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Phenylalanine-4-hydroxylase (PAH) (EC 1.14.16.1) (Phe-4-monooxygenase)

 PH4H_HUMAN              Reviewed;         452 AA.
P00439; Q16717; Q8TC14;
21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
21-JUL-1986, sequence version 1.
27-SEP-2017, entry version 220.
RecName: Full=Phenylalanine-4-hydroxylase;
Short=PAH;
EC=1.14.16.1;
AltName: Full=Phe-4-monooxygenase;
Name=PAH;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Liver;
PubMed=2986678; DOI=10.1021/bi00324a002;
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;
PubMed=15489334; DOI=10.1101/gr.2596504;
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; DOI=10.1042/bj2550193;
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]
PHOSPHORYLATION AT SER-16.
PubMed=12185072; DOI=10.1074/jbc.M112197200;
Miranda F.F., Teigen K., Thorolfsson M., Svebak R.M., Knappskog P.M.,
Flatmark T., Martinez A.;
"Phosphorylation and mutations of Ser(16) in human phenylalanine
hydroxylase. Kinetic and structural effects.";
J. Biol. Chem. 277:40937-40943(2002).
[6]
BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF ILE-283.
PubMed=18835579; DOI=10.1016/j.gene.2008.09.005;
Siltberg-Liberles J., Steen I.H., Svebak R.M., Martinez A.;
"The phylogeny of the aromatic amino acid hydroxylases revisited by
characterizing phenylalanine hydroxylase from Dictyostelium
discoideum.";
Gene 427:86-92(2008).
[7]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21269460; DOI=10.1186/1752-0509-5-17;
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
"Initial characterization of the human central proteome.";
BMC Syst. Biol. 5:17-17(2011).
[8]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Liver;
PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
Wang L., Ye M., Zou H.;
"An enzyme assisted RP-RPLC approach for in-depth analysis of human
liver phosphoproteome.";
J. Proteomics 96:253-262(2014).
[9]
X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 117-424.
PubMed=9406548; DOI=10.1038/nsb1297-995;
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).
[10]
X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 117-424.
PubMed=9843368; DOI=10.1021/bi9815290;
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).
[11]
X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 117-452, AND SUBUNIT.
PubMed=9642259; DOI=10.1074/jbc.273.27.16962;
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).
[12]
X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 118-424.
PubMed=10694386; DOI=10.1021/bi992531+;
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).
[13]
X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 103-427.
PubMed=11718561; DOI=10.1006/jmbi.2001.5061;
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).
[14]
REVIEW ON PKU VARIANTS.
PubMed=1679029;
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).
[15]
REVIEW ON PKU VARIANTS.
PubMed=2246858; DOI=10.1007/BF01799577;
Cotton R.G.;
"Heterogeneity of phenylketonuria at the clinical, protein and DNA
levels.";
J. Inherit. Metab. Dis. 13:739-750(1990).
[16]
REVIEW ON PKU VARIANTS.
PubMed=1301187; DOI=10.1002/humu.1380010104;
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).
[17]
DATABASE OF PKU VARIANTS.
PubMed=8594560; DOI=10.1093/nar/24.1.127;
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).
[18]
VARIANT PKU PRO-311.
PubMed=2840952; DOI=10.1021/bi00408a032;
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).
[19]
VARIANT PKU LYS-280.
PubMed=2564729;
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).
[20]
VARIANT PKU PRO-311.
PubMed=2615649;
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).
[21]
VARIANT PKU LEU-364 DEL.
PubMed=1975559; DOI=10.1007/BF00206750;
Svensson E., Andersson B., Hagenfeldt L.;
"Two mutations within the coding sequence of the phenylalanine
hydroxylase gene.";
Hum. Genet. 85:300-304(1990).
[22]
VARIANT PKU GLN-261.
PubMed=1671810;
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).
[23]
VARIANT PKU SER-255.
PubMed=2014802;
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).
[24]
VARIANTS PKU TRP-252 AND LEU-281.
PubMed=1672294; DOI=10.1016/0888-7543(91)90225-4;
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).
[25]
VARIANT PKU LEU-281.
PubMed=1672290; DOI=10.1016/0888-7543(91)90238-A;
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).
[26]
VARIANTS PKU SER-48 AND GLY-221.
PubMed=1679030;
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).
[27]
VARIANT PKU ILE-94 DEL.
PubMed=1709636;
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).
[28]
VARIANTS NON-PKU HPA VAL-306 AND ASN-415.
PubMed=1358789; DOI=10.1016/S0888-7543(05)80274-5;
Economou-Petersen E., Henriksen K.F., Guldberg P., Guettler F.;
"Molecular basis for nonphenylketonuria hyperphenylalaninemia.";
Genomics 14:1-5(1992).
[29]
VARIANTS PKU GLN-408 AND TRP-408.
PubMed=1355066; DOI=10.1007/BF00221944;
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).
[30]
VARIANT PKU 364-LEU--GLU-368 DEL.
PubMed=1363837; DOI=10.1093/hmg/1.9.763;
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).
[31]
VARIANT PKU LEU-244.
PubMed=1363838; DOI=10.1093/hmg/1.9.765;
Desviat L.R., Perez B., Ugarte M.;
"A new PKU mutation associated with haplotype 12.";
Hum. Mol. Genet. 1:765-766(1992).
[32]
VARIANTS PKU.
PubMed=8406445; DOI=10.1006/geno.1993.1295;
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).
[33]
VARIANT NON-PKU HPA GLY-390.
PubMed=8098245; DOI=10.1093/hmg/2.1.31;
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).
[34]
VARIANT NON-PKU HPA SER-98.
PubMed=8364546; DOI=10.1093/hmg/2.7.1061;
Guldberg P., Lou H.C., Henriksen K.F., Mikkelsen I., Olsen B.,
Holck B., Guettler F.;
"A novel missense mutation in the phenylalanine hydroxylase gene of a
homozygous Pakistani patient with non-PKU hyperphenylalaninemia.";
Hum. Mol. Genet. 2:1061-1062(1993).
[35]
VARIANT PKU VAL-276.
PubMed=8068076; DOI=10.1007/BF00711510;
Goebel-Schreiner B., Schreiner R.;
"Identification of a new missense mutation in Japanese phenylketonuric
patients.";
J. Inherit. Metab. Dis. 16:950-956(1993).
[36]
VARIANTS NON-PKU HPA VAL-47; ARG-87; LEU-176 AND ALA-245.
PubMed=8088845; DOI=10.1006/geno.1994.1296;
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).
[37]
VARIANTS PKU THR-164; ALA-171; SER-239; GLN-252 AND LEU-331.
PubMed=7833954; DOI=10.1002/humu.1380040311;
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).
[38]
CHARACTERIZATION OF VARIANT PKU GLY-143.
PubMed=8889583;
DOI=10.1002/(SICI)1098-1004(1996)8:3<236::AID-HUMU7>3.0.CO;2-7;
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).
[39]
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.
PubMed=8889590;
DOI=10.1002/(SICI)1098-1004(1996)8:3<276::AID-HUMU14>3.3.CO;2-T;
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).
[40]
VARIANTS PKU CYS-204 AND SER-207.
PubMed=9048935; DOI=10.1007/s004390050353;
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).
[41]
VARIANTS PKU.
PubMed=9101291;
DOI=10.1002/(SICI)1098-1004(1997)9:4<316::AID-HUMU3>3.3.CO;2-X;
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).
[42]
CHARACTERIZATION OF VARIANTS.
PubMed=9450897;
DOI=10.1002/(SICI)1098-1004(1998)11:1<4::AID-HUMU2>3.0.CO;2-L;
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).
[43]
VARIANTS PKU SER-48; ASN-65; PRO-213 AND ASN-283, AND VARIANTS NON-PKU
HPA SER-48; LEU-55; TYR-201 AND LEU-269.
