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UniProtKB - P17752 (TPH1_HUMAN)
Protein
Tryptophan 5-hydroxylase 1
Gene
TPH1
Organism
Homo sapiens (Human)
Status
Functioni
Oxidizes L-tryptophan to 5-hydroxy-l-tryptophan in the rate-determining step of serotonin biosynthesis.
By similarityCatalytic activityi
- (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tryptophan + O2 = (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin + 5-hydroxy-L-tryptophanBy similarityEC:1.14.16.4By similarity
Cofactori
Fe2+1 Publication
: serotonin biosynthesis Pathwayi
This protein is involved in step 1 of the subpathway that synthesizes serotonin from L-tryptophan.By similarity 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 235 | TryptophanBy similarity | 1 | |
Binding sitei | 257 | TryptophanBy similarity | 1 | |
Binding sitei | 265 | TryptophanBy similarity | 1 | |
Metal bindingi | 272 | IronCombined sources1 Publication | 1 | |
Metal bindingi | 277 | IronCombined sources1 Publication | 1 | |
Metal bindingi | 317 | IronCombined sources1 Publication | 1 | |
Binding sitei | 336 | TryptophanBy similarity | 1 | |
Binding sitei | 366 | Tryptophan; via carbonyl oxygenBy similarity | 1 |
GO - Molecular functioni
- iron ion binding Source: InterPro
- tryptophan 5-monooxygenase activity Source: GO_Central
GO - Biological processi
- aromatic amino acid family metabolic process Source: InterPro
- platelet degranulation Source: UniProtKB
- regulation of hemostasis Source: UniProtKB
- serotonin biosynthetic process Source: UniProtKB
Keywordsi
Molecular function | Monooxygenase, Oxidoreductase |
Biological process | Serotonin biosynthesis |
Ligand | Iron, Metal-binding |
Enzyme and pathway databases
BRENDAi | 1.14.16.4, 2681 |
PathwayCommonsi | P17752 |
Reactomei | R-HSA-209931, Serotonin and melatonin biosynthesis R-HSA-9031628, NGF-stimulated transcription |
SABIO-RKi | P17752 |
SignaLinki | P17752 |
SIGNORi | P17752 |
UniPathwayi | UPA00846;UER00799 |
Names & Taxonomyi
Protein namesi | Recommended name: Tryptophan 5-hydroxylase 1 (EC:1.14.16.4By similarity)Alternative name(s): Tryptophan 5-monooxygenase 1 |
Gene namesi | Name:TPH1 Synonyms:TPH, TPRH, TRPH |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:12008, TPH1 |
MIMi | 191060, gene |
neXtProti | NX_P17752 |
VEuPathDBi | HostDB:ENSG00000129167 |
Subcellular locationi
Cytosol
- cytosol Source: Reactome
Other locations
- neuron projection Source: GO_Central
Pathology & Biotechi
Organism-specific databases
DisGeNETi | 7166 |
OpenTargetsi | ENSG00000129167 |
PharmGKBi | PA355 |
Miscellaneous databases
Pharosi | P17752, Tclin |
Chemistry databases
ChEMBLi | CHEMBL5689 |
DrugBanki | DB05199, LX1031 DB00360, Sapropterin DB12095, Telotristat ethyl DB00150, Tryptophan |
DrugCentrali | P17752 |
GuidetoPHARMACOLOGYi | 1241 |
Genetic variation databases
BioMutai | TPH1 |
DMDMi | 116242823 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000205568 | 1 – 444 | Tryptophan 5-hydroxylase 1Add BLAST | 444 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 58 | Phosphoserine; by PKASequence analysis | 1 |
Post-translational modificationi
Ubiquitinated, leading to its degradation by the proteasome. Ubiquitinated is triggered by phosphorylation.By similarity
Phosphorylated; triggering degradation by the proteasome.By similarity
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
jPOSTi | P17752 |
MassIVEi | P17752 |
PaxDbi | P17752 |
PeptideAtlasi | P17752 |
PRIDEi | P17752 |
ProteomicsDBi | 53513 [P17752-1] 53514 [P17752-2] |
PTM databases
iPTMneti | P17752 |
PhosphoSitePlusi | P17752 |
Expressioni
Tissue specificityi
Seems to be less widely expressed than isoform 1.1 Publication
Gene expression databases
Bgeei | ENSG00000129167, Expressed in buccal mucosa cell and 124 other tissues |
ExpressionAtlasi | P17752, baseline and differential |
Genevisiblei | P17752, HS |
Organism-specific databases
HPAi | ENSG00000129167, Group enriched (brain, intestine, stomach) |
Interactioni
Subunit structurei
Homotetramer.
