Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH77FBE)

• DOT Name: Glucose-6-phosphate exchanger SLC37A2 (SLC37A2)
• Synonyms: Solute carrier family 37 member 2
• Gene Name: SLC37A2
• UniProt ID: G6PT3_HUMAN
• Pfam ID: PF07690
• Sequence:
  MRSSLAPGVWFFRAFSRDSWFRGLILLLTFLIYACYHMSRKPISIVKSRLHQNCSEQIKP
  INDTHSLNDTMWCSWAPFDKDNYKELLGGVDNAFLIAYAIGMFISGVFGERLPLRYYLSA
  GMLLSGLFTSLFGLGYFWNIHELWYFVVIQVCNGLVQTTGWPSVVTCVGNWFGKGKRGFI
  MGIWNSHTSVGNILGSLIAGIWVNGQWGLSFIVPGIITAVMGVITFLFLIEHPEDVDCAP
  PQHHGEPAENQDNPEDPGNSPCSIRESGLETVAKCSKGPCEEPAAISFFGALRIPGVVEF
  SLCLLFAKLVSYTFLYWLPLYIANVAHFSAKEAGDLSTLFDVGGIIGGIVAGLVSDYTNG
  RATTCCVMLILAAPMMFLYNYIGQDGIASSIVMLIICGGLVNGPYALITTAVSADLGTHK
  SLKGNAKALSTVTAIIDGTGSIGAALGPLLAGLISPTGWNNVFYMLISADVLACLLLCRL
  VYKEILAWKVSLSRGSGYKEI
• Function: Inorganic phosphate and glucose-6-phosphate antiporter. May transport cytoplasmic glucose-6-phosphate into the lumen of the endoplasmic reticulum and translocate inorganic phosphate into the opposite direction. Independent of a lumenal glucose-6-phosphatase. May not play a role in homeostatic regulation of blood glucose levels.
• Tissue Specificity: Detected in intestine and pancreas. Lower expression is also detected in liver and kidney.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Glucose-6-phosphate exchanger SLC37A2 (SLC37A2).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Glucose-6-phosphate exchanger SLC37A2 (SLC37A2).	[2]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Glucose-6-phosphate exchanger SLC37A2 (SLC37A2).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Glucose-6-phosphate exchanger SLC37A2 (SLC37A2).	[4]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Glucose-6-phosphate exchanger SLC37A2 (SLC37A2).	[5]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Glucose-6-phosphate exchanger SLC37A2 (SLC37A2).	[6]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Glucose-6-phosphate exchanger SLC37A2 (SLC37A2).	[7]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Glucose-6-phosphate exchanger SLC37A2 (SLC37A2).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Glucose-6-phosphate exchanger SLC37A2 (SLC37A2).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Glucose-6-phosphate exchanger SLC37A2 (SLC37A2).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Glucose-6-phosphate exchanger SLC37A2 (SLC37A2).	[10]

References

• [1] 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.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [5] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [6] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [7] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [8] Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.