Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ5WHHX)

• DOT Name: Probable G-protein coupled receptor 132 (GPR132)
• Synonyms: G2 accumulation protein
• Gene Name: GPR132
• UniProt ID: GP132_HUMAN
• PDB ID: 8HQE; 8HQM; 8HQN; 8HVI
• Pfam ID: PF00001
• Sequence:
  MCPMLLKNGYNGNATPVTTTAPWASLGLSAKTCNNVSFEESRIVLVVVYSAVCTLGVPAN
  CLTAWLALLQVLQGNVLAVYLLCLALCELLYTGTLPLWVIYIRNQHRWTLGLLACKVTAY
  IFFCNIYVSILFLCCISCDRFVAVVYALESRGRRRRRTAILISACIFILVGIVHYPVFQT
  EDKETCFDMLQMDSRIAGYYYARFTVGFAIPLSIIAFTNHRIFRSIKQSMGLSAAQKAKV
  KHSAIAVVVIFLVCFAPYHLVLLVKAAAFSYYRGDRNAMCGLEERLYTASVVFLCLSTVN
  GVADPIIYVLATDHSRQEVSRIHKGWKEWSMKTDVTRLTHSRDTEELQSPVALADHYTFS
  RPVHPPGSPCPAKRLIEESC
• Function: May be a receptor for oxidized free fatty acids derived from linoleic and arachidonic acids such as 9-hydroxyoctadecadienoic acid (9-HODE). Activates a G alpha protein, most likely G alpha(q). May be involved in apoptosis. Functions at the G2/M checkpoint to delay mitosis. May function as a sensor that monitors the oxidative states and mediates appropriate cellular responses such as secretion of paracrine signals and attenuation of proliferation. May mediate ths accumulation of intracellular inositol phosphates at acidic pH through proton-sensing activity.
• Tissue Specificity: Highly expressed in macrophages and hematopoietic tissues rich in lymphocytes, like spleen and thymus. Weakly expressed in heart and lung. In atherosclerotic plaques, expression is observed around the lipid core and at the shoulder region.
• KEGG Pathway: Efferocytosis (hsa04148)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Class A/1 (Rhodopsin-like receptors) (R-HSA-373076)

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 Probable G-protein coupled receptor 132 (GPR132).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Probable G-protein coupled receptor 132 (GPR132).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Probable G-protein coupled receptor 132 (GPR132).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Probable G-protein coupled receptor 132 (GPR132).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Probable G-protein coupled receptor 132 (GPR132).	[4]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Probable G-protein coupled receptor 132 (GPR132).	[5]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Probable G-protein coupled receptor 132 (GPR132).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Probable G-protein coupled receptor 132 (GPR132).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Probable G-protein coupled receptor 132 (GPR132).	[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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [5] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [6] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [7] 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.
• [8] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.