU 364-LEU--GLU-368 DEL. DOI=10.1093/hmg/1.9.763; PubMed=1363837 [NCBI, ExPASy, EBI, Israel, Japan] Jaruzelska J., Melle D., Matuszak R., Borski K., Munnich A.; "A new 15 bp deletion in exon 11 of the phenylalanine hydroxylase gene in phenylketonuria."; Hum. Mol. Genet. 1:763-764(1992).
[27]	VARIANT PKU LEU-244. DOI=10.1093/hmg/1.9.765; PubMed=1363838 [NCBI, ExPASy, EBI, Israel, Japan] Desviat L.R., Perez B., Ugarte M.; "A new PKU mutation associated with haplotype 12."; Hum. Mol. Genet. 1:765-766(1992).
[28]	VARIANTS PKU. DOI=10.1006/geno.1993.1295; PubMed=8406445 [NCBI, ExPASy, EBI, Israel, Japan] Guldberg P., Henriksen K.F., Guettler F.; "Molecular analysis of phenylketonuria in Denmark: 99% of the mutations detected by denaturing gradient gel electrophoresis."; Genomics 17:141-146(1993).
[29]	VARIANT NON-PKU HPA GLY-390. DOI=10.1093/hmg/2.1.31; PubMed=8098245 [NCBI, ExPASy, EBI, Israel, Japan] Abadie V., Jaruzelska J., Lyonnet S., Millasseau P., Berthelon M., Rey F., Munnich A., Rey J.; "Illegitimate transcription of the phenylalanine hydroxylase gene in lymphocytes for identification of mutations in phenylketonuria."; Hum. Mol. Genet. 2:31-34(1993).
[30]	VARIANT PKU VAL-276. DOI=10.1007/BF00711510; PubMed=8068076 [NCBI, ExPASy, EBI, Israel, Japan] Goebel-Schreiner B., Schreiner R.; "Identification of a new missense mutation in Japanese phenylketonuric patients."; J. Inherit. Metab. Dis. 16:950-956(1993).
[31]	VARIANTS NON-PKU HPA VAL-47; ARG-87; LEU-176 AND ALA-245. DOI=10.1006/geno.1994.1296; PubMed=8088845 [NCBI, ExPASy, EBI, Israel, Japan] Guldberg P., Henriksen K.F., Thoeny B., Blau N., Guettler F.; "Molecular heterogeneity of nonphenylketonuria hyperphenylalaninemia in 25 Danish patients."; Genomics 21:453-455(1994).
[32]	VARIANTS PKU THR-164; ALA-171; SER-239; GLN-252 AND LEU-331. PubMed=7833954 [NCBI, ExPASy, EBI, Israel, Japan] Benit P., Rey F., Melle D., Munnich A., Rey J.; "Five novel missense mutations of the phenylalanine hydroxylase gene in phenylketonuria."; Hum. Mutat. 4:229-231(1994).
[33]	CHARACTERIZATION OF VARIANT PKU GLY-143. DOI=10.1002/(SICI)1098-1004(1996)8:3<236::AID-HUMU7>3.3.CO;2-J; PubMed=8889583 [NCBI, ExPASy, EBI, Israel, Japan] Knappskog P.M., Eiken H.G., Martinez A., Bruland O., Apold J., Flatmark T.; "PKU mutation (D143G) associated with an apparent high residual enzyme activity: expression of a kinetic variant form of phenylalanine hydroxylase in three different systems."; Hum. Mutat. 8:236-246(1996).
[34]	VARIANTS PKU LEU-40; SER-46; SER-48; 63-PRO-ASN-64; THR-65; SER-68; CYS-241; ALA-245; GLN-261; LYS-280; LEU-281; CYS-299; GLY-390; HIS-394; VAL-403; TRP-408 AND CYS-414. DOI=10.1002/(SICI)1098-1004(1996)8:3<276::AID-HUMU14>3.3.CO;2-T; PubMed=8889590 [NCBI, ExPASy, EBI, Israel, Japan] Guldberg P., Mallmann R., Henriksen K.F., Guettler F.; "Phenylalanine hydroxylase deficiency in a population in Germany: mutational profile and nine novel mutations."; Hum. Mutat. 8:276-279(1996).
