Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7OXWSO)

• DOT Name: Protein arginine methyltransferase NDUFAF7, mitochondrial (NDUFAF7)
• Synonyms: EC 2.1.1.320; NADH dehydrogenase complex I, assembly factor 7; Protein midA homolog
• Gene Name: NDUFAF7
• UniProt ID: NDUF7_HUMAN
• EC Number: 2.1.1.320
• Pfam ID: PF02636
• Sequence:
  MSVLLRSGLGPLCAVARAAIPFIWRGKYFSSGNEPAENPVTPMLRHLMYKIKSTGPITVA
  EYMKEVLTNPAKGYYVYRDMLGEKGDFITSPEISQIFGELLGIWFISEWMATGKSTAFQL
  VELGPGRGTLVGDILRVFTQLGSVLKNCDISVHLVEVSQKLSEIQALTLTKEKVPLERNA
  GSPVYMKGVTKSGIPISWYRDLHDVPKGYSFYLAHEFFDVLPVHKFQKTPQGWREVFVDI
  DPQVSDKLRFVLAPSATPAEAFIQHDETRDHVEVCPDAGVIIEELSQRIALTGGAALVAD
  YGHDGTKTDTFRGFCDHKLHDVLIAPGTADLTADVDFSYLRRMAQGKVASLGPIKQHTFL
  KNMGIDVRLKVLLDKSNEPSVRQQLLQGYDMLMNPKKMGERFNFFALLPHQRLQGGRYQR
  NARQSKPFASVVAGFSELAWQ
• Function: Arginine methyltransferase involved in the assembly or stability of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). Acts by mediating symmetric dimethylation of 'Arg-118' of NDUFS2 after it assembles into the complex I, stabilizing the early intermediate complex.
• KEGG Pathway: Thermogenesis (hsa04714)
• Reactome Pathway: Complex I biogenesis (R-HSA-6799198)

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 Protein arginine methyltransferase NDUFAF7, mitochondrial (NDUFAF7).	[1]

6 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 Protein arginine methyltransferase NDUFAF7, mitochondrial (NDUFAF7).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein arginine methyltransferase NDUFAF7, mitochondrial (NDUFAF7).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Protein arginine methyltransferase NDUFAF7, mitochondrial (NDUFAF7).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein arginine methyltransferase NDUFAF7, mitochondrial (NDUFAF7).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein arginine methyltransferase NDUFAF7, mitochondrial (NDUFAF7).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein arginine methyltransferase NDUFAF7, mitochondrial (NDUFAF7).	[7]

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] 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.
• [3] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [4] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [5] 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.
• [6] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [7] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.