Details of Drug Off-Target (DOT)

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

• DOT Name: Proteinase-activated receptor 4 (F2RL3)
• Synonyms: PAR-4; Coagulation factor II receptor-like 3; Thrombin receptor-like 3
• Gene Name: F2RL3
• UniProt ID: PAR4_HUMAN
• PDB ID: 2ZPK; 3QDZ
• Pfam ID: PF00001
• Sequence:
  MWGRLLLWPLVLGFSLSGGTQTPSVYDESGSTGGGDDSTPSILPAPRGYPGQVCANDSDT
  LELPDSSRALLLGWVPTRLVPALYGLVLVVGLPANGLALWVLATQAPRLPSTMLLMNLAA
  ADLLLALALPPRIAYHLRGQRWPFGEAACRLATAALYGHMYGSVLLLAAVSLDRYLALVH
  PLRARALRGRRLALGLCMAAWLMAAALALPLTLQRQTFRLARSDRVLCHDALPLDAQASH
  WQPAFTCLALLGCFLPLLAMLLCYGATLHTLAASGRRYGHALRLTAVVLASAVAFFVPSN
  LLLLLHYSDPSPSAWGNLYGAYVPSLALSTLNSCVDPFIYYYVSAEFRDKVRAGLFQRSP
  GDTVASKASAEGGSRGMGTHSSLLQ
• Function: Receptor for activated thrombin or trypsin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation.
• Tissue Specificity: Widely expressed, with highest levels in lung, pancreas, thyroid, testis and small intestine. Not expressed in brain, kidney, spinal cord and peripheral blood leukocytes. Also detected in platelets.
• KEGG Pathway:
  Rap1 sig.ling pathway (hsa04015)
  Neuroactive ligand-receptor interaction (hsa04080)
  Complement and coagulation cascades (hsa04610)
  Platelet activation (hsa04611)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Thrombin signalling through proteinase activated receptors (PARs) (R-HSA-456926)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DOT

2 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 Proteinase-activated receptor 4 (F2RL3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Proteinase-activated receptor 4 (F2RL3).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Proteinase-activated receptor 4 (F2RL3).	[2]
Bivalirudin	DMECRX1	Approved	Bivalirudin decreases the activity of Proteinase-activated receptor 4 (F2RL3).	[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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Bivalirudin: a new promising direct antithrombin. Indian Heart J. 2007 May-Jun;59(3):288-94.
• [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.