TPH1_RABIT
ID TPH1_RABIT Reviewed; 444 AA.
AC P17290; Q29523;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 128.
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 Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3475690; DOI=10.1073/pnas.84.16.5530;
RA Grenett H.E., Ledley F.D., Reed L.L., Woo S.L.C.;
RT "Full-length cDNA for rabbit tryptophan hydroxylase: functional domains and
RT evolution of aromatic amino acid hydroxylases.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:5530-5534(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=7986090; DOI=10.1006/abbi.1994.1523;
RA Tipper J.P., Citron B.A., Ribeiro P., Kaufman S.;
RT "Cloning and expression of rabbit and human brain tryptophan hydroxylase
RT cDNA in Escherichia coli.";
RL Arch. Biochem. Biophys. 315:445-453(1994).
RN [3]
RP SUBUNIT.
RX PubMed=10636468; DOI=10.1385/jmn:12:1:23;
RA Yohrling G.J. IV, Mockus S.M., Vrana K.E.;
RT "Identification of amino-terminal sequences contributing to tryptophan
RT hydroxylase tetramer formation.";
RL J. Mol. Neurosci. 12:23-34(1999).
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:0000269|PubMed:10636468}.
CC -!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
CC Ubiquitinated is triggered by phosphorylation.
CC {ECO:0000250|UniProtKB:P09810}.
CC -!- PTM: Phosphorylated; triggering degradation by the proteasome.
CC {ECO:0000250|UniProtKB:P09810}.
CC -!- SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid
CC hydroxylase family. {ECO:0000305}.
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DR EMBL; M17250; AAA31487.1; -; mRNA.
DR EMBL; L29305; AAA67051.1; -; mRNA.
DR PIR; S51199; S51199.
DR RefSeq; NP_001075741.1; NM_001082272.1.
DR RefSeq; NP_001093425.1; NM_001099955.1.
DR AlphaFoldDB; P17290; -.
DR SMR; P17290; -.
DR iPTMnet; P17290; -.
DR PRIDE; P17290; -.
DR GeneID; 100009100; -.
DR GeneID; 100101558; -.
DR KEGG; ocu:100009100; -.
DR KEGG; ocu:100101558; -.
DR CTD; 7166; -.
DR InParanoid; P17290; -.
DR OrthoDB; 614557at2759; -.
DR SABIO-RK; P17290; -.
DR UniPathway; UPA00846; UER00799.
DR Proteomes; UP000001811; Unplaced.
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 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_0000205570"
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"
FT CONFLICT 102
FT /note="M -> L (in Ref. 1; AAA31487)"
FT /evidence="ECO:0000305"
FT CONFLICT 151
FT /note="L -> S (in Ref. 2; AAA67051)"
FT /evidence="ECO:0000305"
FT CONFLICT 202..203
FT /note="KY -> ND (in Ref. 1; AAA31487)"
FT /evidence="ECO:0000305"
FT CONFLICT 207
FT /note="R -> Q (in Ref. 2; AAA67051)"
FT /evidence="ECO:0000305"
FT CONFLICT 390
FT /note="T -> K (in Ref. 1; AAA31487)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 444 AA; 51118 MW; BF182451B28ECD80 CRC64;
MIEDNKENKD HSLERGRATL IFSLKNEVGG LIKALKIFQE KHVNLLHIES RKSKRRNSEF
EIFVDCDTNR EQLNDIFHLL KSHTNVLSVT PPDNFTMKEE GMESVPWFPK KISDLDHCAN
RVLMYGSELD ADHPGFKDNV YRKRRKYFAD LAMSYKYGDP IPKVEFTEEE IKTWGTVFRE
LNKLYPTHAC REYLKNLPLL SKYCGYREDN IPQLEDISNF LKERTGFSIR PVAGYLSPRD
FLSGLAFRVF HCTQYVRHSS DPFYTPEPDT CHELLGHVPL LAEPSFAQFS QEIGLASLGA
SEEAVQKLAT CYFFTVEFGL CKQDGQLRVF GAGLLSSISE LKHVLSGHAK VKPFDPKITY
KQECLITTFQ DVYFVSESFE DAKEKMREFT KTIKRPFGVK YNPYTRSIQI LKDAKSITNA
MNELRHDLDV VSDALGKVSR QLSV
