Details of Drug Off-Target (DOT)

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

• DOT Name: Queuine tRNA-ribosyltransferase accessory subunit 2 (QTRT2)
• Synonyms: Queuine tRNA-ribosyltransferase domain-containing protein 1
• Gene Name: QTRT2
• UniProt ID: QTRT2_HUMAN
• PDB ID: 7NQ4
• Pfam ID: PF01702
• Sequence:
  MKLSLTKVVNGCRLGKIKNLGKTGDHTMDIPGCLLYTKTGSAPHLTHHTLHNIHGVPAMA
  QLTLSSLAEHHEVLTEYKEGVGKFIGMPESLLYCSLHDPVSPCPAGYVTNKSVSVWSVAG
  RVEMTVSKFMAIQKALQPDWFQCLSDGEVSCKEATSIKRVRKSVDRSLLFLDNCLRLQEE
  SEVLQKSVIIGVIEGGDVMEERLRSARETAKRPVGGFLLDGFQGNPTTLEARLRLLSSVT
  AELPEDKPRLISGVSRPDEVLECIERGVDLFESFFPYQVTERGCALTFSFDYQPNPEETL
  LQQNGTQEEIKCMDQIKKIETTGCNQEITSFEINLKEKKYQEDFNPLVRGCSCYCCKNHT
  RAYIHHLLVTNELLAGVLLMMHNFEHYFGFFHYIREALKSDKLAQLKELIHRQAS
• Function: Non-catalytic subunit of the queuine tRNA-ribosyltransferase (TGT) that catalyzes the base-exchange of a guanine (G) residue with queuine (Q) at position 34 (anticodon wobble position) in tRNAs with GU(N) anticodons (tRNA-Asp, -Asn, -His and -Tyr), resulting in the hypermodified nucleoside queuosine (7-(((4,5-cis-dihydroxy-2-cyclopenten-1-yl)amino)methyl)-7-deazaguanosine).
• Reactome Pathway: tRNA modification in the nucleus and cytosol (R-HSA-6782315)
• BioCyc Pathway: MetaCyc:HS07747-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

9 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 Queuine tRNA-ribosyltransferase accessory subunit 2 (QTRT2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Queuine tRNA-ribosyltransferase accessory subunit 2 (QTRT2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Queuine tRNA-ribosyltransferase accessory subunit 2 (QTRT2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Queuine tRNA-ribosyltransferase accessory subunit 2 (QTRT2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Queuine tRNA-ribosyltransferase accessory subunit 2 (QTRT2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Queuine tRNA-ribosyltransferase accessory subunit 2 (QTRT2).	[6]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Queuine tRNA-ribosyltransferase accessory subunit 2 (QTRT2).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Queuine tRNA-ribosyltransferase accessory subunit 2 (QTRT2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Queuine tRNA-ribosyltransferase accessory subunit 2 (QTRT2).	[11]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Queuine tRNA-ribosyltransferase accessory subunit 2 (QTRT2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Queuine tRNA-ribosyltransferase accessory subunit 2 (QTRT2).	[9]

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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] 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.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [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] 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.
• [11] 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.