Details of Drug Off-Target (DOT)

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

• DOT Name: Relaxin-3 receptor 2 (RXFP4)
• Synonyms: RLN3 receptor 2; G-protein coupled receptor 100; G-protein coupled receptor GPCR142; Insulin-like peptide INSL5 receptor; Relaxin family peptide receptor 4
• Gene Name: RXFP4
• Related Disease: High blood pressure
• UniProt ID: RL3R2_HUMAN
• PDB ID: 7YJ4; 7YK6; 7YK7
• Pfam ID: PF00001
• Sequence:
  MPTLNTSASPPTFFWANASGGSVLSADDAPMPVKFLALRLMVALAYGLVGAIGLLGNLAV
  LWVLSNCARRAPGPPSDTFVFNLALADLGLALTLPFWAAESALDFHWPFGGALCKMVLTA
  TVLNVYASIFLITALSVARYWVVAMAAGPGTHLSLFWARIATLAVWAAAALVTVPTAVFG
  VEGEVCGVRLCLLRFPSRYWLGAYQLQRVVLAFMVPLGVITTSYLLLLAFLQRRQRRRQD
  SRVVARSVRILVASFFLCWFPNHVVTLWGVLVKFDLVPWNSTFYTIQTYVFPVTTCLAHS
  NSCLNPVLYCLLRREPRQALAGTFRDLRLRLWPQGGGWVQQVALKQVGRRWVASNPRESR
  PSTLLTNLDRGTPG
• Function: High affinity receptor for INSL5. Also acts as a receptor for RLN3/relaxin-3, as well as bradykinin and kallidin. Binding of the ligand inhibit cAMP accumulation.
• Tissue Specificity: Expressed in a broader range of tissues including brain, kidney, testis, thymus, placenta, prostate, salivary gland, thyroid and colon.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Relaxin sig.ling pathway (hsa04926)
• Reactome Pathway:
  Relaxin receptors (R-HSA-444821)
  G alpha (i) signalling events (R-HSA-418594)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
High blood pressure	DISY2OHH	moderate	Genetic Variation	[1]

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 Relaxin-3 receptor 2 (RXFP4).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Relaxin-3 receptor 2 (RXFP4).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Relaxin-3 receptor 2 (RXFP4).	[3]

References

• [1] Relaxin polymorphisms associated with metabolic disturbance in patients treated with antipsychotics.J Psychopharmacol. 2012 Mar;26(3):374-9. doi: 10.1177/0269881111408965. Epub 2011 Jun 21.
• [2] 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.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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.