Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT8WRDA)

• DTT Name: Excitatory amino acid transporter 1 (SLC1A3)
• Synonyms: Solute carrier family 1 member 3; Sodium-dependent glutamate/aspartate transporter 1; GLAST-1; EAAT1
• Gene Name: SLC1A3
• DTT Type: Literature-reported target; [1]
• UniProt ID: EAA1_HUMAN
• TTD ID: T86582
• Sequence:
  MTKSNGEEPKMGGRMERFQQGVRKRTLLAKKKVQNITKEDVKSYLFRNAFVLLTVTAVIV
  GTILGFTLRPYRMSYREVKYFSFPGELLMRMLQMLVLPLIISSLVTGMAALDSKASGKMG
  MRAVVYYMTTTIIAVVIGIIIVIIIHPGKGTKENMHREGKIVRVTAADAFLDLIRNMFPP
  NLVEACFKQFKTNYEKRSFKVPIQANETLVGAVINNVSEAMETLTRITEELVPVPGSVNG
  VNALGLVVFSMCFGFVIGNMKEQGQALREFFDSLNEAIMRLVAVIMWYAPVGILFLIAGK
  IVEMEDMGVIGGQLAMYTVTVIVGLLIHAVIVLPLLYFLVTRKNPWVFIGGLLQALITAL
  GTSSSSATLPITFKCLEENNGVDKRVTRFVLPVGATINMDGTALYEALAAIFIAQVNNFE
  LNFGQIITISITATAASIGAAGIPQAGLVTMVIVLTSVGLPTDDITLIIAVDWFLDRLRT
  TTNVLGDSLGAGIVEHLSRHELKNRDVEMGNSVIEENEMKKPYQLIAQDNETEKPIDSET
  KM
• Function: Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate. Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion. Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport. Plays a redundant role in the rapid removal of released glutamate from the synaptic cleft, which is essential for terminating the postsynaptic action of glutamate (By similarity).
• KEGG Pathway:
  Synaptic vesicle cycle (hsa04721)
  Glutamatergic synapse (hsa04724)
  Huntington disease (hsa05016)
• Reactome Pathway:
  Glutamate Neurotransmitter Release Cycle (R-HSA-210500)
  Transport of inorganic cations/anions and amino acids/oligopeptides (R-HSA-425393)
  Defective SLC1A3 causes episodic ataxia 6 (EA6) (R-HSA-5619062)
  Astrocytic Glutamate-Glutamine Uptake And Metabolism (R-HSA-210455)

Molecular Interaction Atlas (MIA) of This DTT

5 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
D-aspartic acid	DM7Z892	Discovery agent	N.A.	Investigative	[2]
DL-TBOA	DM2HGNU	Discovery agent	N.A.	Investigative	[1]
SYM2081	DM30WDL	Discovery agent	N.A.	Investigative	[2]
UCPH-101	DMTQEDA	Discovery agent	N.A.	Investigative	[3]
[3H]ETB-TBOA	DMWGY61	Discovery agent	N.A.	Investigative	[4]

References

• [1] DL-threo-beta-benzyloxyaspartate, a potent blocker of excitatory amino acid transporters. Mol Pharmacol. 1998 Feb;53(2):195-201.
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 868).
• [3] Discovery of the first selective inhibitor of excitatory amino acid transporter subtype 1. J Med Chem. 2009 Feb 26;52(4):912-5.
• [4] Characterization of the tritium-labeled analog of L-threo-beta-benzyloxyaspartate binding to glutamate transporters. Mol Pharmacol. 2007 Jan;71(1):294-302.