Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO7WA10)

• DOT Name: Probable mitochondrial glutathione transporter SLC25A39 (SLC25A39)
• Synonyms: Solute carrier family 25 member 39
• Gene Name: SLC25A39
• UniProt ID: S2539_HUMAN
• Pfam ID: PF00153
• Sequence:
  MADQDPAGISPLQQMVASGTGAVVTSLFMTPLDVVKVRLQSQRPSMASELMPSSRLWSLS
  YTKLPSSLQSTGKCLLYCNGVLEPLYLCPNGARCATWFQDPTRFTGTMDAFVKIVRHEGT
  RTLWSGLPATLVMTVPATAIYFTAYDQLKAFLCGRALTSDLYAPMVAGALARLGTVTVIS
  PLELMRTKLQAQHVSYRELGACVRTAVAQGGWRSLWLGWGPTALRDVPFSALYWFNYELV
  KSWLNGFRPKDQTSVGMSFVAGGISGTVAAVLTLPFDVVKTQRQVALGAMEAVRVNPLHV
  DSTWLLLRRIRAESGTKGLFAGFLPRIIKAAPSCAIMISTYEFGKSFFQRLNQDRLLGG
• Function: Mitochondrial transporter required for glutathione import into mitochondria. Glutathione, which plays key roles in oxidative metabolism, is produced exclusively in the cytosol and is imported in many organelles. Mitochondrial glutathione is required for the activity and stability of proteins containing iron-sulfur clusters, as well as erythropoiesis.
• Tissue Specificity: Expressed in many tissues . Abundant in testis and kidney .

Molecular Interaction Atlas (MIA) of This DOT

7 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 Probable mitochondrial glutathione transporter SLC25A39 (SLC25A39).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Probable mitochondrial glutathione transporter SLC25A39 (SLC25A39).	[2]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Probable mitochondrial glutathione transporter SLC25A39 (SLC25A39).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Probable mitochondrial glutathione transporter SLC25A39 (SLC25A39).	[4]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Probable mitochondrial glutathione transporter SLC25A39 (SLC25A39).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Probable mitochondrial glutathione transporter SLC25A39 (SLC25A39).	[6]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Probable mitochondrial glutathione transporter SLC25A39 (SLC25A39).	[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] 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] 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.
• [4] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [6] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [7] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.