ID PH4H_HUMAN Reviewed; 452 AA. AC P00439; Q16717; Q8TC14; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 27-MAR-2024, entry version 259. DE RecName: Full=Phenylalanine-4-hydroxylase; DE Short=PAH; DE EC=1.14.16.1 {ECO:0000269|PubMed:18460651, ECO:0000269|PubMed:18835579}; DE AltName: Full=Phe-4-monooxygenase; GN Name=PAH; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Liver; RX PubMed=2986678; DOI=10.1021/bi00324a002; RA Kwok S.C.M., Ledley F.D., Dilella A.G., Robson K.J.H., Woo S.L.C.; RT "Nucleotide sequence of a full-length complementary DNA clone and amino RT acid sequence of human phenylalanine hydroxylase."; RL Biochemistry 24:556-561(1985). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Scriver C.R., Nowacki P.M., Byck S., Prevost L.; RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Liver; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP PROTEIN SEQUENCE OF 131-144. RX PubMed=2461704; DOI=10.1042/bj2550193; RA Cotton R.G., McAdam W., Jennings I., Morgan F.J.; RT "A monoclonal antibody to aromatic amino acid hydroxylases. Identification RT of the epitope."; RL Biochem. J. 255:193-196(1988). RN [5] RP PHOSPHORYLATION AT SER-16. RX PubMed=12185072; DOI=10.1074/jbc.m112197200; RA Miranda F.F., Teigen K., Thorolfsson M., Svebak R.M., Knappskog P.M., RA Flatmark T., Martinez A.; RT "Phosphorylation and mutations of Ser(16) in human phenylalanine RT hydroxylase. Kinetic and structural effects."; RL J. Biol. Chem. 277:40937-40943(2002). RN [6] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=18460651; DOI=10.1096/fj.08-108522; RA Calvo A.C., Pey A.L., Ying M., Loer C.M., Martinez A.; RT "Anabolic function of phenylalanine hydroxylase in Caenorhabditis RT elegans."; RL FASEB J. 22:3046-3058(2008). RN [7] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL RP PROPERTIES, AND MUTAGENESIS OF ILE-283. RX PubMed=18835579; DOI=10.1016/j.gene.2008.09.005; RA Siltberg-Liberles J., Steen I.H., Svebak R.M., Martinez A.; RT "The phylogeny of the aromatic amino acid hydroxylases revisited by RT characterizing phenylalanine hydroxylase from Dictyostelium discoideum."; RL Gene 427:86-92(2008). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-16, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [10] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 117-424. RX PubMed=9406548; DOI=10.1038/nsb1297-995; RA Erlandsen H., Fusetti F., Martinez A., Hough E., Flatmark T., Stevens R.C.; RT "Crystal structure of the catalytic domain of human phenylalanine RT hydroxylase reveals the structural basis for phenylketonuria."; RL Nat. Struct. Biol. 4:995-1000(1997). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 117-424. RX PubMed=9843368; DOI=10.1021/bi9815290; RA Erlandsen H., Flatmark T., Stevens R.C., Hough E.; RT "Crystallographic analysis of the human phenylalanine hydroxylase catalytic RT domain with bound catechol inhibitors at 2.0-A resolution."; RL Biochemistry 37:15638-15646(1998). RN [12] RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 117-452, AND SUBUNIT. RX PubMed=9642259; DOI=10.1074/jbc.273.27.16962; RA Fusetti F., Erlandsen H., Flatmark T., Stevens R.C.; RT "Structure of tetrameric human phenylalanine hydroxylase and its RT implications for phenylketonuria."; RL J. Biol. Chem. 273:16962-16967(1998). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 118-424. RX PubMed=10694386; DOI=10.1021/bi992531+; RA Erlandsen H., Bjorgo E., Flatmark T., Stevens R.C.; RT "Crystal structure and site-specific mutagenesis of pterin-bound human RT phenylalanine hydroxylase."; RL Biochemistry 39:2208-2217(2000). RN [14] RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 103-427. RX PubMed=11718561; DOI=10.1006/jmbi.2001.5061; RA Andersen O.A., Flatmark T., Hough E.; RT "High resolution crystal structures of the catalytic domain of human RT phenylalanine hydroxylase in its catalytically active Fe(II) form and RT binary complex with tetrahydrobiopterin."; RL J. Mol. Biol. 314:279-291(2001). RN [15] RP REVIEW ON PKU VARIANTS, AND PAH VARIANTS DATABASE. RX PubMed=32668217; DOI=10.1016/j.ajhg.2020.06.006; RA Hillert A., Anikster Y., Belanger-Quintana A., Burlina A., Burton B.K., RA Carducci C., Chiesa A.E., Christodoulou J., Dordevic M., Desviat L.R., RA Eliyahu A., Evers R.A.F., Fajkusova L., Feillet F., Bonfim-Freitas P.E., RA Gizewska M., Gundorova P., Karall D., Kneller K., Kutsev S.I., Leuzzi V., RA Levy H.L., Lichter-Konecki U., Muntau A.C., Namour F., Oltarzewski M., RA Paras A., Perez B., Polak E., Polyakov A.V., Porta F., Rohrbach M., RA Scholl-Buergi S., Specola N., Stojiljkovic M., Shen N., RA Santana-da Silva L.C., Skouma A., van Spronsen F., Stoppioni V., Thoeny B., RA Trefz F.K., Vockley J., Yu Y., Zschocke J., Hoffmann G.F., Garbade S.F., RA Blau N.; RT "The Genetic Landscape and Epidemiology of Phenylketonuria."; RL Am. J. Hum. Genet. 107:234-250(2020). RN [16] RP REVIEW ON PKU VARIANTS. RX PubMed=1679029; DOI=10.1007/bf00197152; RA Konecki D.S., Lichter-Konecki U.; RT "The phenylketonuria locus: current knowledge about alleles and mutations RT of the phenylalanine hydroxylase gene in various populations."; RL Hum. Genet. 87:377-388(1991). RN [17] RP REVIEW ON PKU VARIANTS. RX PubMed=2246858; DOI=10.1007/bf01799577; RA Cotton R.G.; RT "Heterogeneity of phenylketonuria at the clinical, protein and DNA RT levels."; RL J. Inherit. Metab. Dis. 13:739-750(1990). RN [18] RP VARIANTS PKU ASP-56; SER-161; VAL-247; VAL-255; VAL-259; PHE-273; ILE-276; RP ASP-277; GLY-322; THR-322; THR-345; VAL-348 AND PRO-418, AND REVIEW. RX PubMed=1301187; DOI=10.1002/humu.1380010104; RA Eisensmith R.C., Woo S.L.C.; RT "Molecular basis of phenylketonuria and related hyperphenylalaninemias: RT mutations and polymorphisms in the human phenylalanine hydroxylase gene."; RL Hum. Mutat. 1:13-22(1992). RN [19] RP DATABASE OF PKU VARIANTS. RX PubMed=8594560; DOI=10.1093/nar/24.1.127; RA Hoang L., Byck S., Prevost L., Scriver C.R.; RT "PAH Mutation Analysis Consortium Database: a database for disease- RT producing and other allelic variation at the human PAH locus."; RL Nucleic Acids Res. 24:127-131(1996). RN [20] RP VARIANT PKU PRO-311. RX PubMed=2840952; DOI=10.1021/bi00408a032; RA Lichter-Konecki U., Konecki D.S., Dilella A.G., Brayton K., Marvit J., RA Hahn T.M., Trefz F.K., Woo S.L.C.; RT "Phenylalanine hydroxylase deficiency caused by a single base substitution RT in an exon of the human phenylalanine hydroxylase gene."; RL Biochemistry 27:2881-2885(1988). RN [21] RP VARIANT PKU LYS-280. RX PubMed=2564729; RA Lyonnet S., Caillaud C., Rey F., Berthelon M., Frezal J., Rey J., RA Munnich A.; RT "Molecular genetics of phenylketonuria in Mediterranean countries: a RT mutation associated with partial phenylalanine hydroxylase deficiency."; RL Am. J. Hum. Genet. 44:511-517(1989). RN [22] RP VARIANT PKU PRO-311. RX PubMed=2615649; RA Hofman K.J., Antonarakis S.E., Missiou-Tsangaraki S., Boehm C.D., Valle D.; RT "Phenylketonuria in the Greek population. Haplotype analysis of the RT phenylalanine hydroxylase gene and identification of a PKU mutation."; RL Mol. Biol. Med. 6:245-250(1989). RN [23] RP VARIANT PKU LEU-364 DEL. RX PubMed=1975559; DOI=10.1007/bf00206750; RA Svensson E., Andersson B., Hagenfeldt L.; RT "Two mutations within the coding sequence of the phenylalanine hydroxylase RT gene."; RL Hum. Genet. 85:300-304(1990). RN [24] RP VARIANT PKU GLN-261. RX PubMed=1671810; RA Dianzani I., Forrest S.M., Camaschella C., Saglio G., Ponzone A., RA Cotton R.G.; RT "Screening for mutations in the phenylalanine hydroxylase gene from Italian RT patients with phenylketonuria by using the chemical cleavage method: a new RT splice mutation."; RL Am. J. Hum. Genet. 48:631-635(1991). RN [25] RP VARIANT PKU SER-255. RX PubMed=2014802; RA Hofman K.J., Steel G., Kazazian H.H. Jr., Valle D.; RT "Phenylketonuria in U.S. blacks: molecular analysis of the phenylalanine RT hydroxylase gene."; RL Am. J. Hum. Genet. 48:791-798(1991). RN [26] RP VARIANTS PKU TRP-252 AND LEU-281. RX PubMed=1672294; DOI=10.1016/0888-7543(91)90225-4; RA Okano Y., Wang T., Eisensmith R.C., Longhi R., Riva E., Giovannini M., RA Cerone R., Romano C., Woo S.L.C.; RT "Phenylketonuria missense mutations in the Mediterranean."; RL Genomics 9:96-103(1991). RN [27] RP VARIANT PKU LEU-281. RX PubMed=1672290; DOI=10.1016/0888-7543(91)90238-a; RA Dworniczak B., Grudda K., Stumper J., Bartholome K., Aulehla-Scholz C., RA Horst J.; RT "Phenylalanine hydroxylase gene: novel missense mutation in exon 7 causing RT severe phenylketonuria."; RL Genomics 9:193-199(1991). RN [28] RP VARIANTS PKU SER-48 AND GLY-221. RX PubMed=1679030; DOI=10.1007/bf00197153; RA Konecki D.S., Schlotter M., Trefz F.K., Lichter-Konecki U.; RT "The identification of two mis-sense mutations at the PAH gene locus in a RT Turkish patient with phenylketonuria."; RL Hum. Genet. 