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P00439 (PH4H_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 189. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Phenylalanine-4-hydroxylase

Short name=PAH
EC=1.14.16.1
Alternative name(s):
Phe-4-monooxygenase
Gene names
Name:PAH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length452 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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; acetoacetate and fumarate from L-phenylalanine: step 1/6.

Subunit structure

Homodimer and homotetramer. Ref.10

Post-translational modification

Phosphorylation at Ser-16 increases basal activity and facilitates activation by the substrate phenylalanine.

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.

Involvement in disease

Phenylketonuria (PKU) [MIM:261600]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.28 Ref.29 Ref.30 Ref.31 Ref.33 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39 Ref.41 Ref.42 Ref.43 Ref.44 Ref.45 Ref.46 Ref.47 Ref.49 Ref.50 Ref.51 Ref.52 Ref.53 Ref.54 Ref.56 Ref.57 Ref.58 Ref.59 Ref.60

Non-phenylketonuria hyperphenylalaninemia (Non-PKU HPA) [MIM:261600]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Hyperphenylalaninemia (HPA) [MIM:261600]: Mildest form of phenylalanine hydroxylase deficiency.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.27 Ref.32 Ref.34 Ref.41 Ref.48 Ref.53 Ref.55 Ref.56 Ref.58

Sequence similarities

Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.

Contains 1 ACT domain.

Biophysicochemical properties

Kinetic parameters:

KM=150 µM for L-Phe with BH4 as cofactor Ref.6

KM=30 µM for BH4

Vmax=3640 nmol/min/mg enzyme with BH4 as cofactor (preincubated with L-Phe)

Vmax=1230 nmol/min/mg enzyme with BH4 as cofactor (preincubated with BH4)

Temperature dependence:

Optimum temperature is 50 degrees Celsius.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 452451Phenylalanine-4-hydroxylase
PRO_0000205548

Regions

Domain36 – 11479ACT

Sites

Metal binding2851Iron By similarity
Metal binding2901Iron By similarity
Metal binding3301Iron By similarity

