Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDJKS39)

• DOT Name: Double-stranded RNA-specific editase B2 (ADARB2)
• Synonyms: EC 3.5.-.-; RNA-dependent adenosine deaminase 3; RNA-editing deaminase 2; RNA-editing enzyme 2; dsRNA adenosine deaminase B2
• Gene Name: ADARB2
• Related Disease:
  Adult glioblastoma
  Advanced cancer
  Brain neoplasm
  Drug dependence
  Glioblastoma multiforme
  Glioma
  Migraine with aura
  Neoplasm
  Ovarian neoplasm
  Parkinson disease
  Substance abuse
  Substance dependence
  Acute myelogenous leukaemia
  Amyotrophic lateral sclerosis
  Astrocytoma
• UniProt ID: RED2_HUMAN
• EC Number: 3.5.-.-
• Pfam ID: PF02137 ; PF00035
• Sequence:
  MASVLGSGRGSGGLSSQLKCKSKRRRRRRSKRKDKVSILSTFLAPFKHLSPGITNTEDDD
  TLSTSSAEVKENRNVGNLAARPPPSGDRARGGAPGAKRKRPLEEGNGGHLCKLQLVWKKL
  SWSVAPKNALVQLHELRPGLQYRTVSQTGPVHAPVFAVAVEVNGLTFEGTGPTKKKAKMR
  AAELALRSFVQFPNACQAHLAMGGGPGPGTDFTSDQADFPDTLFQEFEPPAPRPGLAGGR
  PGDAALLSAAYGRRRLLCRALDLVGPTPATPAAPGERNPVVLLNRLRAGLRYVCLAEPAE
  RRARSFVMAVSVDGRTFEGSGRSKKLARGQAAQAALQELFDIQMPGHAPGRARRTPMPQE
  FADSISQLVTQKFREVTTDLTPMHARHKALAGIVMTKGLDARQAQVVALSSGTKCISGEH
  LSDQGLVVNDCHAEVVARRAFLHFLYTQLELHLSKRREDSERSIFVRLKEGGYRLRENIL
  FHLYVSTSPCGDARLHSPYEITTDLHSSKHLVRKFRGHLRTKIESGEGTVPVRGPSAVQT
  WDGVLLGEQLITMSCTDKIARWNVLGLQGALLSHFVEPVYLQSIVVGSLHHTGHLARVMS
  HRMEGVGQLPASYRHNRPLLSGVSDAEARQPGKSPPFSMNWVVGSADLEIINATTGRRSC
  GGPSRLCKHVLSARWARLYGRLSTRTPSPGDTPSMYCEAKLGAHTYQSVKQQLFKAFQKA
  GLGTWVRKPPEQQQFLLTL
• Function: Lacks editing activity. It prevents the binding of other ADAR enzymes to targets in vitro, and decreases the efficiency of these enzymes. Capable of binding to dsRNA but also to ssRNA.
• Tissue Specificity: Brain specific. Expressed at higher levels in astrocytomas as compared to the normal brain tissue.

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[3]
Drug dependence	DIS9IXRC	Strong	Biomarker	[4]
Glioblastoma multiforme	DISK8246	Strong	Genetic Variation	[5]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Migraine with aura	DISDM7I8	Strong	Genetic Variation	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[7]
Parkinson disease	DISQVHKL	Strong	Biomarker	[8]
Substance abuse	DIS327VW	Strong	Biomarker	[4]
Substance dependence	DISDRAAR	Strong	Biomarker	[4]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[9]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Altered Expression	[10]
Astrocytoma	DISL3V18	Limited	Biomarker	[11]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
NAPQI	DM8F5LR	Investigative	Double-stranded RNA-specific editase B2 (ADARB2) affects the response to substance of NAPQI.	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Double-stranded RNA-specific editase B2 (ADARB2).	[12]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Double-stranded RNA-specific editase B2 (ADARB2).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Double-stranded RNA-specific editase B2 (ADARB2).	[16]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Double-stranded RNA-specific editase B2 (ADARB2).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Double-stranded RNA-specific editase B2 (ADARB2).	[15]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Double-stranded RNA-specific editase B2 (ADARB2).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Double-stranded RNA-specific editase B2 (ADARB2).	[13]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Double-stranded RNA-specific editase B2 (ADARB2).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Double-stranded RNA-specific editase B2 (ADARB2).	[18]

References

• [1] RNA binding candidates for human ADAR3 from substrates of a gain of function mutant expressed in neuronal cells.Nucleic Acids Res. 2019 Nov 18;47(20):10801-10814. doi: 10.1093/nar/gkz815.
• [2] ADAR3 expression is an independent prognostic factor in lower-grade diffuse gliomas and positively correlated with the editing level of GRIA2(Q607R).Cancer Cell Int. 2018 Dec 3;18:196. doi: 10.1186/s12935-018-0695-8. eCollection 2018.
• [3] Altered adenosine-to-inosine RNA editing in human cancer.Genome Res. 2007 Nov;17(11):1586-95. doi: 10.1101/gr.6493107. Epub 2007 Oct 1.
• [4] Genome wide association for addiction: replicated results and comparisons of two analytic approaches.PLoS One. 2010 Jan 21;5(1):e8832. doi: 10.1371/journal.pone.0008832.
• [5] Dynamic inosinome profiles reveal novel patient stratification and gender-specific differences in glioblastoma.Genome Biol. 2019 Feb 13;20(1):33. doi: 10.1186/s13059-019-1647-x.
• [6] Genome-wide meta-analysis identifies new susceptibility loci for migraine.Nat Genet. 2013 Aug;45(8):912-917. doi: 10.1038/ng.2676. Epub 2013 Jun 23.
• [7] Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women.Gynecol Oncol. 2019 May;153(2):343-355. doi: 10.1016/j.ygyno.2019.02.023. Epub 2019 Mar 19.
• [8] Identification of candidate genes for Parkinson's disease through blood transcriptome analysis in LRRK2-G2019S carriers, idiopathic cases, and controls.Neurobiol Aging. 2015 Feb;36(2):1105-9. doi: 10.1016/j.neurobiolaging.2014.10.039. Epub 2014 Nov 5.
• [9] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [10] Profound downregulation of the RNA editing enzyme ADAR2 in ALS spinal motor neurons.Neurobiol Dis. 2012 Mar;45(3):1121-8. doi: 10.1016/j.nbd.2011.12.033. Epub 2011 Dec 28.
• [11] Adenosine Deaminase That Acts on RNA 3 (ADAR3) Binding to Glutamate Receptor Subunit B Pre-mRNA Inhibits RNA Editing in Glioblastoma.J Biol Chem. 2017 Mar 10;292(10):4326-4335. doi: 10.1074/jbc.M117.779868. Epub 2017 Feb 6.
• [12] 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.
• [13] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [14] Characterizing properties of non-estrogenic substituted bisphenol analogs using high throughput microscopy and image analysis. PLoS One. 2017 Jul 13;12(7):e0180141. doi: 10.1371/journal.pone.0180141. eCollection 2017.
• [15] 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.
• [16] 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.
• [17] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [18] 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.
• [19] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [20] Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011 Mar;120(1):33-41. doi: 10.1093/toxsci/kfq375. Epub 2010 Dec 22.