Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7WNTP8)

• DOT Name: eEF1A lysine and N-terminal methyltransferase (METTL13)
• Synonyms: eEF1A-KNMT; Methyltransferase-like protein 13
• Gene Name: METTL13
• UniProt ID: EFNMT_HUMAN
• PDB ID: 5WCJ
• EC Number: 2.1.1.-
• Pfam ID: PF13847 ; PF01564
• Sequence:
  MNLLPKSSREFGSVDYWEKFFQQRGKKAFEWYGTYLELCGVLHKYIKPREKVLVIGCGNS
  ELSEQLYDVGYRDIVNIDISEVVIKQMKECNATRRPQMSFLKMDMTQMEFPDASFQVVLD
  KGTLDAVLTDEEEKTLQQVDRMLAEVGRVLQVGGRYLCISLAQAHILKKAVGHFSREGWM
  VRVHQVANSQDQVLEAEPQFSLPVFAFIMTKFRPVPGSALQIFELCAQEQRKPVRLESAE
  RLAEAVQERQQYAWLCSQLRRKARLGSVSLDLCDGDTGEPRYTLHVVDSPTVKPSRDNHF
  AIFIIPQGRETEWLFGMDEGRKQLAASAGFRRLITVALHRGQQYESMDHIQAELSARVME
  LAPAGMPTQQQVPFLSVGGDIGVRTVQHQDCSPLSGDYVIEDVQGDDKRYFRRLIFLSNR
  NVVQSEARLLKDVSHKAQKKRKKDRKKQRPADAEDLPAAPGQSIDKSYLCCEHHKAMIAG
  LALLRNPELLLEIPLALLVVGLGGGSLPLFVHDHFPKSCIDAVEIDPSMLEVATQWFGFS
  QSDRMKVHIADGLDYIASLAGGGEARPCYDVIMFDVDSKDPTLGMSCPPPAFVEQSFLQK
  VKSILTPEGVFILNLVCRDLGLKDSVLAGLKAVFPLLYVRRIEGEVNEILFCQLHPEQKL
  ATPELLETAQALERTLRKPGRGWDDTYVLSDMLKTVKIV
• Function: Dual methyltransferase that catalyzes methylation of elongation factor 1-alpha (EEF1A1 and EEF1A2) at two different positions, and is therefore involved in the regulation of mRNA translation. Via its C-terminus, methylates EEF1A1 and EEF1A2 at the N-terminal residue 'Gly-2'. Via its N-terminus dimethylates EEF1A1 and EEF1A2 at residue 'Lys-55'. Has no activity towards core histones H2A, H2B, H3 and H4. Negatively regulates cell proliferation at G1/S transition via transcriptional suppression of cell cycle regulatory genes such as CDK4 and CDK6.

Molecular Interaction Atlas (MIA) of This DOT

6 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 eEF1A lysine and N-terminal methyltransferase (METTL13).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of eEF1A lysine and N-terminal methyltransferase (METTL13).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of eEF1A lysine and N-terminal methyltransferase (METTL13).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of eEF1A lysine and N-terminal methyltransferase (METTL13).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of eEF1A lysine and N-terminal methyltransferase (METTL13).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of eEF1A lysine and N-terminal methyltransferase (METTL13).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of eEF1A lysine and N-terminal methyltransferase (METTL13).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of eEF1A lysine and N-terminal methyltransferase (METTL13).	[7]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of eEF1A lysine and N-terminal methyltransferase (METTL13).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Identification of novel gene targets and putative regulators of arsenic-associated DNA methylation in human urothelial cells and bladder cancer. Chem Res Toxicol. 2015 Jun 15;28(6):1144-55. doi: 10.1021/tx500393y. Epub 2015 Jun 3.
• [7] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.