PubMed=9521426;
DOI=10.1002/(SICI)1098-1004(1998)11:3<240::AID-HUMU9>3.0.CO;2-L;
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).
[44]
VARIANTS PKU GLN-243; LEU-349 AND TRP-408.
PubMed=9600453;
DOI=10.1002/(SICI)1098-1004(1998)11:5<354::AID-HUMU2>3.0.CO;2-W;
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).
[45]
VARIANT PKU THR-362.
PubMed=10200057;
DOI=10.1002/(SICI)1098-1004(1998)11:6<482::AID-HUMU15>3.0.CO;2-E;
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).
[46]
VARIANTS PKU HIS-53; ASP-207 AND LEU-388.
PubMed=9452061;
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).
[47]
VARIANTS PKU PHE-39 DEL; THR-65; GLN-158; ILE-167; ALA-190; CYS-241
AND TRP-408.
PubMed=9452062;
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).
[48]
VARIANTS PKU.
PubMed=9792407;
DOI=10.1002/(SICI)1098-1004(1998)12:5<314::AID-HUMU4>3.0.CO;2-D;
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).
[49]
CHARACTERIZATION OF VARIANTS PKU ASP-104 AND ASN-157.
PubMed=9792411;
DOI=10.1002/(SICI)1098-1004(1998)12:5<344::AID-HUMU8>3.0.CO;2-D;
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).
[50]
VARIANTS NON-PKU HPA CYS-241; GLN-243 AND PRO-413.
PubMed=9852673; DOI=10.1007/s100380050079;
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).
[51]
VARIANT PKU LEU-407.
PubMed=9950317; DOI=10.1007/s004310051018;
Corsello G., Bosco P., Cali F., Greco D., Cammarata M., Ciaccio M.,
Piccione M., Romano V.;
"Maternal phenylketonuria in two Sicilian families identified by
maternal blood phenylalanine level screening and identification of a
new phenylalanine hydroxylase gene mutation (P407L).";
Eur. J. Pediatr. 158:83-84(1999).
[52]
VARIANTS PKU.
PubMed=10679941;
DOI=10.1002/(SICI)1098-1004(200003)15:3<254::AID-HUMU6>3.0.CO;2-W;
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).
[53]
CHARACTERIZATION OF VARIANTS PKU.
PubMed=11326337; DOI=10.1086/320604;
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).
[54]
VARIANTS PKU.
PubMed=11180595;
DOI=10.1002/1098-1004(200102)17:2<122::AID-HUMU4>3.0.CO;2-C;
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).
[55]
VARIANTS PKU, AND VARIANTS HPA.
PubMed=11385716; DOI=10.1002/humu.1141.abs;
Yang Y., Drummond-Borg M., Garcia-Heras J.;
"Molecular analysis of phenylketonuria (PKU) in newborns from Texas.";
Hum. Mutat. 17:523-523(2001).
[56]
VARIANTS PKU TRP-252 AND THR-318, AND VARIANT GLU-274.
PubMed=11461196; DOI=10.1006/mgme.2001.3180;
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).
[57]
VARIANT NON-PKU HPA GLY-76.
PubMed=11935335; DOI=10.1007/s00439-002-0677-7;
Chen K.J., Chao H.K., Hsiao K.J., Su T.S.;
"Identification and characterization of a novel liver-specific
enhancer of the human phenylalanine hydroxylase gene.";
Hum. Genet. 110:235-243(2002).
[58]
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, AND 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.
PubMed=12501224; DOI=10.1056/NEJMoa021654;
Muntau A.C., Roschinger W., Habich M., Demmelmair H., Hoffmann B.,
Sommerhoff C.P., Roscher A.A.;
"Tetrahydrobiopterin as an alternative treatment for mild
phenylketonuria.";
N. Engl. J. Med. 347:2122-2132(2002).
[59]
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.
PubMed=18538294; DOI=10.1016/j.ajhg.2008.05.013;
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.;
"Loss of function in phenylketonuria is caused by impaired molecular
motions and conformational instability.";
Am. J. Hum. Genet. 83:5-17(2008).
[60]
VARIANTS HPA PHE-39 DEL; LEU-121; TYR-196; TYR-201; ILE-230; SER-300;
VAL-306; MET-380; GLY-390 AND VAL-403, AND VARIANTS PKU VAL-65;
TRP-252; GLN-261 AND TRP-408.
PubMed=23792259; DOI=10.1016/j.clinbiochem.2013.06.009;
Trunzo R., Santacroce R., D'Andrea G., Longo V., De Girolamo G.,
Dimatteo C., Leccese A., Lillo V., Papadia F., Margaglione M.;
"Mutation analysis in Hyperphenylalaninemia patients from South
Italy.";
Clin. Biochem. 46:1896-1898(2013).
[61]
VARIANTS PKU TYR-290; VAL-322 AND SER-421.
PubMed=22526846; DOI=10.1007/s10545-012-9485-y;
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.;
"Prevalence of tetrahydrobiopterine (BH4)-responsive alleles among
Austrian patients with PAH deficiency: comprehensive results from
molecular analysis in 147 patients.";
J. Inherit. Metab. Dis. 36:7-13(2013).
[62]
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.
PubMed=22513348; DOI=10.1016/j.ymgme.2012.03.015;
Groselj U., Tansek M.Z., Kovac J., Hovnik T., Podkrajsek K.T.,
Battelino T.;
"Five novel mutations and two large deletions in a population analysis
of the phenylalanine hydroxylase gene.";
Mol. Genet. Metab. 106:142-148(2012).
-!- CATALYTIC ACTIVITY: L-phenylalanine + tetrahydrobiopterin + O(2) =
L-tyrosine + 4a-hydroxytetrahydrobiopterin.
-!- COFACTOR:
Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
-!- 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.
-!- BIOPHYSICOCHEMICAL PROPERTIES:
Kinetic parameters:
KM=150 uM for L-Phe with BH(4) as cofactor
{ECO:0000269|PubMed:18835579};
KM=30 uM for BH(4) {ECO:0000269|PubMed:18835579};
Vmax=3640 nmol/min/mg enzyme with BH(4) as cofactor
(preincubated with L-Phe) {ECO:0000269|PubMed:18835579};
Vmax=1230 nmol/min/mg enzyme with BH(4) as cofactor
(preincubated with BH(4)) {ECO:0000269|PubMed:18835579};
Temperature dependence:
Optimum temperature is 50 degrees Celsius.
{ECO:0000269|PubMed:18835579};
-!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation;
acetoacetate and fumarate from L-phenylalanine: step 1/6.
-!- SUBUNIT: Homodimer and homotetramer. {ECO:0000269|PubMed:9642259}.
-!- PTM: Phosphorylation at Ser-16 increases basal activity and
facilitates activation by the substrate phenylalanine.
{ECO:0000269|PubMed:12185072}.
-!- 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: 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. {ECO:0000269|PubMed:10200057,
ECO:0000269|PubMed:10679941, ECO:0000269|PubMed:11180595,
ECO:0000269|PubMed:11326337, ECO:0000269|PubMed:11385716,
ECO:0000269|PubMed:11461196, ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:1355066, ECO:0000269|PubMed:1363837,
ECO:0000269|PubMed:1363838, ECO:0000269|PubMed:1671810,
ECO:0000269|PubMed:1672290, ECO:0000269|PubMed:1672294,
ECO:0000269|PubMed:1679030, ECO:0000269|PubMed:1709636,
ECO:0000269|PubMed:18538294, ECO:0000269|PubMed:1975559,
ECO:0000269|PubMed:2014802, ECO:0000269|PubMed:22513348,
ECO:0000269|PubMed:22526846, ECO:0000269|PubMed:23792259,
ECO:0000269|PubMed:2564729, ECO:0000269|PubMed:2615649,
ECO:0000269|PubMed:2840952, ECO:0000269|PubMed:7833954,
ECO:0000269|PubMed:8068076, ECO:0000269|PubMed:8406445,
ECO:0000269|PubMed:8889583, ECO:0000269|PubMed:8889590,
ECO:0000269|PubMed:9048935, ECO:0000269|PubMed:9101291,
ECO:0000269|PubMed:9452061, ECO:0000269|PubMed:9452062,
ECO:0000269|PubMed:9521426, ECO:0000269|PubMed:9600453,
ECO:0000269|PubMed:9792407, ECO:0000269|PubMed:9792411,
ECO:0000269|PubMed:9950317}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: 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.
