Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE0U1OQ)

• DOT Name: Regulator of G-protein signaling 9-binding protein (RGS9BP)
• Synonyms: RGS9-anchoring protein
• Gene Name: RGS9BP
• Related Disease:
  Bradyopsia
  Neuralgia
• UniProt ID: R9BP_HUMAN
• Sequence:
  MAREECKALLDGLNKTTACYHHLVLTVGGSADSQNLRQELQKTRQKAQELAVSTCARLTA
  VLRDRGLAADERAEFERLWVAFSGCLDLLEADMRRALELGAAFPLHAPRRPLVRTGVAGA
  SSGVAARALSTRSLRLEAEGDFDVADLRELEREVLQVGEMIDNMEMKVNVPRWTVQARQA
  AGAELLSTVSAGPSSVVSLQERGGGCDPRKALAAILFGAVLLAAVALAVCVAKLS
• Function: Regulator of G protein-coupled receptor (GPCR) signaling in phototransduction. Participates in the recovery phase of visual transduction via its interaction with RGS9-1 isoform. Acts as a membrane-anchor that mediates the targeting of RGS9-1 to the photoreceptor outer segment, where phototransduction takes place. Enhances the ability of RGS9-1 to stimulate G protein GTPase activity, allowing the visual signal to be terminated on the physiologically time scale. It also controls the proteolytic stability of RGS9-1, probably by protecting it from degradation.
• Reactome Pathway: Inactivation, recovery and regulation of the phototransduction cascade (R-HSA-2514859)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bradyopsia	DIST8K6C	Definitive	Autosomal recessive	[1]
Neuralgia	DISWO58J	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Regulator of G-protein signaling 9-binding protein (RGS9BP).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Regulator of G-protein signaling 9-binding protein (RGS9BP).	[5]

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 Regulator of G-protein signaling 9-binding protein (RGS9BP).	[4]

References

• [1] Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor deactivation. Nature. 2004 Jan 1;427(6969):75-8. doi: 10.1038/nature02170.
• [2] RGS9-2 Modulates Responses to Oxycodone in Pain-Free and Chronic Pain States.Neuropsychopharmacology. 2017 Jun;42(7):1548-1556. doi: 10.1038/npp.2017.4. Epub 2017 Jan 11.
• [3] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [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] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.