ID   TPH1_RAT                Reviewed;         444 AA.
AC   P09810;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1989, sequence version 2.
DT   27-MAR-2024, entry version 184.
DE   RecName: Full=Tryptophan 5-hydroxylase 1;
DE            EC=1.14.16.4 {ECO:0000269|PubMed:12354109};
DE   AltName: Full=Tryptophan 5-monooxygenase 1;
GN   Name=Tph1; Synonyms=Tph;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Wistar; TISSUE=Pineal gland;
RX   PubMed=3379411; DOI=10.1111/j.1471-4159.1988.tb04871.x;
RA   Darmon M.C., Guibert B., Leviel V., Ehret M., Maitre M., Mallet J.;
RT   "Sequence of two mRNAs encoding active rat tryptophan hydroxylase.";
RL   J. Neurochem. 51:312-316(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1645430; DOI=10.1016/0169-328x(91)90073-7;
RA   Kim K.S., Wessel T.C., Stone D.M., Carver C.H., Joh T.H., Park D.H.;
RT   "Molecular cloning and characterization of cDNA encoding tryptophan
RT   hydroxylase from rat central serotonergic neurons.";
RL   Brain Res. Mol. Brain Res. 9:277-283(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 167-261.
RX   PubMed=2875901; DOI=10.1016/0014-5793(86)81337-0;
RA   Darmon M.C., Grima B., Cash C.D., Maitre M., Mallet J.;
RT   "Isolation of a rat pineal gland cDNA clone homologous to tyrosine and
RT   phenylalanine hydroxylases.";
RL   FEBS Lett. 206:43-46(1986).
RN   [4]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=12354109; DOI=10.1046/j.1432-1033.2002.03188.x;
RA   Iida Y., Sawabe K., Kojima M., Oguro K., Nakanishi N., Hasegawa H.;
RT   "Proteasome-driven turnover of tryptophan hydroxylase is triggered by
RT   phosphorylation in RBL2H3 cells, a serotonin producing mast cell line.";
RL   Eur. J. Biochem. 269:4780-4788(2002).
CC   -!- FUNCTION: Oxidizes L-tryptophan to 5-hydroxy-l-tryptophan in the rate-
CC       determining step of serotonin biosynthesis.
CC       {ECO:0000269|PubMed:12354109}.
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:0000269|PubMed:12354109};
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:0000269|PubMed:12354109}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P70080}.
CC   -!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
CC       Ubiquitinated is triggered by phosphorylation.
CC       {ECO:0000269|PubMed:12354109}.
CC   -!- PTM: Phosphorylated; triggering degradation by the proteasome.
CC       {ECO:0000269|PubMed:12354109}.
CC   -!- SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid
CC       hydroxylase family. {ECO:0000305}.
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DR   EMBL; M28000; AAA42262.1; -; mRNA.
DR   EMBL; X53501; CAA37579.1; -; mRNA.
DR   PIR; JL0034; WHRTW.
DR   RefSeq; NP_001094104.1; NM_001100634.2.
DR   RefSeq; XP_006229281.1; XM_006229219.2.
DR   AlphaFoldDB; P09810; -.
DR   SMR; P09810; -.
DR   STRING; 10116.ENSRNOP00000052959; -.
DR   BindingDB; P09810; -.
DR   ChEMBL; CHEMBL4809; -.
DR   iPTMnet; P09810; -.
DR   PhosphoSitePlus; P09810; -.
DR   PaxDb; 10116-ENSRNOP00000052959; -.
DR   Ensembl; ENSRNOT00000056109.4; ENSRNOP00000052959.2; ENSRNOG00000011672.7.
DR   Ensembl; ENSRNOT00055011087; ENSRNOP00055008671; ENSRNOG00055006768.
DR   Ensembl; ENSRNOT00060019299; ENSRNOP00060015119; ENSRNOG00060011408.
DR   Ensembl; ENSRNOT00065013987; ENSRNOP00065010432; ENSRNOG00065008776.
DR   GeneID; 24848; -.
DR   KEGG; rno:24848; -.
DR   UCSC; RGD:3895; rat.
DR   AGR; RGD:3895; -.
DR   CTD; 7166; -.
DR   RGD; 3895; Tph1.
DR   eggNOG; KOG3820; Eukaryota.
DR   GeneTree; ENSGT00950000182885; -.
DR   HOGENOM; CLU_023198_0_0_1; -.
DR   InParanoid; P09810; -.
DR   OMA; SEVDMPW; -.
