Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTV2J54)

• DOT Name: Ecto-ADP-ribosyltransferase 4 (ART4)
• Synonyms: EC 2.4.2.31; ADP-ribosyltransferase C2 and C3 toxin-like 4; ARTC4; Dombrock blood group carrier molecule; Mono(ADP-ribosyl)transferase 4; NAD(P)(+)--arginine ADP-ribosyltransferase 4; CD antigen CD297
• Gene Name: ART4
• Related Disease: Ocular infection
• UniProt ID: NAR4_HUMAN
• EC Number: 2.4.2.31
• Pfam ID: PF01129
• Sequence:
  MGPLINRCKKILLPTTVPPATMRIWLLGGLLPFLLLLSGLQRPTEGSEVAIKIDFDFAPG
  SFDDQYQGCSKQVMEKLTQGDYFTKDIEAQKNYFRMWQKAHLAWLNQGKVLPQNMTTTHA
  VAILFYTLNSNVHSDFTRAMASVARTPQQYERSFHFKYLHYYLTSAIQLLRKDSIMENGT
  LCYEVHYRTKDVHFNAYTGATIRFGQFLSTSLLKEEAQEFGNQTLFTIFTCLGAPVQYFS
  LKKEVLIPPYELFKVINMSYHPRGDWLQLRSTGNLSTYNCQLLKASSKKCIPDPIAIASL
  SFLTSVIIFSKSRV
• Tissue Specificity: Expressed in spleen and T-cells.
• Reactome Pathway: Post-translational modification (R-HSA-163125)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ocular infection	DISTTJES	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ecto-ADP-ribosyltransferase 4 (ART4).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ecto-ADP-ribosyltransferase 4 (ART4).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ecto-ADP-ribosyltransferase 4 (ART4).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ecto-ADP-ribosyltransferase 4 (ART4).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ecto-ADP-ribosyltransferase 4 (ART4).	[6]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Ecto-ADP-ribosyltransferase 4 (ART4).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ecto-ADP-ribosyltransferase 4 (ART4).	[8]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Ecto-ADP-ribosyltransferase 4 (ART4).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ecto-ADP-ribosyltransferase 4 (ART4).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Ecto-ADP-ribosyltransferase 4 (ART4).	[11]

1 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 Ecto-ADP-ribosyltransferase 4 (ART4).	[5]

References

• [1] Dok-1 and Dok-2 Are Required To Maintain Herpes Simplex Virus 1-Specific CD8(+) T Cells in a Murine Model of Ocular Infection.J Virol. 2017 Jul 12;91(15):e02297-16. doi: 10.1128/JVI.02297-16. Print 2017 Aug 1.
• [2] 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.
• [3] 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.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] 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.
• [6] 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.
• [7] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Molecular mechanisms of action of angiopreventive anti-oxidants on endothelial cells: microarray gene expression analyses. Mutat Res. 2005 Dec 11;591(1-2):198-211.
• [10] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [11] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.