ID PH4H_DROME Reviewed; 452 AA. AC P17276; O46110; Q27599; Q27600; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 3. DT 27-MAR-2024, entry version 210. DE RecName: Full=Protein henna; DE EC=1.14.16.1; DE EC=1.14.16.4; DE AltName: Full=Phe-4-monooxygenase; DE AltName: Full=Phenylalanine-4-hydroxylase; DE Short=PAH; DE AltName: Full=Tryptophan 5-hydroxylase; DE Short=TRH; DE AltName: Full=Tryptophan 5-monooxygenase; GN Name=Hn; Synonyms=pah, Tph; ORFNames=CG7399; OS Drosophila melanogaster (Fruit fly). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; OC Drosophilidae; Drosophila; Sophophora. OX NCBI_TaxID=7227; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RC STRAIN=Canton-S, and Oregon-R; TISSUE=Embryo, and Head; RX PubMed=1371286; DOI=10.1016/s0021-9258(19)50648-2; RA Neckameyer W.S., White K.; RT "A single locus encodes both phenylalanine hydroxylase and tryptophan RT hydroxylase activities in Drosophila."; RL J. Biol. Chem. 267:4199-4206(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2121612; DOI=10.1016/0378-1119(90)90227-i; RA Morales G., Requena J.M., Jimenez-Ruiz A., Lopez M.C., Ugarte M., RA Alonso C.; RT "Sequence and expression of the Drosophila phenylalanine hydroxylase RT mRNA."; RL Gene 93:213-219(1990). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=Canton-S; RX PubMed=8769124; DOI=10.1006/bbrc.1996.1160; RA Ruiz-Vazquez P., Moulard M., Silva F.J.; RT "Structure of the phenylalanine hydroxylase gene in Drosophila melanogaster RT and evidence of alternative promoter usage."; RL Biochem. Biophys. Res. Commun. 225:238-242(1996). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley; RX PubMed=10731132; DOI=10.1126/science.287.5461.2185; RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C., RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., RA Venter J.C.; RT "The genome sequence of Drosophila melanogaster."; RL Science 287:2185-2195(2000). RN [5] RP GENOME REANNOTATION. RC STRAIN=Berkeley; RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083; RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A., RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic RT review."; RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Berkeley; TISSUE=Head; RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080; RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., RA Celniker S.E.; RT "A Drosophila full-length cDNA resource."; RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 5-93 AND 161-412 (MUTANT RP HN-R3). RX PubMed=10333570; DOI=10.1016/s0965-1748(99)00002-8; RA Ruiz-Vazquez P., Silva F.J.; RT "Aberrant splicing of the Drosophila melanogaster phenylalanine hydroxylase RT pre-mRNA caused by the insertion of a B104/roo transposable element in the RT Henna locus."; RL Insect Biochem. Mol. Biol. 29:311-318(1999). 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; CC -!- CATALYTIC ACTIVITY: CC Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tryptophan + O2 CC = (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin + 5- CC hydroxy-L-tryptophan; Xref=Rhea:RHEA:16709, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:15642, ChEBI:CHEBI:57912, ChEBI:CHEBI:58266, CC ChEBI:CHEBI:59560; EC=1.14.16.4; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; 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 -!- PATHWAY: Amino-acid degradation; L-phenylalanine degradation; CC acetoacetate and fumarate from L-phenylalanine: step 1/6. CC -!- TISSUE SPECIFICITY: Phenylalanine hydrolase activity is found in yolk CC granules of embryos, and female abdomen and fat body tissues. CC Tryptophan hydroxylase is expressed in serotonergic neurons. Both CC enzymes are present in cuticular tissues. CC -!- MISCELLANEOUS: In Drosophila, the 2 enzymes, PAH and TRH are found to CC be encoded by the same gene. Preference for the substrate is probably CC due to post-translational modifications such as phosphorylation, or by CC changes in the N-terminal regulatory domain. CC -!- SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid CC hydroxylase family. {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; M81833; -; NOT_ANNOTATED_CDS; Genomic_RNA. DR EMBL; M32802; AAA69513.1; -; mRNA. DR EMBL; X98116; CAA66797.1; -; Genomic_DNA. DR EMBL; X98116; CAA66798.1; -; Genomic_DNA. DR EMBL; AE014296; AAF50517.1; -; Genomic_DNA. DR EMBL; AY069306; AAL39451.1; -; mRNA. DR EMBL; AJ001718; CAA04950.1; -; Genomic_DNA. DR EMBL; AJ001719; CAB51601.1; -; Genomic_DNA. DR EMBL; AJ001720; CAB51601.1; JOINED; Genomic_DNA. DR EMBL; AJ001722; CAB51599.1; -; mRNA. DR EMBL; AJ001723; CAB51597.1; -; mRNA. DR PIR; A42271; A42271. DR PIR; JC4888; JC4888. DR PIR; JQ0766; JQ0766. DR RefSeq; NP_001014573.1; NM_001014573.2. DR RefSeq; NP_001261542.1; NM_001274613.1. DR RefSeq; NP_523963.2; NM_079239.4. DR AlphaFoldDB; P17276; -. DR SMR; P17276; -. DR BioGRID; 64301; 42. DR DIP; DIP-20514N; -. DR IntAct; P17276; 14. DR STRING; 7227.FBpp0076523; -. DR PaxDb; 7227-FBpp0076523; -. DR DNASU; 38871; -. DR EnsemblMetazoa; FBtr0076811; FBpp0076523; FBgn0001208. DR EnsemblMetazoa; FBtr0334645; FBpp0306707; FBgn0001208. DR GeneID; 38871; -. DR KEGG; dme:Dmel_CG7399; -. DR AGR; FB:FBgn0001208; -. DR CTD; 38871; -. DR FlyBase; FBgn0001208; Hn. DR VEuPathDB; VectorBase:FBgn0001208; -. DR eggNOG; KOG3820; Eukaryota. DR GeneTree; ENSGT00950000182885; -. DR InParanoid; P17276; -. DR OMA; FHDEVYR; -. DR OrthoDB; 275463at2759; -. DR PhylomeDB; P17276; -. DR Reactome; R-DME-8964208; Phenylalanine metabolism. DR SignaLink; P17276; -. DR UniPathway; UPA00139; UER00337. DR BioGRID-ORCS; 38871; 0 hits in 3 CRISPR screens. DR ChiTaRS; Hn; fly. DR GenomeRNAi; 38871; -. DR PRO; PR:P17276; -. DR Proteomes; UP000000803; Chromosome 3L. DR Bgee; FBgn0001208; Expressed in head capsule and 19 other cell types or tissues. DR ExpressionAtlas; P17276; baseline and differential. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0004505; F:phenylalanine 4-monooxygenase activity; IDA:FlyBase. DR GO; GO:0004510; F:tryptophan 5-monooxygenase activity; IDA:FlyBase. DR GO; GO:0042416; P:dopamine biosynthetic process; IEP:FlyBase. DR GO; GO:0006726; P:eye pigment biosynthetic process; IDA:FlyBase. DR GO; GO:0007377; P:germ-band extension; IMP:FlyBase. DR GO; GO:0006559; P:L-phenylalanine catabolic process; IMP:FlyBase. DR GO; GO:0007616; P:long-term memory; IGI:FlyBase. DR GO; GO:0006587; P:serotonin biosynthetic process from tryptophan; IMP:FlyBase. DR GO; GO:0006571; P:tyrosine biosynthetic process; IBA:GO_Central. DR CDD; cd04904; ACT_AAAH; 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; 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 Genevisible; P17276; DM. PE 2: Evidence at transcript level; KW Allosteric enzyme; Iron; Metal-binding; Monooxygenase; Oxidoreductase; KW Phenylalanine catabolism; Phosphoprotein; Reference proteome; KW Serotonin biosynthesis. FT CHAIN 1..452 FT /note="Protein henna" FT /id="PRO_0000205552" FT DOMAIN 36..107 FT /note="ACT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01007" FT BINDING 284 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000250" FT BINDING 289 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000250" FT BINDING 329 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000250" FT MOD_RES 272 FT /note="Phosphoserine; by CaMK2" FT /evidence="ECO:0000250" FT CONFLICT 28 FT /note="E -> A (in Ref. 2; AAA69513)" FT /evidence="ECO:0000305" FT CONFLICT 39..47 FT /note="KDSSLSSGA -> RIRRCPAEL (in Ref. 2; AAA69513)" FT /evidence="ECO:0000305" FT CONFLICT 55..56 FT /note="FK -> LR (in Ref. 2; AAA69513)" FT /evidence="ECO:0000305" FT CONFLICT 63..71 FT /note="VHIESRSSL -> CILSRILAPWF (in Ref. 2; AAA69513)" FT /evidence="ECO:0000305" FT CONFLICT 74..114 FT /note="PGYEFFVEADGKSGALGKAIEDVKEQCSYFNIISRDYKDNA -> SSCFWRR FT MENRSLGKSHRGCEGAMLATLTSSCRELQGVMP (in Ref. 2; AAA69513)" FT /evidence="ECO:0000305" FT CONFLICT 154 FT /note="R -> A (in Ref. 2; AAA69513)" FT /evidence="ECO:0000305" FT CONFLICT 164 FT /note="A -> G (in Ref. 2; AAA69513)" FT /evidence="ECO:0000305" FT CONFLICT 171 FT /note="E -> Q (in Ref. 2; AAA69513)" FT /evidence="ECO:0000305" FT CONFLICT 264 FT /note="S -> C (in Ref. 2; AAA69513)" FT /evidence="ECO:0000305" FT CONFLICT 297 FT /note="A -> S (in Ref. 2; AAA69513)" FT /evidence="ECO:0000305" FT CONFLICT 332 FT /note="V -> L (in Ref. 1; M81833 and 2; AAA69513)" FT /evidence="ECO:0000305" FT CONFLICT 333..335 FT /note="CRQ -> LAK (in Ref. 2; AAA69513)" FT /evidence="ECO:0000305" FT CONFLICT 370 FT /note="V -> S (in Ref. 2; AAA69513)" FT /evidence="ECO:0000305" FT CONFLICT 449..452 FT /note="KLRV -> NCASE (in Ref. 1; M81833)" FT /evidence="ECO:0000305" SQ SEQUENCE 452 AA; 51660 MW; 990F554150056867 CRC64; MYQRQVSFDK PTRVEDSAYI VEGVDIKEAR NTCLLFSPKD SSLSSGALAN ILAIFKKHDI NLVHIESRSS LRVPGYEFFV EADGKSGALG KAIEDVKEQC SYFNIISRDY KDNATAVPWF PRRIRDLDRF ANQILSYGSE LDADHPGFTD PEYRKRRKYF ADIAYNYKHG EPLPHVDYTK EEIETWGIIF RNLTKLYKTH ACREYNHVFP LLVDNCGFRE DNIPQLEDVS NFLRDCTGFT LRPVAGLLSS RDFLAGLAFR VFHSTQYIRH PSKPMYTPEP DVCHELMGHV PLFADPAFAQ FSQEIGLASL GAPDDYIEKL STIFWFTVEY GVCRQEGELK AYGAGLLSSY GELEYCLTDK PQLKDFEPEV TGVTKYPITQ FQPLYYVADS FETAKEKTIK FANSIPRPFG VRYNAYTQSV EVLDSKPQIS NLMDNINSEF QILQNAVAKL RV //