Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT02WX1H)

• DOT Name: Gamma-aminobutyric acid receptor subunit rho-1 (GABRR1)
• Synonyms: GABA(A) receptor subunit rho-1; GABA(C) receptor
• Gene Name: GABRR1
• UniProt ID: GBRR1_HUMAN
• PDB ID: 8OP9; 8OQ6; 8OQ7; 8OQ8; 8OQA
• Pfam ID: PF02931 ; PF02932
• Sequence:
  MLAVPNMRFGIFLLWWGWVLATESRMHWPGREVHEMSKKGRPQRQRREVHEDAHKQVSPI
  LRRSPDITKSPLTKSEQLLRIDDHDFSMRPGFGGPAIPVGVDVQVESLDSISEVDMDFTM
  TLYLRHYWKDERLSFPSTNNLSMTFDGRLVKKIWVPDMFFVHSKRSFIHDTTTDNVMLRV
  QPDGKVLYSLRVTVTAMCNMDFSRFPLDTQTCSLEIESYAYTEDDLMLYWKKGNDSLKTD
  ERISLSQFLIQEFHTTTKLAFYSSTGWYNRLYINFTLRRHIFFFLLQTYFPATLMVMLSW
  VSFWIDRRAVPARVPLGITTVLTMSTIITGVNASMPRVSYIKAVDIYLWVSFVFVFLSVL
  EYAAVNYLTTVQERKEQKLREKLPCTSGLPPPRTAMLDGNYSDGEVNDLDNYMPENGEKP
  DRMMVQLTLASERSSPQRKSQRSSYVSMRIDTHAIDKYSRIIFPAAYILFNLIYWSIFS
• 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. Rho-1 GABA receptor could play a role in retinal neurotransmission.
• Tissue Specificity: Highly expressed in the retina and in a lesser extent in brain, lung and thymus.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Retrograde endocan.binoid sig.ling (hsa04723)
  GABAergic sy.pse (hsa04727)
  Morphine addiction (hsa05032)
  Nicotine addiction (hsa05033)
• Reactome Pathway: GABA receptor activation (R-HSA-977443)

Molecular Interaction Atlas (MIA) of This DOT

4 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 Gamma-aminobutyric acid receptor subunit rho-1 (GABRR1).	[1]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Gamma-aminobutyric acid receptor subunit rho-1 (GABRR1).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Gamma-aminobutyric acid receptor subunit rho-1 (GABRR1).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Gamma-aminobutyric acid receptor subunit rho-1 (GABRR1).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Lindane	DMB8CNL	Approved	Lindane affects the binding of Gamma-aminobutyric acid receptor subunit rho-1 (GABRR1).	[3]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Gamma-aminobutyric acid receptor subunit rho-1 (GABRR1).	[4]

References

• [1] 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.
• [2] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [3] Unique insecticide specificity of human homomeric rho 1 GABA(C) receptor. Toxicol Lett. 2002 Mar 24;129(1-2):47-53. doi: 10.1016/s0378-4274(01)00471-4.
• [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] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.