Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDPSIR9)

• DOT Name: Neuronal acetylcholine receptor subunit alpha-10 (CHRNA10)
• Synonyms: Nicotinic acetylcholine receptor subunit alpha-10; NACHR alpha-10
• Gene Name: CHRNA10
• UniProt ID: ACH10_HUMAN
• Pfam ID: PF02931 ; PF02932
• Sequence:
  MGLRSHHLSLGLLLLFLLPAECLGAEGRLALKLFRDLFANYTSALRPVADTDQTLNVTLE
  VTLSQIIDMDERNQVLTLYLWIRQEWTDAYLRWDPNAYGGLDAIRIPSSLVWRPDIVLYN
  KADAQPPGSASTNVVLRHDGAVRWDAPAITRSSCRVDVAAFPFDAQHCGLTFGSWTHGGH
  QLDVRPRGAAASLADFVENVEWRVLGMPARRRVLTYGCCSEPYPDVTFTLLLRRRAAAYV
  CNLLLPCVLISLLAPLAFHLPADSGEKVSLGVTVLLALTVFQLLLAESMPPAESVPLIGK
  YYMATMTMVTFSTALTILIMNLHYCGPSVRPVPAWARALLLGHLARGLCVRERGEPCGQS
  RPPELSPSPQSPEGGAGPPAGPCHEPRCLCRQEALLHHVATIANTFRSHRAAQRCHEDWK
  RLARVMDRFFLAIFFSMALVMSLLVLVQAL
• Function: Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding may induce an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane. In the ear, this may lead to a reduction in basilar membrane motion, altering the activity of auditory nerve fibers and reducing the range of dynamic hearing. This may protect against acoustic trauma.
• Tissue Specificity: Expressed in inner-ear tissue, tonsil, immortalized B-cells, cultured T-cells and peripheral blood lymphocytes.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway: Acetylcholine inhibits contraction of outer hair cells (R-HSA-9667769)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Neuronal acetylcholine receptor subunit alpha-10 (CHRNA10).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Neuronal acetylcholine receptor subunit alpha-10 (CHRNA10).	[2]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Neuronal acetylcholine receptor subunit alpha-10 (CHRNA10).	[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 Neuronal acetylcholine receptor subunit alpha-10 (CHRNA10).	[4]

References

• [1] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [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.