Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT354X3O)

• DOT Name: Lysophosphatidic acid receptor 4 (LPAR4)
• Synonyms: LPA receptor 4; LPA-4; G-protein coupled receptor 23; P2Y purinoceptor 9; P2Y9; P2Y5-like receptor; Purinergic receptor 9
• Gene Name: LPAR4
• UniProt ID: LPAR4_HUMAN
• Pfam ID: PF00001
• Sequence:
  MGDRRFIDFQFQDSNSSLRPRLGNATANNTCIVDDSFKYNLNGAVYSVVFILGLITNSVS
  LFVFCFRMKMRSETAIFITNLAVSDLLFVCTLPFKIFYNFNRHWPFGDTLCKISGTAFLT
  NIYGSMLFLTCISVDRFLAIVYPFRSRTIRTRRNSAIVCAGVWILVLSGGISASLFSTTN
  VNNATTTCFEGFSKRVWKTYLSKITIFIEVVGFIIPLILNVSCSSVVLRTLRKPATLSQI
  GTNKKKVLKMITVHMAVFVVCFVPYNSVLFLYALVRSQAITNCFLERFAKIMYPITLCLA
  TLNCCFDPFIYYFTLESFQKSFYINAHIRMESLFKTETPLTTKPSLPAIQEEVSDQTTNN
  GGELMLESTF
• Function: Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. Transduces a signal by increasing the intracellular calcium ions and by stimulating adenylyl cyclase activity. The rank order of potency for agonists of this receptor is 1-oleoyl- > 1-stearoyl- > 1-palmitoyl- > 1-myristoyl- > 1-alkyl- > 1-alkenyl-LPA.
• Tissue Specificity: High expression in ovary. Not detected in the brain regions thalamus, putamen, caudate, frontal cortex, pons, hypothalamus and hippocampus.
• KEGG Pathway:
  Rap1 sig.ling pathway (hsa04015)
  Phospholipase D sig.ling pathway (hsa04072)
  Neuroactive ligand-receptor interaction (hsa04080)
  PI3K-Akt sig.ling pathway (hsa04151)
  Regulation of actin cytoskeleton (hsa04810)
  Pathogenic Escherichia coli infection (hsa05130)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  P2Y receptors (R-HSA-417957)
  G alpha (q) signalling events (R-HSA-416476)

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 Lysophosphatidic acid receptor 4 (LPAR4).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Lysophosphatidic acid receptor 4 (LPAR4).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Lysophosphatidic acid receptor 4 (LPAR4).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Lysophosphatidic acid receptor 4 (LPAR4).	[2]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Lysophosphatidic acid receptor 4 (LPAR4).	[5]

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] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [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] 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.
• [5] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.