Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSO0JP4)

• DOT Name: 5'-deoxynucleotidase HDDC2 (HDDC2)
• Synonyms: EC 3.1.3.89; HD domain-containing protein 2; Hepatitis C virus NS5A-transactivated protein 2; HCV NS5A-transactivated protein 2
• Gene Name: HDDC2
• Related Disease: Hepatitis C virus infection
• UniProt ID: HDDC2_HUMAN
• PDB ID: 4DMB; 4L1J; 4L7E; 4L7W
• EC Number: 3.1.3.89
• Pfam ID: PF13023
• Sequence:
  MASVSSATFSGHGARSLLQFLRLVGQLKRVPRTGWVYRNVQRPESVSDHMYRMAVMAMVI
  KDDRLNKDRCVRLALVHDMAECIVGDIAPADNIPKEEKHRREEEAMKQITQLLPEDLRKE
  LYELWEEYETQSSAEAKFVKQLDQCEMILQASEYEDLEHKPGRLQDFYDSTAGKFNHPEI
  VQLVSELEAERSTNIAAAASEPHS
• Function: Catalyzes the dephosphorylation of the nucleoside 5'-monophosphates deoxyadenosine monophosphate (dAMP), deoxycytidine monophosphate (dCMP), deoxyguanosine monophosphate (dGMP) and deoxythymidine monophosphate (dTMP).
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Pyrimidine metabolism (hsa00240)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of 5'-deoxynucleotidase HDDC2 (HDDC2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of 5'-deoxynucleotidase HDDC2 (HDDC2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 5'-deoxynucleotidase HDDC2 (HDDC2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 5'-deoxynucleotidase HDDC2 (HDDC2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 5'-deoxynucleotidase HDDC2 (HDDC2).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of 5'-deoxynucleotidase HDDC2 (HDDC2).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of 5'-deoxynucleotidase HDDC2 (HDDC2).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of 5'-deoxynucleotidase HDDC2 (HDDC2).	[10]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of 5'-deoxynucleotidase HDDC2 (HDDC2).	[9]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of 5'-deoxynucleotidase HDDC2 (HDDC2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of 5'-deoxynucleotidase HDDC2 (HDDC2).	[13]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of 5'-deoxynucleotidase HDDC2 (HDDC2).	[14]

2 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 5'-deoxynucleotidase HDDC2 (HDDC2).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of 5'-deoxynucleotidase HDDC2 (HDDC2).	[12]

References

• [1] Cloning and identification of NS5ATP2 gene and its spliced variant transactivated by hepatitis C virus non-structural protein 5A.World J Gastroenterol. 2004 Jun 15;10(12):1735-9. doi: 10.3748/wjg.v10.i12.1735.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [11] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [12] 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.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [14] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.