Details of Drug Off-Target (DOT)

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

• DOT Name: tRNA (TRMT2A)
• Synonyms: uracil-5-)-methyltransferase homolog A (EC 2.1.1.35; mRNA (uracil-5-)-methyltransferase TRMT2A; EC 2.1.1.-
• Gene Name: TRMT2A
• Related Disease: Schizophrenia
• UniProt ID: TRM2A_HUMAN
• PDB ID: 7NTN; 7NTO
• EC Number: 2.1.1.-; 2.1.1.35
• Pfam ID: PF05958
• Sequence:
  MSENLDNEGPKPMESCGQESSSALSCPTVSVPPAAPAALEEVEKEGAGAATGPGPQPGLY
  SYIRDDLFTSEIFKLELQNVPRHASFSDVRRFLGRFGLQPHKTKLFGQPPCAFVTFRSAA
  ERDKALRVLHGALWKGRPLSVRLARPKADPMARRRRQEGESEPPVTRVADVVTPLWTVPY
  AEQLERKQLECEQVLQKLAKEIGSTNRALLPWLLEQRHKHNKACCPLEGVRPSPQQTEYR
  NKCEFLVGVGVDGEDNTVGCRLGKYKGGTCAVAAPFDTVHIPEATKQVVKAFQEFIRSTP
  YSAYDPETYTGHWKQLTVRTSRRHQAMAIAYFHPQKLSPEELAELKTSLAQHFTAGPGRA
  SGVTCLYFVEEGQRKTPSQEGLPLEHVAGDRCIHEDLLGLTFRISPHAFFQVNTPAAEVL
  YTVIQDWAQLDAGSMVLDVCCGTGTIGLALARKVKRVIGVELCPEAVEDARVNAQDNELS
  NVEFHCGRAEDLVPTLVSRLASQHLVAILDPPRAGLHSKVILAIRRAKNLRRLLYVSCNP
  RAAMGNFVDLCRAPSNRVKGIPFRPVKAVAVDLFPQTPHCEMLILFERVEHPNGTGVLGP
  HSPPAQPTPGPPDNTLQETGTFPSS
• Function: S-adenosyl-L-methionine-dependent methyltransferase that catalyzes the formation of 5-methyl-uridine in tRNAs and some mRNAs. Mainly catalyzes the methylation of uridine at position 54 (m5U54) in cytosolic tRNAs. Also able to mediate the formation of 5-methyl-uridine in some mRNAs.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[1]

1 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 (TRMT2A).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of tRNA (TRMT2A).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of tRNA (TRMT2A).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of tRNA (TRMT2A).	[5]

References

• [1] HTF9C gene of 22q11.21 region associates with schizophrenia having deficit-sustained attention.Psychiatr Genet. 2007 Dec;17(6):333-8. doi: 10.1097/YPG.0b013e328133f321.
• [2] 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.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [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] 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.