Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIVFS3H)

• DOT Name: Acid-sensing ion channel 2 (ASIC2)
• Synonyms: ASIC2; Amiloride-sensitive brain sodium channel; Amiloride-sensitive cation channel 1, neuronal; Amiloride-sensitive cation channel neuronal 1; Brain sodium channel 1; BNC1; BNaC1; Mammalian degenerin homolog; MDEG
• Gene Name: ASIC2
• UniProt ID: ASIC2_HUMAN
• PDB ID: 6L6P
• Pfam ID: PF00858
• Sequence:
  MDLKESPSEGSLQPSSIQIFANTSTLHGIRHIFVYGPLTIRRVLWAVAFVGSLGLLLVES
  SERVSYYFSYQHVTKVDEVVAQSLVFPAVTLCNLNGFRFSRLTTNDLYHAGELLALLDVN
  LQIPDPHLADPSVLEALRQKANFKHYKPKQFSMLEFLHRVGHDLKDMMLYCKFKGQECGH
  QDFTTVFTKYGKCYMFNSGEDGKPLLTTVKGGTGNGLEIMLDIQQDEYLPIWGETEETTF
  EAGVKVQIHSQSEPPFIQELGFGVAPGFQTFVATQEQRLTYLPPPWGECRSSEMGLDFFP
  VYSITACRIDCETRYIVENCNCRMVHMPGDAPFCTPEQHKECAEPALGLLAEKDSNYCLC
  RTPCNLTRYNKELSMVKIPSKTSAKYLEKKFNKSEKYISENILVLDIFFEALNYETIEQK
  KAYEVAALLGDIGGQMGLFIGASILTILELFDYIYELIKEKLLDLLGKEEDEGSHDENVS
  TCDTMPNHSETISHTVNVPLQTTLGTLEEIAC
• Function: Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Also permeable for Li(+) and K(+). Generates a biphasic current with a fast inactivating and a slow sustained phase. Heteromeric channel assembly seems to modulate.
• Tissue Specificity: Brain and spinal cord. Isoform 1 is also detected in testis, liver, colon and ovary.
• KEGG Pathway:
  Taste transduction (hsa04742)
  Inflammatory mediator regulation of TRP channels (hsa04750)
• Reactome Pathway: Stimuli-sensing channels (R-HSA-2672351)

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 Acid-sensing ion channel 2 (ASIC2).	[1]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Acid-sensing ion channel 2 (ASIC2).	[3]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Acid-sensing ion channel 2 (ASIC2).	[4]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Acid-sensing ion channel 2 (ASIC2).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Acid-sensing ion channel 2 (ASIC2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Acid-sensing ion channel 2 (ASIC2).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Acid-sensing ion channel 2 (ASIC2).	[7]

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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [3] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [4] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [5] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [6] 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.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.