Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT3KLDP)

• DTT Name: L-Tryptophan hydroxylase 2 (TPH2)
• Synonyms: Tryptophan 5-monooxygenase 2; Tryptophan 5-hydroxylase 2; Neuronal tryptophan hydroxylase; NTPH
• Gene Name: TPH2
• DTT Type: Literature-reported target; [1]
• UniProt ID: TPH2_HUMAN
• TTD ID: T85915
• EC Number: EC 1.14.16.4
• Sequence:
  MQPAMMMFSSKYWARRGFSLDSAVPEEHQLLGSSTLNKPNSGKNDDKGNKGSSKREAATE
  SGKTAVVFSLKNEVGGLVKALRLFQEKRVNMVHIESRKSRRRSSEVEIFVDCECGKTEFN
  ELIQLLKFQTTIVTLNPPENIWTEEEELEDVPWFPRKISELDKCSHRVLMYGSELDADHP
  GFKDNVYRQRRKYFVDVAMGYKYGQPIPRVEYTEEETKTWGVVFRELSKLYPTHACREYL
  KNFPLLTKYCGYREDNVPQLEDVSMFLKERSGFTVRPVAGYLSPRDFLAGLAYRVFHCTQ
  YIRHGSDPLYTPEPDTCHELLGHVPLLADPKFAQFSQEIGLASLGASDEDVQKLATCYFF
  TIEFGLCKQEGQLRAYGAGLLSSIGELKHALSDKACVKAFDPKTTCLQECLITTFQEAYF
  VSESFEEAKEKMRDFAKSITRPFSVYFNPYTQSIEILKDTRSIENVVQDLRSDLNTVCDA
  LNKMNQYLGI
• Function: Rate-limiting enzyme in the synthesis of serotonin (5-hydroxytryptamine, or 5HT). Has functions in peripheral tissues, including the maintenance of vascular tone and gut motility.
• KEGG Pathway:
  Tryptophan metabolism (hsa00380)
  Folate biosynthesis (hsa00790)
  Metabolic pathways (hsa01100)
  Serotonergic synapse (hsa04726)
• Reactome Pathway: Serotonin and melatonin biosynthesis (R-HSA-209931)
• BioCyc Pathway: MetaCyc:HS06603-MON

Molecular Interaction Atlas (MIA) of This DTT

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
6-fluorotryptophan	DM6YD3U	Discovery agent	N.A.	Investigative	[2]
alpha-propyldopacetamide	DMQKMX3	Discovery agent	N.A.	Investigative	[1]
fenclonine	DMUBO3E	Discovery agent	N.A.	Investigative	[1]

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Tryptophan 5-hydroxylase 2 (TPH2) DME Info
• Gene Name: TPH2

2 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-Tryptophan	DMIBH7M	Depression	6A70-6A7Z	Approved	[3]
Tetrahydrobiopterin	DMINZ4W	Malnutrition	5B50-5B71	Approved	[4]

1 Investigative Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sapropterin	DM6GE21	Phenylketonuria	5C50.0	Investigative	[4]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1242).
• [2] (+)-6-fluorotryptophan, an inhibitor of tryptophan hydroxylase: sleep and wakefulness in the rat. Neuropharmacology. 1981 Apr;20(4):335-9.
• [3] Strain differences in basal and post-citalopram extracellular 5-HT in the mouse medial prefrontal cortex and dorsal hippocampus: relation with tryptophan hydroxylase-2 activity. J Neurochem. 2007 Nov;103(3):1111-20.
• [4] Characterization of wild-type and mutant forms of human tryptophan hydroxylase 2. J Neurochem. 2007 Mar;100(6):1648-57.