ID PH4H_DROME STANDARD; PRT; 452 AA. AC P17276; O46110; Q27599; Q27600; DT 01-AUG-1990 (Rel. 15, Created) DT 16-OCT-2001 (Rel. 40, Last sequence update) DT 05-JUL-2004 (Rel. 44, Last annotation update) DE Protein henna [Includes: Phenylalanine-4-hydroxylase (EC 1.14.16.1) DE (PAH) (Phe-4-monooxygenase); Tryptophan 5-monooxygenase (EC 1.14.16.4) DE (TRH) (Tryptophan 5-hydroxylase)]. GN Name=Hn; Synonyms=Tph, pah; ORFNames=CG7399; OS Drosophila melanogaster (Fruit fly). OC Eukaryota; Metazoa; Arthropoda; Hexapoda; Insecta; Pterygota; OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; OC Ephydroidea; Drosophilidae; Drosophila. OX NCBI_TaxID=7227; RN [1] RP SEQUENCE FROM N.A. RC STRAIN=Canton-S, and Oregon-R; TISSUE=Embryo, and Head; RX MEDLINE=92156168; PubMed=1371286; 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 SEQUENCE FROM N.A. RX MEDLINE=91033030; PubMed=2121612; 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 SEQUENCE FROM N.A. RC STRAIN=Canton-S; RX MEDLINE=96332435; PubMed=8769124; RA Ruiz-Vazquez P., Moulard M., Silva F.J.; RT "Structure of the phenylalanine hydroxylase gene in Drosophila RT melanogaster and evidence of alternative promoter usage."; RL Biochem. Biophys. Res. Commun. 225:238-242(1996). RN [4] RP SEQUENCE FROM N.A. RC STRAIN=Berkeley; RX MEDLINE=20196006; 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., RA Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., RA Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., RA Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., RA Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., RA Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., RA Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., RA Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., RA Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., RA de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., RA Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., RA Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., RA Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., RA 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., RA Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., RA Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., RA Kimmel B.E., Kodira C.D., Kraft C., Kravitz S., Kulp D., Lai Z., RA Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., RA Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., RA Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., RA Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., RA Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., RA Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., RA Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., RA Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T., RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., RA Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., RA Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., RA Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., RA Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., RA Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S., Zhu X., Smith H.O., RA Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.; RT "The genome sequence of Drosophila melanogaster."; RL Science 287:2185-2195(2000). RN [5] RP SEQUENCE FROM N.A. RC STRAIN=Berkeley; TISSUE=Head; RX MEDLINE=22426066; PubMed=12537569; RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., RA George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., RA Rubin G.M., Celniker S.E.; RT "A Drosophila full-length cDNA resource."; RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002). RN [6] RP SEQUENCE OF 5-93 AND 161-412 FROM N.A. (MUTANT HN-R3). RX MEDLINE=99266112; PubMed=10333570; RA Ruiz-Vazquez P., Silva F.J.; RT "Aberrant splicing of the Drosophila melanogaster phenylalanine RT hydroxylase pre-mRNA caused by the insertion of a B104/roo RT transposable element in the Henna locus."; RL Insect Biochem. Mol. Biol. 29:311-318(1999). CC -!- CATALYTIC ACTIVITY: L-phenylalanine + tetrahydrobiopterin + O(2) = CC L-tyrosine + 4a-hydroxytetrahydrobiopterin. CC -!- CATALYTIC ACTIVITY: L-tryptophan + tetrahydrobiopterin + O(2) = 5- CC hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin. CC -!- COFACTOR: Ferrous ion. CC -!- ENZYME 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 CC domain in the C-terminal portion of the molecule. CC -!- PATHWAY: Catabolism of phenylalanine; first (rate-limiting) step. CC -!- TISSUE SPECIFICITY: Phenylalanine hydrolase activity is found in CC yolk 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 CC to be encoded by the same gene. Preference for the substrate is CC probably due to post-translational modifications such as CC phosphorylation, or by changes in the N-terminal regulatory CC domain. CC -!- SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid CC hydroxylase family. 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. DR EMBL; M32802; AAA69513.1; -. DR EMBL; X98116; CAA66797.1; -. DR EMBL; X98116; CAA66798.1; -. DR EMBL; AE003558; AAF50517.1; -. DR EMBL; AY069306; AAL39451.1; -. DR EMBL; AJ001718; CAA04950.1; -. DR EMBL; AJ001719; CAB51601.1; -. DR EMBL; AJ001720; CAB51601.1; JOINED. DR EMBL; AJ001722; CAB51599.1; -. DR EMBL; AJ001723; CAB51597.1; -. DR PIR; A42271; A42271. DR PIR; JC4888; JC4888. DR PIR; JQ0766; JQ0766. DR HSSP; P00439; 2PAH. DR IntAct; P17276; -. DR FlyBase; FBgn0001208; Hn. DR InterPro; IPR001273; Aaa_hydroxylase. DR InterPro; IPR002912; ACT. DR InterPro; IPR005961; Phe4hydrxlaseTet. DR Pfam; PF01842; ACT; 1. DR Pfam; PF00351; Biopterin_H; 1. DR PRINTS; PR00372; FYWHYDRXLASE. DR ProDom; PD002559; Aaa_hydroxylase; 1. DR TIGRFAMs; TIGR01268; Phe4hydrox_tetr; 1. DR PROSITE; PS00367; BIOPTERIN_HYDROXYL; 1. KW Allosteric enzyme; Iron; Monooxygenase; Oxidoreductase; KW Phenylalanine catabolism; Phosphorylation; Serotonin biosynthesis. FT MOD_RES 272 272 Phosphoserine (by CaMK2) (By similarity). FT METAL 284 284 Iron (By similarity). FT METAL 289 289 Iron (By similarity). FT METAL 329 329 Iron (By similarity). FT CONFLICT 28 28 E -> A (in Ref. 2). FT CONFLICT 39 47 KDSSLSSGA -> RIRRCPAEL (in Ref. 2). FT CONFLICT 55 56 FK -> LR (in Ref. 2). FT CONFLICT 63 71 VHIESRSSL -> CILSRILAPWF (in Ref. 2). FT CONFLICT 74 114 PGYEFFVEADGKSGALGKAIEDVKEQCSYFNIISRDYKDNA FT -> SSCFWRRMENRSLGKSHRGCEGAMLATLTSSCRELQGV FT MP (in Ref. 2). FT CONFLICT 154 154 R -> A (in Ref. 2). FT CONFLICT 164 164 A -> G (in Ref. 2). FT CONFLICT 171 171 E -> Q (in Ref. 2). FT CONFLICT 264 264 S -> C (in Ref. 2). FT CONFLICT 297 297 A -> S (in Ref. 2). FT CONFLICT 332 332 V -> L (in Ref. 1 and 2). FT CONFLICT 333 335 CRQ -> LAK (in Ref. 2). FT CONFLICT 370 370 V -> S (in Ref. 2). FT CONFLICT 449 452 KLRV -> NCASE (in Ref. 1). 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 //