Details of Drug Off-Target (DOT)

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

• DOT Name: 12S rRNA N4-methylcytidine (METTL15)
• Synonyms: m4C) methyltransferase (12S rRNA m4C methyltransferase; EC 2.1.1.-; Methyltransferase 5 domain-containing protein 1; Methyltransferase-like protein 15
• Gene Name: METTL15
• UniProt ID: MET15_HUMAN
• PDB ID: 7PNX; 7PNY; 7PNZ
• EC Number: 2.1.1.-
• Pfam ID: PF01795
• Sequence:
  MLRYPYFCRMYKECLSCWLESGIPNLGVWPNRIHTTAEKYREYEAREQTDQTQAQELHRS
  QDRDFETMAKLHIPVMVDEVVHCLSPQKGQIFLDMTFGSGGHTKAILQKESDIVLYALDR
  DPTAYALAEHLSELYPKQIRAMLGQFSQAEALLMKAGVQPGTFDGVLMDLGCSSMQLDTP
  ERGFSLRKDGPLDMRMDGGRYPDMPTAADVVNALDQQALASILRTYGEEKHAKKIASAIV
  QARSIYPITRTQQLASIVAGAFPPSAIYTRKDLLQRSTHIATKTFQALRIFVNNELNELY
  TGLKTAQKFLRPGGRLVALSFHSLEDRIVKRFLLGISMTERFNLSVRQQVMKTSQLGSDH
  ENTEEVSMRRAPLMWELIHKKVLSPQDQDVQDNPRGRSAKLRAAIKL
• Function: N4-methylcytidine (m4C) methyltransferase responsible for the methylation of position C839 in mitochondrial 12S rRNA. Involved in the stabilization of 12S rRNA folding, therefore facilitating the assembly of the mitochondrial small ribosomal subunits.

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 decreases the methylation of 12S rRNA N4-methylcytidine (METTL15).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of 12S rRNA N4-methylcytidine (METTL15).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 12S rRNA N4-methylcytidine (METTL15).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of 12S rRNA N4-methylcytidine (METTL15).	[3]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of 12S rRNA N4-methylcytidine (METTL15).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of 12S rRNA N4-methylcytidine (METTL15).	[6]

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] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [5] 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.
• [6] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.