DR   OrthoDB; 275463at2759; -.
DR   PhylomeDB; P09810; -.
DR   TreeFam; TF313327; -.
DR   Reactome; R-RNO-209931; Serotonin and melatonin biosynthesis.
DR   SABIO-RK; P09810; -.
DR   UniPathway; UPA00846; UER00799.
DR   PRO; PR:P09810; -.
DR   Proteomes; UP000002494; Chromosome 1.
DR   Bgee; ENSRNOG00000011672; Expressed in duodenum and 15 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
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; IDA:RGD.
DR   GO; GO:0046849; P:bone remodeling; ISO:RGD.
DR   GO; GO:0007623; P:circadian rhythm; IEP:RGD.
DR   GO; GO:0060749; P:mammary gland alveolus development; ISO:RGD.
DR   GO; GO:0030279; P:negative regulation of ossification; IMP:RGD.
DR   GO; GO:0002576; P:platelet degranulation; ISS:UniProtKB.
DR   GO; GO:0045600; P:positive regulation of fat cell differentiation; ISO:RGD.
DR   GO; GO:1900046; P:regulation of hemostasis; ISS:UniProtKB.
DR   GO; GO:0035902; P:response to immobilization stress; IEP:RGD.
DR   GO; GO:0042427; P:serotonin biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0006587; P:serotonin biosynthetic process from tryptophan; TAS:RGD.
DR   CDD; cd04929; ACT_TPH; 1.
DR   CDD; cd03346; eu_TrpOH; 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.
PE   1: Evidence at protein level;
KW   Iron; Metal-binding; Monooxygenase; Oxidoreductase; Phosphoprotein;
KW   Reference proteome; Serotonin biosynthesis; Ubl conjugation.
FT   CHAIN           1..444
FT                   /note="Tryptophan 5-hydroxylase 1"
FT                   /id="PRO_0000205571"
FT   DOMAIN          19..94
FT                   /note="ACT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01007"
FT   BINDING         235
FT                   /ligand="L-tryptophan"
FT                   /ligand_id="ChEBI:CHEBI:57912"
FT                   /evidence="ECO:0000250|UniProtKB:P70080"
FT   BINDING         257
FT                   /ligand="L-tryptophan"
FT                   /ligand_id="ChEBI:CHEBI:57912"
FT                   /evidence="ECO:0000250|UniProtKB:P70080"
FT   BINDING         265
FT                   /ligand="L-tryptophan"
FT                   /ligand_id="ChEBI:CHEBI:57912"
FT                   /evidence="ECO:0000250|UniProtKB:P70080"
FT   BINDING         272
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000250|UniProtKB:P70080"
FT   BINDING         277
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000250|UniProtKB:P70080"
FT   BINDING         317
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000250|UniProtKB:P70080"
FT   BINDING         336
FT                   /ligand="L-tryptophan"
FT                   /ligand_id="ChEBI:CHEBI:57912"
FT                   /evidence="ECO:0000250|UniProtKB:P70080"
FT   BINDING         366
FT                   /ligand="L-tryptophan"
FT                   /ligand_id="ChEBI:CHEBI:57912"
FT                   /evidence="ECO:0000250|UniProtKB:P70080"
FT   MOD_RES         58
FT                   /note="Phosphoserine; by PKA"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   444 AA;  51068 MW;  C3CF5245727CC825 CRC64;
     MIEDNKENKD HSSERGRVTL IFSLKNEVGG LIKALKIFQE NHVNLLHIES RKSKRRNSEF
     EIFVDCDINR EQLNDIFPLL KSHTTVLSVD SPDQLPEKED VMETVPWFPK KISDLDFCAN
     RVLLYGSELD ADHPGFKDNV YRRRRKYFAE LAMNYKHGDP IPKIEFTEEE IKTWGTIFRE
     LNKLYPTHAC REYLRNLPLL SKYCGYREDN VPQLEDVSNF LKERTGFSIR PVAGYLSPRD
     FLSGLAFRVF HCTQYVRHSS DPLYTPEPDT CHELLGHVPL LAEPSFAQFS QEIGLASLGA
     SEETVQKLAT CYFFTVEFGL CKQDGQLRVF GAGLLSSISE LRHALSGHAK VKPFDPKVAC
     KQECLITSFQ DVYFVSESFE DAKEKMREFA KTVKRPFGVK YNPYTQSIQV LRDSKSITSA
     MNELRHDLDV VNDALARVSR WPSV
//