Amino acid modifications

Modified residue161Phosphoserine; by PKA Ref.5

Natural variations

Natural variant161S → P in PKU.
VAR_000869
Natural variant201Q → L in HPA.
VAR_009239
Natural variant391F → L in HPA and PKU; haplotype 1. Ref.56
VAR_000870
Natural variant391Missing in PKU; haplotypes 9,21. Ref.45 Ref.58
VAR_000871
Natural variant401S → L in PKU. Ref.37
VAR_000872
Natural variant411L → F in PKU.
VAR_000873
Natural variant411L → P in PKU; mild.
VAR_009240
Natural variant421K → I in PKU; haplotype 21.
VAR_000874
Natural variant451V → A in PKU. Ref.60
VAR_067994
Natural variant461G → S in PKU; haplotype 5; significantly reduces phenylalanine binding. Ref.37
VAR_000875
Natural variant471A → V in non-PKU HPA; haplotype 4; significantly reduces phenylalanine binding. Ref.34
VAR_000876
Natural variant481L → S in PKU; mild; haplotypes 3,4. Ref.25 Ref.37 Ref.41 Ref.56 Ref.60
VAR_000877
Natural variant531R → H in PKU. Ref.44
Corresponds to variant rs118092776 [ dbSNP | Ensembl ].
VAR_000878
Natural variant551F → L in HPA and PKU; does not affect oligomerization; results in loss of substrate activation. Ref.41 Ref.56 Ref.57
VAR_000879
Natural variant561E → D in PKU; haplotype 10.
VAR_000880
Natural variant611N → D in PKU. Ref.56
VAR_067995
Natural variant621L → P in PKU. Ref.60
VAR_067996
Natural variant63 – 642TH → PN in PKU; haplotype 1; abolishes phenylalanine binding.
VAR_000881
Natural variant651I → N in PKU. Ref.41
Corresponds to variant rs75193786 [ dbSNP | Ensembl ].
VAR_000882
Natural variant651I → S in PKU; results in disturbed oligomerization; results in loss of substrate activation. Ref.56 Ref.57
Corresponds to variant rs75193786 [ dbSNP | Ensembl ].
VAR_067997
Natural variant651I → T in PKU; haplotypes 1,5,9,21,B; abolishes phenylalanine binding. Ref.37 Ref.45 Ref.56
Corresponds to variant rs75193786 [ dbSNP | Ensembl ].
VAR_000883
Natural variant651I → V in HPA and PKU. Ref.56 Ref.58
VAR_067998
Natural variant671S → P in PKU; haplotype 4.
VAR_000884
Natural variant681R → S in PKU; haplotype 1; significantly reduces phenylalanine binding. Ref.37
VAR_000885
Natural variant761E → A in PKU.
VAR_000886
Natural variant761E → G in non-PKU HPA. Ref.55
VAR_067999
Natural variant841D → Y in PKU; haplotype 4.
VAR_000887
Natural variant871S → R in non-PKU HPA; haplotype 1. Ref.34
VAR_000888
Natural variant921T → I in PKU.
VAR_000889
Natural variant941Missing in PKU; mild; haplotype 2. Ref.26
VAR_000890
Natural variant981L → S in non-PKU HPA.
VAR_000891
Natural variant1041A → D in PKU; mild; haplotype 1. Ref.47
VAR_000892
Natural variant1101S → C in HPA.
VAR_009241
Natural variant1211F → L in HPA. Ref.58
VAR_069776
Natural variant1241T → I in PKU; haplotype 28.
VAR_000893
Natural variant1291D → Y in PKU.
VAR_000894
Natural variant1431D → G in PKU; haplotype 11. Ref.36
VAR_000895
Natural variant1451D → V in PKU.
VAR_011566
Natural variant1461H → Y in PKU.
VAR_000896
Natural variant1481G → S in PKU; haplotypes 1,2,7.
VAR_000897
Natural variant1511D → H in PKU; haplotypes 1,8.
VAR_000898
Natural variant1541Y → N in PKU.
VAR_000899
Natural variant1551R → P in PKU.
VAR_009242
Natural variant1571R → N in PKU; severe; 5% activity; requires 2 nucleotide substitutions. Ref.47
VAR_000900
Natural variant1571R → S in PKU. Ref.60
VAR_068000
Natural variant1581R → Q in PKU; haplotypes 1,2,4,7,16, 28. Ref.45 Ref.56 Ref.60
VAR_000901
Natural variant1581R → W in PKU.
VAR_000902
Natural variant1601Q → P in PKU.
VAR_000903
Natural variant1611F → S in PKU; haplotype 4.
VAR_000904
Natural variant1641I → T in PKU; haplotype 1. Ref.35
VAR_000905
Natural variant1671N → I in PKU. Ref.45
Corresponds to variant rs77554925 [ dbSNP | Ensembl ].
VAR_000906
Natural variant1671N → S in HPA.
Corresponds to variant rs77554925 [ dbSNP | Ensembl ].
VAR_011567
Natural variant1691R → H in PKU.
VAR_011568
Natural variant1701H → D in HPA.
VAR_011569
Natural variant1701H → Q in PKU; does not affect oligomerization. Ref.56 Ref.57
VAR_068001
Natural variant1701H → R in PKU.
VAR_000907
Natural variant1711G → A in PKU; haplotype 1. Ref.35
VAR_000908
Natural variant1711G → R in PKU.
VAR_000909
Natural variant1731P → T in PKU; haplotype 4.
VAR_000910
Natural variant1741I → T in PKU; haplotype 1.
VAR_000911
Natural variant1741I → V in PKU.
VAR_011570
Natural variant1751P → A in PKU.
VAR_000912
Natural variant1761R → L in non-PKU HPA. Ref.34
VAR_000913
Natural variant1761R → P in PKU.
VAR_000914
Natural variant1771V → L in PKU; haplotype 6. Ref.60
VAR_000915
Natural variant1771V → M in HPA. Ref.56
VAR_068002
Natural variant1781E → G in non-PKU HPA. Ref.60
VAR_000916
Natural variant1831E → Q in PKU.
VAR_009243
Natural variant1901V → A in PKU; haplotype 3. Ref.45 Ref.60
