Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3Q11WQ)

• DOT Name: Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2)
• Synonyms: EC 3.1.-.-
• Gene Name: ISG20L2
• UniProt ID: I20L2_HUMAN
• EC Number: 3.1.-.-
• Pfam ID: PF00929
• Sequence:
  MSTLLLNLDFGEPPPKKALEGNAKHRNFVKKRRLLERRGFLSKKNQPPSKAPKLHSEPSK
  KGETPTVDGTWKTPSFPKKKTAASSNGSGQPLDKKAAVSWLTPAPSKKADSVAAKVDLLG
  EFQSALPKINSHPTRSQKKSSQKKSSKKNHPQKNAPQNSTQAHSENKCSGASQKLPRKMV
  AIDCEMVGTGPKGHVSSLARCSIVNYNGDVLYDEYILPPCHIVDYRTRWSGIRKQHMVNA
  TPFKIARGQILKILTGKIVVGHAIHNDFKALQYFHPKSLTRDTSHIPPLNRKADCPENAT
  MSLKHLTKKLLNRDIQVGKSGHSSVEDAQATMELYKLVEVEWEEHLARNPPTD
• Function: 3'-> 5'-exoribonuclease involved in ribosome biogenesis in the processing of the 12S pre-rRNA. Displays a strong specificity for a 3'-end containing a free hydroxyl group.
• Reactome Pathway: Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)

Molecular Interaction Atlas (MIA) of This DOT

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 Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2).	[4]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2).	[5]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2).	[3]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2).	[6]
Mitomycin	DMH0ZJE	Approved	Mitomycin decreases the expression of Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2).	[3]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2).	[3]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea decreases the expression of Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2).	[3]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2).	[3]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2).	[8]

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 Interferon-stimulated 20 kDa exonuclease-like 2 (ISG20L2).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
• [4] 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.
• [5] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [6] Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
• [7] 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.
• [8] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.