Details of Drug Off-Target (DOT)

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

• DOT Name: Methyltransferase-like protein 17, mitochondrial (METTL17)
• Synonyms: EC 2.1.1.-; False p73 target gene protein; Methyltransferase 11 domain-containing protein 1; Protein RSM22 homolog, mitochondrial
• Gene Name: METTL17
• Related Disease: Mitochondrial disease
• UniProt ID: MET17_HUMAN
• PDB ID: 8CSP; 8CSQ; 8CSR; 8CSS; 8CST; 8CSU
• EC Number: 2.1.1.-
• Pfam ID: PF09243
• Sequence:
  MAAALKCLLTLGRWCPGLGVAPQARALAALVPGVTQVDNKSGFLQKRPHRQHPGILKLPH
  VRLPQALANGAQLLLLGSAGPTMENQVQTLTSYLWSRHLPVEPEELQRRARHLEKKFLEN
  PDLSQTEEKLRGAVLHALRKTTYHWQELSYTEGLSLVYMAARLDGGFAAVSRAFHEIRAR
  NPAFQPQTLMDFGSGTGSVTWAAHSIWGQSLREYMCVDRSAAMLVLAEKLLKGGSESGEP
  YIPGVFFRQFLPVSPKVQFDVVVSAFSLSELPSKADRTEVVQTLWRKTGHFLVLVENGTK
  AGHSLLMDARDLVLKGKEKSPLDPRPGFVFAPCPHELPCPQLTNLACSFSQAYHPIPFSW
  NKKPKEEKFSMVILARGSPEEAHRWPRITQPVLKRPRHVHCHLCCPDGHMQHAVLTARRH
  GRDLYRCARVSSWGDLLPVLTPSAFPPSTAQDPSES
• Function: Probable S-adenosyl-L-methionine-dependent RNA methyltransferase required to stabilize the mitochondrial small ribosomal subunit (mt-SSU). Required for protein translation in mitochondria.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mitochondrial disease	DISKAHA3	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Methyltransferase-like protein 17, mitochondrial (METTL17).	[2]

5 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 Methyltransferase-like protein 17, mitochondrial (METTL17).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Methyltransferase-like protein 17, mitochondrial (METTL17).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Methyltransferase-like protein 17, mitochondrial (METTL17).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Methyltransferase-like protein 17, mitochondrial (METTL17).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Methyltransferase-like protein 17, mitochondrial (METTL17).	[6]

References

• [1] Sequence variants in four candidate genes (NIPSNAP1, GBAS, CHCHD1 and METT11D1) in patients with combined oxidative phosphorylation system deficiencies.J Inherit Metab Dis. 2010 Dec;33 Suppl 3:S13-9. doi: 10.1007/s10545-009-0968-4.
• [2] 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.
• [3] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [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] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.