Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVQ0T75)

• DOT Name: Neuropeptide S receptor (NPSR1)
• Synonyms: G-protein coupled receptor 154; G-protein coupled receptor PGR14; G-protein coupled receptor for asthma susceptibility
• Gene Name: NPSR1
• UniProt ID: NPSR1_HUMAN
• Pfam ID: PF00001
• Sequence:
  MPANFTEGSFDSSGTGQTLDSSPVACTETVTFTEVVEGKEWGSFYYSFKTEQLITLWVLF
  VFTIVGNSVVLFSTWRRKKKSRMTFFVTQLAITDSFTGLVNILTDINWRFTGDFTAPDLV
  CRVVRYLQVVLLYASTYVLVSLSIDRYHAIVYPMKFLQGEKQARVLIVIAWSLSFLFSIP
  TLIIFGKRTLSNGEVQCWALWPDDSYWTPYMTIVAFLVYFIPLTIISIMYGIVIRTIWIK
  SKTYETVISNCSDGKLCSSYNRGLISKAKIKAIKYSIIIILAFICCWSPYFLFDILDNFN
  LLPDTQERFYASVIIQNLPALNSAINPLIYCVFSSSISFPCREQRSQDSRMTFRERTERH
  EMQILSKPEFI
• Function: G-protein coupled receptor for neuropeptide S (NPS). Promotes mobilization of intracellular Ca(2+) stores. Inhibits cell growth in response to NPS binding. Involved in pathogenesis of asthma and other IgE-mediated diseases.
• Tissue Specificity: Isoform 4 is ubiquitous; it is detected in glandular epithelia of bronchus, stomach, small intestine, colon, uterus, esophagus, spleen, kidney, pancreas, prostate and breast. Isoform 1 is detected in uterus, colon and prostate, and in the smooth muscle cell layer in bronchial and arterial walls (at protein level) . Isoform 1 is predominantly expressed in smooth muscle. Isoform 4 is predominantly expressed in epithelial cells. In bronchial biopsies, it is expressed in smooth muscle cells of asthma patients, but not in control patients; whereas in epithelial cells, its expression is consistently stronger in asthma patients.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  G alpha (s) signalling events (R-HSA-418555)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Neuropeptide S receptor (NPSR1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Neuropeptide S receptor (NPSR1).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Neuropeptide S receptor (NPSR1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Neuropeptide S receptor (NPSR1).	[2]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Neuropeptide S receptor (NPSR1).	[3]

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] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [3] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [4] 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.
• [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.