ID PH4H_CAEEL Reviewed; 457 AA. AC P90925; I2HA98; Q9XYQ5; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2000, sequence version 2. DT 18-SEP-2019, entry version 148. DE RecName: Full=Phenylalanine-4-hydroxylase {ECO:0000303|PubMed:10928216}; DE Short=PAH; DE EC=1.14.16.1 {ECO:0000269|PubMed:10928216, ECO:0000269|PubMed:18460651}; DE EC=1.14.16.4 {ECO:0000269|PubMed:10928216}; DE AltName: Full=Biogenic amine synthesis protein 2; DE AltName: Full=Phe-4-monooxygenase; DE AltName: Full=Tryptophan 5-monooxygenase {ECO:0000305}; GN Name=pah-1; Synonyms=bas-2; ORFNames=K08F8.4; OS Caenorhabditis elegans. OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; OC Caenorhabditis. OX NCBI_TaxID=6239; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, CATALYTIC ACTIVITY, RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=10928216; DOI=10.3109/01677069909083472; RA Loer C.M., Davidson B., Mckerrow J.; RT "A phenylalanine hydroxylase gene from the nematode C. elegans is RT expressed in the hypodermis."; RL J. Neurogenet. 13:157-180(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Bristol N2; RX PubMed=9851916; DOI=10.1126/science.282.5396.2012; RG The C. elegans sequencing consortium; RT "Genome sequence of the nematode C. elegans: a platform for RT investigating biology."; RL Science 282:2012-2018(1998). RN [3] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL RP PROPERTIES, SUBUNIT, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE. 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). CC -!- FUNCTION: Catalyzes the hydroxylation of L-phenylalanine to L- CC tyrosine (PubMed:18460651, PubMed:10928216). Catalyzes the CC hydroxylation of tryptophan to 5-hydroxy-L-tryptophan CC (PubMed:10928216). Plays a role in the biosynthesis of a melanin- CC like cuticle pigment (PubMed:18460651). CC {ECO:0000269|PubMed:10928216, ECO:0000269|PubMed:18460651}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L- CC phenylalanine + O2 = (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8- CC tetrahydrobiopterin + L-tyrosine; Xref=Rhea:RHEA:20273, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:15642, ChEBI:CHEBI:58095, CC ChEBI:CHEBI:58315, ChEBI:CHEBI:59560; EC=1.14.16.1; CC Evidence={ECO:0000269|PubMed:10928216, CC ECO:0000269|PubMed:18460651}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tryptophan CC + O2 = (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin CC + 5-hydroxy-L-tryptophan; Xref=Rhea:RHEA:16709, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:15642, ChEBI:CHEBI:57912, CC ChEBI:CHEBI:58266, ChEBI:CHEBI:59560; EC=1.14.16.4; CC Evidence={ECO:0000269|PubMed:10928216}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000250|UniProtKB:P04176}; CC -!- ACTIVITY REGULATION: Inhibited by tetrahydrobiopterin. Unlike its CC mammalian orthologs, pah-1 does not exhibit allosteric binding CC behavior for phenylalanine. {ECO:0000269|PubMed:18460651}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=146 uM for L-phenylalanine (at 25 degrees Celsius) CC {ECO:0000269|PubMed:18460651}; CC KM=33 uM for tetrahydrobiopterin (BH(4)) (at 25 degrees Celsius) CC {ECO:0000269|PubMed:18460651}; CC Vmax=3.3 umol/min/mg enzyme towards L-phenylalanine (at 25 CC degrees Celsius) {ECO:0000269|PubMed:18460651}; CC Vmax=3.22 umol/min/mg enzyme towards tetrahydrobiopterin (BH(4)) CC (at 25 degrees Celsius) {ECO:0000269|PubMed:18460651}; CC -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation; CC acetoacetate and fumarate from L-phenylalanine: step 1/6. CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:18460651}. CC -!- INTERACTION: CC O01869:rps-10; NbExp=3; IntAct=EBI-318020, EBI-314419; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10928216}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=a; CC IsoId=P90925-1; Sequence=Displayed; CC Name=b; CC IsoId=P90925-2; Sequence=VSP_059801; CC -!- TISSUE SPECIFICITY: Expressed in the seam cells of the lateral CC hypodermis, in the ventral hypodermis and in the hyp7 hypodermal CC syncytium, in hypodermal cells in the tail and in body wall muscle CC cells (at protein level). {ECO:0000269|PubMed:10928216}. CC -!- DEVELOPMENTAL STAGE: Expressed during all larval stages and in CC adult animals (at protein level). {ECO:0000269|PubMed:10928216, CC ECO:0000269|PubMed:18460651}. CC -!