[35]	VARIANTS PKU CYS-204 AND SER-207. DOI=10.1007/s004390050353; PubMed=9048935 [NCBI, ExPASy, EBI, Israel, Japan] Argiolas A., Bosco P., Cali F., Ceratto N., Anello G., Riva E., Biasucci G., Carducci C., Romano V.; "Two novel PAH gene mutations detected in Italian phenylketonuric patients."; Hum. Genet. 99:275-278(1997).
[36]	VARIANTS PKU. DOI=10.1002/(SICI)1098-1004(1997)9:4<316::AID-HUMU3>3.3.CO;2-X; PubMed=9101291 [NCBI, ExPASy, EBI, Israel, Japan] Byck S., Tyfield L., Carter K., Scriver C.R.; "Prediction of multiple hypermutable codons in the human PAH gene: codon 280 contains recurrent mutations in Quebec and other populations."; Hum. Mutat. 9:316-321(1997).
[37]	CHARACTERIZATION OF VARIANTS. DOI=10.1002/(SICI)1098-1004(1998)11:1<4::AID-HUMU2>3.3.CO;2-8; PubMed=9450897 [NCBI, ExPASy, EBI, Israel, Japan] Waters P.J., Parniak M.A., Nowacki P., Scriver C.R.; "In vitro expression analysis of mutations in phenylalanine hydroxylase: linking genotype to phenotype and structure to function."; Hum. Mutat. 11:4-17(1998).
[38]	VARIANTS PKU AND NON-PKU. DOI=10.1002/(SICI)1098-1004(1998)11:3<240::AID-HUMU9>3.3.CO;2-C; PubMed=9521426 [NCBI, ExPASy, EBI, Israel, Japan] Bosco P., Cali F., Meli C., Mollica F., Zammarchi E., Cerone R., Vanni C., Palillo L., Greco D., Romano V.; "Eight new mutations of the phenylalanine hydroxylase gene in Italian patients with hyperphenylalaninemia."; Hum. Mutat. 11:240-243(1998).
[39]	VARIANTS PKU GLN-243; LEU-349 AND TRP-408. DOI=10.1002/(SICI)1098-1004(1998)11:5<354::AID-HUMU2>3.3.CO;2-N; PubMed=9600453 [NCBI, ExPASy, EBI, Israel, Japan] de Lucca M., Perez B., Desviat L.R., Ugarte M.; "Molecular basis of phenylketonuria in Venezuela: presence of two novel null mutations."; Hum. Mutat. 11:354-359(1998).
[40]	VARIANT PKU THR-362. DOI=10.1002/(SICI)1098-1004(1998)11:6<482::AID-HUMU15>3.3.CO;2-5; PubMed=10200057 [NCBI, ExPASy, EBI, Israel, Japan] Mallolas J., Campistol J., Lambruscini N., Vilaseca M.A., Cambra J.F., Estivill X., Milo M.; "Two novel mutations in exon 11 of the PAH gene (1163/1164 del TG and P362T) associated with classic phenylketonuria and mild phenylketonuria."; Hum. Mutat. 11:482-482(1998).
[41]	VARIANTS PKU HIS-53; ASP-207 AND LEU-388. PubMed=9452061 [NCBI, ExPASy, EBI, Israel, Japan] Park Y.S., Seoung C.S., Lee S.W., Oh K.H., Lee D.H., Yim J.; "Identification of three novel mutations in Korean phenylketonuria patients: R53H, N207D, and Y325X."; Hum. Mutat. Suppl. 1:S121-S122(1998).
[42]	VARIANTS PKU PHE-39 DEL; THR-65; GLN-158; ILE-167; ALA-190; CYS-241 AND TRP-408. PubMed=9452062 [NCBI, ExPASy, EBI, Israel, Japan] Michiels L., Francois B., Raus J., Vandevyver C.; "Identification of seven new mutations in the phenylalanine hydroxylase gene, associated with hyperphenylalaninemia in the Belgian population."; Hum. Mutat. Suppl. 1:S123-S124(1998).
