Details of Drug Off-Target (DOT)

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

• DOT Name: Substance-K receptor (TACR2)
• Synonyms: SKR; NK-2 receptor; NK-2R; Neurokinin A receptor; Tachykinin receptor 2
• Gene Name: TACR2
• UniProt ID: NK2R_HUMAN
• PDB ID: 7XWO
• Pfam ID: PF00001
• Sequence:
  MGTCDIVTEANISSGPESNTTGITAFSMPSWQLALWATAYLALVLVAVTGNAIVIWIILA
  HRRMRTVTNYFIVNLALADLCMAAFNAAFNFVYASHNIWYFGRAFCYFQNLFPITAMFVS
  IYSMTAIAADRYMAIVHPFQPRLSAPSTKAVIAGIWLVALALASPQCFYSTVTMDQGATK
  CVVAWPEDSGGKTLLLYHLVVIALIYFLPLAVMFVAYSVIGLTLWRRAVPGHQAHGANLR
  HLQAMKKFVKTMVLVVLTFAICWLPYHLYFILGSFQEDIYCHKFIQQVYLALFWLAMSST
  MYNPIIYCCLNHRFRSGFRLAFRCCPWVTPTKEDKLELTPTTSLSTRVNRCHTKETLFMA
  GDTAPSEATSGEAGRPQDGSGLWFGYGLLAPTKTHVEI
• Function: This is a receptor for the tachykinin neuropeptide substance K (neurokinin A). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance K > neuromedin-K > substance P.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Tachykinin receptors bind tachykinins (R-HSA-380095)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Capsaicin	DMGMF6V	Approved	Substance-K receptor (TACR2) increases the response to substance of Capsaicin.	[6]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Substance-K receptor (TACR2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Substance-K receptor (TACR2).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Substance-K receptor (TACR2).	[5]

1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Substance-K receptor (TACR2).	[2]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Saredutant	DMSRJY3	Discontinued in Phase 3	Saredutant affects the binding of Substance-K receptor (TACR2).	[4]
neurokinin A	DM9UXRP	Investigative	neurokinin A affects the binding of Substance-K receptor (TACR2).	[4]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [3] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [4] Pharmacology of an original and selective nonpeptide antagonist ligand for the human tachykinin NK2 receptor. Eur J Pharmacol. 2005 Jun 1;516(2):104-11.
• [5] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [6] Association of genetic variations in neurokinin-2 receptor with enhanced cough sensitivity to capsaicin in chronic cough. Thorax. 2006 Dec;61(12):1070-5. doi: 10.1136/thx.2005.054429. Epub 2006 Aug 7.