Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5F9PAE)

• DOT Name: Sodium- and chloride-dependent GABA transporter 3 (SLC6A11)
• Synonyms: GAT-3; Solute carrier family 6 member 11
• Gene Name: SLC6A11
• UniProt ID: S6A11_HUMAN
• Pfam ID: PF00209
• Sequence:
  MTAEKALPLGNGKAAEEARESEAPGGGCSSGGAAPARHPRVKRDKAVHERGHWNNKVEFV
  LSVAGEIIGLGNVWRFPYLCYKNGGGAFLIPYVVFFICCGIPVFFLETALGQFTSEGGIT
  CWRKVCPLFEGIGYATQVIEAHLNVYYIIILAWAIFYLSNCFTTELPWATCGHEWNTENC
  VEFQKLNVSNYSHVSLQNATSPVMEFWEHRVLAISDGIEHIGNLRWELALCLLAAWTICY
  FCIWKGTKSTGKVVYVTATFPYIMLLILLIRGVTLPGASEGIKFYLYPDLSRLSDPQVWV
  DAGTQIFFSYAICLGCLTALGSYNNYNNNCYRDCIMLCCLNSGTSFVAGFAIFSVLGFMA
  YEQGVPIAEVAESGPGLAFIAYPKAVTMMPLSPLWATLFFMMLIFLGLDSQFVCVESLVT
  AVVDMYPKVFRRGYRRELLILALSVISYFLGLVMLTEGGMYIFQLFDSYAASGMCLLFVA
  IFECICIGWVYGSNRFYDNIEDMIGYRPPSLIKWCWMIMTPGICAGIFIFFLIKYKPLKY
  NNIYTYPAWGYGIGWLMALSSMLCIPLWICITVWKTEGTLPEKLQKLTTPSTDLKMRGKL
  GVSPRMVTVNDCDAKLKSDGTIAAITEKETHF
• Function: Mediates sodium- and chloride-dependent transport of gamma-aminobutyric acid (GABA). Can also mediate transport of beta-alanine and to a lower extent that of taurine and hypotaurine.
• Tissue Specificity: Widespread distribution in the brain.
• KEGG Pathway:
  Sy.ptic vesicle cycle (hsa04721)
  GABAergic sy.pse (hsa04727)
• Reactome Pathway:
  Creatine metabolism (R-HSA-71288)
  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 3 (SLC6A11) increases the export of GSK683699.	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Sodium- and chloride-dependent GABA transporter 3 (SLC6A11).	[1]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Sodium- and chloride-dependent GABA transporter 3 (SLC6A11).	[2]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Sodium- and chloride-dependent GABA transporter 3 (SLC6A11).	[3]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Sodium- and chloride-dependent GABA transporter 3 (SLC6A11).	[4]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Sodium- and chloride-dependent GABA transporter 3 (SLC6A11).	[6]

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 3 (SLC6A11).	[5]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] 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.
• [3] Effect of ovarian steroids on gene expression profile in human uterine microvascular endothelial cells. Fertil Steril. 2009 Aug;92(2):709-21.
• [4] 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.
• [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] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [7] Mechanisms of GABA release from human astrocytes. Glia. 2011 Nov;59(11):1600-11. doi: 10.1002/glia.21202. Epub 2011 Jul 11.