[43]	VARIANTS PKU. DOI=10.1002/(SICI)1098-1004(1998)12:5<314::AID-HUMU4>3.0.CO;2-D; PubMed=9792407 [NCBI, ExPASy, EBI, Israel, Japan] Popescu T., Blazkova M., Kozak L., Jebeleanu G., Popescu A.; "Mutation spectrum and phenylalanine hydroxylase RFLP/VNTR background in 44 Romanian phenylketonuric alleles."; Hum. Mutat. 12:314-319(1998).
[44]	CHARACTERIZATION OF VARIANTS PKU ASP-104 AND ASN-157. DOI=10.1002/(SICI)1098-1004(1998)12:5<344::AID-HUMU8>3.3.CO;2-7; PubMed=9792411 [NCBI, ExPASy, EBI, Israel, Japan] Waters P.J., Parniak M.A., Hewson A.S., Scriver C.R.; "Alterations in protein aggregation and degradation due to mild and severe missense mutations (A104D, R157N) in the human phenylalanine hydroxylase gene."; Hum. Mutat. 12:344-354(1998).
[45]	VARIANTS NON-PKU HPA CYS-241; GLN-243 AND PRO-413. DOI=10.1007/s100380050079; PubMed=9852673 [NCBI, ExPASy, EBI, Israel, Japan] Kibayashi M., Nagao M., Chiba S.; "Mutation analysis of the phenylalanine hydroxylase gene and its clinical implications in two Japanese patients with non-phenylketonuria hyperphenylalaninemia."; J. Hum. Genet. 43:231-236(1998).
[46]	VARIANTS PKU. DOI=10.1002/(SICI)1098-1004(200003)15:3<254::AID-HUMU6>3.3.CO;2-N; PubMed=10679941 [NCBI, ExPASy, EBI, Israel, Japan] Hennermann J.B., Vetter B., Wolf C., Windt E., Buehrdel P., Seidel J., Moench E., Kulozik A.E.; "Phenylketonuria and hyperphenylalaninemia in eastern Germany: a characteristic molecular profile and 15 novel mutations."; Hum. Mutat. 15:254-260(2000).
[47]	CHARACTERIZATION OF VARIANTS PKU. DOI=10.1086/320604; PubMed=11326337 [NCBI, ExPASy, EBI, Israel, Japan] Gjetting T., Petersen M., Guldberg P., Guettler F.; "Missense mutations in the N-terminal domain of human phenylalanine hydroxylase interfere with binding of regulatory phenylalanine."; Am. J. Hum. Genet. 68:1353-1360(2001).
[48]	VARIANTS PKU. DOI=10.1002/1098-1004(200102)17:2<122::AID-HUMU4>3.0.CO;2-C; PubMed=11180595 [NCBI, ExPASy, EBI, Israel, Japan] Acosta A.X., Silva W.A. Jr., Carvalho T.M., Gomes M., Zago M.A.; "Mutations of the phenylalanine hydroxylase (PAH) gene in Brazilian patients with phenylketonuria."; Hum. Mutat. 17:122-130(2001).
[49]	VARIANTS PKU, AND VARIANTS HPA. DOI=10.1002/humu.1141.abs; PubMed=11385716 [NCBI, ExPASy, EBI, Israel, Japan] Yang Y., Drummond-Borg M., Garcia-Heras J.; "Molecular analysis of phenylketonuria (PKU) in newborns from Texas."; Hum. Mutat. 17:523-523(2001).
[50]	VARIANTS PKU TRP-252 AND THR-318, AND VARIANT GLU-274. DOI=10.1006/mgme.2001.3180; PubMed=11461196 [NCBI, ExPASy, EBI, Israel, Japan] Gjetting T., Romstad A., Haavik J., Knappskog P.M., Acosta A.X., Silva W.A. Jr., Zago M.A., Guldberg P., Guettler F.; "A phenylalanine hydroxylase amino acid polymorphism with implications for molecular diagnostics."; Mol. Genet. Metab. 73:280-284(2001).