- DISRUPTION PHENOTYPE: Reduced L-phenylalanine hydroxylation. Lack CC of a yellow-orange pheomelanine-like pigment in the cuticle. CC Higher cuticle resistance to physical or chemical disintegration CC factors or oxidizing environments. Increase in superoxide CC dismutase activity. Increased life span. In a bli-3(e767) mutant CC background, growth arrest in early larval development, severe CC cuticle abnormalities with large blisters and increased superoxide CC dismutase activity. {ECO:0000269|PubMed:18460651}. CC -!- SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid CC hydroxylase family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD31643.1; Type=Frameshift; Positions=66, 111; Evidence={ECO:0000305}; 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; AF119388; AAD31643.1; ALT_FRAME; mRNA. DR EMBL; Z66497; CAA91286.1; -; Genomic_DNA. DR EMBL; BX284602; CCH63805.1; -; Genomic_DNA. DR PIR; T23494; T23494. DR RefSeq; NP_001254184.1; NM_001267255.1. [P90925-2] DR RefSeq; NP_001254185.1; NM_001267256.1. [P90925-1] DR SMR; P90925; -. DR BioGrid; 39728; 5. DR DIP; DIP-25264N; -. DR IntAct; P90925; 17. DR STRING; 6239.K08F8.4a; -. DR EPD; P90925; -. DR PaxDb; P90925; -. DR PeptideAtlas; P90925; -. DR PRIDE; P90925; -. DR EnsemblMetazoa; K08F8.4a.1; K08F8.4a.1; WBGene00000240. [P90925-1] DR EnsemblMetazoa; K08F8.4b.1; K08F8.4b.1; WBGene00000240. [P90925-2] DR GeneID; 174401; -. DR KEGG; cel:CELE_K08F8.4; -. DR UCSC; K08F8.4; c. elegans. [P90925-1] DR CTD; 174401; -. DR WormBase; K08F8.4a; CE21050; WBGene00000240; pah-1. [P90925-1] DR WormBase; K08F8.4b; CE47563; WBGene00000240; pah-1. [P90925-2] DR eggNOG; KOG3820; Eukaryota. DR eggNOG; COG3186; LUCA. DR GeneTree; ENSGT00950000182885; -. DR HOGENOM; HOG000233373; -. DR InParanoid; P90925; -. DR KO; K00500; -. DR OMA; YEFFVEC; -. DR OrthoDB; 614557at2759; -. DR PhylomeDB; P90925; -. DR BRENDA; 1.14.16.1; 1045. DR Reactome; R-CEL-8964208; Phenylalanine metabolism. DR UniPathway; UPA00139; UER00337. DR PRO; PR:P90925; -. DR Proteomes; UP000001940; Chromosome II. DR Bgee; WBGene00000240; Expressed in 5 organ(s), highest expression level in material anatomical entity. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0004505; F:phenylalanine 4-monooxygenase activity; IDA:WormBase. DR GO; GO:0004510; F:tryptophan 5-monooxygenase activity; IDA:WormBase. DR GO; GO:0040002; P:collagen and cuticulin-based cuticle development; IGI:WormBase. DR GO; GO:0008340; P:determination of adult lifespan; IMP:WormBase. DR GO; GO:0006559; P:L-phenylalanine catabolic process; IDA:WormBase. DR GO; GO:0042438; P:melanin biosynthetic process; IMP:WormBase. DR GO; GO:0000003; P:reproduction; IMP:WormBase. DR GO; GO:0006979; P:response to oxidative stress; IMP:WormBase. DR GO; GO:0006569; P:tryptophan catabolic process; IDA:WormBase. DR GO; GO:0006571; P:tyrosine biosynthetic process; IDA:WormBase. DR CDD; cd03347; eu_PheOH; 1. DR Gene3D; 1.10.800.10; -; 1. 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 PANTHER; PTHR11473; PTHR11473; 1. DR Pfam; PF01842; ACT; 1. DR Pfam; PF00351; Biopterin_H; 1. DR PIRSF; PIRSF000336; TH; 1. DR PRINTS; PR00372; FYWHYDRXLASE. DR SUPFAM; SSF56534; SSF56534; 1. DR TIGRFAMs; TIGR01268; Phe4hydrox_tetr; 1. DR PROSITE; PS51671; ACT; 1. DR PROSITE; PS00367; BH4_AAA_HYDROXYL_1; 1. DR PROSITE; PS51410; BH4_AAA_HYDROXYL_2; 1. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; Cytoplasm; Iron; KW Metal-binding; Monooxygenase; Oxidoreductase; KW Phenylalanine catabolism; Reference proteome. FT CHAIN 1 457 Phenylalanine-4-hydroxylase. FT /FTId=PRO_0000205551. FT DOMAIN 31 108 ACT. {ECO:0000255|PROSITE- FT ProRule:PRU01007}. FT METAL 285 285 Iron; via tele nitrogen. FT {ECO:0000250|UniProtKB:P04176}. FT METAL 290 290 Iron; via tele nitrogen. FT {ECO:0000250|UniProtKB:P04176}. FT METAL 330 330 Iron; via tele nitrogen. FT {ECO:0000250|UniProtKB:P04176}. FT VAR_SEQ 1 12 MPPAGQDDLDFL -> MNIDEIRK (in isoform b). FT /FTId=VSP_059801. FT CONFLICT 251 251 S -> P (in Ref. 1; AAD31643). FT {ECO:0000305}. FT CONFLICT 258 258 L -> W (in Ref. 1; AAD31643). FT {ECO:0000305}. SQ SEQUENCE 457 AA; 52129 MW; 68365836DFEC8D4F CRC64; MPPAGQDDLD FLKYAMESYV ADVNADIGKT TIVFTLREKA GALAETLKLF QAHDVNLSHI ESRPSKTHEG CYEVLVEFAE AEDHRKIEGV IEHFQQKAEK KVLVQDWNTK NKQNKDSVPW FPQKINDIDQ FANRILSYGA ELDADHPGFK DMTYRERRKF FADIAFNFKH GDKIPTITYT DEEIATWRTV YNELTVMYPK NACQEFNYIF PLLQQNCGFG PDRIPQLQDV SDFLKDCTGY TIRPVAGLLS SRDFLAGLAF RVFHSTQYIR HHSAPKYTPE PDICHELLGH VPLFADVEFA QFSQEIGLAS LGAPDDVIEK LATLYWFTIE FGICQQDGEK KAYGAGLLSS FGELQYALSD KPEVVDFDPA VCCVTKYPIT EYQPKYFLAE SFASAKNKLK SWAATINRPF QIRYNAYTQR VEILDKVAAL QRLARDIRSD ISTLEEALGK VNNLKMK //