Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGKA8WS)

• DOT Name: Gamma-aminobutyric acid receptor subunit pi (GABRP)
• Synonyms: GABA(A) receptor subunit pi
• Gene Name: GABRP
• UniProt ID: GBRP_HUMAN
• Pfam ID: PF02931 ; PF02932
• Sequence:
  MNYSLHLAFVCLSLFTERMCIQGSQFNVEVGRSDKLSLPGFENLTAGYNKFLRPNFGGEP
  VQIALTLDIASISSISESNMDYTATIYLRQRWMDQRLVFEGNKSFTLDARLVEFLWVPDT
  YIVESKKSFLHEVTVGNRLIRLFSNGTVLYALRITTTVACNMDLSKYPMDTQTCKLQLES
  WGYDGNDVEFTWLRGNDSVRGLEHLRLAQYTIERYFTLVTRSQQETGNYTRLVLQFELRR
  NVLYFILETYVPSTFLVVLSWVSFWISLDSVPARTCIGVTTVLSMTTLMIGSRTSLPNTN
  CFIKAIDVYLGICFSFVFGALLEYAVAHYSSLQQMAAKDRGTTKEVEEVSITNIINSSIS
  SFKRKISFASIEISSDNVDYSDLTMKTSDKFKFVFREKMGRIVDYFTIQNPSNVDHYSKL
  LFPLIFMLANVFYWAYYMYF
• Function: GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. In the uterus, the function of the receptor appears to be related to tissue contractility. The binding of this pI subunit with other GABA(A) receptor subunits alters the sensitivity of recombinant receptors to modulatory agents such as pregnanolone.
• Tissue Specificity: Most abundant in the uterus, also expressed in lung, thymus and prostate.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Retrograde endocan.binoid sig.ling (hsa04723)
  GABAergic sy.pse (hsa04727)
  Morphine addiction (hsa05032)
  Nicotine addiction (hsa05033)

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 decreases the methylation of Gamma-aminobutyric acid receptor subunit pi (GABRP).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Gamma-aminobutyric acid receptor subunit pi (GABRP).	[10]

13 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 Gamma-aminobutyric acid receptor subunit pi (GABRP).	[2]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Gamma-aminobutyric acid receptor subunit pi (GABRP).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Gamma-aminobutyric acid receptor subunit pi (GABRP).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Gamma-aminobutyric acid receptor subunit pi (GABRP).	[5]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Gamma-aminobutyric acid receptor subunit pi (GABRP).	[6]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Gamma-aminobutyric acid receptor subunit pi (GABRP).	[7]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Gamma-aminobutyric acid receptor subunit pi (GABRP).	[8]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Gamma-aminobutyric acid receptor subunit pi (GABRP).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Gamma-aminobutyric acid receptor subunit pi (GABRP).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Gamma-aminobutyric acid receptor subunit pi (GABRP).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Gamma-aminobutyric acid receptor subunit pi (GABRP).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Gamma-aminobutyric acid receptor subunit pi (GABRP).	[7]
Cordycepin	DM72Y01	Investigative	Cordycepin decreases the expression of Gamma-aminobutyric acid receptor subunit pi (GABRP).	[14]

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] Gonadal steroids regulate GABAA receptor subunit mRNA expression in NT2-N neurons. Brain Res Mol Brain Res. 2005 Aug 18;138(2):105-15. doi: 10.1016/j.molbrainres.2004.10.047.
• [4] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [5] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [6] HOXA10 regulates endometrial GABAA {pi} receptor expression and membrane translocation. Am J Physiol Endocrinol Metab. 2010 Apr;298(4):E889-93. doi: 10.1152/ajpendo.00577.2009. Epub 2010 Jan 26.
• [7] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [8] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [9] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [10] 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.
• [11] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [12] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [13] 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.
• [14] Cordycepin inhibits the proliferation and progression of NPC by targeting the MAPK/ERK and -catenin pathways. Oncol Lett. 2022 Jan;23(1):20. doi: 10.3892/ol.2021.13138. Epub 2021 Nov 16.