{ECO:0000269|PubMed:1358789, ECO:0000269|PubMed:8088845,
ECO:0000269|PubMed:8098245, ECO:0000269|PubMed:9521426,
ECO:0000269|PubMed:9852673}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: Hyperphenylalaninemia (HPA) [MIM:261600]: Mildest form of
phenylalanine hydroxylase deficiency.
{ECO:0000269|PubMed:11385716, ECO:0000269|PubMed:11935335,
ECO:0000269|PubMed:12501224, ECO:0000269|PubMed:1358789,
ECO:0000269|PubMed:23792259, ECO:0000269|PubMed:8088845,
ECO:0000269|PubMed:8098245, ECO:0000269|PubMed:9521426,
ECO:0000269|PubMed:9852673}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid
hydroxylase family. {ECO:0000305}.
-!- WEB RESOURCE: Name=PAHdb; Note=Phenylalanine hydroxylase locus
knowledgebase;
URL="http://www.pahdb.mcgill.ca/";
-!- WEB RESOURCE: Name=Wikipedia; Note=Phenylalanine hydroxylase
entry;
URL="https://en.wikipedia.org/wiki/Phenylalanine_hydroxylase";
-----------------------------------------------------------------------
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EMBL; K03020; AAA60082.1; -; mRNA.
EMBL; U49897; AAC51772.1; -; mRNA.
EMBL; S61296; AAD13926.1; -; mRNA.
EMBL; BC026251; AAH26251.1; -; mRNA.
CCDS; CCDS9092.1; -.
PIR; A00508; WHHUF.
RefSeq; NP_000268.1; NM_000277.1.
UniGene; Hs.603740; -.
PDB; 1DMW; X-ray; 2.00 A; A=118-424.
PDB; 1J8T; X-ray; 1.70 A; A=103-427.
PDB; 1J8U; X-ray; 1.50 A; A=103-427.
PDB; 1KW0; X-ray; 2.50 A; A=103-427.
PDB; 1LRM; X-ray; 2.10 A; A=103-427.
PDB; 1MMK; X-ray; 2.00 A; A=103-427.
PDB; 1MMT; X-ray; 2.00 A; A=103-427.
PDB; 1PAH; X-ray; 2.00 A; A=117-424.
PDB; 1TDW; X-ray; 2.10 A; A=117-424.
PDB; 1TG2; X-ray; 2.20 A; A=117-424.
PDB; 2PAH; X-ray; 3.10 A; A/B=118-452.
PDB; 3PAH; X-ray; 2.00 A; A=117-424.
PDB; 4ANP; X-ray; 2.11 A; A=104-427.
PDB; 4PAH; X-ray; 2.00 A; A=117-424.
PDB; 5FII; X-ray; 1.80 A; A/B/C/D=19-118.
PDB; 5PAH; X-ray; 2.10 A; A=117-424.
PDB; 6PAH; X-ray; 2.15 A; A=117-424.
PDBsum; 1DMW; -.
PDBsum; 1J8T; -.
PDBsum; 1J8U; -.
PDBsum; 1KW0; -.
PDBsum; 1LRM; -.
PDBsum; 1MMK; -.
PDBsum; 1MMT; -.
PDBsum; 1PAH; -.
PDBsum; 1TDW; -.
PDBsum; 1TG2; -.
PDBsum; 2PAH; -.
PDBsum; 3PAH; -.
PDBsum; 4ANP; -.
PDBsum; 4PAH; -.
PDBsum; 5FII; -.
PDBsum; 5PAH; -.
PDBsum; 6PAH; -.
ProteinModelPortal; P00439; -.
SMR; P00439; -.
BioGrid; 111090; 4.
DIP; DIP-58927N; -.
IntAct; P00439; 3.
STRING; 9606.ENSP00000448059; -.
BindingDB; P00439; -.
ChEMBL; CHEMBL3076; -.
DrugBank; DB03673; Beta(2-Thienyl)Alanine.
DrugBank; DB06262; Droxidopa.
DrugBank; DB00668; Epinephrine.
DrugBank; DB00120; L-Phenylalanine.
DrugBank; DB00368; Norepinephrine.
DrugBank; DB04419; Norleucine.
DrugBank; DB00360; Sapropterin.
GuidetoPHARMACOLOGY; 1240; -.
iPTMnet; P00439; -.
PhosphoSitePlus; P00439; -.
BioMuta; PAH; -.
DMDM; 129973; -.
UCD-2DPAGE; P00439; -.
EPD; P00439; -.
MaxQB; P00439; -.
PaxDb; P00439; -.
PeptideAtlas; P00439; -.
PRIDE; P00439; -.
DNASU; 5053; -.
Ensembl; ENST00000553106; ENSP00000448059; ENSG00000171759.
GeneID; 5053; -.
KEGG; hsa:5053; -.
UCSC; uc001tjq.2; human.
CTD; 5053; -.
DisGeNET; 5053; -.
EuPathDB; HostDB:ENSG00000171759.9; -.
GeneCards; PAH; -.
GeneReviews; PAH; -.
HGNC; HGNC:8582; PAH.
HPA; HPA028407; -.
HPA; HPA031642; -.
MalaCards; PAH; -.
MIM; 261600; phenotype.
MIM; 612349; gene.
neXtProt; NX_P00439; -.
OpenTargets; ENSG00000171759; -.
Orphanet; 79254; Classical phenylketonuria.
Orphanet; 2209; Maternal hyperphenylalaninemia.
Orphanet; 79651; Mild hyperphenylalaninemia.
Orphanet; 79253; Mild phenylketonuria.
Orphanet; 293284; Tetrahydrobiopterin-responsive hyperphenylalaninemia/phenylketonuria.
PharmGKB; PA32911; -.
eggNOG; KOG3820; Eukaryota.
eggNOG; COG3186; LUCA.
GeneTree; ENSGT00390000010268; -.
HOGENOM; HOG000233373; -.
HOVERGEN; HBG006841; -.
InParanoid; P00439; -.
KO; K00500; -.
OMA; YEFFVEC; -.
OrthoDB; EOG091G05MZ; -.
PhylomeDB; P00439; -.
TreeFam; TF313327; -.
BioCyc; MetaCyc:HS10374-MONOMER; -.
BRENDA; 1.14.16.1; 2681.
Reactome; R-HSA-71182; Phenylalanine and tyrosine catabolism.
SABIO-RK; P00439; -.
SIGNOR; P00439; -.
UniPathway; UPA00139; UER00337.
EvolutionaryTrace; P00439; -.
GeneWiki; Phenylalanine_hydroxylase; -.
GenomeRNAi; 5053; -.
PRO; PR:P00439; -.
Proteomes; UP000005640; Chromosome 12.
Bgee; ENSG00000171759; -.
CleanEx; HS_PAH; -.
ExpressionAtlas; P00439; baseline and differential.
Genevisible; P00439; HS.
GO; GO:0005829; C:cytosol; TAS:Reactome.
GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
GO; GO:0005506; F:iron ion binding; IEA:InterPro.
GO; GO:0004505; F:phenylalanine 4-monooxygenase activity; IDA:CACAO.
GO; GO:0042423; P:catecholamine biosynthetic process; NAS:BHF-UCL.
GO; GO:0008652; P:cellular amino acid biosynthetic process; TAS:ProtInc.
GO; GO:0006559; P:L-phenylalanine catabolic process; TAS:Reactome.
