Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNJ7K9K)

• DOT Name: tRNA (TRMO)
• Synonyms: adenine(37)-N6)-methyltransferase (EC 2.1.1.-; tRNA methyltransferase O
• Gene Name: TRMO
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Hypophosphatemia
  Non-small-cell lung cancer
  Psoriasis
  Thiel-Behnke corneal dystrophy
• UniProt ID: TRMO_HUMAN
• EC Number: 2.1.1.-
• Pfam ID: PF01980
• Sequence:
  MRGLEESGPRPTATPCGCVKPALETGNLLTEPVGYLESCFSAKNGTPRQPSICSYSRACL
  RIRKRIFNNPEHSLMGLEQFSHVWILFVFHKNGHLSCKAKVQPPRLNGAKTGVFSTRSPH
  RPNAIGLTLAKLEKVEGGAIYLSGIDMIHGTPVLDIKPYIAEYDSPQNVMEPLADFNLQN
  NQHTPNTVSQSDSKTDSCDQRQLSGCDEPQPHHSTKRKPKCPEDRTSEENYLTHSDTARI
  QQAFPMHREIAVDFGLESRRDQSSSVAEEQIGPYCPEKSFSEKGTDKKLERVEGAAVLQG
  SRAETQPMAPHCPAGRADGAPRSVVPAWVTEAPVATLEVRFTPHAEMDLGQLSSQDVGQA
  SFKYFQSAEEAKRAIEAVLSADPRSVYRRKLCQDRLFYFTVDIAHVTCWFGDGFAEVLRI
  KPASEPVHMTGPVGSLVSLGS
• Function: S-adenosyl-L-methionine-dependent methyltransferase responsible for the addition of the methyl group in the formation of N6-methyl-N6-threonylcarbamoyladenosine at position 37 (m(6)t(6)A37) of the tRNA anticodon loop of tRNA(Ser)(GCU). The methyl group of m(6)t(6)A37 may improve the efficiency of the tRNA decoding ability.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[2]
Hypophosphatemia	DIS9DZYF	Strong	Altered Expression	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[4]
Psoriasis	DIS59VMN	Strong	Altered Expression	[5]
Thiel-Behnke corneal dystrophy	DIS3GK26	Strong	Biomarker	[6]

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 (TRMO).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of tRNA (TRMO).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of tRNA (TRMO).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of tRNA (TRMO).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of tRNA (TRMO).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of tRNA (TRMO).	[12]

References

• [1] Evaluation of the Cepheid Xpert Clostridium difficile Epi assay for diagnosis of Clostridium difficile infection and typing of the NAP1 strain at a cancer hospital.J Clin Microbiol. 2010 Dec;48(12):4519-24. doi: 10.1128/JCM.01648-10. Epub 2010 Oct 13.
• [2] Isolation of hNap1BP which interacts with human Nap1 (NCKAP1) whose expression is down-regulated in Alzheimer's disease.Gene. 2001 Jun 27;271(2):159-69. doi: 10.1016/s0378-1119(01)00521-2.
• [3] Phosphatonin washout in Hyp mice proximal tubules: evidence for posttranscriptional regulation.Am J Physiol Renal Physiol. 2005 Feb;288(2):F363-70. doi: 10.1152/ajprenal.00217.2004. Epub 2004 Sep 28.
• [4] Nck-associated protein 1 associates with HSP90 to drive metastasis in human non-small-cell lung cancer.J Exp Clin Cancer Res. 2019 Mar 11;38(1):122. doi: 10.1186/s13046-019-1124-0.
• [5] Upper keratinocytes of psoriatic skin lesions express high levels of NAP-1/IL-8 mRNA in situ.J Invest Dermatol. 1991 Jul;97(1):73-9. doi: 10.1111/1523-1747.ep12478128.
• [6] Development of a Novel Vaccine Containing Binary Toxin for the Prevention of Clostridium difficile Disease with Enhanced Efficacy against NAP1 Strains.PLoS One. 2017 Jan 26;12(1):e0170640. doi: 10.1371/journal.pone.0170640. eCollection 2017.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] 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.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] 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.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.