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Protein

Tryptophan 5-hydroxylase 1

Gene

TPH1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

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

Cofactori

Pathwayi

Sites

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

GO - Molecular functioni

  1. amino acid binding Source: InterPro
  2. iron ion binding Source: InterPro
  3. tryptophan 5-monooxygenase activity Source: UniProtKB-EC

GO - Biological processi

  1. aromatic amino acid family metabolic process Source: InterPro
  2. bone remodeling Source: Ensembl
  3. cellular nitrogen compound metabolic process Source: Reactome
  4. circadian rhythm Source: Ensembl
  5. indolalkylamine biosynthetic process Source: Reactome
  6. mammary gland alveolus development Source: Ensembl
  7. negative regulation of ossification Source: Ensembl
  8. positive regulation of fat cell differentiation Source: Ensembl
  9. response to immobilization stress Source: Ensembl
  10. serotonin biosynthetic process Source: UniProtKB-UniPathway
  11. small molecule metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Biological processi

Serotonin biosynthesis

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS05250-MONOMER.
ReactomeiREACT_15439. Serotonin and melatonin biosynthesis.
SABIO-RKP17752.
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, TPRH, TRPH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:12008. TPH1.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. neuron projection Source: Ensembl
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA355.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 444444Tryptophan 5-hydroxylase 1PRO_0000205568Add
BLAST

Amino acid modifications

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

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP17752.
PRIDEiP17752.

PTM databases

PhosphoSiteiP17752.

Expressioni

Tissue specificityi

Isoform 2 seems to be less widely expressed than isoform 1.

Gene expression databases

BgeeiP17752.
CleanExiHS_TPH1.
ExpressionAtlasiP17752. baseline and differential.
GenevestigatoriP17752.

Organism-specific databases

HPAiCAB010767.
HPA022483.

Interactioni

Subunit structurei

Homotetramer.By similarity

Protein-protein interaction databases

BioGridi113019. 2 interactions.
IntActiP17752. 1 interaction.
STRINGi9606.ENSP00000250018.

Structurei

Secondary structure

1
444
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi112 – 1176Combined sources
Turni118 – 1203Combined sources
Turni134 – 1374Combined sources
Helixi139 – 15416Combined sources
Helixi168 – 18821Combined sources
Helixi191 – 20414Combined sources
Helixi214 – 22411Combined sources
Beta strandi228 – 2314Combined sources
Beta strandi233 – 2353Combined sources
Helixi238 – 2458Combined sources
Turni246 – 2483Combined sources
Beta strandi249 – 2524Combined sources
Helixi270 – 2767Combined sources
Helixi278 – 2814Combined sources
Helixi284 – 29714Combined sources
Helixi302 – 31312Combined sources
Turni314 – 3185Combined sources
Beta strandi320 – 3234Combined sources
Beta strandi326 – 3294Combined sources
Helixi332 – 3354Combined sources
Helixi338 – 3447Combined sources
Turni345 – 3473Combined sources
Beta strandi349 – 3535Combined sources
Helixi356 – 3594Combined sources
Beta strandi366 – 3683Combined sources
Beta strandi371 – 3755Combined sources
Helixi379 – 39012Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IN9model-A2-444[»]
1MLWX-ray1.71A102-402[»]
3HF6X-ray1.80A105-393[»]
3HF8X-ray1.85A105-393[»]
3HFBX-ray1.92A104-393[»]
ProteinModelPortaliP17752.
SMRiP17752. Positions 9-438.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP17752.

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

eggNOGiCOG3186.
GeneTreeiENSGT00390000010268.
HOGENOMiHOG000233373.
HOVERGENiHBG006841.
InParanoidiP17752.
KOiK00502.
OMAiQNVLMYG.
OrthoDBiEOG7KM5T1.
PhylomeDBiP17752.
TreeFamiTF313327.