By similarityBinary interactionsi
P17752
Protein-protein interaction databases
BioGRIDi | 113019, 12 interactors |
IntActi | P17752, 11 interactors |
STRINGi | 9606.ENSP00000250018 |
Chemistry databases
BindingDBi | P17752 |
Miscellaneous databases
RNActi | P17752, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
AlphaFoldDBi | P17752 |
SMRi | P17752 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P17752 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 19 – 94 | ACTPROSITE-ProRule annotationAdd BLAST | 76 |
Sequence similaritiesi
Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.Curated
Phylogenomic databases
eggNOGi | KOG3820, Eukaryota |
GeneTreei | ENSGT00950000182885 |
HOGENOMi | CLU_023198_0_0_1 |
InParanoidi | P17752 |
OMAi | VTCQEEC |
OrthoDBi | 614557at2759 |
PhylomeDBi | P17752 |
TreeFami | TF313327 |
Family and domain databases
CDDi | cd03346, eu_TrpOH, 1 hit |
Gene3Di | 1.10.800.10, 1 hit |
InterProi | View protein in InterPro IPR045865, ACT-like_dom_sf 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 IPR041904, TrpOH_cat IPR019773, Tyrosine_3-monooxygenase-like |
PANTHERi | PTHR11473, PTHR11473, 1 hit |
Pfami | View protein in Pfam PF00351, Biopterin_H, 1 hit |
PIRSFi | PIRSF000336, TH, 1 hit |
PRINTSi | PR00372, FYWHYDRXLASE |
SUPFAMi | SSF55021, SSF55021, 1 hit SSF56534, SSF56534, 1 hit |
TIGRFAMsi | TIGR01270, Trp_5_monoox, 1 hit |
PROSITEi | View protein in PROSITE PS51671, ACT, 1 hit PS00367, BH4_AAA_HYDROXYL_1, 1 hit PS51410, BH4_AAA_HYDROXYL_2, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis 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 sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PR49 | E9PR49_HUMAN | Tryptophan 5-hydroxylase 1 | TPH1 | 165 | Annotation score: | ||
E7EMX4 | E7EMX4_HUMAN | Tryptophan 5-hydroxylase 1 | TPH1 | 206 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 19 | S → T in AAA67050 (PubMed:7986090).Curated | 1 | |
Sequence conflicti | 68 | I → T in AAA67050 (PubMed:7986090).Curated | 1 | |
Sequence conflicti | 90 – 91 | NL → TP in AAA67050 (PubMed:7986090).Curated | 2 | |
Sequence conflicti | 97 | L → M in AAA67050 (PubMed:7986090).Curated | 1 | |
Sequence conflicti | 100 | D → E in AAA67050 (PubMed:7986090).Curated | 1 | |
Sequence conflicti | 104 | T → S in AAA67050 (PubMed:7986090).Curated | 1 | |
Sequence conflicti | 151 | L → S in AAA67050 (PubMed:7986090).Curated | 1 | |
Sequence conflicti | 154 | N → S in AAA67050 (PubMed:7986090).Curated | 1 | |
Sequence conflicti | 157 | H → Y in AAA67050 (PubMed:7986090).Curated | 1 | |
Sequence conflicti | 179 | Q → R in AAA67050 (PubMed:7986090).Curated | 1 | |
Sequence conflicti | 207 | R → Q in AAA67050 (PubMed:7986090).Curated | 1 | |
Sequence conflicti | 217 | V → I in AAA67050 (PubMed:7986090).Curated | 1 | |
Sequence conflicti | 344 | A → V in AAA67050 (PubMed:7986090).Curated | 1 | |
Sequence conflicti | 414 | T → A in AAA67050 (PubMed:7986090).Curated | 1 | |
Sequence conflicti | 419 | S → N in AAA67050 (PubMed:7986090).Curated | 1 | |
Sequence conflicti | 425 | Q → R in AAA67050 (PubMed:7986090).Curated | 1 | |
Sequence conflicti | 436 | A → G in AAA67050 (PubMed:7986090).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_000546 | 438 – 444 | VSRKPSI → SLNEDVLQVSVFALLLFLPS LHGECHPDT in isoform 2. Curated | 7 |
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 |
CCDSi | CCDS7829.1 [P17752-1] |
PIRi | S10489 |
RefSeqi | NP_004170.1, NM_004179.2 [P17752-1] |
Genome annotation databases
Ensembli | ENST00000250018.6; ENSP00000250018.2; ENSG00000129167.10 ENST00000682019.1; ENSP00000508368.1; ENSG00000129167.10 |
GeneIDi | 7166 |
KEGGi | hsa:7166 |
MANE-Selecti | ENST00000682019.1; ENSP00000508368.1; NM_004179.3; NP_004170.1 |
UCSCi | uc001mnp.3, human [P17752-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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 |
CCDSi | CCDS7829.1 [P17752-1] |
