Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTWHSP9)

• DOT Name: Probable G-protein coupled receptor 32 (GPR32)
• Gene Name: GPR32
• UniProt ID: GPR32_HUMAN
• Pfam ID: PF00001
• Sequence:
  MNGVSEGTRGCSDRQPGVLTRDRSCSRKMNSSGCLSEEVGSLRPLTVVILSASIVVGVLG
  NGLVLWMTVFRMARTVSTVCFFHLALADFMLSLSLPIAMYYIVSRQWLLGEWACKLYITF
  VFLSYFASNCLLVFISVDRCISVLYPVWALNHRTVQRASWLAFGVWLLAAALCSAHLKFR
  TTRKWNGCTHCYLAFNSDNETAQIWIEGVVEGHIIGTIGHFLLGFLGPLAIIGTCAHLIR
  AKLLREGWVHANRPKRLLLVLVSAFFIFWSPFNVVLLVHLWRRVMLKEIYHPRMLLILQA
  SFALGCVNSSLNPFLYVFVGRDFQEKFFQSLTSALARAFGEEEFLSSCPRGNAPRE
• Function: G-protein coupled receptor that binds to several ligands including resolvin D1 (RvD1) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. In macrophages, enhances the RvD1-stimulated phagocytic and clearance functions. Macrophages migrate less toward different chemoattractant stimuli but phagocytose more microbial particles. Prevents the increase in Ca(2+) and activation of ERK1/2 used by histamine and its H1 receptor subtype to induce goblet cell secretion by activating PKC and GRK2 to counter-regulate the histamine receptor.
• Tissue Specificity: Expressed in resting primary human macrophages.
• Reactome Pathway: G alpha (s) signalling events (R-HSA-418555)

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 increases the methylation of Probable G-protein coupled receptor 32 (GPR32).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Probable G-protein coupled receptor 32 (GPR32).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Probable G-protein coupled receptor 32 (GPR32).	[5]

3 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 Probable G-protein coupled receptor 32 (GPR32).	[2]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Probable G-protein coupled receptor 32 (GPR32).	[3]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Probable G-protein coupled receptor 32 (GPR32).	[7]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the secretion of Probable G-protein coupled receptor 32 (GPR32).	[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] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [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] 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.
• [6] Effects of Agricultural Organic Dusts on Human Lung-Resident Mesenchymal Stem (Stromal) Cell Function. Toxicol Sci. 2018 Apr 1;162(2):635-644. doi: 10.1093/toxsci/kfx286.
• [7] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.