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Protein

Tryptophan 5-hydroxylase 1

Gene

TPH1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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), Tryptophan 5-hydroxylase 2 (TPH2)
  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

Keywordsi

Molecular functionMonooxygenase, Oxidoreductase
Biological processSerotonin biosynthesis
LigandIron, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS05250-MONOMER
BRENDAi1.14.16.4 2681
ReactomeiR-HSA-209931 Serotonin and melatonin biosynthesis
SABIO-RKiP17752
SIGNORiP17752
UniPathwayi
UPA00846;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

EuPathDBiHostDB:ENSG00000129167.9
HGNCiHGNC:12008 TPH1
MIMi191060 gene
neXtProtiNX_P17752

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Organism-specific databases

DisGeNETi7166
OpenTargetsiENSG00000129167
PharmGKBiPA355

Chemistry databases

ChEMBLiCHEMBL5689
DrugBankiDB00150 L-Tryptophan
DB05199 LX1031
DB00360 Sapropterin
DB12095 Telotristat

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
ProteomicsDBi53513
53514 [P17752-2]

PTM databases

iPTMnetiP17752
PhosphoSitePlusiP17752

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000129167 Expressed in 99 organ(s), highest expression level in buccal mucosa cell
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, 3 interactors
STRINGi9606.ENSP00000250018

Chemistry databases

BindingDBiP17752

Structurei

Secondary structure

1444
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP17752
SMRiP17752
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP17752

Family & Domainsi

Domains and Repeats

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

Sequence similaritiesi

Phylogenomic databases

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

Family and domain databases

Gene3Di1.10.800.10, 1 hit
InterProiView protein in InterPro
IPR002912 ACT_dom
IPR001273 ArAA_hydroxylase
IPR018301 ArAA_hydroxylase_Fe/CU_BS
IPR036951 ArAA_hydroxylase_sf
IPR036329 Aro-AA_hydroxylase_C_sf
IPR019774 Aromatic-AA_hydroxylase_C
IPR005963 Trp_5_mOase
IPR019773 Tyrosine_3-monooxygenase-like
PANTHERiPTHR11473 PTHR11473, 1 hit
PfamiView protein in Pfam
PF00351 Biopterin_H, 1 hit
PIRSFiPIRSF000336 TH, 1 hit
PRINTSiPR00372 FYWHYDRXLASE
SUPFAMiSSF56534 SSF56534, 1 hit
TIGRFAMsiTIGR01270 Trp_5_monoox, 1 hit
PROSITEiView protein in PROSITE
PS51671 ACT, 1 hit
PS00367 BH4_AAA_HYDROXYL_1, 1 hit
PS51410 BH4_AAA_HYDROXYL_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E7EMX4E7EMX4_HUMAN
Tryptophan 5-hydroxylase 1
TPH1
206Annotation score:
E9PR49E9PR49_HUMAN
Tryptophan 5-hydroxylase 1
TPH1
165Annotation score:

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

Similar proteinsi

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[»]
5L01X-ray1.90A1-444[»]
5TPGX-ray1.50A104-402[»]
ProteinModelPortaliP17752
SMRiP17752
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113019, 6 interactors
IntActiP17752, 3 interactors
STRINGi9606.ENSP00000250018

Chemistry databases

BindingDBiP17752
ChEMBLiCHEMBL5689
DrugBankiDB00150 L-Tryptophan
DB05199 LX1031
DB00360 Sapropterin
DB12095 Telotristat

PTM databases

iPTMnetiP17752
PhosphoSitePlusiP17752

Polymorphism and mutation databases

BioMutaiTPH1
DMDMi116242823

Proteomic databases

PaxDbiP17752
PeptideAtlasiP17752
PRIDEiP17752
ProteomicsDBi53513
53514 [P17752-2]

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
EuPathDBiHostDB:ENSG00000129167.9
GeneCardsiTPH1
HGNCiHGNC:12008 TPH1
HPAiCAB010767
HPA022483
MIMi191060 gene
neXtProtiNX_P17752
OpenTargetsiENSG00000129167
PharmGKBiPA355
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

UniPathwayi
UPA00846;UER00799

BioCyciMetaCyc:HS05250-MONOMER
BRENDAi1.14.16.4 2681
ReactomeiR-HSA-209931 Serotonin and melatonin biosynthesis
SABIO-RKiP17752
SIGNORiP17752

Miscellaneous databases

EvolutionaryTraceiP17752
GeneWikiiTPH1
GenomeRNAii7166
PROiPR:P17752
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000129167 Expressed in 99 organ(s), highest expression level in buccal mucosa cell
CleanExiHS_TPH1
ExpressionAtlasiP17752 baseline and differential
GenevisibleiP17752 HS

Family and domain databases

Gene3Di1.10.800.10, 1 hit
InterProiView protein in InterPro
IPR002912 ACT_dom
IPR001273 ArAA_hydroxylase
IPR018301 ArAA_hydroxylase_Fe/CU_BS
IPR036951 ArAA_hydroxylase_sf
IPR036329 Aro-AA_hydroxylase_C_sf
IPR019774 Aromatic-AA_hydroxylase_C
IPR005963 Trp_5_mOase
IPR019773 Tyrosine_3-monooxygenase-like
PANTHERiPTHR11473 PTHR11473, 1 hit
PfamiView protein in Pfam
PF00351 Biopterin_H, 1 hit
PIRSFiPIRSF000336 TH, 1 hit
PRINTSiPR00372 FYWHYDRXLASE
SUPFAMiSSF56534 SSF56534, 1 hit
TIGRFAMsiTIGR01270 Trp_5_monoox, 1 hit
PROSITEiView protein in PROSITE
PS51671 ACT, 1 hit
PS00367 BH4_AAA_HYDROXYL_1, 1 hit
PS51410 BH4_AAA_HYDROXYL_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTPH1_HUMAN
AccessioniPrimary (citable) accession number: P17752
Secondary accession number(s): D3DQX6
, O95188, O95189, Q16736, Q3KPG8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: October 17, 2006
Last modified: November 7, 2018
This is version 183 of the entry and version 4 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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