Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK0CPOX)

• DOT Name: Queuosine 5'-phosphate N-glycosylase/hydrolase (QNG1)
• Synonyms: EC 3.2.2.-; Q-nucleotide N-glycosylase 1; Queuine salvage protein QNG1; Queuosine-nucleotide N-glycosylase/hydrolase
• Gene Name: QNG1
• UniProt ID: QNG1_HUMAN
• PDB ID: 7UGK; 8DL3
• EC Number: 3.2.2.-
• Pfam ID: PF10343
• Sequence:
  MDGLLNPRESSKFIAENSRDVFIDSGGVRRVAELLLAKAAGPELRVEGWKALHELNPRAA
  DEAAVNWVFVTDTLNFSFWSEQDEHKCVVRYRGKTYSGYWSLCAAVNRALDEGIPITSAS
  YYATVTLDQVRNILRSDTDVSMPLVEERHRILNETGKILLEKFGGSFLNCVRESENSAQK
  LMHLVVESFPSYRDVTLFEGKRVSFYKRAQILVADTWSVLEGKGDGCFKDISSITMFADY
  RLPQVLAHLGALKYSDDLLKKLLKGEMLSYGDRQEVEIRGCSLWCVELIRDCLLELIEQK
  GEKPNGEINSILLDYYLWDYAHDHREDMKGIPFHRIRCIYY
• Function: Catalyzes the hydrolysis of queuosine 5'-phosphate, releasing the nucleobase queuine (q). Is required for salvage of queuine from exogenous queuosine (Q) that is imported and then converted to queuosine 5'-phosphate intracellularly. In vitro, can also catalyze the release of the q base directly from Q as substrate; however, it was shown that Q is not the biologically relevant substrate. Shows a very low activity on queuosine 3',5'-diphosphate, and cannot release q from queuosine 3'-phosphate and from the 5'-nucleotides AMP, UMP, CMP or GMP, indicating specificity for the queuine base. Can complement the yeast mutant SPAC589.05c, restoring Q incorporation into tRNA.

Molecular Interaction Atlas (MIA) of This DOT

11 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 Queuosine 5'-phosphate N-glycosylase/hydrolase (QNG1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Queuosine 5'-phosphate N-glycosylase/hydrolase (QNG1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Queuosine 5'-phosphate N-glycosylase/hydrolase (QNG1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Queuosine 5'-phosphate N-glycosylase/hydrolase (QNG1).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Queuosine 5'-phosphate N-glycosylase/hydrolase (QNG1).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Queuosine 5'-phosphate N-glycosylase/hydrolase (QNG1).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Queuosine 5'-phosphate N-glycosylase/hydrolase (QNG1).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Queuosine 5'-phosphate N-glycosylase/hydrolase (QNG1).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Queuosine 5'-phosphate N-glycosylase/hydrolase (QNG1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Queuosine 5'-phosphate N-glycosylase/hydrolase (QNG1).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Queuosine 5'-phosphate N-glycosylase/hydrolase (QNG1).	[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 increases the methylation of Queuosine 5'-phosphate N-glycosylase/hydrolase (QNG1).	[8]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] 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.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] 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.
• [9] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [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.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.