VAR_000917
Natural variant1941L → P in PKU.
VAR_000918
Natural variant1941Missing in PKU.
VAR_000919
Natural variant1961S → Y in HPA. Ref.58
VAR_069777
Natural variant1971Missing in PKU.
VAR_000920
Natural variant1981Missing in PKU; haplotype 2.
VAR_000921
Natural variant2011H → R in PKU.
VAR_000922
Natural variant2011H → Y in non-PKU HPA; haplotype 1. Ref.41 Ref.58
VAR_000923
Natural variant2041Y → C in PKU; mild; haplotypes 3,4. Ref.38
VAR_000924
Natural variant2051E → A in PKU.
VAR_011571
Natural variant2061Y → D in PKU.
VAR_000925
Natural variant2071N → D in PKU. Ref.44
VAR_000926
Natural variant2071N → S in PKU; severe; haplotype 4. Ref.38
VAR_000927
Natural variant2111P → T in PKU; haplotype 4.
VAR_000928
Natural variant2121L → P in PKU.
VAR_000929
Natural variant2131L → P in PKU; severe. Ref.41
VAR_000930
Natural variant2171C → G in PKU.
VAR_000931
Natural variant2181G → V in PKU; haplotypes 1,2.
VAR_000932
Natural variant2211E → G in PKU; haplotype 4. Ref.25
VAR_000933
Natural variant2221D → V in PKU; haplotypes 3,4.
VAR_000934
Natural variant2241I → M in PKU; haplotype 4.
VAR_000935
Natural variant2251P → R in PKU.
VAR_000936
Natural variant2251P → T in PKU; haplotype 1.
VAR_000937
Natural variant2261Q → H in PKU. Ref.60
VAR_068003
Natural variant2301V → I in non-PKU HPA; haplotype 4. Ref.58
VAR_000938
Natural variant2311S → F in PKU.
VAR_009244
Natural variant2311S → P in PKU.
VAR_000939
Natural variant2331F → L in PKU; haplotypes 2,3.
VAR_000940
Natural variant2381T → P in PKU; haplotype 4.
VAR_000941
Natural variant2391G → S in PKU. Ref.35
VAR_000942
Natural variant2401F → S in PKU.
VAR_011572
Natural variant2411R → C in non-PKU HPA and PKU; haplotype 34. Ref.37 Ref.45 Ref.48
VAR_000943
Natural variant2411R → H in PKU; haplotypes 1,5.
VAR_000944
Natural variant2411R → L in PKU.
VAR_000945
Natural variant2421L → F in PKU.
VAR_000946
Natural variant2431R → Q in non-PKU HPA and PKU; haplotypes 4,7,9. Ref.42 Ref.48
VAR_000947
Natural variant2441P → L in PKU; haplotype 12. Ref.30
VAR_000948
Natural variant2451V → A in PKU, HPA and non-PKU HPA; haplotypes 3,7. Ref.34 Ref.37 Ref.56 Ref.60
VAR_000949
Natural variant2451V → E in PKU; haplotype 11.
VAR_000950
Natural variant2451V → L in PKU.
VAR_000951
Natural variant2461A → D in PKU.
VAR_000952
Natural variant2471G → V in PKU; haplotype 4.
VAR_000953
Natural variant2481L → P in PKU.
VAR_000954
Natural variant2491L → F in PKU; haplotype 1.
VAR_000955
Natural variant2521R → G in PKU; haplotype 7.
VAR_000956
Natural variant2521R → Q in PKU; haplotype 1. Ref.35
VAR_000957
Natural variant2521R → W in PKU; haplotypes 1,6,7,8,42, 69; complete loss of activity. Ref.23 Ref.54 Ref.58 Ref.60
VAR_000958
Natural variant2551L → S in PKU; haplotype 36. Ref.22
VAR_000960
Natural variant2551L → V in PKU; haplotypes 18,21.
VAR_000959
Natural variant2571G → C in PKU.
VAR_000961
Natural variant2591A → T in PKU; haplotype 3.
VAR_000962
Natural variant2591A → V in PKU; haplotypes 7,42.
VAR_000963
Natural variant2611R → P in PKU.
VAR_000964
Natural variant2611R → Q in HPA and PKU; mild; haplotypes 1,2,4,22, 24,28. Ref.21 Ref.37 Ref.56 Ref.58 Ref.60
Corresponds to variant rs5030849 [ dbSNP | Ensembl ].
VAR_000965
Natural variant2631F → L in PKU.
VAR_000966
Natural variant2641H → L in PKU.
VAR_000967
Natural variant2651C → G in PKU.
VAR_000968
Natural variant2691I → L in non-PKU HPA. Ref.41
VAR_000969
Natural variant2701R → K in PKU.
VAR_000970
Natural variant2701R → S in PKU; haplotype 1.
VAR_000971
Natural variant2711H → Y in PKU.
VAR_000972
Natural variant2731S → F in PKU; haplotype 7.
VAR_000973
Natural variant2741K → E. Ref.54
Corresponds to variant rs142934616 [ dbSNP | Ensembl ].
VAR_011573
Natural variant2751P → L in PKU; reduced activity; increased affinity for the substrate; mildly reduced substrate activation; decreased cofactor affinity. Ref.56 Ref.57
VAR_068004
Natural variant2761M → I in PKU.
VAR_000974
Natural variant2761M → V in PKU; haplotype 4. Ref.33
VAR_000975
Natural variant2771Y → C in PKU.
VAR_000976
Natural variant2771Y → D in PKU; haplotype 2.
VAR_000977
Natural variant2781T → A in PKU.
VAR_000978
Natural variant2781T → N in PKU.
VAR_000979
Natural variant2801E → K in PKU; haplotypes 1,2,4,16,38; partial residual activity. Ref.18 Ref.37 Ref.60
VAR_000980
Natural variant2811P → L in PKU; haplotypes 1,4. Ref.23 Ref.24 Ref.37 Ref.56 Ref.60
VAR_000981
Natural variant2821D → N in PKU; haplotype 1.
VAR_000982
Natural variant2831I → F in PKU; haplotype 21.
VAR_000983
Natural variant2831I → N in PKU; severe. Ref.41
VAR_000984
Natural variant2901H → Y in PKU. Ref.59
VAR_067758
Natural variant2971R → C in PKU; haplotype 4.
VAR_000985
Natural variant2971R → H in PKU.
VAR_000986
