Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4CCS0Q)

• DOT Name: C->U-editing enzyme APOBEC-2 (APOBEC2)
• Synonyms: EC 3.5.4.36; mRNA(cytosine(6666)) deaminase 2
• Gene Name: APOBEC2
• Related Disease:
  Carcinoma of liver and intrahepatic biliary tract
  Hepatitis B virus infection
  Liver cancer
  Neoplasm
  Acute leukaemia
  Choriocarcinoma
  Hepatocellular carcinoma
  IgA nephropathy
  Immunodeficiency
  Lung neoplasm
  Myopathy
  Plasma cell myeloma
  Spinocerebellar ataxia type 5
  Leukemia
• UniProt ID: ABEC2_HUMAN
• PDB ID: 2NYT
• EC Number: 3.5.4.36
• Pfam ID: PF18772
• Sequence:
  MAQKEEAAVATEAASQNGEDLENLDDPEKLKELIELPPFEIVTGERLPANFFKFQFRNVE
  YSSGRNKTFLCYVVEAQGKGGQVQASRGYLEDEHAAAHAEEAFFNTILPAFDPALRYNVT
  WYVSSSPCAACADRIIKTLSKTKNLRLLILVGRLFMWEEPEIQAALKKLKEAGCKLRIMK
  PQDFEYVWQNFVEQEEGESKAFQPWEDIQENFLYYEEKLADILK
• Function: Probable C to U editing enzyme whose physiological substrate is not yet known. Does not display detectable apoB mRNA editing. Has a low intrinsic cytidine deaminase activity. May play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation.
• Tissue Specificity: Expressed exclusively in heart and skeletal muscle.
• Reactome Pathway:
  Formation of the Editosome (R-HSA-75094)
  mRNA Editing (R-HSA-72200)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Definitive	Altered Expression	[1]
Hepatitis B virus infection	DISLQ2XY	Definitive	Altered Expression	[1]
Liver cancer	DISDE4BI	Definitive	Altered Expression	[1]
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Acute leukaemia	DISDQFDI	Strong	Genetic Variation	[2]
Choriocarcinoma	DISDBVNL	Strong	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[4]
IgA nephropathy	DISZ8MTK	Strong	Biomarker	[5]
Immunodeficiency	DIS093I0	Strong	Biomarker	[6]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[4]
Myopathy	DISOWG27	Strong	Biomarker	[7]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[8]
Spinocerebellar ataxia type 5	DISPYXJ0	Strong	Genetic Variation	[9]
Leukemia	DISNAKFL	Limited	Altered Expression	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of C->U-editing enzyme APOBEC-2 (APOBEC2).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of C->U-editing enzyme APOBEC-2 (APOBEC2).	[12]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of C->U-editing enzyme APOBEC-2 (APOBEC2).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of C->U-editing enzyme APOBEC-2 (APOBEC2).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of C->U-editing enzyme APOBEC-2 (APOBEC2).	[16]

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 C->U-editing enzyme APOBEC-2 (APOBEC2).	[14]

References

• [1] HBV triggers APOBEC2 expression through miR?22 regulation and affects the proliferation of liver cancer cells.Int J Oncol. 2019 Nov;55(5):1137-1148. doi: 10.3892/ijo.2019.4870. Epub 2019 Sep 4.
• [2] Identification and characterization of the ARP1 gene, a target for the human acute leukemia ALL1 gene.Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4573-8. doi: 10.1073/pnas.95.8.4573.
• [3] The ARP-1 orphan receptor represses steroid-mediated stimulation of human placental lactogen gene expression.J Mol Endocrinol. 1996 Jun;16(3):221-7. doi: 10.1677/jme.0.0160221.
• [4] Excessive activity of apolipoprotein B mRNA editing enzyme catalytic polypeptide 2 (APOBEC2) contributes to liver and lung tumorigenesis.Int J Cancer. 2012 Mar 15;130(6):1294-301. doi: 10.1002/ijc.26114. Epub 2011 May 30.
• [5] Microarray analysis of tonsils in immunoglobulin A nephropathy patients.Biochem Biophys Res Commun. 2010 Mar 19;393(4):565-70. doi: 10.1016/j.bbrc.2010.01.120. Epub 2010 Feb 6.
• [6] Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection.J Clin Invest. 2013 Sep;123(9):3829-38. doi: 10.1172/JCI70266. Epub 2013 Aug 8.
• [7] Apobec2 deficiency causes mitochondrial defects and mitophagy in skeletal muscle.FASEB J. 2018 Mar;32(3):1428-1439. doi: 10.1096/fj.201700493R. Epub 2018 Jan 3.
• [8] DCZ0814 induces apoptosis and G0/G1 phase cell cycle arrest in myeloma by dual inhibition of mTORC1/2.Cancer Manag Res. 2019 May 27;11:4797-4808. doi: 10.2147/CMAR.S194202. eCollection 2019.
• [9] Beta-III spectrin mutation L253P associated with spinocerebellar ataxia type 5 interferes with binding to Arp1 and protein trafficking from the Golgi.Hum Mol Genet. 2010 Sep 15;19(18):3634-41. doi: 10.1093/hmg/ddq279. Epub 2010 Jul 5.
• [10] Papillomavirus can be transmitted through the blood and produce infections in blood recipients: Evidence from two animal models.Emerg Microbes Infect. 2019;8(1):1108-1121. doi: 10.1080/22221751.2019.1637072.
• [11] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [12] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [13] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [14] 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.
• [15] 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.
• [16] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.