ID TPH1_CHICK Reviewed; 445 AA. AC P70080; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1997, sequence version 1. DT 02-SEP-2026, entry version 160. DE RecName: Full=Tryptophan 5-hydroxylase 1; DE EC=1.14.16.4 {ECO:0000250|UniProtKB:P17532}; DE AltName: Full=Tryptophan 5-monooxygenase 1; GN Name=TPH1; Synonyms=TPH; OS Gallus gallus (Chicken). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda; OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae; OC Phasianinae; Gallus. OX NCBI_TaxID=9031; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=White leghorn; TISSUE=Pineal gland; RX PubMed=8915576; DOI=10.1016/s0169-328x(96)00104-0; RA Florez J.C., Seidenman K.J., Barrett R.K., Sangoram A.M., Takahashi J.S.; RT "Molecular cloning of chick pineal tryptophan hydroxylase and circadian RT oscillation of its mRNA levels."; RL Brain Res. Mol. Brain Res. 42:25-30(1996). RN [2] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 101-414 IN COMPLEX WITH TRYPTOPHAN RP AND IMIDAZOLE, SUBUNIT, AND IRON-BINDING SITES. RX PubMed=18937498; DOI=10.1021/bi8015263; RA Windahl M.S., Petersen C.R., Christensen H.E., Harris P.; RT "Crystal structure of tryptophan hydroxylase with bound amino acid RT substrate."; RL Biochemistry 47:12087-12094(2008). CC -!- FUNCTION: Oxidizes L-tryptophan to 5-hydroxy-l-tryptophan in the rate- CC determining step of serotonin biosynthesis. CC {ECO:0000250|UniProtKB:P17532}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tryptophan + O2 CC = 5-hydroxy-L-tryptophan + (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8- CC tetrahydrobiopterin; 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 Evidence={ECO:0000250|UniProtKB:P17532}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; CC Evidence={ECO:0000269|PubMed:18937498}; CC -!- PATHWAY: Aromatic compound metabolism; serotonin biosynthesis; CC serotonin from L-tryptophan: step 1/2. {ECO:0000250|UniProtKB:P17532}. CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:18937498}. 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; U26428; AAC60036.1; -; mRNA. DR RefSeq; NP_990287.1; NM_204956.2. DR PDB; 3E2T; X-ray; 1.90 A; A=101-414. DR AlphaFoldDB; P70080; -. DR SMR; P70080; -. DR FunCoup; P70080; 26. DR STRING; 9031.ENSGALP00000063172; -. DR PaxDb; 9031-ENSGALP00000063172; -. DR GeneID; 395799; -. DR KEGG; gga:395799; -. DR CTD; 7166; -. DR VEuPathDB; HostDB:geneid_395799; -. DR eggNOG; KOG3820; Eukaryota. DR HOGENOM; CLU_023198_0_1_1; -. DR InParanoid; P70080; -. DR OMA; DMPWFPR; -. DR OrthoDB; 983542at2759; -. DR PhylomeDB; P70080; -. DR BRENDA; 1.14.16.4; 1306. DR UniPathway; UPA00846; UER00799. DR EvolutionaryTrace; P70080; -. DR PRO; PR:P70080; -. DR Proteomes; UP000000539; Unassembled WGS sequence. DR GO; GO:0043005; C:neuron projection; IBA:GO_Central. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0004510; F:tryptophan 5-monooxygenase activity; ISS:UniProtKB. DR GO; GO:0009072; P:aromatic amino acid metabolic process; IEA:InterPro. DR GO; GO:0002576; P:platelet degranulation; ISS:UniProtKB. DR GO; GO:1900046; P:regulation of hemostasis; ISS:UniProtKB. DR GO; GO:0042427; P:serotonin biosynthetic process; ISS:UniProtKB. DR CDD; cd04929; ACT_TPH; 1. DR CDD; cd03346; eu_TrpOH; 1. DR FunFam; 1.10.800.10:FF:000001; tryptophan 5-hydroxylase 1; 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; IPR005963; Trp_5_mOase. DR InterPro; IPR041904; TrpOH_cat. DR InterPro; IPR019773; Tyrosine_3-monooxygenase-like. DR NCBIfam; TIGR01270; Trp_5_monoox; 1. DR PANTHER; PTHR11473; AROMATIC AMINO ACID HYDROXYLASE; 1. DR PANTHER; PTHR11473:SF23; TRYPTOPHAN 