Natural variant2991F → C in PKU; haplotype 8. Ref.37
VAR_000987
Natural variant3001A → S in PKU and HPA; haplotype 1; does not affect oligomerization; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. Ref.56 Ref.57 Ref.58 Ref.60
VAR_000988
Natural variant3001A → V in PKU.
VAR_000989
Natural variant3031S → P in PKU; haplotype 5.
VAR_000990
Natural variant3041Q → R in PKU.
VAR_000991
Natural variant3061I → V in non-PKU HPA; haplotype 4. Ref.27 Ref.58
VAR_000992
Natural variant3091A → D in PKU; haplotype 7.
VAR_000993
Natural variant3091A → V in PKU.
VAR_000994
Natural variant3101S → F in PKU; haplotype 7.
VAR_000995
Natural variant3101S → Y in HPA; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. Ref.56 Ref.57
VAR_068005
Natural variant3111L → P in PKU; haplotypes 1,7,10. Ref.17 Ref.19
VAR_000996
Natural variant3141P → H in PKU.
VAR_000997
Natural variant3141P → S in HPA; does not affect oligomerization; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. Ref.56 Ref.57
VAR_068006
Natural variant3181I → T in PKU; partial loss of activity. Ref.54
VAR_011574
Natural variant3221A → G in PKU; haplotype 12.
VAR_000998
Natural variant3221A → T in PKU; haplotype 1.
VAR_000999
Natural variant3221A → V in PKU. Ref.59
VAR_067759
Natural variant3251Y → C in PKU.
VAR_009245
Natural variant3301E → D in PKU.
VAR_009246
Natural variant3311F → L in PKU; haplotype 1. Ref.35
VAR_001000
Natural variant3331L → F in PKU.
VAR_001001
Natural variant3341C → S in PKU.
VAR_001002
Natural variant3371G → V in PKU.
VAR_001003
Natural variant3381D → Y in PKU; haplotype 4.
VAR_001004
Natural variant3411K → R in PKU.
VAR_001005
Natural variant3411K → T in PKU.
VAR_001006
Natural variant3421A → T in PKU; haplotype 5.
VAR_001007
Natural variant3431Y → C in PKU.
VAR_001008
Natural variant3441G → R in PKU.
VAR_009247
Natural variant3441G → V in PKU.
VAR_009248
Natural variant3451A → S in PKU.
VAR_001009
Natural variant3451A → T in PKU; haplotype 7.
VAR_001010
Natural variant3471L → F in PKU.
VAR_001011
Natural variant3481L → V in PKU; mild haplotype 9.
VAR_001012
Natural variant3491S → L in PKU; severe. Ref.42
VAR_001013
Natural variant3491S → P in PKU; haplotypes 1,4. Ref.60
VAR_001014
Natural variant3501S → T in PKU; haplotype 2.
VAR_001015
Natural variant3571C → G in PKU.
VAR_011575
Natural variant3621P → T in PKU. Ref.43
VAR_001016
Natural variant364 – 3685Missing in PKU. Ref.20
VAR_001018
Natural variant3641Missing in PKU; haplotype 5. Ref.20
VAR_001017
Natural variant3661P → H in PKU.
VAR_001019
Natural variant3721T → S in PKU.
VAR_001020
Natural variant3771Y → C in PKU; haplotype 4.
VAR_001021
Natural variant3801T → M in non-PKU HPA; haplotype 4. Ref.58
VAR_001022
Natural variant3861Y → C in PKU; common mutation.
VAR_001023
Natural variant3871Y → H in PKU; haplotype 1.
VAR_001024
Natural variant3881V → L in PKU. Ref.44
VAR_001025
Natural variant3881V → M in PKU; haplotypes 1,4.
VAR_001026
Natural variant3901E → G in PKU and non-PKU HPA; haplotype 4. Ref.32 Ref.37 Ref.56 Ref.58 Ref.60
VAR_001027
Natural variant3941D → A in PKU.
VAR_001028
Natural variant3941D → H in PKU. Ref.37
VAR_001029
Natural variant3951A → G in PKU.
VAR_001030
Natural variant3951A → P in PKU; haplotype 1.
VAR_001031
Natural variant399 – 4002Missing in PKU; haplotype 7.
VAR_001032
Natural variant4031A → V in non-PKU HPA and PKU; haplotype 43. Ref.37 Ref.56 Ref.58 Ref.60
Corresponds to variant rs5030857 [ dbSNP | Ensembl ].
VAR_001033
Natural variant4071P → L in PKU. Ref.49
VAR_068007
Natural variant4071P → S in PKU.
VAR_011576
Natural variant4081R → Q in PKU; haplotypes 4,12. Ref.28
VAR_001034
Natural variant4081R → W in HPA and PKU; haplotypes 1,2,4,5,13,34, 41,44; most common mutation; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. Ref.28 Ref.37 Ref.42 Ref.45 Ref.56 Ref.57 Ref.58 Ref.60
Corresponds to variant rs5030858 [ dbSNP | Ensembl ].
VAR_001035
Natural variant4101F → S in PKU; mild.
VAR_009249
Natural variant4131R → P in non-PKU HPA and PKU; haplotype 4. Ref.48 Ref.56
VAR_001036
Natural variant4131R → S in PKU; haplotype 1.
VAR_001037
Natural variant4141Y → C in HPA and PKU; haplotype 4; does not affect oligomerization; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. Ref.37 Ref.56 Ref.57
VAR_001038
Natural variant4151D → N in PKU, HPA and non-PKU HPA; haplotype 1. Ref.27 Ref.56 Ref.60
VAR_001039
Natural variant4171Y → H in PKU; reduction in activity is probably due to a global conformational change in the protein that reduces allostery. Ref.56 Ref.57
VAR_068008
Natural variant4181T → P in PKU; haplotype 4.
VAR_001040
Natural variant4211I → S in PKU. Ref.59
VAR_067760
Natural variant4301L → P in PKU.
VAR_001041
Natural variant4471A → D in PKU.
VAR_001042