87:389-393(1991). RN [29] RP VARIANT PKU ILE-94 DEL. RX PubMed=1709636; DOI=10.1016/s0021-9258(18)92824-3; RA Caillaud C., Lyonnet S., Rey F., Melle D., Frebourg T., Berthelon M., RA Vilarinho L., Vaz Osorio R., Rey J., Munnich A.; RT "A 3-base pair in-frame deletion of the phenylalanine hydroxylase gene RT results in a kinetic variant of phenylketonuria."; RL J. Biol. Chem. 266:9351-9354(1991). RN [30] RP VARIANTS NON-PKU HPA VAL-306 AND ASN-415. RX PubMed=1358789; DOI=10.1016/s0888-7543(05)80274-5; RA Economou-Petersen E., Henriksen K.F., Guldberg P., Guettler F.; RT "Molecular basis for nonphenylketonuria hyperphenylalaninemia."; RL Genomics 14:1-5(1992). RN [31] RP VARIANTS PKU GLN-408 AND TRP-408. RX PubMed=1355066; DOI=10.1007/bf00221944; RA Lin C.H., Hsiao K.J., Tsai T.F., Chao H.K., Su T.S.; RT "Identification of a missense phenylketonuria mutation at codon 408 in RT Chinese."; RL Hum. Genet. 89:593-596(1992). RN [32] RP VARIANT PKU 364-LEU--GLU-368 DEL. RX PubMed=1363837; DOI=10.1093/hmg/1.9.763; RA Jaruzelska J., Melle D., Matuszak R., Borski K., Munnich A.; RT "A new 15 bp deletion in exon 11 of the phenylalanine hydroxylase gene in RT phenylketonuria."; RL Hum. Mol. Genet. 1:763-764(1992). RN [33] RP VARIANT PKU LEU-244. RX PubMed=1363838; DOI=10.1093/hmg/1.9.765; RA Desviat L.R., Perez B., Ugarte M.; RT "A new PKU mutation associated with haplotype 12."; RL Hum. Mol. Genet. 1:765-766(1992). RN [34] RP VARIANTS PKU. RX PubMed=8406445; DOI=10.1006/geno.1993.1295; RA Guldberg P., Henriksen K.F., Guettler F.; RT "Molecular analysis of phenylketonuria in Denmark: 99% of the mutations RT detected by denaturing gradient gel electrophoresis."; RL Genomics 17:141-146(1993). RN [35] RP VARIANT NON-PKU HPA GLY-390. RX PubMed=8098245; DOI=10.1093/hmg/2.1.31; RA Abadie V., Jaruzelska J., Lyonnet S., Millasseau P., Berthelon M., Rey F., RA Munnich A., Rey J.; RT "Illegitimate transcription of the phenylalanine hydroxylase gene in RT lymphocytes for identification of mutations in phenylketonuria."; RL Hum. Mol. Genet. 2:31-34(1993). RN [36] RP VARIANT NON-PKU HPA SER-98. RX PubMed=8364546; DOI=10.1093/hmg/2.7.1061; RA Guldberg P., Lou H.C., Henriksen K.F., Mikkelsen I., Olsen B., Holck B., RA Guettler F.; RT "A novel missense mutation in the phenylalanine hydroxylase gene of a RT homozygous Pakistani patient with non-PKU hyperphenylalaninemia."; RL Hum. Mol. Genet. 2:1061-1062(1993). RN [37] RP VARIANT PKU VAL-276. RX PubMed=8068076; DOI=10.1007/bf00711510; RA Goebel-Schreiner B., Schreiner R.; RT "Identification of a new missense mutation in Japanese phenylketonuric RT patients."; RL J. Inherit. Metab. Dis. 16:950-956(1993). RN [38] RP VARIANTS NON-PKU HPA VAL-47; ARG-87; LEU-176 AND ALA-245. RX PubMed=8088845; DOI=10.1006/geno.1994.1296; RA Guldberg P., Henriksen K.F., Thoeny B., Blau N., Guettler F.; RT "Molecular heterogeneity of nonphenylketonuria hyperphenylalaninemia in 25 RT Danish patients."; RL Genomics 21:453-455(1994). RN [39] RP VARIANTS PKU THR-164; ALA-171; SER-239; GLN-252 AND LEU-331. RX PubMed=7833954; DOI=10.1002/humu.1380040311; RA Benit P., Rey F., Melle D., Munnich A., Rey J.; RT "Five novel missense mutations of the phenylalanine hydroxylase gene in RT phenylketonuria."; RL Hum. Mutat. 4:229-231(1994). RN [40] RP CHARACTERIZATION OF VARIANT PKU GLY-143. RX PubMed=8889583; RX DOI=10.1002/(sici)1098-1004(1996)8:3<236::aid-humu7>3.0.co;2-7; RA Knappskog P.M., Eiken H.G., Martinez A., Bruland O., Apold J., Flatmark T.; RT "PKU mutation (D143G) associated with an apparent high residual enzyme RT activity: expression of a kinetic variant form of phenylalanine hydroxylase RT in three different systems."; RL Hum. Mutat. 8:236-246(1996). RN [41] RP VARIANTS PKU LEU-40; SER-46; SER-48; 63-THR-HIS-64 DELINS PRO-ASN; THR-65; RP SER-68; CYS-241; ALA-245; GLN-261; LYS-280; LEU-281; CYS-299; GLY-390; RP HIS-394; VAL-403; TRP-408 AND CYS-414. RX PubMed=8889590; RX DOI=10.1002/(sici)1098-1004(1996)8:3<276::aid-humu14>3.0.co;2-#; RA Guldberg P., Mallmann R., Henriksen K.F., Guettler F.; RT "Phenylalanine hydroxylase deficiency in a population in Germany: RT mutational profile and nine novel mutations."; RL Hum. Mutat. 8:276-279(1996). RN [42] RP VARIANTS PKU CYS-204 AND SER-207. RX PubMed=9048935; DOI=10.1007/s004390050353; RA Argiolas A., Bosco P., Cali F., Ceratto N., Anello G., Riva E., RA Biasucci G., Carducci C., Romano V.; RT "Two novel PAH gene mutations detected in Italian phenylketonuric RT patients."; RL Hum. Genet. 99:275-278(1997). RN [43] RP VARIANTS PKU, AND VARIANTS PKU GLN-158; TRP-158; LEU-176; PRO-176; ILE-230; RP CYS-241; HIS-241; LEU-241; GLN-243; GLN-252; GLY-252; TRP-252; GLN-261; RP PRO-261; LYS-280; LEU-281; CYS-297; HIS-297; THR-322; MET-380; LEU-388; RP MET-388; GLN-408; TRP-408; PRO-413; SER-413 AND ASN-415. RX PubMed=9101291; RX DOI=10.1002/(sici)1098-1004(1997)9:4<316::aid-humu3>3.0.co;2-3; RA Byck S., Tyfield L., Carter K., Scriver C.R.; RT "Prediction of multiple hypermutable codons in the human PAH gene: codon RT 280 contains recurrent mutations in Quebec and other populations."; RL Hum. Mutat. 9:316-321(1997). RN [44] RP VARIANTS PKU PHE-41; 63-THR-HIS-64 DELINS PRO-ASN; PRO-67; ILE-92; THR-174; RP PRO-194; VAL-218; PRO-231; SER-239; GLU-245; GLY-252; VAL-259; ASN-282; RP PHE-283; PRO-303; HIS-314; LEU-331; PHE-333; THR-342; THR-350; HIS-366; RP ALA-394; GLY-395 AND PRO-395. RX PubMed=9634518; DOI=10.1086/301920; RA Guldberg P., Rey F., Zschocke J., Romano V., Francois B., Michiels L., RA Ullrich K., Hoffmann G.F., Burgard P., Schmidt H., Meli C., Riva E., RA Dianzani I., Ponzone A., Rey J., Guettler F.; RT "A European multicenter study of phenylalanine hydroxylase deficiency: RT classification of 105 mutations and a general system for genotype-based RT prediction of metabolic phenotype."; RL Am. J. Hum. Genet. 63:71-79(1998). RN [45] RP CHARACTERIZATION OF VARIANTS, AND VARIANTS PKU PRO-231 AND THR-259. RX PubMed=9450897; RX DOI=10.1002/(sici)1098-1004(1998)11:1<4::aid-humu2>3.0.co;2-l; RA Waters P.J., Parniak M.A., Nowacki P., Scriver C.R.; RT "In vitro expression analysis of mutations in phenylalanine hydroxylase: RT linking genotype to phenotype and structure to function."; RL Hum. Mutat. 11:4-17(1998). RN [46] RP VARIANTS PKU SER-48; ASN-65; PRO-213 AND ASN-283, AND VARIANTS NON-PKU HPA RP SER-48; LEU-55; TYR-201 AND LEU-269. RX PubMed=9521426; RX DOI=10.1002/(sici)1098-1004(1998)11:3<240::aid-humu9>3.0.co;2-l; RA Bosco P., Cali F., Meli C., Mollica F., Zammarchi E., Cerone R., Vanni C., RA Palillo L., Greco D., Romano V.; RT "Eight new mutations of the phenylalanine hydroxylase gene in Italian RT patients with hyperphenylalaninemia."; RL Hum. Mutat. 11:240-243(1998). RN [47] RP VARIANTS PKU GLN-243; LEU-349 AND TRP-408. RX PubMed=9600453; RX DOI=10.1002/(sici)1098-1004(1998)11:5<354::aid-humu2>3.0.co;2-w; RA de Lucca M., Perez B., Desviat L.R., Ugarte M.; RT "Molecular basis of phenylketonuria in Venezuela: presence of two novel RT null mutations."; RL Hum. Mutat. 11:354-359(1998). RN [48] RP VARIANT PKU THR-362. RX PubMed=10200057; RA Mallolas J., Campistol J., Lambruscini N., Vilaseca M.A., Cambra J.F., RA Estivill X., Milo M.; RT "Two novel mutations in exon 11 of the PAH gene (1163/1164 del TG and RT P362T) associated with classic phenylketonuria and mild phenylketonuria."; RL Hum. Mutat. 11:482-482(1998). RN [49] RP VARIANTS PKU HIS-53; ASP-207 AND LEU-388. RX PubMed=9452061; DOI=10.1002/humu.1380110140; RA Park Y.S., Seoung C.S., Lee S.W., Oh K.H., Lee D.H., Yim J.; RT "Identification of three novel mutations in Korean phenylketonuria RT patients: R53H, N207D, and Y325X."; RL Hum. Mutat. Suppl. 1:S121-S122(1998). RN [50] RP VARIANTS PKU PHE-39 DEL; THR-65; GLN-158; ILE-167; ALA-190; CYS-241 AND RP TRP-408. RX PubMed=9452062; DOI=10.1002/humu.1380110141; RA Michiels L., Francois B., Raus J., Vandevyver C.; RT "Identification of seven new mutations in the phenylalanine hydroxylase RT gene, associated with hyperphenylalaninemia in the Belgian population."; RL Hum. Mutat. Suppl. 1:S123-S124(1998). RN [51] RP VARIANTS PKU GLY-178 AND THR-225. RX PubMed=9792407; RX DOI=10.1002/(sici)1098-1004(1998)12:5<314::aid-humu4>3.0.co;2-d; RA Popescu T., Blazkova M., Kozak L., Jebeleanu G., Popescu A.; RT "Mutation spectrum and phenylalanine hydroxylase RFLP/VNTR background in 44 RT Romanian phenylketonuric alleles."; RL Hum. Mutat. 12:314-319(1998). RN [52] RP CHARACTERIZATION OF VARIANTS PKU ASP-104 AND ASN-157. RX PubMed=9792411; RX DOI=10.1002/(sici)1098-1004(1998)12:5<344::aid-humu8>3.0.co;2-d; RA Waters P.J., Parniak M.A., Hewson A.S., Scriver C.R.; RT "Alterations in protein aggregation and degradation due to mild and severe RT missense mutations (A104D, R157N) in the human phenylalanine hydroxylase RT gene."; RL Hum. Mutat. 