GO; GO:0042136; P:neurotransmitter biosynthetic process; NAS:BHF-UCL.
Gene3D; 1.10.800.10; -; 1.
InterPro; IPR002912; ACT_dom.
InterPro; IPR001273; ArAA_hydroxylase.
InterPro; IPR018301; ArAA_hydroxylase_Fe/CU_BS.
InterPro; IPR019774; Aromatic-AA_hydroxylase_C.
InterPro; IPR005961; Phe-4-hydroxylase_tetra.
InterPro; IPR019773; Tyrosine_3-monooxygenase-like.
PANTHER; PTHR11473; PTHR11473; 1.
Pfam; PF01842; ACT; 1.
Pfam; PF00351; Biopterin_H; 1.
PIRSF; PIRSF000336; TH; 1.
PRINTS; PR00372; FYWHYDRXLASE.
SUPFAM; SSF56534; SSF56534; 1.
TIGRFAMs; TIGR01268; Phe4hydrox_tetr; 1.
PROSITE; PS51671; ACT; 1.
PROSITE; PS00367; BH4_AAA_HYDROXYL_1; 1.
PROSITE; PS51410; BH4_AAA_HYDROXYL_2; 1.
1: Evidence at protein level;
3D-structure; Allosteric enzyme; Complete proteome;
Direct protein sequencing; Disease mutation; Iron; Metal-binding;
Monooxygenase; Oxidoreductase; Phenylalanine catabolism;
Phenylketonuria; Phosphoprotein; Polymorphism; Reference proteome.
CHAIN 1 452 Phenylalanine-4-hydroxylase.
/FTId=PRO_0000205548.
DOMAIN 36 114 ACT. {ECO:0000255|PROSITE-
ProRule:PRU01007}.
METAL 285 285 Iron; via tele nitrogen.
{ECO:0000250|UniProtKB:P04176}.
METAL 290 290 Iron; via tele nitrogen.
{ECO:0000250|UniProtKB:P04176}.
METAL 330 330 Iron. {ECO:0000250|UniProtKB:P04176}.
MOD_RES 16 16 Phosphoserine; by PKA.
{ECO:0000244|PubMed:24275569,
ECO:0000269|PubMed:12185072}.
VARIANT 16 16 S -> P (in PKU; dbSNP:rs62642946).
/FTId=VAR_000869.
VARIANT 20 20 Q -> L (in HPA; dbSNP:rs199475662).
/FTId=VAR_009239.
VARIANT 39 39 F -> L (in HPA and PKU; haplotype 1;
dbSNP:rs62642926).
{ECO:0000269|PubMed:12501224}.
/FTId=VAR_000870.
VARIANT 39 39 Missing (in PKU; haplotypes 9,21).
{ECO:0000269|PubMed:23792259,
ECO:0000269|PubMed:9452062}.
/FTId=VAR_000871.
VARIANT 40 40 S -> L (in PKU; dbSNP:rs62642938).
{ECO:0000269|PubMed:8889590}.
/FTId=VAR_000872.
VARIANT 41 41 L -> F (in PKU; dbSNP:rs62642928).
/FTId=VAR_000873.
VARIANT 41 41 L -> P (in PKU; mild; dbSNP:rs62642916).
/FTId=VAR_009240.
VARIANT 42 42 K -> I (in PKU; haplotype 21;
dbSNP:rs62635346).
/FTId=VAR_000874.
VARIANT 45 45 V -> A (in PKU).
{ECO:0000269|PubMed:22513348}.
/FTId=VAR_067994.
VARIANT 46 46 G -> S (in PKU; haplotype 5;
significantly reduces phenylalanine
binding; dbSNP:rs74603784).
{ECO:0000269|PubMed:8889590}.
/FTId=VAR_000875.
VARIANT 47 47 A -> V (in non-PKU HPA; haplotype 4;
significantly reduces phenylalanine
binding; dbSNP:rs118203925).
{ECO:0000269|PubMed:8088845}.
/FTId=VAR_000876.
VARIANT 48 48 L -> S (in PKU; mild; haplotypes 3,4;
dbSNP:rs5030841).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:1679030,
ECO:0000269|PubMed:22513348,
ECO:0000269|PubMed:8889590,
ECO:0000269|PubMed:9521426}.
/FTId=VAR_000877.
VARIANT 53 53 R -> H (in PKU; dbSNP:rs118092776).
{ECO:0000269|PubMed:9452061}.
/FTId=VAR_000878.
VARIANT 55 55 F -> L (in HPA and PKU; does not affect
oligomerization; results in loss of
substrate activation; dbSNP:rs199475598).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:18538294,
ECO:0000269|PubMed:9521426}.
/FTId=VAR_000879.
VARIANT 56 56 E -> D (in PKU; haplotype 10;
dbSNP:rs199475567).
/FTId=VAR_000880.
VARIANT 61 61 N -> D (in PKU; dbSNP:rs199475651).
{ECO:0000269|PubMed:12501224}.
/FTId=VAR_067995.
VARIANT 62 62 L -> P (in PKU).
{ECO:0000269|PubMed:22513348}.
/FTId=VAR_067996.
VARIANT 63 64 TH -> PN (in PKU; haplotype 1; abolishes
phenylalanine binding).
/FTId=VAR_000881.
VARIANT 65 65 I -> N (in PKU; dbSNP:rs75193786).
{ECO:0000269|PubMed:9521426}.
/FTId=VAR_000882.
VARIANT 65 65 I -> S (in PKU; results in disturbed
oligomerization; results in loss of
substrate activation; dbSNP:rs75193786).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:18538294}.
/FTId=VAR_067997.
VARIANT 65 65 I -> T (in PKU; haplotypes 1,5,9,21,B;
abolishes phenylalanine binding;
dbSNP:rs75193786).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:8889590,
ECO:0000269|PubMed:9452062}.
/FTId=VAR_000883.
VARIANT 65 65 I -> V (in HPA and PKU;
dbSNP:rs199475643).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:23792259}.
/FTId=VAR_067998.
VARIANT 67 67 S -> P (in PKU; haplotype 4;
dbSNP:rs5030842).
/FTId=VAR_000884.
VARIANT 68 68 R -> S (in PKU; haplotype 1;
dbSNP:rs76394784).
{ECO:0000269|PubMed:8889590}.
/FTId=VAR_000885.
VARIANT 76 76 E -> A (in PKU; dbSNP:rs62507347).
/FTId=VAR_000886.
VARIANT 76 76 E -> G (in non-PKU HPA;
dbSNP:rs62507347).
{ECO:0000269|PubMed:11935335}.
/FTId=VAR_067999.
VARIANT 84 84 D -> Y (in PKU; haplotype 4;
dbSNP:rs62514902).
/FTId=VAR_000887.
VARIANT 87 87 S -> R (in non-PKU HPA; haplotype 1;
dbSNP:rs62516151).
{ECO:0000269|PubMed:8088845}.
/FTId=VAR_000888.
VARIANT 92 92 T -> I (in PKU; dbSNP:rs62514903).
/FTId=VAR_000889.
VARIANT 94 94 Missing (in PKU; mild; haplotype 2).
{ECO:0000269|PubMed:1709636}.
/FTId=VAR_000890.
VARIANT 98 98 L -> S (in non-PKU HPA;
dbSNP:rs62517167).
{ECO:0000269|PubMed:8364546}.
/FTId=VAR_000891.
VARIANT 104 104 A -> D (in PKU; mild; haplotype 1;
dbSNP:rs62642929).
{ECO:0000269|PubMed:9792411}.
/FTId=VAR_000892.
VARIANT 110 110 S -> C (in HPA).
/FTId=VAR_009241.
VARIANT 121 121 F -> L (in HPA).
{ECO:0000269|PubMed:23792259}.
/FTId=VAR_069776.
VARIANT 124 124 T -> I (in PKU; haplotype 28;
dbSNP:rs199475571).
/FTId=VAR_000893.