Experimental info

Mutagenesis2831I → C: Loss of positive cooperativity and reduction of fold-activation by L-Phe preincubation. Ref.6
Sequence conflict1831E → G in AAH26251. Ref.3

Secondary structure

.......................................................... 452
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P00439 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 018F00EBBBDDCE2F

FASTA45251,862
        10         20         30         40         50         60 
MSTAVLENPG LGRKLSDFGQ ETSYIEDNCN QNGAISLIFS LKEEVGALAK VLRLFEENDV 

        70         80         90        100        110        120 
NLTHIESRPS RLKKDEYEFF THLDKRSLPA LTNIIKILRH DIGATVHELS RDKKKDTVPW 

       130        140        150        160        170        180 
FPRTIQELDR FANQILSYGA ELDADHPGFK DPVYRARRKQ FADIAYNYRH GQPIPRVEYM 

       190        200        210        220        230        240 
EEEKKTWGTV FKTLKSLYKT HACYEYNHIF PLLEKYCGFH EDNIPQLEDV SQFLQTCTGF 

       250        260        270        280        290        300 
RLRPVAGLLS SRDFLGGLAF RVFHCTQYIR HGSKPMYTPE PDICHELLGH VPLFSDRSFA 

       310        320        330        340        350        360 
QFSQEIGLAS LGAPDEYIEK LATIYWFTVE FGLCKQGDSI KAYGAGLLSS FGELQYCLSE 

       370        380        390        400        410        420 
KPKLLPLELE KTAIQNYTVT EFQPLYYVAE SFNDAKEKVR NFAATIPRPF SVRYDPYTQR 

