Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ3S9AL)

• DOT Name: Deoxyribonuclease TATDN1 (TATDN1)
• Synonyms: EC 3.1.21.-; Hepatocarcinoma high expression protein
• Gene Name: TATDN1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Hepatocellular carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Asthma
• UniProt ID: TATD1_HUMAN
• PDB ID: 2XIO; 8EFG
• EC Number: 3.1.21.-
• Pfam ID: PF01026
• Sequence:
  MSRFKFIDIGINLTDPMFRGIYRGVQKHQDDLQDVIGRAVEIGVKKFMITGGNLQDSKDA
  LHLAQTNGMFFSTVGCHPTRCGEFEKNNPDLYLKELLNLAENNKGKVVAIGECGLDFDRL
  QFCPKDTQLKYFEKQFELSEQTKLPMFLHCRNSHAEFLDIMKRNRDRCVGGVVHSFDGTK
  EAAAALIDLDLYIGFNGCSLKTEANLEVLKSIPSEKLMIETDAPWCGVKSTHAGSKYIRT
  AFPTKKKWESGHCLKDRNEPCHIIQILEIMSAVRDEDPLELANTLYNNTIKVFFPGI
• Function: Deoxyribonuclease which catalyzes (in vitro) the decatenation of kinetoplast DNA, which are circular DNA catenated to each other, producing linear DNA molecules. Plays an important role in chromosomal segregation and cell cycle progression during eye development probably via its DNA decatenation activity.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[3]
Asthma	DISW9QNS	Limited	Genetic Variation	[4]

7 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 Deoxyribonuclease TATDN1 (TATDN1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Deoxyribonuclease TATDN1 (TATDN1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Deoxyribonuclease TATDN1 (TATDN1).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Deoxyribonuclease TATDN1 (TATDN1).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Deoxyribonuclease TATDN1 (TATDN1).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Deoxyribonuclease TATDN1 (TATDN1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Deoxyribonuclease TATDN1 (TATDN1).	[11]

References

• [1] TATDN1 promotes the development and progression of breast cancer by targeting microRNA-140-3p.Eur Rev Med Pharmacol Sci. 2019 Jun;23(12):5293-5300. doi: 10.26355/eurrev_201906_18196.
• [2] LncRNA TATDN1 induces the progression of hepatocellular carcinoma via targeting miRNA-6089.Eur Rev Med Pharmacol Sci. 2019 Aug;23(15):6459-6466. doi: 10.26355/eurrev_201908_18529.
• [3] LncRNA TATDN1 contributes to the cisplatin resistance of non-small cell lung cancer through TATDN1/miR-451/TRIM66 axis.Cancer Biol Ther. 2019;20(3):261-271. doi: 10.1080/15384047.2018.1529091. Epub 2018 Nov 27.
• [4] Association study in African-admixed populations across the Americas recapitulates asthma risk loci in non-African populations.Nat Commun. 2019 Feb 20;10(1):880. doi: 10.1038/s41467-019-08469-7.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [7] 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.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [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] 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.