VARIANT 129 129 D -> Y (in PKU; dbSNP:rs199475606).
/FTId=VAR_000894.
VARIANT 143 143 D -> G (in PKU; haplotype 11;
dbSNP:rs199475572).
{ECO:0000269|PubMed:8889583}.
/FTId=VAR_000895.
VARIANT 145 145 D -> V (in PKU; dbSNP:rs140175796).
/FTId=VAR_011566.
VARIANT 146 146 H -> Y (in PKU; dbSNP:rs199475599).
/FTId=VAR_000896.
VARIANT 148 148 G -> S (in PKU; haplotypes 1,2,7;
dbSNP:rs80297647).
/FTId=VAR_000897.
VARIANT 151 151 D -> H (in PKU; haplotypes 1,8;
dbSNP:rs199475597).
/FTId=VAR_000898.
VARIANT 154 154 Y -> N (in PKU; dbSNP:rs199475587).
/FTId=VAR_000899.
VARIANT 155 155 R -> P (in PKU; dbSNP:rs199475663).
/FTId=VAR_009242.
VARIANT 157 157 R -> N (in PKU; severe; 5% activity;
requires 2 nucleotide substitutions).
{ECO:0000269|PubMed:9792411}.
/FTId=VAR_000900.
VARIANT 157 157 R -> S (in PKU; dbSNP:rs199475612).
{ECO:0000269|PubMed:22513348}.
/FTId=VAR_068000.
VARIANT 158 158 R -> Q (in PKU; haplotypes 1,2,4,7,16,
28; dbSNP:rs5030843).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:22513348,
ECO:0000269|PubMed:9452062}.
/FTId=VAR_000901.
VARIANT 158 158 R -> W (in PKU; dbSNP:rs75166491).
/FTId=VAR_000902.
VARIANT 160 160 Q -> P (in PKU; dbSNP:rs199475601).
/FTId=VAR_000903.
VARIANT 161 161 F -> S (in PKU; haplotype 4;
dbSNP:rs79635844).
/FTId=VAR_000904.
VARIANT 164 164 I -> T (in PKU; haplotype 1;
dbSNP:rs199475595).
{ECO:0000269|PubMed:7833954}.
/FTId=VAR_000905.
VARIANT 167 167 N -> I (in PKU; dbSNP:rs77554925).
{ECO:0000269|PubMed:9452062}.
/FTId=VAR_000906.
VARIANT 167 167 N -> S (in HPA; dbSNP:rs77554925).
/FTId=VAR_011567.
VARIANT 169 169 R -> H (in PKU; dbSNP:rs199475679).
/FTId=VAR_011568.
VARIANT 170 170 H -> D (in HPA; dbSNP:rs199475655).
/FTId=VAR_011569.
VARIANT 170 170 H -> Q (in PKU; does not affect
oligomerization; dbSNP:rs199475652).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:18538294}.
/FTId=VAR_068001.
VARIANT 170 170 H -> R (in PKU; dbSNP:rs199475573).
/FTId=VAR_000907.
VARIANT 171 171 G -> A (in PKU; haplotype 1;
dbSNP:rs199475596).
{ECO:0000269|PubMed:7833954}.
/FTId=VAR_000908.
VARIANT 171 171 G -> R (in PKU; dbSNP:rs199475613).
/FTId=VAR_000909.
VARIANT 173 173 P -> T (in PKU; haplotype 4;
dbSNP:rs199475574).
/FTId=VAR_000910.
VARIANT 174 174 I -> T (in PKU; haplotype 1;
dbSNP:rs138809906).
/FTId=VAR_000911.
VARIANT 174 174 I -> V (in PKU; dbSNP:rs199475632).
/FTId=VAR_011570.
VARIANT 175 175 P -> A (in PKU; dbSNP:rs199475604).
/FTId=VAR_000912.
VARIANT 176 176 R -> L (in non-PKU HPA;
dbSNP:rs74486803).
{ECO:0000269|PubMed:8088845}.
/FTId=VAR_000913.
VARIANT 176 176 R -> P (in PKU; dbSNP:rs74486803).
/FTId=VAR_000914.
VARIANT 177 177 V -> L (in PKU; haplotype 6;
dbSNP:rs199475602).
{ECO:0000269|PubMed:22513348}.
/FTId=VAR_000915.
VARIANT 177 177 V -> M (in HPA; dbSNP:rs199475602).
{ECO:0000269|PubMed:12501224}.
/FTId=VAR_068002.
VARIANT 178 178 E -> G (in non-PKU HPA;
dbSNP:rs77958223).
{ECO:0000269|PubMed:22513348}.
/FTId=VAR_000916.
VARIANT 183 183 E -> Q (in PKU; dbSNP:rs199475664).
/FTId=VAR_009243.
VARIANT 190 190 V -> A (in PKU; haplotype 3;
dbSNP:rs62514919).
{ECO:0000269|PubMed:22513348,
ECO:0000269|PubMed:9452062}.
/FTId=VAR_000917.
VARIANT 194 194 L -> P (in PKU; dbSNP:rs5030844).
/FTId=VAR_000918.
VARIANT 194 194 Missing (in PKU).
/FTId=VAR_000919.
VARIANT 196 196 S -> Y (in HPA).
{ECO:0000269|PubMed:23792259}.
/FTId=VAR_069777.
VARIANT 197 197 Missing (in PKU).
/FTId=VAR_000920.
VARIANT 198 198 Missing (in PKU; haplotype 2).
/FTId=VAR_000921.
VARIANT 201 201 H -> R (in PKU; dbSNP:rs62517180).
/FTId=VAR_000922.
VARIANT 201 201 H -> Y (in non-PKU HPA; haplotype 1;
dbSNP:rs62517205).
{ECO:0000269|PubMed:23792259,
ECO:0000269|PubMed:9521426}.
/FTId=VAR_000923.
VARIANT 204 204 Y -> C (in PKU; mild; haplotypes 3,4;
dbSNP:rs62514927).
{ECO:0000269|PubMed:9048935}.
/FTId=VAR_000924.
VARIANT 205 205 E -> A (in PKU; dbSNP:rs62508593).
/FTId=VAR_011571.
VARIANT 206 206 Y -> D (in PKU; dbSNP:rs62517170).
/FTId=VAR_000925.
VARIANT 207 207 N -> D (in PKU; dbSNP:rs62508572).
{ECO:0000269|PubMed:9452061}.
/FTId=VAR_000926.
VARIANT 207 207 N -> S (in PKU; severe; haplotype 4;
dbSNP:rs62508721).
{ECO:0000269|PubMed:9048935}.
/FTId=VAR_000927.
VARIANT 211 211 P -> T (in PKU; haplotype 4;
dbSNP:rs62514931).
/FTId=VAR_000928.
VARIANT 212 212 L -> P (in PKU; dbSNP:rs62517198).
/FTId=VAR_000929.
VARIANT 213 213 L -> P (in PKU; severe;
dbSNP:rs62516109).
{ECO:0000269|PubMed:9521426}.
/FTId=VAR_000930.
VARIANT 217 217 C -> G (in PKU; dbSNP:rs62508718).
/FTId=VAR_000931.
VARIANT 218 218 G -> V (in PKU; haplotypes 1,2;
dbSNP:rs62514933).
/FTId=VAR_000932.
VARIANT 221 221 E -> G (in PKU; haplotype 4;
dbSNP:rs62514934).
{ECO:0000269|PubMed:1679030}.
/FTId=VAR_000933.
VARIANT 222 222 D -> V (in PKU; haplotypes 3,4;
dbSNP:rs62507319).
/FTId=VAR_000934.
VARIANT 224 224 I -> M (in PKU; haplotype 4;
dbSNP:rs199475576).
/FTId=VAR_000935.
VARIANT 225 225 P -> R (in PKU; dbSNP:rs62517204).
/FTId=VAR_000936.
VARIANT 225 225 P -> T (in PKU; haplotype 1;
dbSNP:rs199475589).