5-HYDROXYLASE 1; 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 PDBsum; 3E2T; -. PE 1: Evidence at protein level; KW 3D-structure; Iron; Metal-binding; Monooxygenase; Oxidoreductase; KW Phosphoprotein; Reference proteome; Serotonin biosynthesis. FT CHAIN 1..445 FT /note="Tryptophan 5-hydroxylase 1" FT /id="PRO_0000205572" FT DOMAIN 19..94 FT /note="ACT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01007" FT BINDING 236 FT /ligand="L-tryptophan" FT /ligand_id="ChEBI:CHEBI:57912" FT /evidence="ECO:0000269|PubMed:18937498" FT BINDING 258 FT /ligand="L-tryptophan" FT /ligand_id="ChEBI:CHEBI:57912" FT /evidence="ECO:0000269|PubMed:18937498" FT BINDING 266 FT /ligand="L-tryptophan" FT /ligand_id="ChEBI:CHEBI:57912" FT /evidence="ECO:0000269|PubMed:18937498" FT BINDING 273 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000269|PubMed:18937498" FT BINDING 278 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000269|PubMed:18937498" FT BINDING 318 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000269|PubMed:18937498" FT BINDING 337 FT /ligand="L-tryptophan" FT /ligand_id="ChEBI:CHEBI:57912" FT /evidence="ECO:0000269|PubMed:18937498" FT BINDING 367 FT /ligand="L-tryptophan" FT /ligand_id="ChEBI:CHEBI:57912" FT /evidence="ECO:0000269|PubMed:18937498" FT MOD_RES 58 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000255" FT HELIX 113..117 FT /evidence="ECO:0007829|PDB:3E2T" FT TURN 127..129 FT /evidence="ECO:0007829|PDB:3E2T" FT HELIX 135..138 FT /evidence="ECO:0007829|PDB:3E2T" FT HELIX 140..155 FT /evidence="ECO:0007829|PDB:3E2T" FT HELIX 161..164 FT /evidence="ECO:0007829|PDB:3E2T" FT HELIX 169..189 FT /evidence="ECO:0007829|PDB:3E2T" FT HELIX 192..196 FT /evidence="ECO:0007829|PDB:3E2T" FT HELIX 198..205 FT /evidence="ECO:0007829|PDB:3E2T" FT HELIX 212..214 FT /evidence="ECO:0007829|PDB:3E2T" FT HELIX 215..226 FT /evidence="ECO:0007829|PDB:3E2T" FT STRAND 229..232 FT /evidence="ECO:0007829|PDB:3E2T" FT STRAND 234..237 FT /evidence="ECO:0007829|PDB:3E2T" FT HELIX 239..247 FT /evidence="ECO:0007829|PDB:3E2T" FT STRAND 250..253 FT /evidence="ECO:0007829|PDB:3E2T" FT HELIX 273..278 FT /evidence="ECO:0007829|PDB:3E2T" FT HELIX 279..282 FT /evidence="ECO:0007829|PDB:3E2T" FT HELIX 285..298 FT /evidence="ECO:0007829|PDB:3E2T" FT HELIX 303..313 FT /evidence="ECO:0007829|PDB:3E2T" FT HELIX 314..318 FT /evidence="ECO:0007829|PDB:3E2T" FT STRAND 321..324 FT /evidence="ECO:0007829|PDB:3E2T" FT STRAND 327..330 FT /evidence="ECO:0007829|PDB:3E2T" FT HELIX 333..336 FT /evidence="ECO:0007829|PDB:3E2T" FT HELIX 339..345 FT /evidence="ECO:0007829|PDB:3E2T" FT STRAND 352..354 FT /evidence="ECO:0007829|PDB:3E2T" FT HELIX 357..360 FT /evidence="ECO:0007829|PDB:3E2T" FT STRAND 367..369 FT /evidence="ECO:0007829|PDB:3E2T" FT STRAND 374..379 FT /evidence="ECO:0007829|PDB:3E2T" FT HELIX 380..391 FT /evidence="ECO:0007829|PDB:3E2T" FT STRAND 401..403 FT /evidence="ECO:0007829|PDB:3E2T" FT TURN 404..407 FT /evidence="ECO:0007829|PDB:3E2T" FT STRAND 408..410 FT /evidence="ECO:0007829|PDB:3E2T" SQ SEQUENCE 445 AA; 51139 MW; FF0041D7C4B159F6 CRC64; MIEDNKENKD HAPERGRTAI IFSLKNEVGG LVKALKLFQE KHVNLVHIES RKSKRRNSEF EIFVDCDSNR EQLNEIFQLL KSHVSIVSMN PTEHFNVQED GDMENIPWYP KKISDLDKCA NRVLMYGSDL DADHPGFKDN VYRKRRKYFA DLAMNYKHGD PIPEIEFTEE EIKTWGTVYR ELNKLYPTHA CREYLKNLPL LTKYCGYRED NIPQLEDVSR FLKERTGFTI RPVAGYLSPR DFLAGLAFRV FHCTQYVRHS SDPLYTPEPD TCHELLGHVP LLAEPSFAQF SQEIGLASLG ASDEAVQKLA TCYFFTVEFG LCKQEGQLRV YGAGLLSSIS ELKHSLSGSA KVKPFDPKVT CKQECLITTF QEVYFVSESF EEAKEKMREF AKTIKRPFGV KYNPYTQSVQ ILKDTKSIAS VVNELRHELD IVSDALSKMG KQLEV //