Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4EA7TB)

DOT Name	Tryptophan 5-hydroxylase 1 (TPH1)
Synonyms	EC 1.14.16.4; Tryptophan 5-monooxygenase 1
Gene Name	TPH1
UniProt ID	TPH1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1MLW; 3HF6; 3HF8; 3HFB; 5J6D; 5L01; 5TPG; 7ZIF; 7ZIG; 7ZIH; 7ZII; 7ZIJ; 7ZIK
EC Number	1.14.16.4
Pfam ID	PF00351
Sequence	MIEDNKENKDHSLERGRASLIFSLKNEVGGLIKALKIFQEKHVNLLHIESRKSKRRNSEF EIFVDCDINREQLNDIFHLLKSHTNVLSVNLPDNFTLKEDGMETVPWFPKKISDLDHCAN RVLMYGSELDADHPGFKDNVYRKRRKYFADLAMNYKHGDPIPKVEFTEEEIKTWGTVFQE LNKLYPTHACREYLKNLPLLSKYCGYREDNIPQLEDVSNFLKERTGFSIRPVAGYLSPRD FLSGLAFRVFHCTQYVRHSSDPFYTPEPDTCHELLGHVPLLAEPSFAQFSQEIGLASLGA SEEAVQKLATCYFFTVEFGLCKQDGQLRVFGAGLLSSISELKHALSGHAKVKPFDPKITC KQECLITTFQDVYFVSESFEDAKEKMREFTKTIKRPFGVKYNPYTRSIQILKDTKSITSA MNELQHDLDVVSDALAKVSRKPSI
Function	Oxidizes L-tryptophan to 5-hydroxy-l-tryptophan in the rate-determining step of serotonin biosynthesis.
Tissue Specificity	.Seems to be less widely expressed than isoform 1.
KEGG Pathway	Tryptophan metabolism (hsa00380 ) Folate biosynthesis (hsa00790 ) Metabolic pathways (hsa01100 ) Serotonergic sy.pse (hsa04726 )
Reactome Pathway	NGF-stimulated transcription (R-HSA-9031628 ) Serotonin and melatonin biosynthesis (R-HSA-209931 )
BioCyc Pathway	MetaCyc:HS05250-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Serotonin	DMOFCRY	Investigative	Tryptophan 5-hydroxylase 1 (TPH1) increases the abundance of Serotonin.	[4]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tryptophan 5-hydroxylase 1 (TPH1).	[1]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Tryptophan 5-hydroxylase 1 (TPH1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tryptophan 5-hydroxylase 1 (TPH1).	[3]
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References

1	Nephrotoxicity induced by cisplatin is primarily due to the activation of the 5-hydroxytryptamine degradation system in proximal renal tubules. Chem Biol Interact. 2021 Nov 1;349:109662. doi: 10.1016/j.cbi.2021.109662. Epub 2021 Sep 21.
2	Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
3	Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
4	Hyperserotonemia in autism: the potential role of 5HT-related gene variants. Coll Antropol. 2008 Jan;32 Suppl 1:75-80.