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Protein

Tryptophan 5-hydroxylase 1

Gene

TPH1

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

L-tryptophan + tetrahydrobiopterin + O2 = 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin.

Cofactori

Pathwayi: serotonin biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes serotonin from L-tryptophan.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Tryptophan 5-hydroxylase 1 (TPH1)
  2. no protein annotated in this organism
This subpathway is part of the pathway serotonin biosynthesis, which is itself part of Aromatic compound metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes serotonin from L-tryptophan, the pathway serotonin biosynthesis and in Aromatic compound metabolism.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei235 – 2351TryptophanBy similarity
Binding sitei257 – 2571TryptophanBy similarity
Binding sitei265 – 2651TryptophanBy similarity
Metal bindingi272 – 2721IronBy similarity
Metal bindingi277 – 2771IronBy similarity
Metal bindingi317 – 3171IronBy similarity
Binding sitei336 – 3361TryptophanBy similarity
Binding sitei366 – 3661Tryptophan; via carbonyl oxygenBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Biological processi

Serotonin biosynthesis

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

SABIO-RKP17290.
UniPathwayiUPA00846; UER00799.

Names & Taxonomyi

Protein namesi
Recommended name:
Tryptophan 5-hydroxylase 1 (EC:1.14.16.4)
Alternative name(s):
Tryptophan 5-monooxygenase 1
Gene namesi
Name:TPH1
Synonyms:TPH
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Unplaced

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 444444Tryptophan 5-hydroxylase 1PRO_0000205570Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei58 – 581Phosphoserine; by PKASequence analysis

Keywords - PTMi

Phosphoprotein

PTM databases

iPTMnetiP17290.

Interactioni

Subunit structurei

Homotetramer.1 Publication

Structurei

3D structure databases

ProteinModelPortaliP17290.
SMRiP17290. Positions 104-439.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini19 – 9476ACTPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 ACT domain.PROSITE-ProRule annotation

Phylogenomic databases

HOVERGENiHBG006841.
InParanoidiP17290.
KOiK00502.

Family and domain databases

Gene3Di1.10.800.10. 1 hit.
InterProiIPR002912. ACT_dom.
IPR001273. ArAA_hydroxylase.
IPR018301. ArAA_hydroxylase_Fe/CU_BS.
IPR019774. Aromatic-AA_hydroxylase_C.
IPR005963. Trp_5_mOase.
IPR019773. Tyrosine_3-monooxygenase-like.
[Graphical view]
PANTHERiPTHR11473. PTHR11473. 1 hit.
PfamiPF00351. Biopterin_H. 1 hit.
[Graphical view]
PIRSFiPIRSF000336. TH. 1 hit.
PRINTSiPR00372. FYWHYDRXLASE.
SUPFAMiSSF56534. SSF56534. 1 hit.
TIGRFAMsiTIGR01270. Trp_5_monoox. 1 hit.
PROSITEiPS51671. ACT. 1 hit.
PS00367. BH4_AAA_HYDROXYL_1. 1 hit.
PS51410. BH4_AAA_HYDROXYL_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P17290-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIEDNKENKD HSLERGRATL IFSLKNEVGG LIKALKIFQE KHVNLLHIES
60 70 80 90 100
RKSKRRNSEF EIFVDCDTNR EQLNDIFHLL KSHTNVLSVT PPDNFTMKEE
110 120 130 140 150
GMESVPWFPK KISDLDHCAN RVLMYGSELD ADHPGFKDNV YRKRRKYFAD
160 170 180 190 200
LAMSYKYGDP IPKVEFTEEE IKTWGTVFRE LNKLYPTHAC REYLKNLPLL
210 220 230 240 250
SKYCGYREDN IPQLEDISNF LKERTGFSIR PVAGYLSPRD FLSGLAFRVF
260 270 280 290 300
HCTQYVRHSS DPFYTPEPDT CHELLGHVPL LAEPSFAQFS QEIGLASLGA
310 320 330 340 350
SEEAVQKLAT CYFFTVEFGL CKQDGQLRVF GAGLLSSISE LKHVLSGHAK
360 370 380 390 400
VKPFDPKITY KQECLITTFQ DVYFVSESFE DAKEKMREFT KTIKRPFGVK
410 420 430 440
YNPYTRSIQI LKDAKSITNA MNELRHDLDV VSDALGKVSR QLSV
Length:444
Mass (Da):51,118
Last modified:November 1, 1997 - v2
Checksum:iBF182451B28ECD80
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti102 – 1021M → L in AAA31487 (PubMed:3475690).Curated
Sequence conflicti151 – 1511L → S in AAA67051 (PubMed:7986090).Curated
Sequence conflicti202 – 2032KY → ND in AAA31487 (PubMed:3475690).Curated
Sequence conflicti207 – 2071R → Q in AAA67051 (PubMed:7986090).Curated
Sequence conflicti390 – 3901T → K in AAA31487 (PubMed:3475690).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M17250 mRNA. Translation: AAA31487.1.
L29305 mRNA. Translation: AAA67051.1.
PIRiS51199.
RefSeqiNP_001075741.1. NM_001082272.1.
NP_001093425.1. NM_001099955.1.
UniGeneiOcu.2025.
Ocu.6909.

