Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT68OFVT)

• DOT Name: Ecto-ADP-ribosyltransferase 3 (ART3)
• Synonyms: EC 2.4.2.31; ADP-ribosyltransferase C2 and C3 toxin-like 3; ARTC3; Mono(ADP-ribosyl)transferase 3; NAD(P)(+)--arginine ADP-ribosyltransferase 3
• Gene Name: ART3
• Related Disease:
  Azoospermia
  Fatty liver disease
  Neoplasm
  Melanoma
  Patent ductus arteriosus
• UniProt ID: NAR3_HUMAN
• EC Number: 2.4.2.31
• Pfam ID: PF01129
• Sequence:
  MKTGHFEIVTMLLATMILVDIFQVKAEVLDMADNAFDDEYLKCTDRMEIKYVPQLLKEEK
  ASHQQLDTVWENAKAKWAARKTQIFLPMNFKDNHGIALMAYISEAQEQTPFYHLFSEAVK
  MAGQSREDYIYGFQFKAFHFYLTRALQLLRKPCEASSKTVVYRTSQGTSFTFGGLNQARF
  GHFTLAYSAKPQAANDQLTVLSIYTCLGVDIENFLDKESERITLIPLNEVFQVSQEGAGN
  NLILQSINKTCSHYECAFLGGLKTENCIENLEYFQPIYVYNPGEKNQKLEDHSEKNWKLE
  DHGEKNQKLEDHGVKILEPTQIPGMKIPEPFPLPEDKSQGNINNPTPGPVPVPGPKSHPS
  ASSGKLLLPQFGMVIILISVSAINLFVAL
• Tissue Specificity: Testis specific.
• Reactome Pathway: Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Azoospermia	DIS94181	Strong	Altered Expression	[1]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[3]
Melanoma	DIS1RRCY	Limited	Biomarker	[4]
Patent ductus arteriosus	DIS9P8YS	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Ecto-ADP-ribosyltransferase 3 (ART3).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Ecto-ADP-ribosyltransferase 3 (ART3).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ecto-ADP-ribosyltransferase 3 (ART3).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ecto-ADP-ribosyltransferase 3 (ART3).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ecto-ADP-ribosyltransferase 3 (ART3).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ecto-ADP-ribosyltransferase 3 (ART3).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Ecto-ADP-ribosyltransferase 3 (ART3).	[11]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Ecto-ADP-ribosyltransferase 3 (ART3).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ecto-ADP-ribosyltransferase 3 (ART3).	[14]

References

• [1] Genome-wide expression of azoospermia testes demonstrates a specific profile and implicates ART3 in genetic susceptibility.PLoS Genet. 2008 Feb;4(2):e26. doi: 10.1371/journal.pgen.0040026.
• [2] Loss of the Mono-ADP-ribosyltransferase, Tiparp, Increases Sensitivity to Dioxin-induced Steatohepatitis and Lethality.J Biol Chem. 2015 Jul 3;290(27):16824-40. doi: 10.1074/jbc.M115.660100. Epub 2015 May 13.
• [3] LOH analysis of genes around D4S2964 identifies ARD1B as a prognostic predictor of hepatocellular carcinoma.World J Gastroenterol. 2010 Apr 28;16(16):2046-54. doi: 10.3748/wjg.v16.i16.2046.
• [4] Targeted silencing of the ADP-ribosyltransferase 3 gene inhibits the migration ability of melanoma cells.Oncol Lett. 2018 May;15(5):7053-7059. doi: 10.3892/ol.2018.8252. Epub 2018 Mar 13.
• [5] Antenatal Administration of Betamethasone Contributes to Intimal Thickening of the Rat Ductus Arteriosus.Circ J. 2019 Feb 25;83(3):654-661. doi: 10.1253/circj.CJ-18-1033. Epub 2019 Feb 7.
• [6] 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.
• [7] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [8] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [9] 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.
• [10] 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.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [13] 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.
• [14] Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells. Mol Cancer Ther. 2014 May;13(5):1142-54.