Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVYLVG8)

• DOT Name: D-aminoacyl-tRNA deacylase 2 (DTD2)
• Synonyms: EC 3.1.1.96; Animalia-specific tRNA deacylase; ATD; D-tyrosyl-tRNA(Tyr) deacylase 2; L-alanyl-tRNA deacylase
• Gene Name: DTD2
• UniProt ID: DTD2_HUMAN
• EC Number: 3.1.1.96
• Pfam ID: PF02580
• Sequence:
  MAEGSRIPQARALLQQCLHARLQIRPADGDVAAQWVEVQRGLVIYVCFFKGADKELLPKM
  VNTLLNVKLSETENGKHVSILDLPGNILIIPQATLGGRLKGRNMQYHSNSGKEEGFELYS
  QFVTLCEKEVAANSKCAEARVVVEHGTYGNRQVLKLDTNGPFTHLIEF
• Function: Deacylates mischarged D-aminoacyl-tRNAs. Also deacylates mischarged glycyl-tRNA(Ala), protecting cells against glycine mischarging by AlaRS. Probably acts by rejecting L-amino acids from its binding site rather than specific recognition of D-amino acids. Catalyzes the hydrolysis of D-tyrosyl-tRNA(Tyr), has no activity on correctly charged L-tyrosyl-tRNA(Tyr). By recycling D-aminoacyl-tRNA to D-amino acids and free tRNA molecules, this enzyme counteracts the toxicity associated with the formation of D-aminoacyl-tRNA entities in vivo and helps enforce protein L-homochirality. In contrast to DTD1, deacylates L-Ala mischarged on tRNA(Thr)(G4.U69) by alanine-tRNA ligase AARS. Can deacylate L-Ala due to a relaxed specificity for substrate chirality caused by the trans conformation of the Gly-Pro motif in the active site. Also hydrolyzes correctly charged, achiral, glycyl-tRNA(Gly) in vitro, although in vivo EEF1A1/EF-Tu may protect cognate achiral glycyl-tRNA(Gly) from DTD2-mediated deacetylation.

Molecular Interaction Atlas (MIA) of This DOT

7 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 D-aminoacyl-tRNA deacylase 2 (DTD2).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of D-aminoacyl-tRNA deacylase 2 (DTD2).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of D-aminoacyl-tRNA deacylase 2 (DTD2).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of D-aminoacyl-tRNA deacylase 2 (DTD2).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of D-aminoacyl-tRNA deacylase 2 (DTD2).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of D-aminoacyl-tRNA deacylase 2 (DTD2).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of D-aminoacyl-tRNA deacylase 2 (DTD2).	[9]

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 D-aminoacyl-tRNA deacylase 2 (DTD2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of D-aminoacyl-tRNA deacylase 2 (DTD2).	[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] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.