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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: 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 2 (TPH2), 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)DescriptionActionsGraphical viewLength
Binding sitei235TryptophanBy similarity1
Binding sitei257TryptophanBy similarity1
Binding sitei265TryptophanBy similarity1
Metal bindingi272Iron1
Metal bindingi277Iron1
Metal bindingi317Iron1
Binding sitei336TryptophanBy similarity1
Binding sitei366Tryptophan; via carbonyl oxygenBy similarity1

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

BioCyciMetaCyc:HS05250-MONOMER.
ZFISH:HS05250-MONOMER.
BRENDAi1.14.16.4. 2681.
ReactomeiR-HSA-209931. Serotonin and melatonin biosynthesis.
SABIO-RKP17752.
SIGNORiP17752.
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
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:12008. TPH1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi7166.
OpenTargetsiENSG00000129167.
PharmGKBiPA355.

Chemistry databases

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

Polymorphism and mutation databases

BioMutaiTPH1.
DMDMi116242823.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002055681 – 444Tryptophan 5-hydroxylase 1Add BLAST444

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei58Phosphoserine; by PKASequence analysis1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP17752.
PeptideAtlasiP17752.
PRIDEiP17752.

PTM databases

iPTMnetiP17752.
PhosphoSitePlusiP17752.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000129167.
CleanExiHS_TPH1.
ExpressionAtlasiP17752. baseline and differential.
GenevisibleiP17752. HS.

Organism-specific databases

HPAiCAB010767.
HPA022483.

Interactioni

Subunit structurei

Homotetramer.By similarity

Protein-protein interaction databases

BioGridi113019. 6 interactors.
IntActiP17752. 1 interactor.
STRINGi9606.ENSP00000250018.

Chemistry databases

BindingDBiP17752.

Structurei

Secondary structure

1444
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi112 – 117Combined sources6
Turni118 – 120Combined sources3
Turni126 – 128Combined sources3
Turni134 – 137Combined sources4
Helixi139 – 154Combined sources16
Helixi168 – 188Combined sources21
Helixi191 – 204Combined sources14
Helixi214 – 224Combined sources11
Beta strandi228 – 231Combined sources4
Beta strandi233 – 235Combined sources3
Helixi238 – 245Combined sources8
Turni246 – 248Combined sources3
Beta strandi249 – 252Combined sources4
Helixi270 – 276Combined sources7
Helixi278 – 281Combined sources4
Helixi284 – 297Combined sources14
Helixi302 – 313Combined sources12
Turni314 – 318Combined sources5
Beta strandi320 – 323Combined sources4
Beta strandi326 – 329Combined sources4
Helixi332 – 335Combined sources4
Helixi338 – 344Combined sources7
Turni345 – 347Combined sources3
Beta strandi349 – 353Combined sources5
Helixi356 – 359Combined sources4
Beta strandi366 – 368Combined sources3
Beta strandi371 – 375Combined sources5
Helixi379 – 390Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IN9model-A2-444[»]
1MLWX-ray1.71A102-402[»]
3HF6X-ray1.80A105-393[»]
3HF8X-ray1.85A105-393[»]
3HFBX-ray1.92A104-393[»]
5J6DX-ray1.90A/B102-402[»]
ProteinModelPortaliP17752.
SMRiP17752.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP17752.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini19 – 94ACTPROSITE-ProRule annotationAdd BLAST76

Sequence similaritiesi

Contains 1 ACT domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3820. Eukaryota.
COG3186. LUCA.
GeneTreeiENSGT00390000010268.
HOGENOMiHOG000233373.
HOVERGENiHBG006841.
InParanoidiP17752.
KOiK00502.
OMAiQHAITAE.
OrthoDBiEOG091G05MZ.
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.
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]

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)DescriptionActionsGraphical viewLength
Sequence conflicti19S → T in AAA67050 (PubMed:7986090).Curated1
Sequence conflicti68I → T in AAA67050 (PubMed:7986090).Curated1
Sequence conflicti90 – 91NL → TP in AAA67050 (PubMed:7986090).Curated2
Sequence conflicti97L → M in AAA67050 (PubMed:7986090).Curated1
Sequence conflicti100D → E in AAA67050 (PubMed:7986090).Curated1
Sequence conflicti104T → S in AAA67050 (PubMed:7986090).Curated1
Sequence conflicti151L → S in AAA67050 (PubMed:7986090).Curated1
Sequence conflicti154N → S in AAA67050 (PubMed:7986090).Curated1
Sequence conflicti157H → Y in AAA67050 (PubMed:7986090).Curated1
Sequence conflicti179Q → R in AAA67050 (PubMed:7986090).Curated1
Sequence conflicti207R → Q in AAA67050 (PubMed:7986090).Curated1
Sequence conflicti217V → I in AAA67050 (PubMed:7986090).Curated1
Sequence conflicti344A → V in AAA67050 (PubMed:7986090).Curated1
Sequence conflicti414T → A in AAA67050 (PubMed:7986090).Curated1
Sequence conflicti419S → N in AAA67050 (PubMed:7986090).Curated1
Sequence conflicti425Q → R in AAA67050 (PubMed:7986090).Curated1
Sequence conflicti436A → G in AAA67050 (PubMed:7986090).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000546438 – 444VSRKPSI → SLNEDVLQVSVFALLLFLPS LHGECHPDT in isoform 2. Curated7

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.3. human. [P17752-1]

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IN9model-A2-444[»]
1MLWX-ray1.71A102-402[»]
3HF6X-ray1.80A105-393[»]
3HF8X-ray1.85A105-393[»]
3HFBX-ray1.92A104-393[»]
5J6DX-ray1.90A/B102-402[»]
ProteinModelPortaliP17752.
SMRiP17752.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113019. 6 interactors.
IntActiP17752. 1 interactor.
STRINGi9606.ENSP00000250018.

Chemistry databases

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

PTM databases

iPTMnetiP17752.
PhosphoSitePlusiP17752.

Polymorphism and mutation databases

BioMutaiTPH1.
DMDMi116242823.

Proteomic databases

PaxDbiP17752.
PeptideAtlasiP17752.
PRIDEiP17752.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000250018; ENSP00000250018; ENSG00000129167. [P17752-1]
GeneIDi7166.
KEGGihsa:7166.
UCSCiuc001mnp.3. human. [P17752-1]

Organism-specific databases

CTDi7166.
DisGeNETi7166.
GeneCardsiTPH1.
HGNCiHGNC:12008. TPH1.
HPAiCAB010767.
HPA022483.
MIMi191060. gene.
neXtProtiNX_P17752.
OpenTargetsiENSG00000129167.
PharmGKBiPA355.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3820. Eukaryota.
COG3186. LUCA.
GeneTreeiENSGT00390000010268.
HOGENOMiHOG000233373.
HOVERGENiHBG006841.
InParanoidiP17752.
KOiK00502.
OMAiQHAITAE.
OrthoDBiEOG091G05MZ.
PhylomeDBiP17752.
TreeFamiTF313327.

Enzyme and pathway databases

UniPathwayiUPA00846; UER00799.
BioCyciMetaCyc:HS05250-MONOMER.
ZFISH:HS05250-MONOMER.
BRENDAi1.14.16.4. 2681.
ReactomeiR-HSA-209931. Serotonin and melatonin biosynthesis.
SABIO-RKP17752.
SIGNORiP17752.

Miscellaneous databases

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

Gene expression databases

BgeeiENSG00000129167.
CleanExiHS_TPH1.
ExpressionAtlasiP17752. baseline and differential.
GenevisibleiP17752. HS.

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...

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: November 2, 2016
This is version 170 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

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.