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.
PfamiPF01842. ACT. 1 hit.
PF00351. 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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P17752-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MIEDNKENKD HSLERGRASL IFSLKNEVGG LIKALKIFQE KHVNLLHIES
60 70 80 90 100
RKSKRRNSEF EIFVDCDINR EQLNDIFHLL KSHTNVLSVN LPDNFTLKED
110 120 130 140 150
GMETVPWFPK KISDLDHCAN RVLMYGSELD ADHPGFKDNV YRKRRKYFAD
160 170 180 190 200
LAMNYKHGDP IPKVEFTEEE IKTWGTVFQE LNKLYPTHAC REYLKNLPLL
210 220 230 240 250
SKYCGYREDN IPQLEDVSNF LKERTGFSIR PVAGYLSPRD FLSGLAFRVF
260 270 280 290 300
HCTQYVRHSS DPFYTPEPDT CHELLGHVPL LAEPSFAQFS QEIGLASLGA
310 320 330 340 350
SEEAVQKLAT CYFFTVEFGL CKQDGQLRVF GAGLLSSISE LKHALSGHAK
360 370 380 390 400
VKPFDPKITC KQECLITTFQ DVYFVSESFE DAKEKMREFT KTIKRPFGVK
410 420 430 440
YNPYTRSIQI LKDTKSITSA MNELQHDLDV VSDALAKVSR KPSI
Length:444
Mass (Da):50,985
Last modified:October 17, 2006 - v4
Checksum:iDFAD501446953A91
GO
Isoform 2 (identifier: P17752-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     438-444: VSRKPSI → SLNEDVLQVSVFALLLFLPSLHGECHPDT

Show »
Length:466
Mass (Da):53,394
Checksum:iCAFE34D6173BA604
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti19 – 191S → T in AAA67050 (PubMed:7986090).Curated
Sequence conflicti68 – 681I → T in AAA67050 (PubMed:7986090).Curated
Sequence conflicti90 – 912NL → TP in AAA67050 (PubMed:7986090).Curated
Sequence conflicti97 – 971L → M in AAA67050 (PubMed:7986090).Curated
Sequence conflicti100 – 1001D → E in AAA67050 (PubMed:7986090).Curated
Sequence conflicti104 – 1041T → S in AAA67050 (PubMed:7986090).Curated
Sequence conflicti151 – 1511L → S in AAA67050 (PubMed:7986090).Curated
Sequence conflicti154 – 1541N → S in AAA67050 (PubMed:7986090).Curated
Sequence conflicti157 – 1571H → Y in AAA67050 (PubMed:7986090).Curated
Sequence conflicti179 – 1791Q → R in AAA67050 (PubMed:7986090).Curated
Sequence conflicti207 – 2071R → Q in AAA67050 (PubMed:7986090).Curated
Sequence conflicti217 – 2171V → I in AAA67050 (PubMed:7986090).Curated
Sequence conflicti344 – 3441A → V in AAA67050 (PubMed:7986090).Curated
Sequence conflicti414 – 4141T → A in AAA67050 (PubMed:7986090).Curated
Sequence conflicti419 – 4191S → N in AAA67050 (PubMed:7986090).Curated
Sequence conflicti425 – 4251Q → R in AAA67050 (PubMed:7986090).Curated
Sequence conflicti436 – 4361A → G in AAA67050 (PubMed:7986090).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei438 – 4447VSRKPSI → SLNEDVLQVSVFALLLFLPS LHGECHPDT in isoform 2. CuratedVSP_000546

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52836 mRNA. Translation: CAA37018.1.
L29306 mRNA. Translation: AAA67050.1.
CH471064 Genomic DNA. Translation: EAW68421.1.
CH471064 Genomic DNA. Translation: EAW68422.1.
BC106739 mRNA. Translation: AAI06740.1.
AF057280 Genomic DNA. Translation: AAC69458.1.
AF057280 Genomic DNA. Translation: AAC69459.1.
CCDSiCCDS7829.1. [P17752-1]
PIRiS10489.
RefSeqiNP_004170.1. NM_004179.2. [P17752-1]
UniGeneiHs.591999.