       430        440        450 
IEVLDNTQQL KILADSINSE IGILCSALQK IK 

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References

« Hide 'large scale' references
[1]"Nucleotide sequence of a full-length complementary DNA clone and amino acid sequence of human phenylalanine hydroxylase."
Kwok S.C.M., Ledley F.D., Dilella A.G., Robson K.J.H., Woo S.L.C.
Biochemistry 24:556-561(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]Scriver C.R., Nowacki P.M., Byck S., Prevost L.
Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Liver.
[4]"A monoclonal antibody to aromatic amino acid hydroxylases. Identification of the epitope."
Cotton R.G., McAdam W., Jennings I., Morgan F.J.
Biochem. J. 255:193-196(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 131-144.
[5]"Phosphorylation and mutations of Ser(16) in human phenylalanine hydroxylase. Kinetic and structural effects."
Miranda F.F., Teigen K., Thorolfsson M., Svebak R.M., Knappskog P.M., Flatmark T., Martinez A.
J. Biol. Chem. 277:40937-40943(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-16.
[6]"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] [Europe PMC] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ILE-283.
[7]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria."
Erlandsen H., Fusetti F., Martinez A., Hough E., Flatmark T., Stevens R.C.
Nat. Struct. Biol. 4:995-1000(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 117-424.
[9]"Crystallographic analysis of the human phenylalanine hydroxylase catalytic domain with bound catechol inhibitors at 2.0-A resolution."
Erlandsen H., Flatmark T., Stevens R.C., Hough E.
Biochemistry 37:15638-15646(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 117-424.
[10]"Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria."
Fusetti F., Erlandsen H., Flatmark T., Stevens R.C.
J. Biol. Chem. 273:16962-16967(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 117-452, SUBUNIT.
[11]"Crystal structure and site-specific mutagenesis of pterin-bound human phenylalanine hydroxylase."
Erlandsen H., Bjorgo E., Flatmark T., Stevens R.C.
Biochemistry 39:2208-2217(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 118-424.
[12]"High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin."
Andersen O.A., Flatmark T., Hough E.
J. Mol. Biol. 314:279-291(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 103-427.
[13]"The phenylketonuria locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations."
Konecki D.S., Lichter-Konecki U.
Hum. Genet. 87:377-388(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON PKU VARIANTS.
[14]"Heterogeneity of phenylketonuria at the clinical, protein and DNA levels."
Cotton R.G.
J. Inherit. Metab. Dis. 13:739-750(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON PKU VARIANTS.
[15]"Molecular basis of phenylketonuria and related hyperphenylalaninemias: mutations and polymorphisms in the human phenylalanine hydroxylase gene."
Eisensmith R.C., Woo S.L.C.
Hum. Mutat. 1:13-22(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON PKU VARIANTS.
[16]"PAH Mutation Analysis Consortium Database: a database for disease-producing and other allelic variation at the human PAH locus."
Hoang L., Byck S., Prevost L., Scriver C.R.
Nucleic Acids Res. 24:127-131(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: DATABASE OF PKU VARIANTS.
[17]"Phenylalanine hydroxylase deficiency caused by a single base substitution in an exon of the human phenylalanine hydroxylase gene."
Lichter-Konecki U., Konecki D.S., Dilella A.G., Brayton K., Marvit J., Hahn T.M., Trefz F.K., Woo S.L.C.
Biochemistry 27:2881-2885(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKU PRO-311.
[18]"Molecular genetics of phenylketonuria in Mediterranean countries: a mutation associated with partial phenylalanine hydroxylase deficiency."
Lyonnet S., Caillaud C., Rey F., Berthelon M., Frezal J., Rey J., Munnich A.
Am. J. Hum. Genet. 44:511-517(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKU LYS-280.
[19]"Phenylketonuria in the Greek population. Haplotype analysis of the phenylalanine hydroxylase gene and identification of a PKU mutation."
Hofman K.J., Antonarakis S.E., Missiou-Tsangaraki S., Boehm C.D., Valle D.
Mol. Biol. Med. 6:245-250(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKU PRO-311.
[20]"Two mutations within the coding sequence of the phenylalanine hydroxylase gene."
Svensson E., Andersson B., Hagenfeldt L.
Hum. Genet. 85:300-304(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKU LEU-364 DEL.
[21]"Screening for mutations in the phenylalanine hydroxylase gene from Italian patients with phenylketonuria by using the chemical cleavage method: a new splice mutation."
Dianzani I., Forrest S.M., Camaschella C., Saglio G., Ponzone A., Cotton R.G.
Am. J. Hum. Genet. 48:631-635(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKU GLN-261.
[22]"Phenylketonuria in U.S. blacks: molecular analysis of the phenylalanine hydroxylase gene."
Hofman K.J., Steel G., Kazazian H.H. Jr., Valle D.
Am. J. Hum. Genet. 48:791-798(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKU SER-255.
[23]"Phenylketonuria missense mutations in the Mediterranean."
Okano Y., Wang T., Eisensmith R.C., Longhi R., Riva E., Giovannini M., Cerone R., Romano C., Woo S.L.C.
Genomics 9:96-103(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKU TRP-252 AND LEU-281.
[24]"Phenylalanine hydroxylase gene: novel missense mutation in exon 7 causing severe phenylketonuria."
Dworniczak B., Grudda K., Stumper J., Bartholome K., Aulehla-Scholz C., Horst J.
Genomics 9:193-199(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKU LEU-281.
[25]"The identification of two mis-sense mutations at the PAH gene locus in a Turkish patient with phenylketonuria."
Konecki D.S., Schlotter M., Trefz F.K., Lichter-Konecki U.
Hum. Genet. 87:389-393(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKU SER-48 AND GLY-221.
[26]"A 3-base pair in-frame deletion of the phenylalanine hydroxylase gene results in a kinetic variant of phenylketonuria."
Caillaud C., Lyonnet S., Rey F., Melle D., Frebourg T., Berthelon M., Vilarinho L., Vaz Osorio R., Rey J., Munnich A.
J. Biol. Chem. 266:9351-9354(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKU ILE-94 DEL.
[27]"Molecular basis for nonphenylketonuria hyperphenylalaninemia."
Economou-Petersen E., Henriksen K.F., Guldberg P., Guettler F.
Genomics 14:1-5(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NON-PKU HPA VAL-306 AND ASN-415.
[28]"Identification of a missense phenylketonuria mutation at codon 408 in Chinese."
Lin C.H., Hsiao K.J., Tsai T.F., Chao H.K., Su T.S.
Hum. Genet. 89:593-596(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKU GLN-408 AND TRP-408.
[29]"A new 15 bp deletion in exon 11 of the phenylalanine hydroxylase gene in phenylketonuria."
Jaruzelska J., Melle D., Matuszak R., Borski K., Munnich A.
Hum. Mol. Genet. 1:763-764(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKU 364-LEU--GLU-368 DEL.
[30]"A new PKU mutation associated with haplotype 12."
Desviat L.R., Perez B., Ugarte M.
Hum. Mol. Genet. 1:765-766(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKU LEU-244.
[31]"Molecular analysis of phenylketonuria in Denmark: 99% of the mutations detected by denaturing gradient gel electrophoresis."
Guldberg P., Henriksen K.F., Guettler F.
Genomics 17:141-146(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKU.
[32]"Illegitimate transcription of the phenylalanine hydroxylase gene in lymphocytes for identification of mutations in phenylketonuria."
Abadie V., Jaruzelska J., Lyonnet S., Millasseau P., Berthelon M., Rey F., Munnich A., Rey J.
Hum. Mol. Genet. 2:31-34(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NON-PKU HPA GLY-390.
[33]"Identification of a new missense mutation in Japanese phenylketonuric patients."
Goebel-Schreiner B., Schreiner R.
J. Inherit. Metab. Dis. 16:950-956(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKU VAL-276.
[34]"Molecular heterogeneity of nonphenylketonuria hyperphenylalaninemia in 25 Danish patients."
Guldberg P., Henriksen K.F., Thoeny B., Blau N., Guettler F.
Genomics 21:453-455(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NON-PKU HPA VAL-47; ARG-87; LEU-176 AND ALA-245.
[35]"Five novel missense mutations of the phenylalanine hydroxylase gene in phenylketonuria."
Benit P., Rey F., Melle D., Munnich A., Rey J.
