Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU3UPEE)

• DOT Name: Probable tRNA methyltransferase 9B (TRMT9B)
• Synonyms: Probable tRNA methyltransferase 9-like protein; EC 2.1.1.-
• Gene Name: TRMT9B
• Related Disease:
  Lung cancer
  Lung carcinoma
  Advanced cancer
  B-cell neoplasm
  Carcinoma
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
  Colorectal carcinoma
  Colorectal neoplasm
• UniProt ID: TRM9B_HUMAN
• EC Number: 2.1.1.-
• Pfam ID: PF08241
• Sequence:
  MDHEAAQLEKQHVHNVYESTAPYFSDLQSKAWPRVRQFLQEQKPGSLIADIGCGTGKYLK
  VNSQVHTVGCDYCGPLVEIARNRGCEAMVCDNLNLPFRDEGFDAIISIGVIHHFSTKQRR
  IRAIKEMARVLVPGGQLMIYVWAMEQKNRHFEKQDVLVPWNRALCSQLFSESSQSGRKRQ
  CGYPERGHPYHPPCSECSCSVCFKEQCGSKRSHSVGYEPAMARTCFANISKEGEEEYGFY
  STLGKSFRSWFFSRSLDESTLRKQIERVRPLKNTEVWASSTVTVQPSRHSSLDFDHQEPF
  STKGQSLDEEVFVESSSGKHLEWLRAPGTLKHLNGDHQGEMRRNGGGNFLDSTNTGVNCV
  DAGNIEDDNPSASKILRRISAVDSTDFNPDDTMSVEDPQTDVLDSTAFMRYYHVFREGEL
  CSLLKENVSELRILSSGNDHGNWCIIAEKKRGCD
• Function: May modify wobble uridines in specific arginine and glutamic acid tRNAs. Acts as a tumor suppressor by promoting the expression of LIN9.
• Tissue Specificity: Down-regulated in breast, bladder, colorectal, cervix and testicular carcinomas.
• Reactome Pathway: tRNA modification in the nucleus and cytosol (R-HSA-6782315)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Definitive	Altered Expression	[1]
Lung carcinoma	DISTR26C	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
B-cell neoplasm	DISVY326	Strong	Biomarker	[3]
Carcinoma	DISH9F1N	Strong	Altered Expression	[4]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[3]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[3]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[5]
Colorectal neoplasm	DISR1UCN	Limited	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Probable tRNA methyltransferase 9B (TRMT9B).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Probable tRNA methyltransferase 9B (TRMT9B).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Probable tRNA methyltransferase 9B (TRMT9B).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Probable tRNA methyltransferase 9B (TRMT9B).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Probable tRNA methyltransferase 9B (TRMT9B).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Probable tRNA methyltransferase 9B (TRMT9B).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Probable tRNA methyltransferase 9B (TRMT9B).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Probable tRNA methyltransferase 9B (TRMT9B).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Probable tRNA methyltransferase 9B (TRMT9B).	[13]

References

• [1] Expression of KIAA1456 in lung cancer tissue and its effects on proliferation, migration and invasion of lung cancer cells.Oncol Lett. 2018 Sep;16(3):3791-3795. doi: 10.3892/ol.2018.9119. Epub 2018 Jul 10.
• [2] Phosphorylation of human TRM9L integrates multiple stress-signaling pathways for tumor growth suppression.Sci Adv. 2018 Jul 11;4(7):eaas9184. doi: 10.1126/sciadv.aas9184. eCollection 2018 Jul.
• [3] Ovarian cancer proliferation and apoptosis are regulated by human transfer RNA methyltransferase 9-likevia LIN9.Oncol Lett. 2017 Oct;14(4):4461-4466. doi: 10.3892/ol.2017.6750. Epub 2017 Aug 14.
• [4] A human tRNA methyltransferase 9-like protein prevents tumour growth by regulating LIN9 and HIF1-.EMBO Mol Med. 2013 Mar;5(3):366-83. doi: 10.1002/emmm.201201161. Epub 2013 Feb 4.
• [5] Mapping of a candidate colorectal cancer tumor-suppressor gene to a 900-kilobase region on the short arm of chromosome 8.Genes Chromosomes Cancer. 2004 Jul;40(3):247-60. doi: 10.1002/gcc.20039.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [9] 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.
• [10] 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.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] 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.
• [13] 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.
• [14] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.