12:344-354(1998). RN [53] RP VARIANTS NON-PKU HPA CYS-241; GLN-243 AND PRO-413. RX PubMed=9852673; DOI=10.1007/s100380050079; RA Kibayashi M., Nagao M., Chiba S.; RT "Mutation analysis of the phenylalanine hydroxylase gene and its clinical RT implications in two Japanese patients with non-phenylketonuria RT hyperphenylalaninemia."; RL J. Hum. Genet. 43:231-236(1998). RN [54] RP VARIANT PKU LEU-407. RX PubMed=9950317; DOI=10.1007/s004310051018; RA Corsello G., Bosco P., Cali F., Greco D., Cammarata M., Ciaccio M., RA Piccione M., Romano V.; RT "Maternal phenylketonuria in two Sicilian families identified by maternal RT blood phenylalanine level screening and identification of a new RT phenylalanine hydroxylase gene mutation (P407L)."; RL Eur. J. Pediatr. 158:83-84(1999). RN [55] RP VARIANTS PKU LEU-39; PRO-41; SER-48; LEU-55; THR-65; SER-68; TYR-84; RP ASP-104; PRO-155; GLN-158; GLN-183; ALA-190; THR-211; ILE-230; PHE-231; RP GLN-243; ALA-245; TRP-252; GLN-261; LEU-281; CYS-299; SER-300; VAL-306; RP VAL-309; CYS-325; ASP-330; ARG-344; VAL-344; VAL-348; PRO-349; CYS-386; RP GLY-390; PRO-395; VAL-403; TRP-408; SER-410 AND CYS-414, AND VARIANTS HPA RP LEU-20 AND CYS-110. RX PubMed=10679941; RX DOI=10.1002/(sici)1098-1004(200003)15:3<254::aid-humu6>3.0.co;2-w; RA Hennermann J.B., Vetter B., Wolf C., Windt E., Buehrdel P., Seidel J., RA Moench E., Kulozik A.E.; RT "Phenylketonuria and hyperphenylalaninemia in eastern Germany: a RT characteristic molecular profile and 15 novel mutations."; RL Hum. Mutat. 15:254-260(2000). RN [56] RP CHARACTERIZATION OF VARIANTS PKU. RX PubMed=11326337; DOI=10.1086/320604; RA Gjetting T., Petersen M., Guldberg P., Guettler F.; RT "Missense mutations in the N-terminal domain of human phenylalanine RT hydroxylase interfere with binding of regulatory phenylalanine."; RL Am. J. Hum. Genet. 68:1353-1360(2001). RN [57] RP VARIANTS PKU VAL-145; LEU-176; ALA-205; SER-240; CYS-241; LYS-270; GLU-274; RP SER-300; PRO-311; THR-318; VAL-348; GLY-357 AND GLY-390. RX PubMed=11180595; RX DOI=10.1002/1098-1004(200102)17:2<122::aid-humu4>3.0.co;2-c; RA Acosta A.X., Silva W.A. Jr., Carvalho T.M., Gomes M., Zago M.A.; RT "Mutations of the phenylalanine hydroxylase (PAH) gene in Brazilian RT patients with phenylketonuria."; RL Hum. Mutat. 17:122-130(2001). RN [58] RP VARIANTS PKU, AND VARIANTS HPA. RX PubMed=11385716; DOI=10.1002/humu.1141.abs; RA Yang Y., Drummond-Borg M., Garcia-Heras J.; RT "Molecular analysis of phenylketonuria (PKU) in newborns from Texas."; RL Hum. Mutat. 17:523-523(2001). RN [59] RP VARIANTS PKU TRP-252 AND THR-318, AND VARIANT GLU-274. RX PubMed=11461196; DOI=10.1006/mgme.2001.3180; RA Gjetting T., Romstad A., Haavik J., Knappskog P.M., Acosta A.X., RA Silva W.A. Jr., Zago M.A., Guldberg P., Guettler F.; RT "A phenylalanine hydroxylase amino acid polymorphism with implications for RT molecular diagnostics."; RL Mol. Genet. Metab. 73:280-284(2001). RN [60] RP VARIANT NON-PKU HPA GLY-76. RX PubMed=11935335; DOI=10.1007/s00439-002-0677-7; RA Chen K.J., Chao H.K., Hsiao K.J., Su T.S.; RT "Identification and characterization of a novel liver-specific enhancer of RT the human phenylalanine hydroxylase gene."; RL Hum. Genet. 110:235-243(2002). RN [61] RP VARIANTS HPA LEU-39; LEU-55; VAL-65; MET-177; ALA-245; GLN-261; TYR-310; RP SER-314; VAL-403; TRP-408; CYS-414 AND ASN-415, AND VARIANTS PKU SER-48; RP ASP-61; SER-65; THR-65; VAL-65; GLN-158; GLN-170; GLN-261; LEU-275; RP LEU-281; SER-300; GLY-390; TRP-408; PRO-413; CYS-414 AND HIS-417. RX PubMed=12501224; DOI=10.1056/nejmoa021654; RA Muntau A.C., Roschinger W., Habich M., Demmelmair H., Hoffmann B., RA Sommerhoff C.P., Roscher A.A.; RT "Tetrahydrobiopterin as an alternative treatment for mild RT phenylketonuria."; RL N. Engl. J. Med. 347:2122-2132(2002). RN [62] RP CHARACTERIZATION OF VARIANTS PKU LEU-55; SER-65; GLN-170; LEU-275; SER-300; RP TYR-310; SER-314; TRP-408; CYS-414 AND HIS-417. RX PubMed=18538294; DOI=10.1016/j.ajhg.2008.05.013; RA Gersting S.W., Kemter K.F., Staudigl M., Messing D.D., Danecka M.K., RA Lagler F.B., Sommerhoff C.P., Roscher A.A., Muntau A.C.; RT "Loss of function in phenylketonuria is caused by impaired molecular RT motions and conformational instability."; RL Am. J. Hum. Genet. 83:5-17(2008). RN [63] RP VARIANTS HPA PHE-39 DEL; LEU-121; TYR-196; TYR-201; ILE-230; SER-300; RP VAL-306; MET-380; GLY-390 AND VAL-403, AND VARIANTS PKU VAL-65; TRP-252; RP GLN-261 AND TRP-408. RX PubMed=23792259; DOI=10.1016/j.clinbiochem.2013.06.009; RA Trunzo R., Santacroce R., D'Andrea G., Longo V., De Girolamo G., RA Dimatteo C., Leccese A., Lillo V., Papadia F., Margaglione M.; RT "Mutation analysis in Hyperphenylalaninemia patients from South Italy."; RL Clin. Biochem. 46:1896-1898(2013). RN [64] RP VARIANTS PKU TYR-290; VAL-322 AND SER-421. RX PubMed=22526846; DOI=10.1007/s10545-012-9485-y; RA Sterl E., Paul K., Paschke E., Zschocke J., Brunner-Krainz M., Windisch E., RA Konstantopoulou V., Moslinger D., Karall D., Scholl-Burgi S., Sperl W., RA Lagler F., Plecko B.; RT "Prevalence of tetrahydrobiopterine (BH4)-responsive alleles among Austrian RT patients with PAH deficiency: comprehensive results from molecular analysis RT in 147 patients."; RL J. Inherit. Metab. Dis. 36:7-13(2013). RN [65] RP VARIANTS PKU ALA-45; SER-48; PRO-62; SER-157; GLN-158; LEU-177; GLY-178; RP ALA-190; HIS-226; ALA-245; TRP-252; GLN-261; LYS-280; LEU-281; SER-300; RP PRO-349; GLY-390; VAL-403; TRP-408 AND ASN-415. RX PubMed=22513348; DOI=10.1016/j.ymgme.2012.03.015; RA Groselj U., Tansek M.Z., Kovac J., Hovnik T., Podkrajsek K.T., RA Battelino T.; RT "Five novel mutations and two large deletions in a population analysis of RT the phenylalanine hydroxylase gene."; RL Mol. Genet. Metab. 106:142-148(2012). CC -!- FUNCTION: Catalyzes the hydroxylation of L-phenylalanine to L-tyrosine. CC {ECO:0000269|PubMed:18460651, ECO:0000269|PubMed:18835579}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-phenylalanine + CC O2 = (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin + L- CC tyrosine; Xref=Rhea:RHEA:20273, ChEBI:CHEBI:15379, ChEBI:CHEBI:15642, CC ChEBI:CHEBI:58095, ChEBI:CHEBI:58315, ChEBI:CHEBI:59560; CC EC=1.14.16.1; Evidence={ECO:0000269|PubMed:18460651, CC ECO:0000269|PubMed:18835579}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000250|UniProtKB:P04176}; CC -!- ACTIVITY REGULATION: N-terminal region of PAH is thought to contain CC allosteric binding sites for phenylalanine and to constitute an CC 'inhibitory' domain that regulates the activity of a catalytic domain CC in the C-terminal portion of the molecule. CC {ECO:0000269|PubMed:18460651, ECO:0000269|PubMed:18835579}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=150 uM for L-phenylalanine {ECO:0000269|PubMed:18835579}; CC KM=154 uM for L-phenylalanine (at 25 degrees Celsius) CC {ECO:0000269|PubMed:18460651}; CC KM=30 uM for tetrahydrobiopterin (BH(4)) CC {ECO:0000269|PubMed:18835579}; CC KM=36 uM for tetrahydrobiopterin (BH(4)) (at 25 degrees Celsius) CC {ECO:0000269|PubMed:18460651}; CC Vmax=3500 nmol/min/mg enzyme towards L-phenylalanine (at 25 degrees CC Celsius) {ECO:0000269|PubMed:18460651}; CC Vmax=3600 nmol/min/mg enzyme towards tetrahydrobiopterin (BH(4)) (at CC 25 degrees Celsius) {ECO:0000269|PubMed:18460651}; CC Vmax=3640 nmol/min/mg enzyme towards L-phenylalanine (preincubated CC with L-Phe) {ECO:0000269|PubMed:18835579}; CC Vmax=1230 nmol/min/mg enzyme towards L-phenylalanine (preincubated CC with BH(4)) {ECO:0000269|PubMed:18835579}; CC Temperature dependence: CC Optimum temperature is 50 degrees Celsius. CC {ECO:0000269|PubMed:18835579}; CC -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation; CC acetoacetate and fumarate from L-phenylalanine: step 1/6. CC -!- SUBUNIT: Homodimer and homotetramer. {ECO:0000269|PubMed:9642259}. CC -!- PTM: Phosphorylation at Ser-16 increases basal activity and facilitates CC activation by the substrate phenylalanine. CC {ECO:0000269|PubMed:12185072}. CC -!- POLYMORPHISM: The Glu-274 variant occurs on approximately 4% of CC African-American PAH alleles. The enzyme activity of the variant CC protein is indistinguishable from that of the wild-type form. CC -!