Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFN3RPP)

• DOT Name: 5'(3')-deoxyribonucleotidase, cytosolic type (NT5C)
• Synonyms: EC 3.1.3.-; Cytosolic 5',3'-pyrimidine nucleotidase; Deoxy-5'-nucleotidase 1; dNT-1
• Gene Name: NT5C
• UniProt ID: NT5C_HUMAN
• PDB ID: 2I7D; 4L57; 4YIH; 6G2N
• EC Number: 3.1.3.-
• Pfam ID: PF06941
• Sequence:
  MARSVRVLVDMDGVLADFEAGLLRGFRRRFPEEPHVPLEQRRGFLAREQYRALRPDLADK
  VASVYEAPGFFLDLEPIPGALDAVREMNDLPDTQVFICTSPLLKYHHCVGEKYRWVEQHL
  GPQFVERIILTRDKTVVLGDLLIDDKDTVRGQEETPSWEHILFTCCHNRHLVLPPTRRRL
  LSWSDNWREILDSKRGAAQRE
• Function: Dephosphorylates the 5' and 2'(3')-phosphates of deoxyribonucleotides, with a preference for dUMP and dTMP, intermediate activity towards dGMP, and low activity towards dCMP and dAMP.
• Tissue Specificity: Detected in skeletal muscle, heart and pancreas.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Pyrimidine metabolism (hsa00240)
  Nicoti.te and nicoti.mide metabolism (hsa00760)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
• Reactome Pathway:
  Purine catabolism (R-HSA-74259)
  Pyrimidine catabolism (R-HSA-73621)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of 5'(3')-deoxyribonucleotidase, cytosolic type (NT5C).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of 5'(3')-deoxyribonucleotidase, cytosolic type (NT5C).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 5'(3')-deoxyribonucleotidase, cytosolic type (NT5C).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of 5'(3')-deoxyribonucleotidase, cytosolic type (NT5C).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of 5'(3')-deoxyribonucleotidase, cytosolic type (NT5C).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 5'(3')-deoxyribonucleotidase, cytosolic type (NT5C).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of 5'(3')-deoxyribonucleotidase, cytosolic type (NT5C).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of 5'(3')-deoxyribonucleotidase, cytosolic type (NT5C).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of 5'(3')-deoxyribonucleotidase, cytosolic type (NT5C).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of 5'(3')-deoxyribonucleotidase, cytosolic type (NT5C).	[11]

2 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 5'(3')-deoxyribonucleotidase, cytosolic type (NT5C).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of 5'(3')-deoxyribonucleotidase, cytosolic type (NT5C).	[12]

References

• [1] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] Aberrantly expressed genes in HaCaT keratinocytes chronically exposed to arsenic trioxide. Biomark Insights. 2011 Feb 8;6:7-16.
• [8] A high concentration of genistein down-regulates activin A, Smad3 and other TGF-beta pathway genes in human uterine leiomyoma cells. Exp Mol Med. 2012 Apr 30;44(4):281-92.
• [9] 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.
• [10] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [11] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [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.