Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7NDLYO)

• DOT Name: Histidine protein methyltransferase 1 homolog (METTL18)
• Synonyms: EC 2.1.1.85; Arsenic-transactivated protein 2; AsTP2; Methyltransferase-like protein 18
• Gene Name: METTL18
• UniProt ID: MET18_HUMAN
• PDB ID: 4RFQ
• EC Number: 2.1.1.85
• Pfam ID: PF13489
• Sequence:
  MTFQFNFTIEDHLENELTPIRDGALTLDSSKELSVSESQKGEERDRKCSAEQFDLPQDHL
  WEHKSMENAAPSQDTDSPLSAASSSRNLEPHGKQPSLRAAKEHAMPKDLKKMLENKVIET
  LPGFQHVKLSVVKTILLKENFPGENIVSKSFSSHSDLITGVYEGGLKIWECTFDLLAYFT
  KAKVKFAGKKVLDLGCGSGLLGITAFKGGSKEIHFQDYNSMVIDEVTLPNVVANSTLEDE
  ENDVNEPDVKRCRKPKVTQLYKCRFFSGEWSEFCKLVLSSEKLFVKYDLILTSETIYNPD
  YYSNLHQTFLRLLSKNGRVLLASKAHYFGVGGGVHLFQKFVEERDVFKTRILKIIDEGLK
  RFIIEITFKFPG
• Function: Protein-L-histidine N-tele-methyltransferase that specifically monomethylates RPL3, thereby regulating translation elongation. Histidine methylation of RPL3 regulates translation elongation by slowing ribosome traversal on tyrosine codons: slower elongation provides enough time for proper folding of synthesized proteins and prevents cellular aggregation of tyrosine-rich proteins.

Molecular Interaction Atlas (MIA) of This DOT

1 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 Histidine protein methyltransferase 1 homolog (METTL18).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Histidine protein methyltransferase 1 homolog (METTL18).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Histidine protein methyltransferase 1 homolog (METTL18).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Histidine protein methyltransferase 1 homolog (METTL18).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Histidine protein methyltransferase 1 homolog (METTL18).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Histidine protein methyltransferase 1 homolog (METTL18).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Histidine protein methyltransferase 1 homolog (METTL18).	[7]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Histidine protein methyltransferase 1 homolog (METTL18).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Histidine protein methyltransferase 1 homolog (METTL18).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Histidine protein methyltransferase 1 homolog (METTL18).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Histidine protein methyltransferase 1 homolog (METTL18).	[11]

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] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [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] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [9] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [10] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.