Comments

CATALYTIC ACTIVITY: L-phenylalanine + tetrahydrobiopterin + O₂ = L-tyrosine + 4a-hydroxytetrahydrobiopterin.
COFACTOR: Fe(2+) 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: Homodimer.
POLYMORPHISM: The Glu-274 variant occurs on approximately 4% of African-American PAH alleles. The enzyme activity of the variant protein is indistinguishable from that of the wild-type form.
DISEASE: Defects in PAH are the cause of phenylketonuria (PKU) [MIM:261600]. PKU is an autosomal recessive inborn error of phenylalanine metabolism, due to severe phenylalanine hydroxylase deficiency. It is characterized by blood concentrations of phenylalanine persistently above 1200 mumol (normal concentration 100 mumol) which usually causes mental retardation (unless low phenylalanine diet is introduced early in life). They tend to have light pigmentation, rashes similar to eczema, epilepsy, extreme hyperactivity, psychotic states and an unpleasant 'mousy' odor.
DISEASE: Defects in PAH are the cause of non-phenylketonuria hyperphenylalaninemia (Non-PKU HPA) [MIM:261600]. Non-PKU HPA is a mild form of phenylalanine hydroxylase deficiency characterized by phenylalanine levels persistently below 600 mumol, which allows normal intellectual and behavioral development without treatment. Non-PKU HPA is usually caused by the combined effect of a mild hyperphenylalaninemia mutation and a severe one.
DISEASE: Defects in PAH are the cause of hyperphenylalaninemia (HPA) [MIM:261600]. HPA is the mildest form of phenylalanine hydroxylase deficiency.
SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.
SIMILARITY: Contains 1 ACT domain.
WEB RESOURCE: Name=PAHdb; Note=Phenylalanine hydroxylase locus knowledgebase; URL="http://www.pahdb.mcgill.ca/";.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=PAH";.
WEB RESOURCE: Name=Wikipedia; Note=Phenylalanine hydroxylase entry; URL="http://en.wikipedia.org/wiki/Phenylalanine_hydroxylase";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

K03020; AAA60082.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U49897; AAC51772.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
S61296; AAD13926.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC026251; AAH26251.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

A00508; WHHUF.

NP_000268.1; -.

3D structure databases

PDB

1DMW; X-ray; 2.00 A; A=118-424.	[ExPASy / RCSB / EBI]
1J8T; X-ray; 1.70 A; A=103-427.	[ExPASy / RCSB / EBI]
1J8U; X-ray; 1.50 A; A=103-427.	[ExPASy / RCSB / EBI]
1KW0; X-ray; 2.50 A; A=103-427.	[ExPASy / RCSB / EBI]
1LRM; X-ray; 2.10 A; A=103-427.	[ExPASy / RCSB / EBI]
1MMK; X-ray; 2.00 A; A=103-427.	[ExPASy / RCSB / EBI]
1MMT; X-ray; 2.00 A; A=103-427.	[ExPASy / RCSB / EBI]
1PAH; X-ray; 2.00 A; A=117-424.	[ExPASy / RCSB / EBI]
1TDW; X-ray; 2.10 A; A=117-424.	[ExPASy / RCSB / EBI]
1TG2; X-ray; 2.20 A; A=117-424.	[ExPASy / RCSB / EBI]
2PAH; X-ray; 3.10 A; A/B=118-452.	[ExPASy / RCSB / EBI]
3PAH; X-ray; 2.00 A; A=117-424.	[ExPASy / RCSB / EBI]
4PAH; X-ray; 2.00 A; A=117-424.	[ExPASy / RCSB / EBI]
5PAH; X-ray; 2.10 A; A=117-424.	[ExPASy / RCSB / EBI]
6PAH; X-ray; 2.15 A; A=117-424.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

PDBsum

1DMW; -.
1J8T; -.
1J8U; -.
1KW0; -.
1LRM; -.
1MMK; -.
1MMT; -.
1PAH; -.
1TDW; -.
1TG2; -.
2PAH; -.
3PAH; -.
4PAH; -.
5PAH; -.
6PAH; -.

P00439; 19-427.

PTM databases

P00439; -.

Enzyme and pathway databases

BioCyc

MetaCyc:MON-12066; -.

Reactome

REACT_13; Metabolism of amino acids.

2D gel databases

HSC-2DPAGE

P00439; -.

Organism-specific databases

HIX0010929; -.

HGNC:8582; PAH.

PAH.

261600; gene+phenotype. [NCBI / EBI]

Orphanet

716; Phenylketonuria.

PharmGKB

PA32911; -.

GeneCards

P00439.

Gene expression databases

ArrayExpress

P00439; -.

CleanEx

HS_PAH; -.

GermOnline

ENSG00000171759; Homo sapiens.

Ontologies

GO:0004505;	Molecular function: phenylalanine 4-monooxygenase activity (traceable author statement from ProtInc).
GO:0008652;	Biological process: amino acid biosynthetic process (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR001273; Aaa_hydroxylase.
IPR002912; ACT_bd.
IPR005961; Phe-4-hydroxylase_tetra.
Graphical view of domain structure.

Gene3D

G3DSA:1.10.800.10; Aaa_hydroxylase; 1.

