Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMIXQQ6)

DOT Name	tRNA (TRMT61A)
Synonyms	adenine(58)-N(1))-methyltransferase catalytic subunit TRMT61A (EC 2.1.1.220; mRNA methyladenosine-N(1)-methyltransferase catalytic subunit TRMT61A; EC 2.1.1.-; tRNA(m1A58)-methyltransferase subunit TRMT61A; tRNA(m1A58)MTase subunit TRMT61A
Gene Name	TRMT61A
Related Disease	Glioblastoma multiforme ( )
UniProt ID	TRM61_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	5CCB; 5CCX; 5CD1
EC Number	2.1.1.-; 2.1.1.220
Pfam ID	PF08704
Sequence	MSFVAYEELIKEGDTAILSLGHGAMVAVRVQRGAQTQTRHGVLRHSVDLIGRPFGSKVTC GRGGWVYVLHPTPELWTLNLPHRTQILYSTDIALITMMLELRPGSVVCESGTGSGSVSHA IIRTIAPTGHLHTVEFHQQRAEKAREEFQEHRVGRWVTVRTQDVCRSGFGVSHVADAVFL DIPSPWEAVGHAWDALKVEGGRFCSFSPCIEQVQRTCQALAARGFSELSTLEVLPQVYNV RTVSLPPPDLGTGTDGPAGSDTSPFRSGTPMKEAVGHTGYLTFATKTPG
Function	Catalytic subunit of tRNA (adenine-N(1)-)-methyltransferase, which catalyzes the formation of N(1)-methyladenine at position 58 (m1A58) in initiator methionyl-tRNA. Catalytic subunit of mRNA N(1)-methyltransferase complex, which mediates methylation of adenosine residues at the N(1) position of a small subset of mRNAs: N(1) methylation takes place in tRNA T-loop-like structures of mRNAs and is only present at low stoichiometries.
Reactome Pathway	tRNA modification in the nucleus and cytosol (R-HSA-6782315 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance		REF
Glioblastoma multiforme	DISK8246	moderate	Altered Expression	[1]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas 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 affects the expression of tRNA (TRMT61A).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of tRNA (TRMT61A).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of tRNA (TRMT61A).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of tRNA (TRMT61A).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of tRNA (TRMT61A).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of tRNA (TRMT61A).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of tRNA (TRMT61A).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of tRNA (TRMT61A).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of tRNA (TRMT61A).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of tRNA (TRMT61A).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of tRNA (TRMT61A).	[13]
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⏷ Show the Full List of 11 Drug(s)

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 affects the methylation of tRNA (TRMT61A).	[11]
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References

1	TRM6/61 connects PKC with translational control through tRNAi(Met) stabilization: impact on tumorigenesis.Oncogene. 2016 Apr 7;35(14):1785-96. doi: 10.1038/onc.2015.244. Epub 2015 Aug 3.
2	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.
3	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
4	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
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	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.
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	Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
10	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.
11	Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
12	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.
13	Low dose of bisphenol a modulates ovarian cancer gene expression profile and promotes epithelial to mesenchymal transition via canonical Wnt pathway. Toxicol Sci. 2018 Aug 1;164(2):527-538.