Details of Drug Off-Target (DOT)

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

• DOT Name: ADP-ribose glycohydrolase OARD1 (OARD1)
• Synonyms: O-acetyl-ADP-ribose deacetylase 1; EC 3.5.1.-; Terminal ADP-ribose protein glycohydrolase 1; hydrolase OARD1; EC 3.2.2.-
• Gene Name: OARD1
• Related Disease:
  Stomach cancer
  Acute myelogenous leukaemia
• UniProt ID: OARD1_HUMAN
• PDB ID: 2EEE; 2L8R; 2LGR; 4J5Q; 4J5R; 4J5S
• EC Number: 3.2.2.-; 3.5.1.-
• Pfam ID: PF01661
• Sequence:
  MASSLNEDPEGSRITYVKGDLFACPKTDSLAHCISEDCRMGAGIAVLFKKKFGGVQELLN
  QQKKSGEVAVLKRDGRYIYYLITKKRASHKPTYENLQKSLEAMKSHCLKNGVTDLSMPRI
  GCGLDRLQWENVSAMIEEVFEATDIKITVYTL
• Function: ADP-ribose glycohydrolase that hydrolyzes ADP-ribose and acts on different substrates, such as proteins ADP-ribosylated on glutamate and O-acetyl-ADP-D-ribose. Specifically acts as a glutamate mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to glutamate residues on proteins. Does not act on poly-ADP-ribosylated proteins: the poly-ADP-ribose chain of poly-ADP-ribosylated glutamate residues must by hydrolyzed into mono-ADP-ribosylated glutamate by PARG to become a substrate for OARD1. Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins. Catalyzes the deacylation of O-acetyl-ADP-ribose, O-propionyl-ADP-ribose and O-butyryl-ADP-ribose, yielding ADP-ribose plus acetate, propionate and butyrate, respectively.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[2]

11 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 ADP-ribose glycohydrolase OARD1 (OARD1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of ADP-ribose glycohydrolase OARD1 (OARD1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of ADP-ribose glycohydrolase OARD1 (OARD1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ADP-ribose glycohydrolase OARD1 (OARD1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of ADP-ribose glycohydrolase OARD1 (OARD1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ADP-ribose glycohydrolase OARD1 (OARD1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of ADP-ribose glycohydrolase OARD1 (OARD1).	[9]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of ADP-ribose glycohydrolase OARD1 (OARD1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ADP-ribose glycohydrolase OARD1 (OARD1).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of ADP-ribose glycohydrolase OARD1 (OARD1).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of ADP-ribose glycohydrolase OARD1 (OARD1).	[12]

References

• [1] Genome-wide association study of gastric adenocarcinoma in Asia: a comparison of associations between cardia and non-cardia tumours.Gut. 2016 Oct;65(10):1611-8. doi: 10.1136/gutjnl-2015-309340. Epub 2015 Jun 30.
• [2] 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.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [6] 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.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] Quercetin induced cell apoptosis and altered gene expression in AGS human gastric cancer cells. Environ Toxicol. 2018 Nov;33(11):1168-1181. doi: 10.1002/tox.22623. Epub 2018 Aug 27.
• [10] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.