PANTHER

PTHR11473; Aaa_hydroxylase; 1.

Pfam

PF01842; ACT; 1.
PF00351; Biopterin_H; 1.
Pfam graphical view of domain structure.

PRINTS

PR00372; FYWHYDRXLASE.

ProDom

PD002559; Aaa_hydroxylase; 1.
[Domain structure / List of seq. sharing at least 1 domain]

TIGRFAMs

TIGR01268; Phe4hydrox_tetr; 1.

PROSITE

PS00367; BIOPTERIN_HYDROXYL; 1.

BLOCKS

P00439.

Genome annotation databases

Ensembl

ENSG00000171759; Homo sapiens. [Contig view]

GeneID

5053; -.

KEGG

hsa:5053; -.

NMPDR

fig|9606.3.peg.8135; -.

Phylogenomic databases

HOGENOM

P00439; -.

HOVERGEN

P00439; -.

Other

DrugBank

DB00668; Epinephrine.
DB00120; L-Phenylalanine.
DB01235; Levodopa.
DB00368; Norepinephrine.
DB00360; Tetrahydrobiopterin.

P00439; -.

PAH; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Allosteric enzyme; Direct protein sequencing; Disease mutation; Iron; Metal-binding; Monooxygenase; Oxidoreductase; Phenylalanine catabolism; Phenylketonuria; Phosphoprotein; Polymorphism.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 452`	`452`	`Phenylalanine-4-hydroxylase.`	`PRO_0000205548`
`DOMAIN`	`35 110`	`76`	`ACT.`
`METAL`	`285 285`		`Iron (By similarity).`
`METAL`	`290 290`		`Iron (By similarity).`
`METAL`	`330 330`		`Iron (By similarity).`
`MOD_RES`	`16 16`		`Phosphoserine; by PKA (By similarity).`
`VARIANT`	`16 16`	`1`	`S -> P (in PKU).`	`VAR_000869`
`VARIANT`	`20 20`	`1`	`Q -> L (in HPA).`	`VAR_009239`
`VARIANT`	`39 39`	`1`	`F -> L (in PKU; haplotype 1).`	`VAR_000870`
`VARIANT`	`39 39`	`1`	`Missing (in PKU; haplotypes 9,21).`	`VAR_000871`
`VARIANT`	`40 40`	`1`	`S -> L (in PKU).`	`VAR_000872`
`VARIANT`	`41 41`	`1`	`L -> F (in PKU).`	`VAR_000873`
`VARIANT`	`41 41`	`1`	`L -> P (in PKU; mild).`	`VAR_009240`
`VARIANT`	`42 42`	`1`	`K -> I (in PKU; haplotype 21).`	`VAR_000874`
`VARIANT`	`46 46`	`1`	`G -> S (in PKU; haplotype 5; significantly reduces phenylalanine binding).`	`VAR_000875`
`VARIANT`	`47 47`	`1`	`A -> V (in non-PKU HPA; haplotype 4; significantly reduces phenylalanine binding).`	`VAR_000876`
`VARIANT`	`48 48`	`1`	`L -> S (in PKU; mild; haplotypes 3,4).`	`VAR_000877`
`VARIANT`	`53 53`	`1`	`R -> H (in PKU).`	`VAR_000878`
`VARIANT`	`55 55`	`1`	`F -> L (in PKU).`	`VAR_000879`
`VARIANT`	`56 56`	`1`	`E -> D (in PKU; haplotype 10).`	`VAR_000880`
`VARIANT`	`63 64`	`2`	`TH -> PN (in PKU; haplotype 1; abolishes phenylalanine binding).`	`VAR_000881`
`VARIANT`	`65 65`	`1`	`I -> N (in PKU).`	`VAR_000882`
`VARIANT`	`65 65`	`1`	`I -> T (in PKU; haplotypes 1,5,9,21,B; abolishes phenylalanine binding).`	`VAR_000883`
`VARIANT`	`67 67`	`1`	`S -> P (in PKU; haplotype 4).`	`VAR_000884`
`VARIANT`	`68 68`	`1`	`R -> S (in PKU; haplotype 1; significantly reduces phenylalanine binding).`	`VAR_000885`
`VARIANT`	`76 76`	`1`	`E -> A (in PKU).`	`VAR_000886`
`VARIANT`	`84 84`	`1`	`D -> Y (in PKU; haplotype 4).`	`VAR_000887`