Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXXY58N)

• DOT Name: Vesicular inhibitory amino acid transporter (SLC32A1)
• Synonyms: GABA and glycine transporter; Solute carrier family 32 member 1; Vesicular GABA transporter; hVIAAT
• Gene Name: SLC32A1
• UniProt ID: VIAAT_HUMAN
• Pfam ID: PF01490
• Sequence:
  MATLLRSKLSNVATSVSNKSQAKMSGMFARMGFQAATDEEAVGFAHCDDLDFEHRQGLQM
  DILKAEGEPCGDEGAEAPVEGDIHYQRGSGAPLPPSGSKDQVGGGGEFGGHDKPKITAWE
  AGWNVTNAIQGMFVLGLPYAILHGGYLGLFLIIFAAVVCCYTGKILIACLYEENEDGEVV
  RVRDSYVAIANACCAPRFPTLGGRVVNVAQIIELVMTCILYVVVSGNLMYNSFPGLPVSQ
  KSWSIIATAVLLPCAFLKNLKAVSKFSLLCTLAHFVINILVIAYCLSRARDWAWEKVKFY
  IDVKKFPISIGIIVFSYTSQIFLPSLEGNMQQPSEFHCMMNWTHIAACVLKGLFALVAYL
  TWADETKEVITDNLPGSIRAVVNIFLVAKALLSYPLPFFAAVEVLEKSLFQEGSRAFFPA
  CYSGDGRLKSWGLTLRCALVVFTLLMAIYVPHFALLMGLTGSLTGAGLCFLLPSLFHLRL
  LWRKLLWHQVFFDVAIFVIGGICSVSGFVHSLEGLIEAYRTNAED
• Function: Antiporter that exchanges vesicular protons for cytosolic 4-aminobutanoate or to a lesser extend glycine, thus allowing their secretion from nerve terminals. The transport is equally dependent on the chemical and electrical components of the proton gradient. May also transport beta-alanine. Acidification of GABAergic synaptic vesicles is a prerequisite for 4-aminobutanoate uptake.
• Tissue Specificity: Retina. Expressed throughout the horizontal cells or more specifically at the terminals.
• KEGG Pathway:
  Sy.ptic vesicle cycle (hsa04721)
  Retrograde endocan.binoid sig.ling (hsa04723)
  GABAergic sy.pse (hsa04727)
  Morphine addiction (hsa05032)
  Nicotine addiction (hsa05033)
• Reactome Pathway:
  GABA synthesis, release, reuptake and degradation (R-HSA-888590)
  Transport of inorganic cations/anions and amino acids/oligopeptides (R-HSA-425393)

Molecular Interaction Atlas (MIA) of This DOT

3 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 Vesicular inhibitory amino acid transporter (SLC32A1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Vesicular inhibitory amino acid transporter (SLC32A1).	[1]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Vesicular inhibitory amino acid transporter (SLC32A1).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Vesicular inhibitory amino acid transporter (SLC32A1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Vesicular inhibitory amino acid transporter (SLC32A1).	[3]

References

• [1] Neuronal and cardiac toxicity of pharmacological compounds identified through transcriptomic analysis of human pluripotent stem cell-derived embryoid bodies. Toxicol Appl Pharmacol. 2021 Dec 15;433:115792. doi: 10.1016/j.taap.2021.115792. Epub 2021 Nov 3.
• [2] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [3] 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.
• [4] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.