Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRNEOZ0)

• DOT Name: Cysteinyl leukotriene receptor 2 (CYSLTR2)
• Synonyms: CysLTR2; G-protein coupled receptor GPCR21; hGPCR21; G-protein coupled receptor HG57; HPN321
• Gene Name: CYSLTR2
• UniProt ID: CLTR2_HUMAN
• Pfam ID: PF00001
• Sequence:
  MERKFMSLQPSISVSEMEPNGTFSNNNSRNCTIENFKREFFPIVYLIIFFWGVLGNGLSI
  YVFLQPYKKSTSVNVFMLNLAISDLLFISTLPFRADYYLRGSNWIFGDLACRIMSYSLYV
  NMYSSIYFLTVLSVVRFLAMVHPFRLLHVTSIRSAWILCGIIWILIMASSIMLLDSGSEQ
  NGSVTSCLELNLYKIAKLQTMNYIALVVGCLLPFFTLSICYLLIIRVLLKVEVPESGLRV
  SHRKALTTIIITLIIFFLCFLPYHTLRTVHLTTWKVGLCKDRLHKALVITLALAAANACF
  NPLLYYFAGENFKDRLKSALRKGHPQKAKTKCVFPVSVWLRKETRV
• Function: Receptor for cysteinyl leukotrienes. The response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Stimulation by BAY u9773, a partial agonist, induces specific contractions of pulmonary veins and might also have an indirect role in the relaxation of the pulmonary vascular endothelium. The rank order of affinities for the leukotrienes is LTC4 = LTD4 >> LTE4.
• Tissue Specificity: Widely expressed, with highest levels in the heart, placenta, spleen, peripheral blood leukocytes and adrenal gland. In lung, expressed in the interstitial macrophages, and slightly in smooth muscle cells.
• KEGG Pathway:
  Calcium sig.ling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  G alpha (s) signalling events (R-HSA-418555)
  LTC4-CYSLTR mediated IL4 production (R-HSA-9664535)
  Leukotriene receptors (R-HSA-391906)

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
Aspirin	DM672AH	Approved	Cysteinyl leukotriene receptor 2 (CYSLTR2) affects the response to substance of Aspirin.	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cysteinyl leukotriene receptor 2 (CYSLTR2).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cysteinyl leukotriene receptor 2 (CYSLTR2).	[2]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cysteinyl leukotriene receptor 2 (CYSLTR2).	[3]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Cysteinyl leukotriene receptor 2 (CYSLTR2).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cysteinyl leukotriene receptor 2 (CYSLTR2).	[5]

References

• [1] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [4] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [5] 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.
• [6] Genetic and ethnic risk factors associated with drug hypersensitivity. Curr Opin Allergy Clin Immunol. 2010 Aug;10(4):280-90. doi: 10.1097/ACI.0b013e32833b1eb3.