Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPCR8F7)

• DOT Name: G-protein coupled receptor 20 (GPR20)
• Gene Name: GPR20
• UniProt ID: GPR20_HUMAN
• PDB ID: 8HS2; 8HS3; 8HSC
• Pfam ID: PF00001
• Sequence:
  MPSVSPAGPSAGAVPNATAVTTVRTNASGLEVPLFHLFARLDEELHGTFPGLWLALMAVH
  GAIFLAGLVLNGLALYVFCCRTRAKTPSVIYTINLVVTDLLVGLSLPTRFAVYYGARGCL
  RCAFPHVLGYFLNMHCSILFLTCICVDRYLAIVRPEGSRRCRQPACARAVCAFVWLAAGA
  VTLSVLGVTGSRPCCRVFALTVLEFLLPLLVISVFTGRIMCALSRPGLLHQGRQRRVRAM
  QLLLTVLIIFLVCFTPFHARQVAVALWPDMPHHTSLVVYHVAVTLSSLNSCMDPIVYCFV
  TSGFQATVRGLFGQHGEREPSSGDVVSMHRSSKGSGRHHILSAGPHALTQALANGPEA
• Function: Orphan receptor with constitutive G(i) signaling activity that activate cyclic AMP.
• Tissue Specificity: Ubiquitous with highest levels in intestinal tissues. In the brain detected in thalamus, putamen, and caudate, but not in frontal cortex, pons and hypothalamus.
• Reactome Pathway: G alpha (s) signalling events (R-HSA-418555)

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 G-protein coupled receptor 20 (GPR20).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of G-protein coupled receptor 20 (GPR20).	[5]

8 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 G-protein coupled receptor 20 (GPR20).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of G-protein coupled receptor 20 (GPR20).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of G-protein coupled receptor 20 (GPR20).	[4]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of G-protein coupled receptor 20 (GPR20).	[3]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of G-protein coupled receptor 20 (GPR20).	[3]
Gentamicin	DMKINJO	Approved	Gentamicin increases the expression of G-protein coupled receptor 20 (GPR20).	[3]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of G-protein coupled receptor 20 (GPR20).	[6]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of G-protein coupled receptor 20 (GPR20).	[7]

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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Effect of nephrotoxicants and hepatotoxicants on gene expression profile in human peripheral blood mononuclear cells. Biochem Biophys Res Commun. 2010 Oct 15;401(2):245-50. doi: 10.1016/j.bbrc.2010.09.039. Epub 2010 Sep 16.
• [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] 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.
• [6] 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.
• [7] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.