Genome annotation databases

GeneIDi100009100.
100101558.
KEGGiocu:100009100.
ocu:100101558.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M17250 mRNA. Translation: AAA31487.1.
L29305 mRNA. Translation: AAA67051.1.
PIRiS51199.
RefSeqiNP_001075741.1. NM_001082272.1.
NP_001093425.1. NM_001099955.1.
UniGeneiOcu.2025.
Ocu.6909.

3D structure databases

ProteinModelPortaliP17290.
SMRiP17290. Positions 104-439.
ModBaseiSearch...
MobiDBiSearch...

PTM databases

iPTMnetiP17290.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100009100.
100101558.
KEGGiocu:100009100.
ocu:100101558.

Organism-specific databases

CTDi7166.

Phylogenomic databases

HOVERGENiHBG006841.
InParanoidiP17290.
KOiK00502.

Enzyme and pathway databases

UniPathwayiUPA00846; UER00799.
SABIO-RKP17290.

Family and domain databases

Gene3Di1.10.800.10. 1 hit.
InterProiIPR002912. ACT_dom.
IPR001273. ArAA_hydroxylase.
IPR018301. ArAA_hydroxylase_Fe/CU_BS.
IPR019774. Aromatic-AA_hydroxylase_C.
IPR005963. Trp_5_mOase.
IPR019773. Tyrosine_3-monooxygenase-like.
[Graphical view]
PANTHERiPTHR11473. PTHR11473. 1 hit.
PfamiPF00351. Biopterin_H. 1 hit.
[Graphical view]
PIRSFiPIRSF000336. TH. 1 hit.
PRINTSiPR00372. FYWHYDRXLASE.
SUPFAMiSSF56534. SSF56534. 1 hit.
TIGRFAMsiTIGR01270. Trp_5_monoox. 1 hit.
PROSITEiPS51671. ACT. 1 hit.
PS00367. BH4_AAA_HYDROXYL_1. 1 hit.
PS51410. BH4_AAA_HYDROXYL_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Full-length cDNA for rabbit tryptophan hydroxylase: functional domains and evolution of aromatic amino acid hydroxylases."
    Grenett H.E., Ledley F.D., Reed L.L., Woo S.L.C.
    Proc. Natl. Acad. Sci. U.S.A. 84:5530-5534(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Cloning and expression of rabbit and human brain tryptophan hydroxylase cDNA in Escherichia coli."
    Tipper J.P., Citron B.A., Ribeiro P., Kaufman S.
    Arch. Biochem. Biophys. 315:445-453(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  3. "Identification of amino-terminal sequences contributing to tryptophan hydroxylase tetramer formation."
    Yohrling G.J. IV, Mockus S.M., Vrana K.E.
    J. Mol. Neurosci. 12:23-34(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.

Entry informationi

Entry nameiTPH1_RABIT
AccessioniPrimary (citable) accession number: P17290
Secondary accession number(s): Q29523
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: November 1, 1997
Last modified: January 20, 2016
This is version 110 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.