ID   TPH1_XENLA              Reviewed;         481 AA.
AC   Q92142;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   03-AUG-2022, entry version 110.
DE   RecName: Full=Tryptophan 5-hydroxylase;
DE            EC=1.14.16.4 {ECO:0000250|UniProtKB:P17532};
DE   AltName: Full=Tryptophan 5-monooxygenase;
GN   Name=tph1;
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Retina;
RX   PubMed=8189245; DOI=10.1046/j.1471-4159.1994.62062420.x;
RA   Green C.B., Besharse J.C.;
RT   "Tryptophan hydroxylase expression is regulated by a circadian clock in
RT   Xenopus laevis retina.";
RL   J. Neurochem. 62:2420-2428(1994).
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         = (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         Evidence={ECO:0000250|UniProtKB:P17532};
CC   -!- COFACTOR:
CC       Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC         Evidence={ECO:0000250|UniProtKB:P17752};
CC   -!- PATHWAY: Aromatic compound metabolism; serotonin biosynthesis;
CC       serotonin from L-tryptophan: step 1/2. {ECO:0000250|UniProtKB:P17532}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P70080}.
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; L20679; AAA21306.1; -; mRNA.
DR   PIR; I51567; I51567.
DR   RefSeq; NP_001080923.1; NM_001087454.1.
DR   AlphaFoldDB; Q92142; -.
DR   SMR; Q92142; -.
DR   GeneID; 387560; -.
DR   KEGG; xla:387560; -.
DR   CTD; 387560; -.
DR   Xenbase; XB-GENE-996927; tph1.L.
DR   OrthoDB; 614557at2759; -.
DR   UniPathway; UPA00846; UER00799.
DR   Proteomes; UP000186698; Chromosome 4L.
DR   Bgee; 387560; Expressed in zone of skin and 8 other tissues.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0004510; F:tryptophan 5-monooxygenase activity; IEA:UniProtKB-EC.
DR   GO; GO:0009072; P:aromatic amino acid family 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; cd03346; eu_TrpOH; 1.
DR   Gene3D; 1.10.800.10; -; 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   PANTHER; PTHR11473; PTHR11473; 1.
DR   Pfam; PF00351; Biopterin_H; 1.
DR   PIRSF; PIRSF000336; TH; 1.
DR   PRINTS; PR00372; FYWHYDRXLASE.
DR   SUPFAM; SSF55021; SSF55021; 1.
DR   SUPFAM; SSF56534; SSF56534; 1.
DR   TIGRFAMs; TIGR01270; Trp_5_monoox; 1.
DR   PROSITE; PS51671; ACT; 1.
DR   PROSITE; PS00367; BH4_AAA_HYDROXYL_1; 1.
DR   PROSITE; PS51410; BH4_AAA_HYDROXYL_2; 1.
PE   2: Evidence at transcript level;
KW   Iron; Metal-binding; Monooxygenase; Oxidoreductase; Reference proteome;
KW   Serotonin biosynthesis.
FT   CHAIN           1..481
FT                   /note="Tryptophan 5-hydroxylase"
FT                   /id="PRO_0000205573"
FT   DOMAIN          56..131
FT                   /note="ACT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01007"
FT   BINDING         272
FT                   /ligand="L-tryptophan"
FT                   /ligand_id="ChEBI:CHEBI:57912"
FT                   /evidence="ECO:0000250|UniProtKB:P70080"
FT   BINDING         294
FT                   /ligand="L-tryptophan"
FT                   /ligand_id="ChEBI:CHEBI:57912"
FT                   /evidence="ECO:0000250|UniProtKB:P70080"
FT   BINDING         302
FT                   /ligand="L-tryptophan"
FT                   /ligand_id="ChEBI:CHEBI:57912"
FT                   /evidence="ECO:0000250|UniProtKB:P70080"
FT   BINDING         309
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000250|UniProtKB:P70080"
FT   BINDING         314
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000250|UniProtKB:P70080"
FT   BINDING         354
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000250|UniProtKB:P70080"
FT   BINDING         373
FT                   /ligand="L-tryptophan"
FT                   /ligand_id="ChEBI:CHEBI:57912"
FT                   /evidence="ECO:0000250|UniProtKB:P70080"
FT   BINDING         403
FT                   /ligand="L-tryptophan"
FT                   /ligand_id="ChEBI:CHEBI:57912"
FT                   /evidence="ECO:0000250|UniProtKB:P70080"
SQ   SEQUENCE   481 AA;  55406 MW;  6852C33EFF8DEBA0 CRC64;
     MYSNRKECPR RVKSFDSVNS GLDENQINNE FNKSTYIKIE DNKEYSENVC ERGKASVIFS
     LKNEIGGLVK ALKLFQEKHV NLIHIESRKS KRRNSEFEIF VDCDSNREQL NEIFQLLKPH
     VNVISMSPPE NFTVQEDDME SVPWFPKKIS DLDKCANRVL MYGSDLDADH PGFKDNVYRK
     RRKYFADVAM SYKYGDPIPH IEFTEEEIQT WGTVFRELNK LYPTHACREY LKNLPLLSKH
     CGYREDNIPQ LEDVSRFLRE RTGFTIRPVA GYLSPRDFLA GLAFRVFHCT QYVRHDSDPL
     NTPEPDTCHE LLGHVPLLAE PSFAQFSQEI GLASLGASDE AVQKLATCYF FTVEFGLCKQ
     EGKLKVYGAG LLSSISELKH SLSGNAKVKP FDPMVTCNQE CIITSFQELY FVSESFEEAK
     EKMREFAKTI QRPFGLKYNP FTQSVDILKD TKSIAMVVRE LRHELDIVND ALNKMNKQLG
     V