Details of Drug Off-Target (DOT)

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

• DOT Name: Sodium- and chloride-dependent GABA transporter 2 (SLC6A13)
• Synonyms: GAT-2; Solute carrier family 6 member 13
• Gene Name: SLC6A13
• UniProt ID: S6A13_HUMAN
• Pfam ID: PF00209
• Sequence:
  MDSRVSGTTSNGETKPVYPVMEKKEEDGTLERGHWNNKMEFVLSVAGEIIGLGNVWRFPY
  LCYKNGGGAFFIPYLVFLFTCGIPVFLLETALGQYTSQGGVTAWRKICPIFEGIGYASQM
  IVILLNVYYIIVLAWALFYLFSSFTIDLPWGGCYHEWNTEHCMEFQKTNGSLNGTSENAT
  SPVIEFWERRVLKISDGIQHLGALRWELALCLLLAWVICYFCIWKGVKSTGKVVYFTATF
  PYLMLVVLLIRGVTLPGAAQGIQFYLYPNLTRLWDPQVWMDAGTQIFFSFAICLGCLTAL
  GSYNKYHNNCYRDCIALCFLNSGTSFVAGFAIFSILGFMSQEQGVPISEVAESGPGLAFI
  AYPRAVVMLPFSPLWACCFFFMVVLLGLDSQFVCVESLVTALVDMYPHVFRKKNRREVLI
  LGVSVVSFLVGLIMLTEGGMYVFQLFDYYAASGMCLLFVAIFESLCVAWVYGAKRFYDNI
  EDMIGYRPWPLIKYCWLFLTPAVCTATFLFSLIKYTPLTYNKKYTYPWWGDALGWLLALS
  SMVCIPAWSLYRLGTLKGPFRERIRQLMCPAEDLPQRNPAGPSAPATPRTSLLRLTELES
  HC
• Function: Mediates sodium- and chloride-dependent transport of gamma-aminobutyric acid (GABA). Mediates transport of beta-alanine. Can also mediate transport of taurine and hypotaurine.
• Tissue Specificity: Expressed in brain, kidney, lung, liver and testis.
• KEGG Pathway:
  Sy.ptic vesicle cycle (hsa04721)
  GABAergic sy.pse (hsa04727)
• Reactome Pathway:
  Reuptake of GABA (R-HSA-888593)
  Na+/Cl- dependent neurotransmitter transporters (R-HSA-442660)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
GSK683699	DMTW79H	Phase 2	Sodium- and chloride-dependent GABA transporter 2 (SLC6A13) increases the export of GSK683699.	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Sodium- and chloride-dependent GABA transporter 2 (SLC6A13).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Sodium- and chloride-dependent GABA transporter 2 (SLC6A13).	[2]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Sodium- and chloride-dependent GABA transporter 2 (SLC6A13).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Sodium- and chloride-dependent GABA transporter 2 (SLC6A13).	[4]

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 decreases the methylation of Sodium- and chloride-dependent GABA transporter 2 (SLC6A13).	[5]

References

• [1] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [2] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [3] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] 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.
• [6] Mechanisms of GABA release from human astrocytes. Glia. 2011 Nov;59(11):1600-11. doi: 10.1002/glia.21202. Epub 2011 Jul 11.