Genome annotation databases

EnsembliENST00000250018; ENSP00000250018; ENSG00000129167. [P17752-1]
GeneIDi7166.
KEGGihsa:7166.
UCSCiuc001mnp.2. human. [P17752-1]

Polymorphism databases

DMDMi116242823.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52836 mRNA. Translation: CAA37018.1.
L29306 mRNA. Translation: AAA67050.1.
CH471064 Genomic DNA. Translation: EAW68421.1.
CH471064 Genomic DNA. Translation: EAW68422.1.
BC106739 mRNA. Translation: AAI06740.1.
AF057280 Genomic DNA. Translation: AAC69458.1.
AF057280 Genomic DNA. Translation: AAC69459.1.
CCDSiCCDS7829.1. [P17752-1]
PIRiS10489.
RefSeqiNP_004170.1. NM_004179.2. [P17752-1]
UniGeneiHs.591999.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IN9model-A2-444[»]
1MLWX-ray1.71A102-402[»]
3HF6X-ray1.80A105-393[»]
3HF8X-ray1.85A105-393[»]
3HFBX-ray1.92A104-393[»]
ProteinModelPortaliP17752.
SMRiP17752. Positions 9-438.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113019. 2 interactions.
IntActiP17752. 1 interaction.
STRINGi9606.ENSP00000250018.

Chemistry

BindingDBiP17752.
ChEMBLiCHEMBL5689.
DrugBankiDB00150. L-Tryptophan.
DB00360. Tetrahydrobiopterin.
GuidetoPHARMACOLOGYi1241.

PTM databases

PhosphoSiteiP17752.

Polymorphism databases

DMDMi116242823.

Proteomic databases

PaxDbiP17752.
PRIDEiP17752.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000250018; ENSP00000250018; ENSG00000129167. [P17752-1]
GeneIDi7166.
KEGGihsa:7166.
UCSCiuc001mnp.2. human. [P17752-1]

Organism-specific databases

CTDi7166.
GeneCardsiGC11M018040.
HGNCiHGNC:12008. TPH1.
HPAiCAB010767.
HPA022483.
MIMi191060. gene.
neXtProtiNX_P17752.
PharmGKBiPA355.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG3186.
GeneTreeiENSGT00390000010268.
HOGENOMiHOG000233373.
HOVERGENiHBG006841.
InParanoidiP17752.
KOiK00502.
OMAiQNVLMYG.
OrthoDBiEOG7KM5T1.
PhylomeDBiP17752.
TreeFamiTF313327.

Enzyme and pathway databases

UniPathwayiUPA00846; UER00799.
BioCyciMetaCyc:HS05250-MONOMER.
ReactomeiREACT_15439. Serotonin and melatonin biosynthesis.
SABIO-RKP17752.

Miscellaneous databases

EvolutionaryTraceiP17752.
GeneWikiiTPH1.
GenomeRNAii7166.
NextBioi28062.
PROiP17752.
SOURCEiSearch...

Gene expression databases

BgeeiP17752.
CleanExiHS_TPH1.
ExpressionAtlasiP17752. baseline and differential.
GenevestigatoriP17752.

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.
PfamiPF01842. ACT. 1 hit.
PF00351. 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

« Hide 'large scale' publications
  1. "Complete coding sequence of human tryptophan hydroxylase."
    Boulalard S., Darmon M.C., Ganem Y., Launay J.-M., Mallet J.
    Nucleic Acids Res. 18:4257-4257(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Carcinoma.
  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] (ISOFORM 1).
    Tissue: Brain.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  5. "Alternative splicing at the 3'-cDNA of human tryptophan hydroxylase."
    Wang G.A., Coon S.L., Kaufman S.
    J. Neurochem. 71:1769-1772(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 388-444 (ISOFORMS 1 AND 2).
  6. "Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin."
    Wang L., Erlandsen H., Haavik J., Knappskog P.M., Stevens R.C.
    Biochemistry 41:12569-12574(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 102-402.

Entry informationi

Entry nameiTPH1_HUMAN
AccessioniPrimary (citable) accession number: P17752
Secondary accession number(s): D3DQX6
, O95188, O95189, Q16736, Q3KPG8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: October 17, 2006
Last modified: March 4, 2015
This is version 156 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.