TPH1_RAT
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 03-AUG-2022, entry version 177.
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; P09810; -.
DR Ensembl; ENSRNOT00000056109; ENSRNOP00000052959; ENSRNOG00000011672.
DR GeneID; 24848; -.
DR KEGG; rno:24848; -.
DR UCSC; RGD:3895; rat.
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; VTCQEEC; -.
DR OrthoDB; 614557at2759; -.
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 tissues.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
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; 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 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