PIRi | S10489 |
RefSeqi | NP_004170.1, NM_004179.2 [P17752-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1MLW | X-ray | 1.71 | A | 102-402 | [»] | |
3HF6 | X-ray | 1.80 | A | 105-393 | [»] | |
3HF8 | X-ray | 1.85 | A | 105-393 | [»] | |
3HFB | X-ray | 1.92 | A | 104-393 | [»] | |
5J6D | X-ray | 1.90 | A/B | 102-402 | [»] | |
5L01 | X-ray | 1.90 | A | 1-444 | [»] | |
5TPG | X-ray | 1.50 | A | 104-402 | [»] | |
AlphaFoldDBi | P17752 | |||||
SMRi | P17752 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 113019, 12 interactors |
IntActi | P17752, 11 interactors |
STRINGi | 9606.ENSP00000250018 |
Chemistry databases
BindingDBi | P17752 |
ChEMBLi | CHEMBL5689 |
DrugBanki | DB05199, LX1031 DB00360, Sapropterin DB12095, Telotristat ethyl DB00150, Tryptophan |
DrugCentrali | P17752 |
GuidetoPHARMACOLOGYi | 1241 |
PTM databases
iPTMneti | P17752 |
PhosphoSitePlusi | P17752 |
Genetic variation databases
BioMutai | TPH1 |
DMDMi | 116242823 |
Proteomic databases
jPOSTi | P17752 |
MassIVEi | P17752 |
PaxDbi | P17752 |
PeptideAtlasi | P17752 |
PRIDEi | P17752 |
ProteomicsDBi | 53513 [P17752-1] 53514 [P17752-2] |
Protocols and materials databases
Antibodypediai | 4386, 624 antibodies from 43 providers |
DNASUi | 7166 |
Genome annotation databases
Ensembli | ENST00000250018.6; ENSP00000250018.2; ENSG00000129167.10 ENST00000682019.1; ENSP00000508368.1; ENSG00000129167.10 |
GeneIDi | 7166 |
KEGGi | hsa:7166 |
MANE-Selecti | ENST00000682019.1; ENSP00000508368.1; NM_004179.3; NP_004170.1 |
UCSCi | uc001mnp.3, human [P17752-1] |
Organism-specific databases
CTDi | 7166 |
DisGeNETi | 7166 |
GeneCardsi | TPH1 |
HGNCi | HGNC:12008, TPH1 |
HPAi | ENSG00000129167, Group enriched (brain, intestine, stomach) |
MIMi | 191060, gene |
neXtProti | NX_P17752 |
OpenTargetsi | ENSG00000129167 |
PharmGKBi | PA355 |
VEuPathDBi | HostDB:ENSG00000129167 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3820, Eukaryota |
GeneTreei | ENSGT00950000182885 |
HOGENOMi | CLU_023198_0_0_1 |
InParanoidi | P17752 |
OMAi | VTCQEEC |
OrthoDBi | 614557at2759 |
PhylomeDBi | P17752 |
TreeFami | TF313327 |
Enzyme and pathway databases
UniPathwayi | UPA00846;UER00799 |
BRENDAi | 1.14.16.4, 2681 |
PathwayCommonsi | P17752 |
Reactomei | R-HSA-209931, Serotonin and melatonin biosynthesis R-HSA-9031628, NGF-stimulated transcription |
SABIO-RKi | P17752 |
SignaLinki | P17752 |
SIGNORi | P17752 |
Miscellaneous databases
BioGRID-ORCSi | 7166, 19 hits in 1074 CRISPR screens |
ChiTaRSi | TPH1, human |
EvolutionaryTracei | P17752 |
GeneWikii | TPH1 |
GenomeRNAii | 7166 |
Pharosi | P17752, Tclin |
PROi | PR:P17752 |
RNActi | P17752, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000129167, Expressed in buccal mucosa cell and 124 other tissues |
ExpressionAtlasi | P17752, baseline and differential |
Genevisiblei | P17752, HS |
Family and domain databases
CDDi | cd03346, eu_TrpOH, 1 hit |
Gene3Di | 1.10.800.10, 1 hit |
InterProi | View protein in InterPro IPR045865, ACT-like_dom_sf 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 IPR041904, TrpOH_cat IPR019773, Tyrosine_3-monooxygenase-like |
PANTHERi | PTHR11473, PTHR11473, 1 hit |
Pfami | View protein in Pfam PF00351, Biopterin_H, 1 hit |
PIRSFi | PIRSF000336, TH, 1 hit |
PRINTSi | PR00372, FYWHYDRXLASE |
SUPFAMi | SSF55021, SSF55021, 1 hit SSF56534, SSF56534, 1 hit |
TIGRFAMsi | TIGR01270, Trp_5_monoox, 1 hit |
PROSITEi | View protein in PROSITE PS51671, ACT, 1 hit PS00367, BH4_AAA_HYDROXYL_1, 1 hit PS51410, BH4_AAA_HYDROXYL_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TPH1_HUMAN | |
Accessioni | P17752Primary (citable) accession number: P17752 Secondary accession number(s): D3DQX6 Q3KPG8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1990 |
Last sequence update: | October 17, 2006 | |
Last modified: | May 25, 2022 | |
This is version 204 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families