Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRK0IOR)

• DOT Name: tRNA (TRMT11)
• Synonyms: guanine(10)-N2)-methyltransferase homolog (EC 2.1.1.-; tRNA guanosine-2'-O-methyltransferase TRM11 homolog
• Gene Name: TRMT11
• Related Disease:
  Alopecia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colon cancer
  Colonic neoplasm
  Esophageal cancer
  Glioblastoma multiforme
  Liver cancer
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
• UniProt ID: TRM11_HUMAN
• EC Number: 2.1.1.-
• Pfam ID: PF01170
• Sequence:
  MALSCTLNRYLLLMAQEHLEFRLPEIKSLLLLFGGQFASSQETYGKSPFWILSIPSEDIA
  RNLMKRTVCAKSIFELWGHGQSPEELYSSLKNYPVEKMVPFLHSDSTYKIKIHTFNKTLT
  QEEKIKRIDALEFLPFEGKVNLKKPQHVFSVLEDYGLDPNCIPENPHNIYFGRWIADGQR
  ELIESYSVKKRHFIGNTSMDAGLSFIMANHGKVKENDIVFDPFVGTGGLLIACAHFGAYV
  YGTDIDYNTVHGLGKATRKNQKWRGPDENIRANLRQYGLEKYYLDVLVSDASKPSWRKGT
  YFDAIITDPPYGIRESTRRTGSQKEIPKGIEKWEKCPESHVPVSLSYHLSDMFLDLLNFA
  AETLVLGGRLVYWLPVYTPEYTEEMVPWHPCLELVSNCEQKLSSHTSRRLITMEKVKKFE
  NRDQYSHLLSDHFLPYQGHNSFREKYFSGVTKRIAKEEKSTQE
• Function: Catalytic subunit of an S-adenosyl-L-methionine-dependent tRNA methyltransferase complex that mediates the methylation of the guanosine nucleotide at position 10 (m2G10) in tRNAs.
• Reactome Pathway: tRNA modification in the nucleus and cytosol (R-HSA-6782315)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alopecia	DIS37HU4	Limited	Genetic Variation	[1]
Breast cancer	DIS7DPX1	Limited	Biomarker	[2]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[2]
Breast neoplasm	DISNGJLM	Limited	Biomarker	[2]
Colon cancer	DISVC52G	Limited	Biomarker	[2]
Colonic neoplasm	DISSZ04P	Limited	Biomarker	[2]
Esophageal cancer	DISGB2VN	Limited	Biomarker	[2]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[2]
Liver cancer	DISDE4BI	Limited	Biomarker	[2]
Neoplasm of esophagus	DISOLKAQ	Limited	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[2]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[2]
Ovarian neoplasm	DISEAFTY	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of tRNA (TRMT11).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of tRNA (TRMT11).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of tRNA (TRMT11).	[5]
Selenium	DM25CGV	Approved	Selenium decreases the expression of tRNA (TRMT11).	[6]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of tRNA (TRMT11).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of tRNA (TRMT11).	[7]

References

• [1] Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
• [2] Identification of recurrent fusion genes across multiple cancer types.Sci Rep. 2019 Jan 31;9(1):1074. doi: 10.1038/s41598-019-38550-6.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [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] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [7] 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.