/FTId=VAR_000937.
VARIANT 226 226 Q -> H (in PKU; dbSNP:rs62508615).
{ECO:0000269|PubMed:22513348}.
/FTId=VAR_068003.
VARIANT 230 230 V -> I (in non-PKU HPA; haplotype 4;
dbSNP:rs62516152).
{ECO:0000269|PubMed:23792259}.
/FTId=VAR_000938.
VARIANT 231 231 S -> F (in PKU; dbSNP:rs62508577).
/FTId=VAR_009244.
VARIANT 231 231 S -> P (in PKU; dbSNP:rs5030845).
/FTId=VAR_000939.
VARIANT 233 233 F -> L (in PKU; haplotypes 2,3;
dbSNP:rs62517208).
/FTId=VAR_000940.
VARIANT 238 238 T -> P (in PKU; haplotype 4;
dbSNP:rs199475577).
/FTId=VAR_000941.
VARIANT 239 239 G -> S (in PKU; dbSNP:rs62517178).
{ECO:0000269|PubMed:7833954}.
/FTId=VAR_000942.
VARIANT 240 240 F -> S (in PKU; dbSNP:rs62508594).
/FTId=VAR_011572.
VARIANT 241 241 R -> C (in non-PKU HPA and PKU; haplotype
34; dbSNP:rs76687508).
{ECO:0000269|PubMed:8889590,
ECO:0000269|PubMed:9452062,
ECO:0000269|PubMed:9852673}.
/FTId=VAR_000943.
VARIANT 241 241 R -> H (in PKU; haplotypes 1,5;
dbSNP:rs62508730).
/FTId=VAR_000944.
VARIANT 241 241 R -> L (in PKU; dbSNP:rs62508730).
/FTId=VAR_000945.
VARIANT 242 242 L -> F (in PKU; dbSNP:rs199475578).
/FTId=VAR_000946.
VARIANT 243 243 R -> Q (in non-PKU HPA and PKU;
haplotypes 4,7,9; dbSNP:rs62508588).
{ECO:0000269|PubMed:9600453,
ECO:0000269|PubMed:9852673}.
/FTId=VAR_000947.
VARIANT 244 244 P -> L (in PKU; haplotype 12;
dbSNP:rs118203923).
{ECO:0000269|PubMed:1363838}.
/FTId=VAR_000948.
VARIANT 245 245 V -> A (in PKU, HPA and non-PKU HPA;
haplotypes 3,7; dbSNP:rs796052017).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:22513348,
ECO:0000269|PubMed:8088845,
ECO:0000269|PubMed:8889590}.
/FTId=VAR_000949.
VARIANT 245 245 V -> E (in PKU; haplotype 11;
dbSNP:rs76212747).
/FTId=VAR_000950.
VARIANT 245 245 V -> L (in PKU; dbSNP:rs62508694).
/FTId=VAR_000951.
VARIANT 246 246 A -> D (in PKU; dbSNP:rs199475610).
/FTId=VAR_000952.
VARIANT 247 247 G -> V (in PKU; haplotype 4;
dbSNP:rs199475579).
/FTId=VAR_000953.
VARIANT 248 248 L -> P (in PKU; dbSNP:rs62507340).
/FTId=VAR_000954.
VARIANT 249 249 L -> F (in PKU; haplotype 1;
dbSNP:rs74503222).
/FTId=VAR_000955.
VARIANT 252 252 R -> G (in PKU; haplotype 7;
dbSNP:rs5030847).
/FTId=VAR_000956.
VARIANT 252 252 R -> Q (in PKU; haplotype 1;
dbSNP:rs62644503).
{ECO:0000269|PubMed:7833954}.
/FTId=VAR_000957.
VARIANT 252 252 R -> W (in PKU; haplotypes 1,6,7,8,42,
69; complete loss of activity;
dbSNP:rs5030847).
{ECO:0000269|PubMed:11461196,
ECO:0000269|PubMed:1672294,
ECO:0000269|PubMed:22513348,
ECO:0000269|PubMed:23792259}.
/FTId=VAR_000958.
VARIANT 255 255 L -> S (in PKU; haplotype 36;
dbSNP:rs62642930).
{ECO:0000269|PubMed:2014802}.
/FTId=VAR_000960.
VARIANT 255 255 L -> V (in PKU; haplotypes 18,21;
dbSNP:rs62642931).
/FTId=VAR_000959.
VARIANT 257 257 G -> C (in PKU; dbSNP:rs5030848).
/FTId=VAR_000961.
VARIANT 259 259 A -> T (in PKU; haplotype 3;
dbSNP:rs62642932).
/FTId=VAR_000962.
VARIANT 259 259 A -> V (in PKU; haplotypes 7,42;
dbSNP:rs118203921).
/FTId=VAR_000963.
VARIANT 261 261 R -> P (in PKU; dbSNP:rs5030849).
/FTId=VAR_000964.
VARIANT 261 261 R -> Q (in HPA and PKU; mild; haplotypes
1,2,4,22, 24,28; dbSNP:rs5030849).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:1671810,
ECO:0000269|PubMed:22513348,
ECO:0000269|PubMed:23792259,
ECO:0000269|PubMed:8889590}.
/FTId=VAR_000965.
VARIANT 263 263 F -> L (in PKU; dbSNP:rs62642944).
/FTId=VAR_000966.
VARIANT 264 264 H -> L (in PKU; dbSNP:rs199475580).
/FTId=VAR_000967.
VARIANT 265 265 C -> G (in PKU; dbSNP:rs62517181).
/FTId=VAR_000968.
VARIANT 269 269 I -> L (in non-PKU HPA;
dbSNP:rs62508692).
{ECO:0000269|PubMed:9521426}.
/FTId=VAR_000969.
VARIANT 270 270 R -> K (in PKU; dbSNP:rs62514950).
/FTId=VAR_000970.
VARIANT 270 270 R -> S (in PKU; haplotype 1;
dbSNP:rs62514951).
/FTId=VAR_000971.
VARIANT 271 271 H -> Y (in PKU; dbSNP:rs62517164).
/FTId=VAR_000972.
VARIANT 273 273 S -> F (in PKU; haplotype 7;
dbSNP:rs62514953).
/FTId=VAR_000973.
VARIANT 274 274 K -> E (in dbSNP:rs142934616).
{ECO:0000269|PubMed:11461196}.
/FTId=VAR_011573.
VARIANT 275 275 P -> L (in PKU; reduced activity;
increased affinity for the substrate;
mildly reduced substrate activation;
decreased cofactor affinity;
dbSNP:rs62508715).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:18538294}.
/FTId=VAR_068004.
VARIANT 276 276 M -> I (in PKU; dbSNP:rs62514954).
/FTId=VAR_000974.
VARIANT 276 276 M -> V (in PKU; haplotype 4;
dbSNP:rs62516149).
{ECO:0000269|PubMed:8068076}.
/FTId=VAR_000975.
VARIANT 277 277 Y -> C (in PKU; dbSNP:rs62516155).
/FTId=VAR_000976.
VARIANT 277 277 Y -> D (in PKU; haplotype 2;
dbSNP:rs78655458).
/FTId=VAR_000977.
VARIANT 278 278 T -> A (in PKU; dbSNP:rs62516156).
/FTId=VAR_000978.
VARIANT 278 278 T -> N (in PKU; dbSNP:rs62507262).
/FTId=VAR_000979.
VARIANT 280 280 E -> K (in PKU; haplotypes 1,2,4,16,38;
partial residual activity;
dbSNP:rs62508698).
{ECO:0000269|PubMed:22513348,
ECO:0000269|PubMed:2564729,
ECO:0000269|PubMed:8889590}.
/FTId=VAR_000980.
VARIANT 281 281 P -> L (in PKU; haplotypes 1,4;
dbSNP:rs5030851).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:1672290,
ECO:0000269|PubMed:1672294,
ECO:0000269|PubMed:22513348,
ECO:0000269|PubMed:8889590}.