- DISEASE: Phenylketonuria (PKU) [MIM:261600]: Autosomal recessive inborn CC error of phenylalanine metabolism, due to severe phenylalanine CC hydroxylase deficiency. It is characterized by blood concentrations of CC phenylalanine persistently above 1200 mumol (normal concentration 100 CC mumol) which usually causes intellectual disability (unless low CC phenylalanine diet is introduced early in life). They tend to have CC light pigmentation, rashes similar to eczema, epilepsy, extreme CC hyperactivity, psychotic states and an unpleasant 'mousy' odor. CC {ECO:0000269|PubMed:10200057, ECO:0000269|PubMed:10679941, CC ECO:0000269|PubMed:11180595, ECO:0000269|PubMed:11326337, CC ECO:0000269|PubMed:11385716, ECO:0000269|PubMed:11461196, CC ECO:0000269|PubMed:12501224, ECO:0000269|PubMed:1301187, CC ECO:0000269|PubMed:1355066, ECO:0000269|PubMed:1363837, CC ECO:0000269|PubMed:1363838, ECO:0000269|PubMed:1671810, CC ECO:0000269|PubMed:1672290, ECO:0000269|PubMed:1672294, CC ECO:0000269|PubMed:1679030, ECO:0000269|PubMed:1709636, CC ECO:0000269|PubMed:18538294, ECO:0000269|PubMed:1975559, CC ECO:0000269|PubMed:2014802, ECO:0000269|PubMed:22513348, CC ECO:0000269|PubMed:22526846, ECO:0000269|PubMed:23792259, CC ECO:0000269|PubMed:2564729, ECO:0000269|PubMed:2615649, CC ECO:0000269|PubMed:2840952, ECO:0000269|PubMed:32668217, CC ECO:0000269|PubMed:7833954, ECO:0000269|PubMed:8068076, CC ECO:0000269|PubMed:8406445, ECO:0000269|PubMed:8889583, CC ECO:0000269|PubMed:8889590, ECO:0000269|PubMed:9048935, CC ECO:0000269|PubMed:9101291, ECO:0000269|PubMed:9450897, CC ECO:0000269|PubMed:9452061, ECO:0000269|PubMed:9452062, CC ECO:0000269|PubMed:9521426, ECO:0000269|PubMed:9600453, CC ECO:0000269|PubMed:9634518, ECO:0000269|PubMed:9792407, CC ECO:0000269|PubMed:9792411, ECO:0000269|PubMed:9950317}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Non-phenylketonuria hyperphenylalaninemia (Non-PKU HPA) CC [MIM:261600]: Mild form of phenylalanine hydroxylase deficiency CC characterized by phenylalanine levels persistently below 600 mumol, CC which allows normal intellectual and behavioral development without CC treatment. Non-PKU HPA is usually caused by the combined effect of a CC mild hyperphenylalaninemia mutation and a severe one. CC {ECO:0000269|PubMed:1358789, ECO:0000269|PubMed:8088845, CC ECO:0000269|PubMed:8098245, ECO:0000269|PubMed:9521426, CC ECO:0000269|PubMed:9852673}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Hyperphenylalaninemia (HPA) [MIM:261600]: Mildest form of CC phenylalanine hydroxylase deficiency. {ECO:0000269|PubMed:10679941, CC ECO:0000269|PubMed:11385716, ECO:0000269|PubMed:11935335, CC ECO:0000269|PubMed:12501224, ECO:0000269|PubMed:1358789, CC ECO:0000269|PubMed:23792259, ECO:0000269|PubMed:8088845, CC ECO:0000269|PubMed:8098245, ECO:0000269|PubMed:9521426, CC ECO:0000269|PubMed:9852673}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid CC hydroxylase family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=PAHvdb; Note=Phenylalanine Hydroxylase Gene CC Locus-Specific Database; CC URL="https://www.biopku.org/home/pah.asp"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Phenylalanine hydroxylase entry; CC URL="https://en.wikipedia.org/wiki/Phenylalanine_hydroxylase"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; K03020; AAA60082.1; -; mRNA. DR EMBL; U49897; AAC51772.1; -; mRNA. DR EMBL; S61296; AAD13926.1; -; mRNA. DR EMBL; BC026251; AAH26251.1; -; mRNA. DR CCDS; CCDS9092.1; -. DR PIR; A00508; WHHUF. DR RefSeq; NP_000268.1; NM_000277.1. DR PDB; 1DMW; X-ray; 2.00 A; A=118-424. DR PDB; 1J8T; X-ray; 1.70 A; A=103-427. DR PDB; 1J8U; X-ray; 1.50 A; A=103-427. DR PDB; 1KW0; X-ray; 2.50 A; A=103-427. DR PDB; 1LRM; X-ray; 2.10 A; A=103-427. DR PDB; 1MMK; X-ray; 2.00 A; A=103-427. DR PDB; 1MMT; X-ray; 2.00 A; A=103-427. DR PDB; 1PAH; X-ray; 2.00 A; A=117-424. DR PDB; 1TDW; X-ray; 2.10 A; A=117-424. DR PDB; 1TG2; X-ray; 2.20 A; A=117-424. DR PDB; 2PAH; X-ray; 3.10 A; A/B=118-452. DR PDB; 3PAH; X-ray; 2.00 A; A=117-424. DR PDB; 4ANP; X-ray; 2.11 A; A=104-427. DR PDB; 4PAH; X-ray; 2.00 A; A=117-424. DR PDB; 5FII; X-ray; 1.80 A; A/B/C/D=19-118. DR PDB; 5PAH; X-ray; 2.10 A; A=117-424. DR PDB; 6HPO; X-ray; 1.67 A; A=1-452. DR PDB; 6HYC; X-ray; 3.18 A; A/B/C/D=1-452. DR PDB; 6N1K; X-ray; 3.06 A; A/B/C/D=2-452. DR PDB; 6PAH; X-ray; 2.15 A; A=117-424. DR PDBsum; 1DMW; -. DR PDBsum; 1J8T; -. DR PDBsum; 1J8U; -. DR PDBsum; 1KW0; -. DR PDBsum; 1LRM; -. DR PDBsum; 1MMK; -. DR PDBsum; 1MMT; -. DR PDBsum; 1PAH; -. DR PDBsum; 1TDW; -. DR PDBsum; 1TG2; -. DR PDBsum; 2PAH; -. DR PDBsum; 3PAH; -. DR PDBsum; 4ANP; -. DR PDBsum; 4PAH; -. DR PDBsum; 5FII; -. DR PDBsum; 5PAH; -. DR PDBsum; 6HPO; -. DR PDBsum; 6HYC; -. DR PDBsum; 6N1K; -. DR PDBsum; 6PAH; -. DR AlphaFoldDB; P00439; -. DR EMDB; EMD-4605; -. DR SASBDB; P00439; -. DR SMR; P00439; -. DR BioGRID; 111090; 9. DR DIP; DIP-58927N; -. DR IntAct; P00439; 5. DR MINT; P00439; -. DR STRING; 9606.ENSP00000448059; -. DR BindingDB; P00439; -. DR ChEMBL; CHEMBL3076; -. DR DrugBank; DB03673; beta-2-Thienyl-L-alanine. DR DrugBank; DB04339; Carbocisteine. DR DrugBank; DB06778; Cupric sulfate. DR DrugBank; DB04419; D-norleucine. DR DrugBank; DB06262; Droxidopa. DR DrugBank; DB04400; L-erythro-7,8-dihydrobiopterin. DR DrugBank; DB00368; Norepinephrine. DR DrugBank; DB00120; Phenylalanine. DR DrugBank; DB02562; Quinonoid 7,8-Tetrahydrobiopterin. DR DrugBank; DB00360; Sapropterin. DR DrugCentral; P00439; -. DR GuidetoPHARMACOLOGY; 1240; -. DR iPTMnet; P00439; -. DR PhosphoSitePlus; P00439; -. DR BioMuta; PAH; -. DR DMDM; 129973; -. DR EPD; P00439; -. DR MassIVE; P00439; -. DR MaxQB; P00439; -. DR PaxDb; 9606-ENSP00000448059; -. DR PeptideAtlas; P00439; -. DR ProteomicsDB; 51249; -. DR Antibodypedia; 30481; 331 antibodies from 32 providers. DR DNASU; 5053; -. DR Ensembl; ENST00000553106.6; ENSP00000448059.1; ENSG00000171759.10. DR GeneID; 5053; -. DR KEGG; hsa:5053; -. DR MANE-Select; ENST00000553106.6; ENSP00000448059.1; NM_000277.3; NP_000268.1. DR UCSC; uc001tjq.2; human. DR AGR; HGNC:8582; -. DR CTD; 5053; -. DR DisGeNET; 5053; -. DR GeneCards; PAH; -. DR GeneReviews; PAH; -. DR HGNC; HGNC:8582; PAH. DR HPA; ENSG00000171759; Group enriched (kidney, liver). DR MalaCards; PAH; -. DR MIM; 261600; phenotype. DR MIM; 612349; gene. DR neXtProt; NX_P00439; -. DR OpenTargets; ENSG00000171759; -. DR Orphanet; 79254; Classic phenylketonuria. DR Orphanet; 2209; Maternal phenylketonuria. DR Orphanet; 79651; Mild hyperphenylalaninemia. DR Orphanet; 79253; Mild phenylketonuria. DR Orphanet; 293284; Tetrahydrobiopterin-responsive hyperphenylalaninemia/phenylketonuria. DR PharmGKB; PA32911; -. DR VEuPathDB; HostDB:ENSG00000171759; -. DR eggNOG; KOG3820; Eukaryota. DR GeneTree; ENSGT00950000182885; -. DR HOGENOM; CLU_023198_0_1_1; -. DR InParanoid; P00439; -. DR OMA; FHDEVYR; -. DR OrthoDB; 275463at2759; -. DR PhylomeDB; P00439; -. DR TreeFam; TF313327; -. DR BioCyc; MetaCyc:HS10374-MONOMER; -. DR BRENDA; 1.14.16.1; 2681. DR PathwayCommons; P00439; -. DR Reactome; R-HSA-2160456; Phenylketonuria. DR Reactome; R-HSA-8964208; Phenylalanine metabolism. DR SABIO-RK; P00439; -. DR SignaLink; P00439; -. DR SIGNOR; P00439; -. DR UniPathway; UPA00139; UER00337. DR BioGRID-ORCS; 5053; 8 hits in 1162 CRISPR screens. DR ChiTaRS; PAH; human. DR EvolutionaryTrace; P00439; -. DR GeneWiki; Phenylalanine_hydroxylase; -. DR GenomeRNAi; 5053; -. DR Pharos; P00439; Tclin. DR PRO; PR:P00439; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P00439; Protein. DR Bgee; ENSG00000171759; Expressed in right lobe of liver and 124 other cell types or tissues. DR ExpressionAtlas; P00439; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0004505; F:phenylalanine 4-monooxygenase activity; IDA:CACAO. DR GO; GO:0008652; P:amino acid biosynthetic process; TAS:ProtInc. DR GO; GO:0042423; P:catecholamine biosynthetic process; NAS:BHF-UCL. DR GO; GO:0006559; P:L-phenylalanine catabolic process; IEA:UniProtKB-UniPathway. DR GO; GO:0006571; P:tyrosine biosynthetic process; IBA:GO_Central. DR CDD; cd04931; ACT_PAH; 1. DR CDD; cd03347; eu_PheOH; 1. DR Gene3D; 1.10.800.10; Aromatic amino acid hydroxylase; 1. DR InterPro; IPR045865; ACT-like_dom_sf. DR InterPro; IPR002912; ACT_dom. DR InterPro; IPR001273; ArAA_hydroxylase. DR InterPro; IPR018301; ArAA_hydroxylase_Fe/CU_BS. DR InterPro; IPR036951; ArAA_hydroxylase_sf. DR InterPro; IPR036329; Aro-AA_hydroxylase_C_sf. DR InterPro; IPR019774; Aromatic-AA_hydroxylase_C. DR InterPro; IPR041912; Euk_PheOH_cat. DR InterPro; IPR005961; Phe-4-hydroxylase_tetra. DR InterPro; IPR019773; Tyrosine_3-monooxygenase-like. DR NCBIfam; TIGR01268; Phe4hydrox_tetr; 1. DR PANTHER; PTHR11473; AROMATIC AMINO ACID HYDROXYLASE; 1. DR PANTHER; PTHR11473:SF24; PHENYLALANINE-4-HYDROXYLASE; 1. DR Pfam; PF01842; ACT; 1. DR Pfam; PF00351; Biopterin_H; 1. DR PIRSF; PIRSF000336; TH; 1. DR PRINTS; PR00372; FYWHYDRXLASE. DR SUPFAM; SSF55021; ACT-like; 1. DR SUPFAM; SSF56534; Aromatic aminoacid monoxygenases, catalytic and oligomerization domains; 1. DR PROSITE; PS51671; ACT; 1. DR PROSITE; PS00367; BH4_AAA_HYDROXYL_1; 1. DR PROSITE; PS51410; BH4_AAA_HYDROXYL_2; 1. DR UCD-2DPAGE; P00439; -. DR Genevisible; P00439; HS. PE 1: Evidence at protein level; KW 3D-structure; Allosteric enzyme; Direct protein sequencing; KW Disease variant; Iron; Metal-binding; Monooxygenase; Oxidoreductase; KW Phenylalanine catabolism; Phenylketonuria; Phosphoprotein; KW Reference proteome. FT CHAIN 1..452 FT /note="Phenylalanine-4-hydroxylase" FT /id="PRO_0000205548" FT DOMAIN 36..114 FT /note="ACT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01007" FT BINDING 285 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000250|UniProtKB:P04176" FT BINDING 290 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000250|UniProtKB:P04176" FT BINDING 330 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000250|UniProtKB:P04176" FT MOD_RES 16 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:12185072, FT ECO:0007744|PubMed:24275569" FT VARIANT 16 FT /note="S -> P (in PKU; uncertain significance; FT dbSNP:rs62642946)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000869" FT VARIANT 20 FT /note="Q -> L (in HPA; dbSNP:rs199475662)" FT /evidence="ECO:0000269|PubMed:10679941" FT /id="VAR_009239" FT VARIANT 39 FT /note="F -> L (in HPA and PKU; haplotype 1; FT dbSNP:rs62642926)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:11385716, ECO:0000269|PubMed:12501224" FT /id="VAR_000870" FT VARIANT 39 FT /note="Missing (in PKU; haplotypes 9,21)" FT /evidence="ECO:0000269|PubMed:23792259, FT ECO:0000269|PubMed:9452062" FT /id="VAR_000871" FT VARIANT 40 FT /note="S -> L (in PKU; dbSNP:rs62642938)" FT /evidence="ECO:0000269|PubMed:8889590" FT /id="VAR_000872" FT VARIANT 41 FT /note="L -> F (in PKU; dbSNP:rs62642928)" FT /evidence="ECO:0000269|PubMed:9634518" FT /id="VAR_000873" FT VARIANT 41 FT /note="L -> P (in PKU; mild; dbSNP:rs62642916)" FT /evidence="ECO:0000269|PubMed:10679941" FT /id="VAR_009240" FT VARIANT 42 FT /note="K -> I (in PKU; haplotype 21; dbSNP:rs62635346)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000874" FT VARIANT 45 FT /note="V -> A (in PKU; dbSNP:rs1592988883)" FT /evidence="ECO:0000269|PubMed:22513348" FT /id="VAR_067994" FT VARIANT 46 FT /note="G -> S (in PKU; haplotype 5; significantly reduces FT phenylalanine binding; dbSNP:rs74603784)" FT /evidence="ECO:0000269|PubMed:8889590" FT /id="VAR_000875" FT VARIANT 47 FT /note="A -> V (in non-PKUHPA; haplotype 4; significantly FT reduces phenylalanine binding; dbSNP:rs118203925)" FT /evidence="ECO:0000269|PubMed:8088845" FT /id="VAR_000876" FT VARIANT 48 FT /note="L -> S (in PKU; mild; haplotypes 3,4; FT dbSNP:rs5030841)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:12501224, ECO:0000269|PubMed:1679030, FT ECO:0000269|PubMed:22513348, ECO:0000269|PubMed:8889590, FT ECO:0000269|PubMed:9521426" FT /id="VAR_000877" FT VARIANT 53 FT /note="R -> H (in PKU; dbSNP:rs118092776)" FT /evidence="ECO:0000269|PubMed:9452061" FT /id="VAR_000878" FT VARIANT 55 FT /note="F -> L (in HPA and PKU; does not affect FT oligomerization; results in loss of substrate activation; FT dbSNP:rs199475598)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:12501224, ECO:0000269|PubMed:18538294, FT ECO:0000269|PubMed:9521426" FT /id="VAR_000879" FT VARIANT 56 FT /note="E -> D (in PKU; haplotype 10; dbSNP:rs199475567)" FT /evidence="ECO:0000269|PubMed:1301187" FT /id="VAR_000880" FT VARIANT 61 FT /note="N -> D (in PKU; dbSNP:rs199475651)" FT /evidence="ECO:0000269|PubMed:12501224" FT /id="VAR_067995" FT VARIANT 62 FT /note="L -> P (in PKU; dbSNP:rs1877437661)" FT /evidence="ECO:0000269|PubMed:22513348" FT /id="VAR_067996" FT VARIANT 63..64 FT /note="TH -> PN (in PKU; haplotype 1; abolishes FT phenylalanine binding)" FT /evidence="ECO:0000269|PubMed:8889590, FT ECO:0000269|PubMed:9634518" FT /id="VAR_000881" FT VARIANT 65 FT /note="I -> N (in PKU; dbSNP:rs75193786)" FT /evidence="ECO:0000269|PubMed:9521426" FT /id="VAR_000882" FT VARIANT 65 FT /note="I -> S (in PKU; results in disturbed FT oligomerization; results in loss of substrate activation; FT dbSNP:rs75193786)" FT /evidence="ECO:0000269|PubMed:12501224, FT ECO:0000269|PubMed:18538294" FT /id="VAR_067997" FT VARIANT 65 FT /note="I -> T (in PKU; haplotypes 1,5,9,21,B; abolishes FT phenylalanine binding; dbSNP:rs75193786)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:12501224, ECO:0000269|PubMed:8889590, FT ECO:0000269|PubMed:9452062" FT /id="VAR_000883" FT VARIANT 65 FT /note="I -> V (in HPA and PKU; dbSNP:rs199475643)" FT /evidence="ECO:0000269|PubMed:12501224, FT ECO:0000269|PubMed:23792259" FT /id="VAR_067998" FT VARIANT 67 FT /note="S -> P (in PKU; haplotype 4; dbSNP:rs5030842)" FT /evidence="ECO:0000269|PubMed:9634518" FT /id="VAR_000884" FT VARIANT 68 FT /note="R -> S (in PKU; haplotype 1; dbSNP:rs76394784)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:8889590" FT /id="VAR_000885" FT VARIANT 76 FT /note="E -> A (in PKU; dbSNP:rs62507347)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000886" FT VARIANT 76 FT /note="E -> G (in non-PKUHPA; dbSNP:rs62507347)" FT /evidence="ECO:0000269|PubMed:11935335" FT /id="VAR_067999" FT VARIANT 84 FT /note="D -> Y (in PKU; haplotype 4; dbSNP:rs62514902)" FT /evidence="ECO:0000269|PubMed:10679941" FT /id="VAR_000887" FT VARIANT 87 FT /note="S -> R (in non-PKUHPA; haplotype 1; FT dbSNP:rs62516151)" FT /evidence="ECO:0000269|PubMed:8088845" FT /id="VAR_000888" FT VARIANT 92 FT /note="T -> I (in PKU; dbSNP:rs62514903)" FT /evidence="ECO:0000269|PubMed:9634518" FT /id="VAR_000889" FT VARIANT 94 FT /note="Missing (in PKU; mild; haplotype 2)" FT /evidence="ECO:0000269|PubMed:1709636" FT /id="VAR_000890" FT VARIANT 98 FT /note="L -> S (in non-PKUHPA; dbSNP:rs62517167)" FT /evidence="ECO:0000269|PubMed:8364546" FT /id="VAR_000891" FT VARIANT 104 FT /note="A -> D (in PKU; mild; haplotype 1; FT dbSNP:rs62642929)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:9792411" FT /id="VAR_000892" FT VARIANT 110 FT /note="S -> C (in HPA)" FT /evidence="ECO:0000269|PubMed:10679941" FT /id="VAR_009241" FT VARIANT 121 FT /note="F -> L (in HPA)" FT /evidence="ECO:0000269|PubMed:23792259" FT /id="VAR_069776" FT VARIANT 124 FT /note="T -> I (in PKU; haplotype 28; dbSNP:rs199475571)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000893" FT VARIANT 129 FT /note="D -> Y (in PKU; dbSNP:rs199475606)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000894" FT VARIANT 143 FT /note="D -> G (in PKU; haplotype 11; dbSNP:rs199475572)" FT /evidence="ECO:0000269|PubMed:8889583" FT /id="VAR_000895" FT VARIANT 145 FT /note="D -> V (in PKU; dbSNP:rs140175796)" FT /evidence="ECO:0000269|PubMed:11180595, FT ECO:0000269|PubMed:11385716" FT /id="VAR_011566" FT VARIANT 146 FT /note="H -> Y (in PKU; dbSNP:rs199475599)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000896" FT VARIANT 148 FT /note="G -> S (in PKU; haplotypes 1,2,7; dbSNP:rs80297647)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000897" FT VARIANT 151 FT /note="D -> H (in PKU; haplotypes 1,8; dbSNP:rs199475597)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000898" FT VARIANT 154 FT /note="Y -> N (in PKU; dbSNP:rs199475587)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000899" FT VARIANT 155 FT /note="R -> P (in PKU; dbSNP:rs199475663)" FT /evidence="ECO:0000269|PubMed:10679941" FT /id="VAR_009242" FT VARIANT 157 FT /note="R -> N (in PKU; severe; 5% activity; requires 2 FT nucleotide substitutions; dbSNP:rs1565853495)" FT /evidence="ECO:0000269|PubMed:9792411" FT /id="VAR_000900" FT VARIANT 157 FT /note="R -> S (in PKU; dbSNP:rs199475612)" FT /evidence="ECO:0000269|PubMed:22513348" FT /id="VAR_068000" FT VARIANT 158 FT /note="R -> Q (in PKU; haplotypes 1,2,4,7,16, 28; FT dbSNP:rs5030843)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:12501224, ECO:0000269|PubMed:22513348, FT ECO:0000269|PubMed:9101291, ECO:0000269|PubMed:9452062" FT /id="VAR_000901" FT VARIANT 158 FT /note="R -> W (in PKU; dbSNP:rs75166491)" FT /evidence="ECO:0000269|PubMed:9101291" FT /id="VAR_000902" FT VARIANT 160 FT /note="Q -> P (in PKU; dbSNP:rs199475601)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000903" FT VARIANT 161 FT /note="F -> S (in PKU; haplotype 4; dbSNP:rs79635844)" FT /evidence="ECO:0000269|PubMed:1301187" FT /id="VAR_000904" FT VARIANT 164 FT /note="I -> T (in PKU; haplotype 1; dbSNP:rs199475595)" FT /evidence="ECO:0000269|PubMed:7833954" FT /id="VAR_000905" FT VARIANT 167 FT /note="N -> I (in PKU; dbSNP:rs77554925)" FT /evidence="ECO:0000269|PubMed:9452062" FT /id="VAR_000906" FT VARIANT 167 FT /note="N -> S (in HPA; dbSNP:rs77554925)" FT /evidence="ECO:0000269|PubMed:11385716" FT /id="VAR_011567" FT VARIANT 169 FT /note="R -> H (in PKU; dbSNP:rs199475679)" FT /evidence="ECO:0000269|PubMed:11385716" FT /id="VAR_011568" FT VARIANT 170 FT /note="H -> D (in HPA; dbSNP:rs199475655)" FT /evidence="ECO:0000269|PubMed:11385716" FT /id="VAR_011569" FT VARIANT 170 FT /note="H -> Q (in PKU; does not affect oligomerization; FT dbSNP:rs199475652)" FT /evidence="ECO:0000269|PubMed:12501224, FT ECO:0000269|PubMed:18538294" FT /id="VAR_068001" FT VARIANT 170 FT /note="H -> R (in PKU; dbSNP:rs199475573)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000907" FT VARIANT 171 FT /note="G -> A (in PKU; haplotype 1; dbSNP:rs199475596)" FT /evidence="ECO:0000269|PubMed:7833954" FT /id="VAR_000908" FT