Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8O301E)

• DOT Name: tRNA (TRMT2B)
• Synonyms: uracil-5-)-methyltransferase homolog B (EC 2.1.1.35; TRM2 homolog B; rRNA (uracil-5-)-methyltransferase TRMT2B; EC 2.1.1.-
• Gene Name: TRMT2B
• UniProt ID: TRM2B_HUMAN
• EC Number: 2.1.1.-; 2.1.1.35
• Pfam ID: PF05958
• Sequence:
  MAGLKRRVPLHSLRYFISMVGLFSKPGLLPWYARNPPGWSQLFLGTVCKGDFTRVIATKC
  QKGQKSQKKPSHLGPLDGSWQERLADVVTPLWRLSYEEQLKVKFAAQKKILQRLESYIQM
  LNGVSVTTAVPKSERLSCLLHPIIPSPVINGYRNKSTFSVNRGPDGNPKTVGFYLGTWRD
  GNVVCVQSNHLKNIPEKHSQVAQYYEVFLRQSPLEPCLVFHEGGYWRELTVRTNSQGHTM
  AIITFHPQKLSQEELHVQKEIVKEFFIRGPGAACGLTSLYFQESTMTRCSHQQSPYQLLF
  GEPYIFEELLSLKIRISPDAFFQINTAGAEMLYRTVGELTGVNSDTILLDICCGTGVIGL
  SLAQHTSRVLGIELLEQAVEDARWTAAFNGITNSEFHTGQAEKILPGLLKSKEDGQSIVA
  VVNPARAGLHYKVIQAIRNFRAIHTLVFVSCKLHGESTRNVIELCCPPDPAKKLLGEPFV
  LQQAVPVDLFPHTPHCELVLLFTR
• Function: Mitochondrial S-adenosyl-L-methionine-dependent methyltransferase that catalyzes the formation of 5-methyl-uridine in tRNAs and 12S rRNA. Catalyzes the methylation of uridine at position 54 (m5U54) in all tRNAs. Specifically methylates the uridine in position 429 of 12S rRNA (m5U429). Does not affect RNA stability or mitochondrial translation.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of tRNA (TRMT2B).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of tRNA (TRMT2B).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of tRNA (TRMT2B).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of tRNA (TRMT2B).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of tRNA (TRMT2B).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of tRNA (TRMT2B).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of tRNA (TRMT2B).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of tRNA (TRMT2B).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of tRNA (TRMT2B).	[9]

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] 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] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] 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.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.