Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZAI8L7)

• DOT Name: Nuclease EXOG, mitochondrial (EXOG)
• Synonyms: EC 3.1.30.-; Endonuclease G-like 1; Endo G-like 1
• Gene Name: EXOG
• Related Disease: Non-insulin dependent diabetes
• UniProt ID: EXOG_HUMAN
• PDB ID: 4A1N; 5T3V; 5T40; 5T4I; 5T5C; 5ZKI; 5ZKJ; 6IID; 7R6T; 7R6V
• EC Number: 3.1.30.-
• Pfam ID: PF01223 ; PF18026
• Sequence:
  MAIKSIASRLRGSRRFLSGFVAGAVVGAAGAGLAALQFFRSQGAEGALTGKQPDGSAEKA
  VLEQFGFPLTGTEARCYTNHALSYDQAKRVPRWVLEHISKSKIMGDADRKHCKFKPDPNI
  PPTFSAFNEDYVGSGWSRGHMAPAGNNKFSSKAMAETFYLSNIVPQDFDNNSGYWNRIEM
  YCRELTERFEDVWVVSGPLTLPQTRGDGKKIVSYQVIGEDNVAVPSHLYKVILARRSSVS
  TEPLALGAFVVPNEAIGFQPQLTEFQVSLQDLEKLSGLVFFPHLDRTSDIRNICSVDTCK
  LLDFQEFTLYLSTRKIEGARSVLRLEKIMENLKNAEIEPDDYFMSRYEKKLEELKAKEQS
  GTQIRKPS
• Function: Endo/exonuclease with nicking activity towards supercoiled DNA, a preference for single-stranded DNA and 5'-3' exonuclease activity.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	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 increases the expression of Nuclease EXOG, mitochondrial (EXOG).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nuclease EXOG, mitochondrial (EXOG).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nuclease EXOG, mitochondrial (EXOG).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Nuclease EXOG, mitochondrial (EXOG).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Nuclease EXOG, mitochondrial (EXOG).	[6]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Nuclease EXOG, mitochondrial (EXOG).	[7]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Nuclease EXOG, mitochondrial (EXOG).	[8]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Nuclease EXOG, mitochondrial (EXOG).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Nuclease EXOG, mitochondrial (EXOG).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Nuclease EXOG, mitochondrial (EXOG).	[12]

1 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 decreases the methylation of Nuclease EXOG, mitochondrial (EXOG).	[10]

References

• [1] Genetic association of single nucleotide polymorphisms in endonuclease G-like 1 gene with type 2 diabetes in a Japanese population.Diabetologia. 2007 Jun;50(6):1218-27. doi: 10.1007/s00125-007-0631-2. Epub 2007 Apr 6.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] 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.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [7] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [8] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [9] 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.
• [10] 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.
• [11] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [12] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.