VARIANT 171 FT /note="G -> R (in PKU; dbSNP:rs199475613)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000909" FT VARIANT 173 FT /note="P -> T (in PKU; haplotype 4; dbSNP:rs199475574)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000910" FT VARIANT 174 FT /note="I -> T (in PKU; haplotype 1; dbSNP:rs138809906)" FT /evidence="ECO:0000269|PubMed:9634518" FT /id="VAR_000911" FT VARIANT 174 FT /note="I -> V (in PKU; dbSNP:rs199475632)" FT /evidence="ECO:0000269|PubMed:11385716" FT /id="VAR_011570" FT VARIANT 175 FT /note="P -> A (in PKU; dbSNP:rs199475604)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000912" FT VARIANT 176 FT /note="R -> L (in non-PKUHPA and PKU; dbSNP:rs74486803)" FT /evidence="ECO:0000269|PubMed:11180595, FT ECO:0000269|PubMed:8088845, ECO:0000269|PubMed:9101291" FT /id="VAR_000913" FT VARIANT 176 FT /note="R -> P (in PKU; dbSNP:rs74486803)" FT /evidence="ECO:0000269|PubMed:9101291" FT /id="VAR_000914" FT VARIANT 177 FT /note="V -> L (in PKU; haplotype 6; dbSNP:rs199475602)" FT /evidence="ECO:0000269|PubMed:22513348" FT /id="VAR_000915" FT VARIANT 177 FT /note="V -> M (in HPA; dbSNP:rs199475602)" FT /evidence="ECO:0000269|PubMed:12501224" FT /id="VAR_068002" FT VARIANT 178 FT /note="E -> G (in non-PKUHPA; dbSNP:rs77958223)" FT /evidence="ECO:0000269|PubMed:22513348, FT ECO:0000269|PubMed:9792407" FT /id="VAR_000916" FT VARIANT 183 FT /note="E -> Q (in PKU; dbSNP:rs199475664)" FT /evidence="ECO:0000269|PubMed:10679941" FT /id="VAR_009243" FT VARIANT 190 FT /note="V -> A (in PKU; haplotype 3; dbSNP:rs62514919)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:22513348, ECO:0000269|PubMed:9452062" FT /id="VAR_000917" FT VARIANT 194 FT /note="L -> P (in PKU; dbSNP:rs5030844)" FT /evidence="ECO:0000269|PubMed:9634518" FT /id="VAR_000918" FT VARIANT 196 FT /note="S -> Y (in HPA; dbSNP:rs865899394)" FT /evidence="ECO:0000269|PubMed:23792259" FT /id="VAR_069777" FT VARIANT 201 FT /note="H -> R (in PKU; dbSNP:rs62517180)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000922" FT VARIANT 201 FT /note="H -> Y (in non-PKUHPA; haplotype 1; FT dbSNP:rs62517205)" FT /evidence="ECO:0000269|PubMed:23792259, FT ECO:0000269|PubMed:9521426" FT /id="VAR_000923" FT VARIANT 204 FT /note="Y -> C (in PKU; mild; haplotypes 3,4; FT dbSNP:rs62514927)" FT /evidence="ECO:0000269|PubMed:9048935" FT /id="VAR_000924" FT VARIANT 205 FT /note="E -> A (in PKU; dbSNP:rs62508593)" FT /evidence="ECO:0000269|PubMed:11180595" FT /id="VAR_011571" FT VARIANT 206 FT /note="Y -> D (in PKU; dbSNP:rs62517170)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000925" FT VARIANT 207 FT /note="N -> D (in PKU; dbSNP:rs62508572)" FT /evidence="ECO:0000269|PubMed:9452061" FT /id="VAR_000926" FT VARIANT 207 FT /note="N -> S (in PKU; severe; haplotype 4; FT dbSNP:rs62508721)" FT /evidence="ECO:0000269|PubMed:9048935" FT /id="VAR_000927" FT VARIANT 211 FT /note="P -> T (in PKU; haplotype 4; dbSNP:rs62514931)" FT /evidence="ECO:0000269|PubMed:10679941" FT /id="VAR_000928" FT VARIANT 212 FT /note="L -> P (in PKU; dbSNP:rs62517198)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000929" FT VARIANT 213 FT /note="L -> P (in PKU; severe; dbSNP:rs62516109)" FT /evidence="ECO:0000269|PubMed:9521426" FT /id="VAR_000930" FT VARIANT 217 FT /note="C -> G (in PKU; dbSNP:rs62508718)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000931" FT VARIANT 218 FT /note="G -> V (in PKU; haplotypes 1,2; dbSNP:rs62514933)" FT /evidence="ECO:0000269|PubMed:9634518" FT /id="VAR_000932" FT VARIANT 221 FT /note="E -> G (in PKU; haplotype 4; dbSNP:rs62514934)" FT /evidence="ECO:0000269|PubMed:1679030" FT /id="VAR_000933" FT VARIANT 222 FT /note="D -> V (in PKU; haplotypes 3,4; dbSNP:rs62507319)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000934" FT VARIANT 224 FT /note="I -> M (in PKU; haplotype 4; dbSNP:rs199475576)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000935" FT VARIANT 225 FT /note="P -> R (in PKU; dbSNP:rs62517204)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000936" FT VARIANT 225 FT /note="P -> T (in PKU; haplotype 1; dbSNP:rs199475589)" FT /evidence="ECO:0000269|PubMed:9792407" FT /id="VAR_000937" FT VARIANT 226 FT /note="Q -> H (in PKU; dbSNP:rs62508615)" FT /evidence="ECO:0000269|PubMed:22513348" FT /id="VAR_068003" FT VARIANT 230 FT /note="V -> I (in non-PKUHPA and PKU; haplotype 4; FT dbSNP:rs62516152)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:23792259, ECO:0000269|PubMed:9101291" FT /id="VAR_000938" FT VARIANT 231 FT /note="S -> F (in PKU; dbSNP:rs62508577)" FT /evidence="ECO:0000269|PubMed:10679941" FT /id="VAR_009244" FT VARIANT 231 FT /note="S -> P (in PKU; dbSNP:rs5030845)" FT /evidence="ECO:0000269|PubMed:9450897, FT ECO:0000269|PubMed:9634518" FT /id="VAR_000939" FT VARIANT 233 FT /note="F -> L (in PKU; haplotypes 2,3; dbSNP:rs62517208)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000940" FT VARIANT 238 FT /note="T -> P (in PKU; haplotype 4; dbSNP:rs199475577)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000941" FT VARIANT 239 FT /note="G -> S (in PKU; dbSNP:rs62517178)" FT /evidence="ECO:0000269|PubMed:7833954, FT ECO:0000269|PubMed:9634518" FT /id="VAR_000942" FT VARIANT 240 FT /note="F -> S (in PKU; dbSNP:rs62508594)" FT /evidence="ECO:0000269|PubMed:11180595" FT /id="VAR_011572" FT VARIANT 241 FT /note="R -> C (in non-PKUHPA and PKU; haplotype 34; FT dbSNP:rs76687508)" FT /evidence="ECO:0000269|PubMed:11180595, FT ECO:0000269|PubMed:8889590, ECO:0000269|PubMed:9101291, FT ECO:0000269|PubMed:9452062, ECO:0000269|PubMed:9852673" FT /id="VAR_000943" FT VARIANT 241 FT /note="R -> H (in PKU; haplotypes 1,5; dbSNP:rs62508730)" FT /evidence="ECO:0000269|PubMed:9101291" FT /id="VAR_000944" FT VARIANT 241 FT /note="R -> L (in PKU; dbSNP:rs62508730)" FT /evidence="ECO:0000269|PubMed:11385716, FT ECO:0000269|PubMed:9101291" FT /id="VAR_000945" FT VARIANT 242 FT /note="L -> F (in PKU; dbSNP:rs199475578)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000946" FT VARIANT 243 FT /note="R -> Q (in non-PKUHPA and PKU; haplotypes 4,7,9; FT dbSNP:rs62508588)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:9101291, ECO:0000269|PubMed:9600453, FT ECO:0000269|PubMed:9852673" FT /id="VAR_000947" FT VARIANT 244 FT /note="P -> L (in PKU; haplotype 12; dbSNP:rs118203923)" FT /evidence="ECO:0000269|PubMed:1363838" FT /id="VAR_000948" FT VARIANT 245 FT /note="V -> A (in PKU, HPA and non-PKUHPA; haplotypes 3,7; FT dbSNP:rs796052017)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:12501224, ECO:0000269|PubMed:22513348, FT ECO:0000269|PubMed:8088845, ECO:0000269|PubMed:8889590" FT /id="VAR_000949" FT VARIANT 245 FT /note="V -> E (in PKU; haplotype 11; dbSNP:rs76212747)" FT /evidence="ECO:0000269|PubMed:9634518" FT /id="VAR_000950" FT VARIANT 245 FT /note="V -> L (in PKU; dbSNP:rs62508694)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000951" FT VARIANT 246 FT /note="A -> D (in PKU; dbSNP:rs199475610)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000952" FT VARIANT 247 FT /note="G -> V (in PKU; haplotype 4; dbSNP:rs199475579)" FT /evidence="ECO:0000269|PubMed:1301187" FT /id="VAR_000953" FT VARIANT 248 FT /note="L -> P (in PKU; dbSNP:rs62507340)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000954" FT VARIANT 249 FT /note="L -> F (in PKU; haplotype 1; dbSNP:rs74503222)" FT /evidence="ECO:0000269|PubMed:11385716" FT /id="VAR_000955" FT VARIANT 252 FT /note="R -> G (in PKU; haplotype 7; dbSNP:rs5030847)" FT /evidence="ECO:0000269|PubMed:9101291, FT ECO:0000269|PubMed:9634518" FT /id="VAR_000956" FT VARIANT 252 FT /note="R -> Q (in PKU; haplotype 1; dbSNP:rs62644503)" FT /evidence="ECO:0000269|PubMed:7833954, FT ECO:0000269|PubMed:9101291" FT /id="VAR_000957" FT VARIANT 252 FT /note="R -> W (in PKU; haplotypes 1,6,7,8,42, 69; complete FT loss of activity; dbSNP:rs5030847)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:11461196, ECO:0000269|PubMed:1672294, FT ECO:0000269|PubMed:22513348, ECO:0000269|PubMed:23792259, FT ECO:0000269|PubMed:9101291" FT /id="VAR_000958" FT VARIANT 255 FT /note="L -> S (in PKU; haplotype 36; dbSNP:rs62642930)" FT /evidence="ECO:0000269|PubMed:2014802" FT /id="VAR_000960" FT VARIANT 255 FT /note="L -> V (in PKU; haplotypes 18,21; dbSNP:rs62642931)" FT /evidence="ECO:0000269|PubMed:1301187" FT /id="VAR_000959" FT VARIANT 257 FT /note="G -> C (in PKU; dbSNP:rs5030848)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000961" FT VARIANT 259 FT /note="A -> T (in PKU; haplotype 3; dbSNP:rs62642932)" FT /evidence="ECO:0000269|PubMed:9450897" FT /id="VAR_000962" FT VARIANT 259 FT /note="A -> V (in PKU; haplotypes 7,42; dbSNP:rs118203921)" FT /evidence="ECO:0000269|PubMed:1301187, FT ECO:0000269|PubMed:9634518" FT /id="VAR_000963" FT VARIANT 261 FT /note="R -> P (in PKU; dbSNP:rs5030849)" FT /evidence="ECO:0000269|PubMed:9101291" FT /id="VAR_000964" FT VARIANT 261 FT /note="R -> Q (in HPA and PKU; mild; haplotypes 1,2,4,22, FT 24,28; dbSNP:rs5030849)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:12501224, ECO:0000269|PubMed:1671810, FT ECO:0000269|PubMed:22513348, ECO:0000269|PubMed:23792259, FT ECO:0000269|PubMed:8889590, ECO:0000269|PubMed:9101291" FT /id="VAR_000965" FT VARIANT 263 FT /note="F -> L (in PKU; dbSNP:rs62642944)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000966" FT VARIANT 264 FT /note="H -> L (in PKU; dbSNP:rs199475580)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000967" FT VARIANT 265 FT /note="C -> G (in PKU; dbSNP:rs62517181)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000968" FT VARIANT 269 FT /note="I -> L (in non-PKUHPA; dbSNP:rs62508692)" FT /evidence="ECO:0000269|PubMed:9521426" FT /id="VAR_000969" FT VARIANT 270 FT /note="R -> K (in PKU; dbSNP:rs62514950)" FT /evidence="ECO:0000269|PubMed:11180595" FT /id="VAR_000970" FT VARIANT 270 FT /note="R -> S (in PKU; haplotype 1; dbSNP:rs62514951)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000971" FT VARIANT 271 FT /note="H -> Y (in PKU; dbSNP:rs62517164)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000972" FT VARIANT 273 FT /note="S -> F (in PKU; haplotype 7; dbSNP:rs62514953)" FT /evidence="ECO:0000269|PubMed:1301187" FT /id="VAR_000973" FT VARIANT 274 FT /note="K -> E (in PKU; dbSNP:rs142934616)" FT /evidence="ECO:0000269|PubMed:11180595, FT ECO:0000269|PubMed:11461196" FT /id="VAR_011573" FT VARIANT 275 FT /note="P -> L (in PKU; reduced activity; increased affinity FT for the substrate; mildly reduced substrate activation; FT decreased cofactor affinity; dbSNP:rs62508715)" FT /evidence="ECO:0000269|PubMed:12501224, FT ECO:0000269|PubMed:18538294" FT /id="VAR_068004" FT VARIANT 276 FT /note="M -> I (in PKU; dbSNP:rs62514954)" FT /evidence="ECO:0000269|PubMed:1301187" FT /id="VAR_000974" FT VARIANT 276 FT /note="M -> V (in PKU; haplotype 4; dbSNP:rs62516149)" FT /evidence="ECO:0000269|PubMed:8068076" FT /id="VAR_000975" FT VARIANT 277 FT /note="Y -> C (in PKU; dbSNP:rs62516155)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000976" FT VARIANT 277 FT /note="Y -> D (in PKU; haplotype 2; dbSNP:rs78655458)" FT /evidence="ECO:0000269|PubMed:1301187" FT /id="VAR_000977" FT VARIANT 278 FT /note="T -> A (in PKU; dbSNP:rs62516156)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000978" FT VARIANT 278 FT /note="T -> N (in PKU; dbSNP:rs62507262)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000979" FT VARIANT 280 FT /note="E -> K (in PKU; haplotypes 1,2,4,16,38; partial FT residual activity; dbSNP:rs62508698)" FT /evidence="ECO:0000269|PubMed:22513348, FT ECO:0000269|PubMed:2564729, ECO:0000269|PubMed:8889590, FT ECO:0000269|PubMed:9101291" FT /id="VAR_000980" FT VARIANT 281 FT /note="P -> L (in PKU; haplotypes 1,4; dbSNP:rs5030851)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:12501224, ECO:0000269|PubMed:1672290, FT ECO:0000269|PubMed:1672294, ECO:0000269|PubMed:22513348, FT ECO:0000269|PubMed:8889590, ECO:0000269|PubMed:9101291" FT /id="VAR_000981" FT VARIANT 282 FT /note="D -> N (in PKU; haplotype 1; dbSNP:rs199475582)" FT /evidence="ECO:0000269|PubMed:9634518" FT /id="VAR_000982" FT VARIANT 283 FT /note="I -> F (in PKU; haplotype 21; dbSNP:rs62517168)" FT /evidence="ECO:0000269|PubMed:9634518" FT /id="VAR_000983" FT VARIANT 283 FT /note="I -> N (in PKU; severe; dbSNP:rs62508693)" FT /evidence="ECO:0000269|PubMed:9521426" FT /id="VAR_000984" FT VARIANT 290 FT /note="H -> Y (in PKU; dbSNP:rs1486763160)" FT /evidence="ECO:0000269|PubMed:22526846" FT /id="VAR_067758" FT VARIANT 297 FT /note="R -> C (in PKU; haplotype 4; dbSNP:rs62642945)" FT /evidence="ECO:0000269|PubMed:9101291" FT /id="VAR_000985" FT VARIANT 297 FT /note="R -> H (in PKU; dbSNP:rs62642939)" FT /evidence="ECO:0000269|PubMed:9101291" FT /id="VAR_000986" FT VARIANT 299 FT /note="F -> C (in PKU; haplotype 8; dbSNP:rs62642933)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:11385716, ECO:0000269|PubMed:8889590" FT /id="VAR_000987" FT VARIANT 300 FT /note="A -> S (in PKU and HPA; haplotype 1; does not affect FT oligomerization; reduction in activity is probably due to a FT global conformational change in the protein that reduces FT allostery; dbSNP:rs5030853)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:11180595, ECO:0000269|PubMed:12501224, FT ECO:0000269|PubMed:18538294, ECO:0000269|PubMed:22513348, FT ECO:0000269|PubMed:23792259" FT /id="VAR_000988" FT VARIANT 300 FT /note="A -> V (in PKU; dbSNP:rs199475609)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000989" FT VARIANT 303 FT /note="S -> P (in PKU; haplotype 5; dbSNP:rs199475608)" FT /evidence="ECO:0000269|PubMed:9634518" FT /id="VAR_000990" FT VARIANT 304 FT /note="Q -> R (in PKU; dbSNP:rs199475592)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000991" FT VARIANT 306 FT /note="I -> V (in non-PKUHPA and PKU; haplotype 4; FT dbSNP:rs62642934)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:1358789, ECO:0000269|PubMed:23792259" FT /id="VAR_000992" FT VARIANT 309 FT /note="A -> D (in PKU; haplotype 7; dbSNP:rs62642935)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000993" FT VARIANT 309 FT /note="A -> V (in PKU; dbSNP:rs62642935)" FT /evidence="ECO:0000269|PubMed:10679941" FT /id="VAR_000994" FT VARIANT 310 FT /note="S -> F (in PKU; haplotype 7; dbSNP:rs62642913)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_000995" FT VARIANT 310 FT /note="S -> Y (in HPA; reduction in activity is probably FT due to a global conformational change in the protein that FT reduces allostery; dbSNP:rs62642913)" FT /evidence="ECO:0000269|PubMed:12501224, FT ECO:0000269|PubMed:18538294" FT /id="VAR_068005" FT VARIANT 311 FT /note="L -> P (in PKU; haplotypes 1,7,10; FT dbSNP:rs62642936)" FT /evidence="ECO:0000269|PubMed:11180595, FT ECO:0000269|PubMed:2615649, ECO:0000269|PubMed:2840952" FT /id="VAR_000996" FT VARIANT 314 FT /note="P -> H (in PKU; dbSNP:rs62642940)" FT /evidence="ECO:0000269|PubMed:9634518" FT /id="VAR_000997" FT VARIANT 314 FT /note="P -> S (in HPA; does not affect oligomerization; FT reduction in activity is probably due to a global FT conformational change in the protein that reduces FT allostery; dbSNP:rs199475650)" FT /evidence="ECO:0000269|PubMed:12501224, FT ECO:0000269|PubMed:18538294" FT /id="VAR_068006" FT VARIANT 318 FT /note="I -> T (in PKU; partial loss of activity; FT dbSNP:rs62642918)" FT /evidence="ECO:0000269|PubMed:11180595, FT ECO:0000269|PubMed:11461196" FT /id="VAR_011574" FT VARIANT 322 FT /note="A -> G (in PKU; haplotype 12; dbSNP:rs62514958)" FT /evidence="ECO:0000269|PubMed:1301187" FT /id="VAR_000998" FT VARIANT 322 FT /note="A -> T (in PKU; haplotype 1; dbSNP:rs62514957)" FT /evidence="ECO:0000269|PubMed:1301187, FT ECO:0000269|PubMed:9101291" FT /id="VAR_000999" FT VARIANT 322 FT /note="A -> V (in PKU; dbSNP:rs62514958)" FT /evidence="ECO:0000269|PubMed:22526846" FT /id="VAR_067759" FT VARIANT 325 FT /note="Y -> C (in PKU; dbSNP:rs62508578)" FT /evidence="ECO:0000269|PubMed:10679941" FT /id="VAR_009245" FT VARIANT 330 FT /note="E -> D (in PKU; dbSNP:rs62508580)" FT /evidence="ECO:0000269|PubMed:10679941" FT /id="VAR_009246" FT VARIANT 331 FT /note="F -> L (in PKU; haplotype 1; dbSNP:rs62517179)" FT /evidence="ECO:0000269|PubMed:7833954, FT ECO:0000269|PubMed:9634518" FT /id="VAR_001000" FT VARIANT 333 FT /note="L -> F (in PKU; dbSNP:rs62516060)" FT /evidence="ECO:0000269|PubMed:9634518" FT /id="VAR_001001" FT VARIANT 334 FT /note="C -> S (in PKU; dbSNP:rs62517174)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_001002" FT VARIANT 337 FT /note="G -> V (in PKU; dbSNP:rs62517206)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_001003" FT VARIANT 338 FT /note="D -> Y (in PKU; haplotype 4; dbSNP:rs62516150)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_001004" FT VARIANT 341 FT /note="K -> R (in PKU; dbSNP:rs62516153)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_001005" FT VARIANT 341 FT /note="K -> T (in PKU; dbSNP:rs62516153)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_001006" FT VARIANT 342 FT /note="A -> T (in PKU; haplotype 5; dbSNP:rs62507282)" FT /evidence="ECO:0000269|PubMed:9634518" FT /id="VAR_001007" FT VARIANT 343 FT /note="Y -> C (in PKU; dbSNP:rs62507265)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_001008" FT VARIANT 344 FT /note="G -> R (in PKU; dbSNP:rs62508679)" FT /evidence="ECO:0000269|PubMed:10679941" FT /id="VAR_009247" FT VARIANT 344 FT /note="G -> V (in PKU; dbSNP:rs62508582)" FT /evidence="ECO:0000269|PubMed:10679941" FT /id="VAR_009248" FT VARIANT 345 FT /note="A -> S (in PKU; dbSNP:rs62516062)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_001009" FT VARIANT 345 FT /note="A -> T (in PKU; haplotype 7; dbSNP:rs62516062)" FT /evidence="ECO:0000269|PubMed:1301187" FT /id="VAR_001010" FT VARIANT 347 FT /note="L -> F (in PKU; dbSNP:rs62516154)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_001011" FT VARIANT 348 FT /note="L -> V (in PKU; mild haplotype 9; dbSNP:rs62516092)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:11180595, ECO:0000269|PubMed:1301187" FT /id="VAR_001012" FT VARIANT 349 FT /note="S -> L (in PKU; severe; dbSNP:rs62507279)" FT /evidence="ECO:0000269|PubMed:9600453" FT /id="VAR_001013" FT VARIANT 349 FT /note="S -> P (in PKU; haplotypes 1,4; dbSNP:rs62508646)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:22513348" FT /id="VAR_001014" FT VARIANT 350 FT /note="S -> T (in PKU; haplotype 2; dbSNP:rs62517183)" FT /evidence="ECO:0000269|PubMed:9634518" FT /id="VAR_001015" FT VARIANT 357 FT /note="C -> G (in PKU; dbSNP:rs62508595)" FT /evidence="ECO:0000269|PubMed:11180595" FT /id="VAR_011575" FT VARIANT 362 FT /note="P -> T (in PKU; dbSNP:rs62507329)" FT /evidence="ECO:0000269|PubMed:10200057" FT /id="VAR_001016" FT VARIANT 364..368 FT /note="Missing (in PKU; dbSNP:rs62516096)" FT /evidence="ECO:0000269|PubMed:1363837" FT /id="VAR_001018" FT VARIANT 364 FT /note="Missing (in PKU; haplotype 5; dbSNP:rs62516096)" FT /evidence="ECO:0000269|PubMed:1975559" FT /id="VAR_001017" FT VARIANT 366 FT /note="P -> H (in PKU; dbSNP:rs62516098)" FT /evidence="ECO:0000269|PubMed:9634518" FT /id="VAR_001019" FT VARIANT 372 FT /note="T -> S (in PKU; dbSNP:rs62517163)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_001020" FT VARIANT 377 FT /note="Y -> C (in PKU; haplotype 4; dbSNP:rs62642942)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_001021" FT VARIANT 380 FT /note="T -> M (in non-PKUHPA and PKU; haplotype 4; FT dbSNP:rs62642937)" FT /evidence="ECO:0000269|PubMed:23792259, FT ECO:0000269|PubMed:9101291" FT /id="VAR_001022" FT VARIANT 386 FT /note="Y -> C (in PKU; dbSNP:rs62516141)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:11385716" FT /id="VAR_001023" FT VARIANT 387 FT /note="Y -> H (in PKU; haplotype 1; dbSNP:rs62517194)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_001024" FT VARIANT 388 FT /note="V -> L (in PKU; dbSNP:rs62516101)" FT /evidence="ECO:0000269|PubMed:9101291, FT ECO:0000269|PubMed:9452061" FT /id="VAR_001025" FT VARIANT 388 FT /note="V -> M (in PKU; haplotypes 1,4; dbSNP:rs62516101)" FT /evidence="ECO:0000269|PubMed:11385716, FT ECO:0000269|PubMed:9101291" FT /id="VAR_001026" FT VARIANT 390 FT /note="E -> G (in PKU and non-PKUHPA; haplotype 4; FT dbSNP:rs5030856)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:11180595, ECO:0000269|PubMed:12501224, FT ECO:0000269|PubMed:22513348, ECO:0000269|PubMed:23792259, FT ECO:0000269|PubMed:8098245, ECO:0000269|PubMed:8889590" FT /id="VAR_001027" FT VARIANT 394 FT /note="D -> A (in PKU; dbSNP:rs62516102)" FT /evidence="ECO:0000269|PubMed:9634518" FT /id="VAR_001028" FT VARIANT 394 FT /note="D -> H (in PKU; dbSNP:rs62516142)" FT /evidence="ECO:0000269|PubMed:8889590" FT /id="VAR_001029" FT VARIANT 395 FT /note="A -> G (in PKU; dbSNP:rs62508736)" FT /evidence="ECO:0000269|PubMed:9634518" FT /id="VAR_001030" FT VARIANT 395 FT /note="A -> P (in PKU; haplotype 1; dbSNP:rs62516103)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:9634518" FT /id="VAR_001031" FT VARIANT 403 FT /note="A -> V (in non-PKUHPA and PKU; haplotype 43; FT dbSNP:rs5030857)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:11385716, ECO:0000269|PubMed:12501224, FT ECO:0000269|PubMed:22513348, ECO:0000269|PubMed:23792259, FT ECO:0000269|PubMed:8889590" FT /id="VAR_001033" FT VARIANT 407 FT /note="P -> L (in PKU; dbSNP:rs62644473)" FT /evidence="ECO:0000269|PubMed:9950317" FT /id="VAR_068007" FT VARIANT 407 FT /note="P -> S (in PKU; dbSNP:rs62644465)" FT /evidence="ECO:0000269|PubMed:11385716" FT /id="VAR_011576" FT VARIANT 408 FT /note="R -> Q (in PKU; haplotypes 4,12; dbSNP:rs5030859)" FT /evidence="ECO:0000269|PubMed:1355066, FT ECO:0000269|PubMed:9101291" FT /id="VAR_001034" FT VARIANT 408 FT /note="R -> W (in HPA and PKU; haplotypes FT 1,2,4,5,13,34,41,44; most common mutation; reduction in FT activity is probably due to a global conformational change FT in the protein that reduces allostery; dbSNP:rs5030858)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:12501224, ECO:0000269|PubMed:1355066, FT ECO:0000269|PubMed:18538294, ECO:0000269|PubMed:22513348, FT ECO:0000269|PubMed:23792259, ECO:0000269|PubMed:8889590, FT ECO:0000269|PubMed:9101291, ECO:0000269|PubMed:9452062, FT ECO:0000269|PubMed:9600453" FT /id="VAR_001035" FT VARIANT 410 FT /note="F -> S (in PKU; mild; dbSNP:rs62644475)" FT /evidence="ECO:0000269|PubMed:10679941" FT /id="VAR_009249" FT VARIANT 413 FT /note="R -> P (in non-PKUHPA and PKU; haplotype 4; FT dbSNP:rs79931499)" FT /evidence="ECO:0000269|PubMed:12501224, FT ECO:0000269|PubMed:9101291, ECO:0000269|PubMed:9852673" FT /id="VAR_001036" FT VARIANT 413 FT /note="R -> S (in PKU; haplotype 1; dbSNP:rs62644467)" FT /evidence="ECO:0000269|PubMed:9101291" FT /id="VAR_001037" FT VARIANT 414 FT /note="Y -> C (in HPA and PKU; haplotype 4; does not affect FT oligomerization; reduction in activity is probably due to a FT global conformational change in the protein that reduces FT allostery; dbSNP:rs5030860)" FT /evidence="ECO:0000269|PubMed:10679941, FT ECO:0000269|PubMed:11385716, ECO:0000269|PubMed:12501224, FT ECO:0000269|PubMed:18538294, ECO:0000269|PubMed:8889590" FT /id="VAR_001038" FT VARIANT 415 FT /note="D -> N (in PKU, HPA and non-PKUHPA; haplotype 1; FT dbSNP:rs62644499)" FT /evidence="ECO:0000269|PubMed:12501224, FT ECO:0000269|PubMed:1358789, ECO:0000269|PubMed:22513348, FT ECO:0000269|PubMed:9101291" FT /id="VAR_001039" FT VARIANT 417 FT /note="Y -> H (in PKU; reduction in activity is probably FT due to a global conformational change in the protein that FT reduces allostery; dbSNP:rs62644471)" FT /evidence="ECO:0000269|PubMed:12501224, FT ECO:0000269|PubMed:18538294" FT /id="VAR_068008" FT VARIANT 418 FT /note="T -> P (in PKU; haplotype 4; dbSNP:rs62644501)" FT /evidence="ECO:0000269|PubMed:1301187" FT /id="VAR_001040" FT VARIANT 421 FT /note="I -> S (in PKU; dbSNP:rs199475696)" FT /evidence="ECO:0000269|PubMed:22526846" FT /id="VAR_067760" FT VARIANT 430 FT /note="L -> P (in PKU; dbSNP:rs199475607)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_001041" FT VARIANT 447 FT /note="A -> D (in PKU; dbSNP:rs76542238)" FT /evidence="ECO:0000269|PubMed:32668217" FT /id="VAR_001042" FT MUTAGEN 283 FT /note="I->C: Loss of positive cooperativity and reduction FT of fold-activation by L-Phe preincubation." FT /evidence="ECO:0000269|PubMed:18835579" FT CONFLICT 183 FT /note="E -> G (in Ref. 3; AAH26251)" FT /evidence="ECO:0000305" FT STRAND 35..42 FT /evidence="ECO:0007829|PDB:5FII" FT HELIX 47..57 FT /evidence="ECO:0007829|PDB:5FII" FT STRAND 62..69 FT /evidence="ECO:0007829|PDB:5FII" FT STRAND 71..73 FT /evidence="ECO:0007829|PDB:6HYC" FT STRAND 76..83 FT /evidence="ECO:0007829|PDB:5FII" FT HELIX 85..90 FT /evidence="ECO:0007829|PDB:5FII" FT HELIX 91..102 FT /evidence="ECO:0007829|PDB:5FII" FT STRAND 105..108 FT /evidence="ECO:0007829|PDB:5FII" FT HELIX 125..133 FT /evidence="ECO:0007829|PDB:1J8U" FT STRAND 135..138 FT /evidence="ECO:0007829|PDB:1PAH" FT HELIX 140..142 FT /evidence="ECO:0007829|PDB:1J8U" FT TURN 147..150 FT /evidence="ECO:0007829|PDB:1J8U" FT HELIX 152..167 FT /evidence="ECO:0007829|PDB:1J8U" FT STRAND 170..172 FT /evidence="ECO:0007829|PDB:6N1K" FT HELIX 181..201 FT /evidence="ECO:0007829|PDB:1J8U" FT HELIX 204..217 FT /evidence="ECO:0007829|PDB:1J8U" FT HELIX 227..238 FT /evidence="ECO:0007829|PDB:1J8U" FT STRAND 241..244 FT /evidence="ECO:0007829|PDB:1J8U" FT STRAND 246..248 FT /evidence="ECO:0007829|PDB:1MMT" FT HELIX 251..259 FT /evidence="ECO:0007829|PDB:1J8U" FT STRAND 262..265 FT /evidence="ECO:0007829|PDB:1J8U" FT HELIX 283..289 FT /evidence="ECO:0007829|PDB:1J8U" FT HELIX 291..294 FT /evidence="ECO:0007829|PDB:1J8U" FT HELIX 297..310 FT /evidence="ECO:0007829|PDB:1J8U" FT HELIX 315..327 FT /evidence="ECO:0007829|PDB:1J8U" FT TURN 328..331 FT /evidence="ECO:0007829|PDB:1J8U" FT STRAND 333..336 FT /evidence="ECO:0007829|PDB:1J8U" FT STRAND 339..342 FT /evidence="ECO:0007829|PDB:1J8U" FT HELIX 345..348 FT /evidence="ECO:0007829|PDB:1J8U" FT HELIX 351..357 FT /evidence="ECO:0007829|PDB:1J8U" FT STRAND 359..366 FT /evidence="ECO:0007829|PDB:1J8U" FT HELIX 369..372 FT /evidence="ECO:0007829|PDB:1J8U" FT STRAND 379..381 FT /evidence="ECO:0007829|PDB:1J8U" FT STRAND 384..390 FT /evidence="ECO:0007829|PDB:1J8U" FT HELIX 392..403 FT /evidence="ECO:0007829|PDB:1J8U" FT STRAND 409..415 FT /evidence="ECO:0007829|PDB:1J8U" FT TURN 416..419 FT /evidence="ECO:0007829|PDB:1J8U" FT STRAND 420..424 FT /evidence="ECO:0007829|PDB:1J8U" FT HELIX 428..439 FT /evidence="ECO:0007829|PDB:6N1K" SQ 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 //