Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT32BWT)

• DOT Name: tRNA N6-adenosine threonylcarbamoyltransferase, mitochondrial (OSGEPL1)
• Synonyms: EC 2.3.1.234; N6-L-threonylcarbamoyladenine synthase; t(6)A synthase; O-sialoglycoprotein endopeptidase-like protein 1; OSGEP-like protein 1; t(6)A37 threonylcarbamoyladenosine biosynthesis protein OSGEPL1; tRNA threonylcarbamoyladenosine biosynthesis protein OSGEPL1
• Gene Name: OSGEPL1
• UniProt ID: OSGL1_HUMAN
• EC Number: 2.3.1.234
• Pfam ID: PF00814
• Sequence:
  MLILTKTAGVFFKPSKRKVYEFLRSFNFHPGTLFLHKIVLGIETSCDDTAAAVVDETGNV
  LGEAIHSQTEVHLKTGGIVPPAAQQLHRENIQRIVQEALSASGVSPSDLSAIATTIKPGL
  ALSLGVGLSFSLQLVGQLKKPFIPIHHMEAHALTIRLTNKVEFPFLVLLISGGHCLLALV
  QGVSDFLLLGKSLDIAPGDMLDKVARRLSLIKHPECSTMSGGKAIEHLAKQGNRFHFDIK
  PPLHHAKNCDFSFTGLQHVTDKIIMKKEKEEGIEKGQILSSAADIAATVQHTMACHLVKR
  THRAILFCKQRDLLPQNNAVLVASGGVASNFYIRRALEILTNATQCTLLCPPPRLCTDNG
  IMIAWNGIERLRAGLGILHDIEGIRYEPKCPLGVDISKEVGEASIKVPQLKMEI
• Function: Required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in mitochondrial tRNAs that read codons beginning with adenine. Probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. Involved in mitochondrial genome maintenance.
• Tissue Specificity: Widely expressed, with maximum expression in pituitary gland, prostate, rectum and uterus.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of tRNA N6-adenosine threonylcarbamoyltransferase, mitochondrial (OSGEPL1).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of tRNA N6-adenosine threonylcarbamoyltransferase, mitochondrial (OSGEPL1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of tRNA N6-adenosine threonylcarbamoyltransferase, mitochondrial (OSGEPL1).	[11]

11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of tRNA N6-adenosine threonylcarbamoyltransferase, mitochondrial (OSGEPL1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of tRNA N6-adenosine threonylcarbamoyltransferase, mitochondrial (OSGEPL1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of tRNA N6-adenosine threonylcarbamoyltransferase, mitochondrial (OSGEPL1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of tRNA N6-adenosine threonylcarbamoyltransferase, mitochondrial (OSGEPL1).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of tRNA N6-adenosine threonylcarbamoyltransferase, mitochondrial (OSGEPL1).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of tRNA N6-adenosine threonylcarbamoyltransferase, mitochondrial (OSGEPL1).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of tRNA N6-adenosine threonylcarbamoyltransferase, mitochondrial (OSGEPL1).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of tRNA N6-adenosine threonylcarbamoyltransferase, mitochondrial (OSGEPL1).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of tRNA N6-adenosine threonylcarbamoyltransferase, mitochondrial (OSGEPL1).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of tRNA N6-adenosine threonylcarbamoyltransferase, mitochondrial (OSGEPL1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of tRNA N6-adenosine threonylcarbamoyltransferase, mitochondrial (OSGEPL1).	[14]

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] 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] 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] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [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] 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.
• [7] 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.
• [8] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [9] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] 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.
• [14] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.