/FTId=VAR_000981.
VARIANT 282 282 D -> N (in PKU; haplotype 1;
dbSNP:rs199475582).
/FTId=VAR_000982.
VARIANT 283 283 I -> F (in PKU; haplotype 21;
dbSNP:rs62517168).
/FTId=VAR_000983.
VARIANT 283 283 I -> N (in PKU; severe;
dbSNP:rs62508693).
{ECO:0000269|PubMed:9521426}.
/FTId=VAR_000984.
VARIANT 290 290 H -> Y (in PKU).
{ECO:0000269|PubMed:22526846}.
/FTId=VAR_067758.
VARIANT 297 297 R -> C (in PKU; haplotype 4;
dbSNP:rs62642945).
/FTId=VAR_000985.
VARIANT 297 297 R -> H (in PKU; dbSNP:rs62642939).
/FTId=VAR_000986.
VARIANT 299 299 F -> C (in PKU; haplotype 8;
dbSNP:rs62642933).
{ECO:0000269|PubMed:8889590}.
/FTId=VAR_000987.
VARIANT 300 300 A -> 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; dbSNP:rs5030853).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:18538294,
ECO:0000269|PubMed:22513348,
ECO:0000269|PubMed:23792259}.
/FTId=VAR_000988.
VARIANT 300 300 A -> V (in PKU; dbSNP:rs199475609).
/FTId=VAR_000989.
VARIANT 303 303 S -> P (in PKU; haplotype 5;
dbSNP:rs199475608).
/FTId=VAR_000990.
VARIANT 304 304 Q -> R (in PKU; dbSNP:rs199475592).
/FTId=VAR_000991.
VARIANT 306 306 I -> V (in non-PKU HPA; haplotype 4;
dbSNP:rs62642934).
{ECO:0000269|PubMed:1358789,
ECO:0000269|PubMed:23792259}.
/FTId=VAR_000992.
VARIANT 309 309 A -> D (in PKU; haplotype 7;
dbSNP:rs62642935).
/FTId=VAR_000993.
VARIANT 309 309 A -> V (in PKU; dbSNP:rs62642935).
/FTId=VAR_000994.
VARIANT 310 310 S -> F (in PKU; haplotype 7;
dbSNP:rs62642913).
/FTId=VAR_000995.
VARIANT 310 310 S -> Y (in HPA; reduction in activity is
probably due to a global conformational
change in the protein that reduces
allostery; dbSNP:rs62642913).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:18538294}.
/FTId=VAR_068005.
VARIANT 311 311 L -> P (in PKU; haplotypes 1,7,10;
dbSNP:rs62642936).
{ECO:0000269|PubMed:2615649,
ECO:0000269|PubMed:2840952}.
/FTId=VAR_000996.
VARIANT 314 314 P -> H (in PKU; dbSNP:rs62642940).
/FTId=VAR_000997.
VARIANT 314 314 P -> S (in HPA; does not affect
oligomerization; reduction in activity is
probably due to a global conformational
change in the protein that reduces
allostery; dbSNP:rs199475650).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:18538294}.
/FTId=VAR_068006.
VARIANT 318 318 I -> T (in PKU; partial loss of activity;
dbSNP:rs62642918).
{ECO:0000269|PubMed:11461196}.
/FTId=VAR_011574.
VARIANT 322 322 A -> G (in PKU; haplotype 12;
dbSNP:rs62514958).
/FTId=VAR_000998.
VARIANT 322 322 A -> T (in PKU; haplotype 1;
dbSNP:rs62514957).
/FTId=VAR_000999.
VARIANT 322 322 A -> V (in PKU).
{ECO:0000269|PubMed:22526846}.
/FTId=VAR_067759.
VARIANT 325 325 Y -> C (in PKU; dbSNP:rs62508578).
/FTId=VAR_009245.
VARIANT 330 330 E -> D (in PKU; dbSNP:rs62508580).
/FTId=VAR_009246.
VARIANT 331 331 F -> L (in PKU; haplotype 1;
dbSNP:rs62517179).
{ECO:0000269|PubMed:7833954}.
/FTId=VAR_001000.
VARIANT 333 333 L -> F (in PKU; dbSNP:rs62516060).
/FTId=VAR_001001.
VARIANT 334 334 C -> S (in PKU; dbSNP:rs62517174).
/FTId=VAR_001002.
VARIANT 337 337 G -> V (in PKU; dbSNP:rs62517206).
/FTId=VAR_001003.
VARIANT 338 338 D -> Y (in PKU; haplotype 4;
dbSNP:rs62516150).
/FTId=VAR_001004.
VARIANT 341 341 K -> R (in PKU; dbSNP:rs62516153).
/FTId=VAR_001005.
VARIANT 341 341 K -> T (in PKU; dbSNP:rs62516153).
/FTId=VAR_001006.
VARIANT 342 342 A -> T (in PKU; haplotype 5;
dbSNP:rs62507282).
/FTId=VAR_001007.
VARIANT 343 343 Y -> C (in PKU; dbSNP:rs62507265).
/FTId=VAR_001008.
VARIANT 344 344 G -> R (in PKU; dbSNP:rs62508679).
/FTId=VAR_009247.
VARIANT 344 344 G -> V (in PKU; dbSNP:rs62508582).
/FTId=VAR_009248.
VARIANT 345 345 A -> S (in PKU; dbSNP:rs62516062).
/FTId=VAR_001009.
VARIANT 345 345 A -> T (in PKU; haplotype 7;
dbSNP:rs62516062).
/FTId=VAR_001010.
VARIANT 347 347 L -> F (in PKU; dbSNP:rs62516154).
/FTId=VAR_001011.
VARIANT 348 348 L -> V (in PKU; mild haplotype 9;
dbSNP:rs62516092).
/FTId=VAR_001012.
VARIANT 349 349 S -> L (in PKU; severe;
dbSNP:rs62507279).
{ECO:0000269|PubMed:9600453}.
/FTId=VAR_001013.
VARIANT 349 349 S -> P (in PKU; haplotypes 1,4;
dbSNP:rs62508646).
{ECO:0000269|PubMed:22513348}.
/FTId=VAR_001014.
VARIANT 350 350 S -> T (in PKU; haplotype 2;
dbSNP:rs62517183).
/FTId=VAR_001015.
VARIANT 357 357 C -> G (in PKU; dbSNP:rs62508595).
/FTId=VAR_011575.
VARIANT 362 362 P -> T (in PKU; dbSNP:rs62507329).
{ECO:0000269|PubMed:10200057}.
/FTId=VAR_001016.
VARIANT 364 368 Missing (in PKU).
{ECO:0000269|PubMed:1363837}.
/FTId=VAR_001018.
VARIANT 364 364 Missing (in PKU; haplotype 5).
{ECO:0000269|PubMed:1975559}.
/FTId=VAR_001017.
VARIANT 366 366 P -> H (in PKU; dbSNP:rs62516098).
/FTId=VAR_001019.
VARIANT 372 372 T -> S (in PKU; dbSNP:rs62517163).
/FTId=VAR_001020.
VARIANT 377 377 Y -> C (in PKU; haplotype 4;
dbSNP:rs62642942).
/FTId=VAR_001021.
VARIANT 380 380 T -> M (in non-PKU HPA; haplotype 4;
dbSNP:rs62642937).
{ECO:0000269|PubMed:23792259}.
/FTId=VAR_001022.
VARIANT 386 386 Y -> C (in PKU; common mutation;
dbSNP:rs62516141).
/FTId=VAR_001023.
VARIANT 387 387 Y -> H (in PKU; haplotype 1;
dbSNP:rs62517194).
/FTId=VAR_001024.
VARIANT 388 388 V -> L (in PKU; dbSNP:rs62516101).
{ECO:0000269|PubMed:9452061}.
/FTId=VAR_001025.