Hum. Mutat. 4:229-231(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKU THR-164; ALA-171; SER-239; GLN-252 AND LEU-331.
[36]"PKU mutation (D143G) associated with an apparent high residual enzyme activity: expression of a kinetic variant form of phenylalanine hydroxylase in three different systems."
Knappskog P.M., Eiken H.G., Martinez A., Bruland O., Apold J., Flatmark T.
Hum. Mutat. 8:236-246(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT PKU GLY-143.
[37]"Phenylalanine hydroxylase deficiency in a population in Germany: mutational profile and nine novel mutations."
Guldberg P., Mallmann R., Henriksen K.F., Guettler F.
Hum. Mutat. 8:276-279(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: 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.
[38]"Two novel PAH gene mutations detected in Italian phenylketonuric patients."
Argiolas A., Bosco P., Cali F., Ceratto N., Anello G., Riva E., Biasucci G., Carducci C., Romano V.
Hum. Genet. 99:275-278(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKU CYS-204 AND SER-207.
[39]"Prediction of multiple hypermutable codons in the human PAH gene: codon 280 contains recurrent mutations in Quebec and other populations."
Byck S., Tyfield L., Carter K., Scriver C.R.
Hum. Mutat. 9:316-321(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKU.
[40]"In vitro expression analysis of mutations in phenylalanine hydroxylase: linking genotype to phenotype and structure to function."
Waters P.J., Parniak M.A., Nowacki P., Scriver C.R.
Hum. Mutat. 11:4-17(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS.
[41]"Eight new mutations of the phenylalanine hydroxylase gene in Italian patients with hyperphenylalaninemia."
Bosco P., Cali F., Meli C., Mollica F., Zammarchi E., Cerone R., Vanni C., Palillo L., Greco D., Romano V.
Hum. Mutat. 11:240-243(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKU SER-48; ASN-65; PRO-213 AND ASN-283, VARIANTS NON-PKU HPA SER-48; LEU-55; TYR-201 AND LEU-269.
[42]"Molecular basis of phenylketonuria in Venezuela: presence of two novel null mutations."
de Lucca M., Perez B., Desviat L.R., Ugarte M.
Hum. Mutat. 11:354-359(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKU GLN-243; LEU-349 AND TRP-408.
[43]"Two novel mutations in exon 11 of the PAH gene (1163/1164 del TG and P362T) associated with classic phenylketonuria and mild phenylketonuria."
Mallolas J., Campistol J., Lambruscini N., Vilaseca M.A., Cambra J.F., Estivill X., Milo M.
Hum. Mutat. 11:482-482(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKU THR-362.
[44]"Identification of three novel mutations in Korean phenylketonuria patients: R53H, N207D, and Y325X."
Park Y.S., Seoung C.S., Lee S.W., Oh K.H., Lee D.H., Yim J.
Hum. Mutat. Suppl. 1:S121-S122(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKU HIS-53; ASP-207 AND LEU-388.
[45]"Identification of seven new mutations in the phenylalanine hydroxylase gene, associated with hyperphenylalaninemia in the Belgian population."
Michiels L., Francois B., Raus J., Vandevyver C.
Hum. Mutat. Suppl. 1:S123-S124(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKU PHE-39 DEL; THR-65; GLN-158; ILE-167; ALA-190; CYS-241 AND TRP-408.
[46]"Mutation spectrum and phenylalanine hydroxylase RFLP/VNTR background in 44 Romanian phenylketonuric alleles."
Popescu T., Blazkova M., Kozak L., Jebeleanu G., Popescu A.
Hum. Mutat. 12:314-319(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKU.
[47]"Alterations in protein aggregation and degradation due to mild and severe missense mutations (A104D, R157N) in the human phenylalanine hydroxylase gene."
Waters P.J., Parniak M.A., Hewson A.S., Scriver C.R.
Hum. Mutat. 12:344-354(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS PKU ASP-104 AND ASN-157.
[48]"Mutation analysis of the phenylalanine hydroxylase gene and its clinical implications in two Japanese patients with non-phenylketonuria hyperphenylalaninemia."
Kibayashi M., Nagao M., Chiba S.
J. Hum. Genet. 43:231-236(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NON-PKU HPA CYS-241; GLN-243 AND PRO-413.
[49]"Maternal phenylketonuria in two Sicilian families identified by maternal blood phenylalanine level screening and identification of a new phenylalanine hydroxylase gene mutation (P407L)."
Corsello G., Bosco P., Cali F., Greco D., Cammarata M., Ciaccio M., Piccione M., Romano V.
Eur. J. Pediatr. 158:83-84(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PKU LEU-407.
[50]"Phenylketonuria and hyperphenylalaninemia in eastern Germany: a characteristic molecular profile and 15 novel mutations."
Hennermann J.B., Vetter B., Wolf C., Windt E., Buehrdel P., Seidel J., Moench E., Kulozik A.E.
Hum. Mutat. 15:254-260(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKU.
[51]"Missense mutations in the N-terminal domain of human phenylalanine hydroxylase interfere with binding of regulatory phenylalanine."
Gjetting T., Petersen M., Guldberg P., Guettler F.
Am. J. Hum. Genet. 68:1353-1360(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS PKU.
[52]"Mutations of the phenylalanine hydroxylase (PAH) gene in Brazilian patients with phenylketonuria."
Acosta A.X., Silva W.A. Jr., Carvalho T.M., Gomes M., Zago M.A.
Hum. Mutat. 17:122-130(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKU.
[53]"Molecular analysis of phenylketonuria (PKU) in newborns from Texas."
Yang Y., Drummond-Borg M., Garcia-Heras J.
Hum. Mutat. 17:523-523(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKU, VARIANTS HPA.
[54]"A phenylalanine hydroxylase amino acid polymorphism with implications for molecular diagnostics."
Gjetting T., Romstad A., Haavik J., Knappskog P.M., Acosta A.X., Silva W.A. Jr., Zago M.A., Guldberg P., Guettler F.
Mol. Genet. Metab. 73:280-284(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKU TRP-252 AND THR-318, VARIANT GLU-274.
[55]"Identification and characterization of a novel liver-specific enhancer of the human phenylalanine hydroxylase gene."
Chen K.J., Chao H.K., Hsiao K.J., Su T.S.
Hum. Genet. 110:235-243(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NON-PKU HPA GLY-76.
[56]"Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria."
Muntau A.C., Roschinger W., Habich M., Demmelmair H., Hoffmann B., Sommerhoff C.P., Roscher A.A.
N. Engl. J. Med. 347:2122-2132(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPA LEU-39; LEU-55; VAL-65; MET-177; ALA-245; GLN-261; TYR-310; SER-314; VAL-403; TRP-408; CYS-414 AND ASN-415, VARIANTS PKU SER-48; ASP-61; SER-65; THR-65; VAL-65; GLN-158; GLN-170; GLN-261; LEU-275; LEU-281; SER-300; GLY-390; TRP-408; PRO-413; CYS-414 AND HIS-417.
[57]"Loss of function in phenylketonuria is caused by impaired molecular motions and conformational instability."
Gersting S.W., Kemter K.F., Staudigl M., Messing D.D., Danecka M.K., Lagler F.B., Sommerhoff C.P., Roscher A.A., Muntau A.C.
Am. J. Hum. Genet. 83:5-17(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS PKU LEU-55; SER-65; GLN-170; LEU-275; SER-300; TYR-310; SER-314; TRP-408; CYS-414 AND HIS-417.
[58]"Mutation analysis in Hyperphenylalaninemia patients from South Italy."
Trunzo R., Santacroce R., D'Andrea G., Longo V., De Girolamo G., Dimatteo C., Leccese A., Lillo V., Papadia F., Margaglione M.
Clin. Biochem. 46:1896-1898(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HPA PHE-39 DEL; LEU-121; TYR-196; TYR-201; ILE-230; SER-300; VAL-306; MET-380; GLY-390 AND VAL-403, VARIANTS PKU VAL-65; TRP-252; GLN-261 AND TRP-408.
[59]"Prevalence of tetrahydrobiopterine (BH4)-responsive alleles among Austrian patients with PAH deficiency: comprehensive results from molecular analysis in 147 patients."
Sterl E., Paul K., Paschke E., Zschocke J., Brunner-Krainz M., Windisch E., Konstantopoulou V., Moslinger D., Karall D., Scholl-Burgi S., Sperl W., Lagler F., Plecko B.
J. Inherit. Metab. Dis. 36:7-13(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKU TYR-290; VAL-322 AND SER-421.
[60]"Five novel mutations and two large deletions in a population analysis of the phenylalanine hydroxylase gene."
Groselj U., Tansek M.Z., Kovac J., Hovnik T., Podkrajsek K.T., Battelino T.
Mol. Genet. Metab. 106:142-148(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PKU ALA-45; SER-48; PRO-62; SER-157; GLN-158; LEU-177; GLY-178; ALA-190; HIS-226; ALA-245; TRP-252; GLN-261; LYS-280; LEU-281; SER-300; PRO-349; GLY-390; VAL-403; TRP-408 AND ASN-415.
+Additional computationally mapped references.

