Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT6T2A0)

• DOT Name: Lysophosphatidic acid receptor 5 (LPAR5)
• Synonyms: LPA receptor 5; LPA-5; G-protein coupled receptor 92; G-protein coupled receptor 93
• Gene Name: LPAR5
• UniProt ID: LPAR5_HUMAN
• Pfam ID: PF00001
• Sequence:
  MLANSSSTNSSVLPCPDYRPTHRLHLVVYSLVLAAGLPLNALALWVFLRALRVHSVVSVY
  MCNLAASDLLFTLSLPVRLSYYALHHWPFPDLLCQTTGAIFQMNMYGSCIFLMLINVDRY
  AAIVHPLRLRHLRRPRVARLLCLGVWALILVFAVPAARVHRPSRCRYRDLEVRLCFESFS
  DELWKGRLLPLVLLAEALGFLLPLAAVVYSSGRVFWTLARPDATQSQRRRKTVRLLLANL
  VIFLLCFVPYNSTLAVYGLLRSKLVAASVPARDRVRGVLMVMVLLAGANCVLDPLVYYFS
  AEGFRNTLRGLGTPHRARTSATNGTRAALAQSERSAVTTDATRPDAASQGLLRPSDSHSL
  SSFTQCPQDSAL
• Function: Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities.
• Tissue Specificity: Not expressed in frontal cortex, basal forebrain, caudate putamen, thalamus, or hippocampus.
• KEGG Pathway:
  Rap1 sig.ling pathway (hsa04015)
  Phospholipase D sig.ling pathway (hsa04072)
  PI3K-Akt sig.ling pathway (hsa04151)
  Regulation of actin cytoskeleton (hsa04810)
  Pathogenic Escherichia coli infection (hsa05130)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Lysosphingolipid and LPA receptors (R-HSA-419408)
  G alpha (q) signalling events (R-HSA-416476)

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 Lysophosphatidic acid receptor 5 (LPAR5).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Lysophosphatidic acid receptor 5 (LPAR5).	[4]

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 Lysophosphatidic acid receptor 5 (LPAR5).	[2]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Lysophosphatidic acid receptor 5 (LPAR5).	[3]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Lysophosphatidic acid receptor 5 (LPAR5).	[5]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Lysophosphatidic acid receptor 5 (LPAR5).	[6]

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] 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.
• [3] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [6] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.