VARIANT 388 388 V -> M (in PKU; haplotypes 1,4;
dbSNP:rs62516101).
/FTId=VAR_001026.
VARIANT 390 390 E -> G (in PKU and non-PKU HPA; haplotype
4; dbSNP:rs5030856).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:22513348,
ECO:0000269|PubMed:23792259,
ECO:0000269|PubMed:8098245,
ECO:0000269|PubMed:8889590}.
/FTId=VAR_001027.
VARIANT 394 394 D -> A (in PKU; dbSNP:rs62516102).
/FTId=VAR_001028.
VARIANT 394 394 D -> H (in PKU; dbSNP:rs62516142).
{ECO:0000269|PubMed:8889590}.
/FTId=VAR_001029.
VARIANT 395 395 A -> G (in PKU; dbSNP:rs62508736).
/FTId=VAR_001030.
VARIANT 395 395 A -> P (in PKU; haplotype 1;
dbSNP:rs62516103).
/FTId=VAR_001031.
VARIANT 399 400 Missing (in PKU; haplotype 7).
/FTId=VAR_001032.
VARIANT 403 403 A -> V (in non-PKU HPA and PKU; haplotype
43; dbSNP:rs5030857).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:22513348,
ECO:0000269|PubMed:23792259,
ECO:0000269|PubMed:8889590}.
/FTId=VAR_001033.
VARIANT 407 407 P -> L (in PKU; dbSNP:rs62644473).
{ECO:0000269|PubMed:9950317}.
/FTId=VAR_068007.
VARIANT 407 407 P -> S (in PKU; dbSNP:rs62644465).
/FTId=VAR_011576.
VARIANT 408 408 R -> Q (in PKU; haplotypes 4,12;
dbSNP:rs5030859).
{ECO:0000269|PubMed:1355066}.
/FTId=VAR_001034.
VARIANT 408 408 R -> 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; dbSNP:rs5030858).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:1355066,
ECO:0000269|PubMed:18538294,
ECO:0000269|PubMed:22513348,
ECO:0000269|PubMed:23792259,
ECO:0000269|PubMed:8889590,
ECO:0000269|PubMed:9452062,
ECO:0000269|PubMed:9600453}.
/FTId=VAR_001035.
VARIANT 410 410 F -> S (in PKU; mild; dbSNP:rs62644475).
/FTId=VAR_009249.
VARIANT 413 413 R -> P (in non-PKU HPA and PKU; haplotype
4; dbSNP:rs79931499).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:9852673}.
/FTId=VAR_001036.
VARIANT 413 413 R -> S (in PKU; haplotype 1;
dbSNP:rs62644467).
/FTId=VAR_001037.
VARIANT 414 414 Y -> 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; dbSNP:rs5030860).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:18538294,
ECO:0000269|PubMed:8889590}.
/FTId=VAR_001038.
VARIANT 415 415 D -> N (in PKU, HPA and non-PKU HPA;
haplotype 1; dbSNP:rs62644499).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:1358789,
ECO:0000269|PubMed:22513348}.
/FTId=VAR_001039.
VARIANT 417 417 Y -> H (in PKU; reduction in activity is
probably due to a global conformational
change in the protein that reduces
allostery; dbSNP:rs62644471).
{ECO:0000269|PubMed:12501224,
ECO:0000269|PubMed:18538294}.
/FTId=VAR_068008.
VARIANT 418 418 T -> P (in PKU; haplotype 4;
dbSNP:rs62644501).
/FTId=VAR_001040.
VARIANT 421 421 I -> S (in PKU).
{ECO:0000269|PubMed:22526846}.
/FTId=VAR_067760.
VARIANT 430 430 L -> P (in PKU; dbSNP:rs199475607).
/FTId=VAR_001041.
VARIANT 447 447 A -> D (in PKU; dbSNP:rs76542238).
/FTId=VAR_001042.
MUTAGEN 283 283 I->C: Loss of positive cooperativity and
reduction of fold-activation by L-Phe
preincubation.
{ECO:0000269|PubMed:18835579}.
CONFLICT 183 183 E -> G (in Ref. 3; AAH26251).
{ECO:0000305}.
STRAND 35 42 {ECO:0000244|PDB:5FII}.
HELIX 47 57 {ECO:0000244|PDB:5FII}.
STRAND 62 69 {ECO:0000244|PDB:5FII}.
STRAND 76 83 {ECO:0000244|PDB:5FII}.
HELIX 85 90 {ECO:0000244|PDB:5FII}.
HELIX 91 102 {ECO:0000244|PDB:5FII}.
STRAND 105 108 {ECO:0000244|PDB:5FII}.
HELIX 125 133 {ECO:0000244|PDB:1J8U}.
STRAND 135 138 {ECO:0000244|PDB:1PAH}.
HELIX 140 142 {ECO:0000244|PDB:1J8U}.
TURN 147 150 {ECO:0000244|PDB:1J8U}.
HELIX 152 167 {ECO:0000244|PDB:1J8U}.
HELIX 181 201 {ECO:0000244|PDB:1J8U}.
HELIX 204 217 {ECO:0000244|PDB:1J8U}.
HELIX 227 238 {ECO:0000244|PDB:1J8U}.
STRAND 241 244 {ECO:0000244|PDB:1J8U}.
STRAND 246 248 {ECO:0000244|PDB:1MMT}.
HELIX 251 259 {ECO:0000244|PDB:1J8U}.
STRAND 262 265 {ECO:0000244|PDB:1J8U}.
HELIX 283 289 {ECO:0000244|PDB:1J8U}.
HELIX 291 294 {ECO:0000244|PDB:1J8U}.
HELIX 297 310 {ECO:0000244|PDB:1J8U}.
HELIX 315 327 {ECO:0000244|PDB:1J8U}.
TURN 328 331 {ECO:0000244|PDB:1J8U}.
STRAND 333 336 {ECO:0000244|PDB:1J8U}.
STRAND 339 342 {ECO:0000244|PDB:1J8U}.
HELIX 345 348 {ECO:0000244|PDB:1J8U}.
HELIX 351 357 {ECO:0000244|PDB:1J8U}.
STRAND 359 366 {ECO:0000244|PDB:1J8U}.
HELIX 369 372 {ECO:0000244|PDB:1J8U}.
STRAND 379 381 {ECO:0000244|PDB:1J8U}.
STRAND 384 390 {ECO:0000244|PDB:1J8U}.
HELIX 392 403 {ECO:0000244|PDB:1J8U}.
STRAND 409 415 {ECO:0000244|PDB:1J8U}.
TURN 416 419 {ECO:0000244|PDB:1J8U}.
STRAND 420 424 {ECO:0000244|PDB:1J8U}.
HELIX 426 450 {ECO:0000244|PDB:2PAH}.
SEQUENCE 452 AA; 51862 MW; 018F00EBBBDDCE2F CRC64;
MSTAVLENPG LGRKLSDFGQ ETSYIEDNCN QNGAISLIFS LKEEVGALAK VLRLFEENDV
NLTHIESRPS RLKKDEYEFF THLDKRSLPA LTNIIKILRH DIGATVHELS RDKKKDTVPW
FPRTIQELDR FANQILSYGA ELDADHPGFK DPVYRARRKQ FADIAYNYRH GQPIPRVEYM
EEEKKTWGTV FKTLKSLYKT HACYEYNHIF PLLEKYCGFH EDNIPQLEDV SQFLQTCTGF
RLRPVAGLLS SRDFLGGLAF RVFHCTQYIR HGSKPMYTPE PDICHELLGH VPLFSDRSFA
QFSQEIGLAS LGAPDEYIEK LATIYWFTVE FGLCKQGDSI KAYGAGLLSS FGELQYCLSE
KPKLLPLELE KTAIQNYTVT EFQPLYYVAE SFNDAKEKVR NFAATIPRPF SVRYDPYTQR
IEVLDNTQQL KILADSINSE IGILCSALQK IK


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