Web resources

PAHdb

Phenylalanine hydroxylase locus knowledgebase

Wikipedia

Phenylalanine hydroxylase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
K03020 mRNA. Translation: AAA60082.1.
U49897 mRNA. Translation: AAC51772.1.
S61296 mRNA. Translation: AAD13926.1.
BC026251 mRNA. Translation: AAH26251.1.
CCDSCCDS9092.1.
PIRWHHUF. A00508.
RefSeqNP_000268.1. NM_000277.1.
UniGeneHs.603740.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1DMWX-ray2.00A118-424[»]
1J8TX-ray1.70A103-427[»]
1J8UX-ray1.50A103-427[»]
1KW0X-ray2.50A103-427[»]
1LRMX-ray2.10A103-427[»]
1MMKX-ray2.00A103-427[»]
1MMTX-ray2.00A103-427[»]
1PAHX-ray2.00A117-424[»]
1TDWX-ray2.10A117-424[»]
1TG2X-ray2.20A117-424[»]
2PAHX-ray3.10A/B118-452[»]
3PAHX-ray2.00A117-424[»]
4ANPX-ray2.11A104-427[»]
4PAHX-ray2.00A117-424[»]
5PAHX-ray2.10A117-424[»]
6PAHX-ray2.15A117-424[»]
ProteinModelPortalP00439.
SMRP00439. Positions 19-452.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111090. 4 interactions.
DIPDIP-58927N.
IntActP00439. 2 interactions.
STRING9606.ENSP00000303500.

Chemistry

BindingDBP00439.
ChEMBLCHEMBL3076.
DrugBankDB00668. Epinephrine.
DB00120. L-Phenylalanine.
DB01235. Levodopa.
DB00368. Norepinephrine.
DB00360. Tetrahydrobiopterin.
GuidetoPHARMACOLOGY1240.

PTM databases

PhosphoSiteP00439.

Polymorphism databases

DMDM129973.

2D gel databases

UCD-2DPAGEP00439.

Proteomic databases

MaxQBP00439.
PaxDbP00439.
PRIDEP00439.

Protocols and materials databases

DNASU5053.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000553106; ENSP00000448059; ENSG00000171759.
GeneID5053.
KEGGhsa:5053.
UCSCuc001tjq.1. human.

Organism-specific databases

CTD5053.
GeneCardsGC12M103230.
GeneReviewsPAH.
HGNCHGNC:8582. PAH.
HPAHPA028407.
HPA031642.
MIM261600. phenotype.
612349. gene.
neXtProtNX_P00439.
Orphanet79254. Classical phenylketonuria.
2209. Maternal hyperphenylalaninemia.
79651. Mild hyperphenylalaninemia.
79253. Mild phenylketonuria.
293284. Tetrahydrobiopterin-responsive hyperphenylalaninemia/phenylketonuria.
PharmGKBPA32911.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3186.
HOGENOMHOG000233373.
HOVERGENHBG006841.
InParanoidP00439.
KOK00500.
OMARYNAYTQ.
OrthoDBEOG7KM5T1.
PhylomeDBP00439.
TreeFamTF313327.

Enzyme and pathway databases

BioCycMetaCyc:HS10374-MONOMER.
BRENDA1.14.16.1. 2681.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
SABIO-RKP00439.
UniPathwayUPA00139; UER00337.

Gene expression databases

ArrayExpressP00439.
BgeeP00439.
CleanExHS_PAH.
GenevestigatorP00439.

Family and domain databases

Gene3D1.10.800.10. 1 hit.
InterProIPR002912. ACT_dom.
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]
PANTHERPTHR11473. PTHR11473. 1 hit.
PfamPF01842. ACT. 1 hit.
PF00351. Biopterin_H. 1 hit.
[Graphical view]
PIRSFPIRSF000336. TH. 1 hit.
PRINTSPR00372. FYWHYDRXLASE.
SUPFAMSSF56534. SSF56534. 1 hit.
TIGRFAMsTIGR01268. Phe4hydrox_tetr. 1 hit.
PROSITEPS51671. ACT. 1 hit.
PS00367. BH4_AAA_HYDROXYL_1. 1 hit.
PS51410. BH4_AAA_HYDROXYL_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP00439.
GeneWikiPhenylalanine_hydroxylase.
GenomeRNAi5053.
NextBio19476.
PROP00439.
SOURCESearch...

Entry information

Entry namePH4H_HUMAN
AccessionPrimary (citable) accession number: P00439
Secondary accession number(s): Q16717, Q8TC14
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: July 9, 2014
This is version 189 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM