Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT2F078)

• DTT Name: Excitatory amino acid transporter 2 (SLC1A2)
• Synonyms: Solute carrier family 1 member 2; Sodium-dependent glutamate/aspartate transporter 2; Glutamate/aspartatetransporter II; Glutamate/aspartate transporter II; GLT1; EAAT2
• Gene Name: SLC1A2
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Dicarboxylate/amino acid:cation symporter
• UniProt ID: EAA2_HUMAN
• TTD ID: T95438
• Sequence:
  MASTEGANNMPKQVEVRMHDSHLGSEEPKHRHLGLRLCDKLGKNLLLTLTVFGVILGAVC
  GGLLRLASPIHPDVVMLIAFPGDILMRMLKMLILPLIISSLITGLSGLDAKASGRLGTRA
  MVYYMSTTIIAAVLGVILVLAIHPGNPKLKKQLGPGKKNDEVSSLDAFLDLIRNLFPENL
  VQACFQQIQTVTKKVLVAPPPDEEANATSAVVSLLNETVTEVPEETKMVIKKGLEFKDGM
  NVLGLIGFFIAFGIAMGKMGDQAKLMVDFFNILNEIVMKLVIMIMWYSPLGIACLICGKI
  IAIKDLEVVARQLGMYMVTVIIGLIIHGGIFLPLIYFVVTRKNPFSFFAGIFQAWITALG
  TASSAGTLPVTFRCLEENLGIDKRVTRFVLPVGATINMDGTALYEAVAAIFIAQMNGVVL
  DGGQIVTVSLTATLASVGAASIPSAGLVTMLLILTAVGLPTEDISLLVAVDWLLDRMRTS
  VNVVGDSFGAGIVYHLSKSELDTIDSQHRVHEDIEMTKTQSIYDDMKNHRESNSNQCVYA
  AHNSVIVDECKVTLAANGKSADCSVEEEPWKREK
• Function: 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. Essential for the rapid removal of released glutamate from the synaptic cleft, and for terminating the postsynaptic action of glutamate. Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate.
• KEGG Pathway:
  Synaptic vesicle cycle (hsa04721)
  Glutamatergic synapse (hsa04724)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
• Reactome Pathway:
  Glutamate Neurotransmitter Release Cycle (R-HSA-210500)
  Transport of inorganic cations/anions and amino acids/oligopeptides (R-HSA-425393)
  Astrocytic Glutamate-Glutamine Uptake And Metabolism (R-HSA-210455)

Molecular Interaction Atlas (MIA) of This DTT

6 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	[3]
SYM2081	DM30WDL	Discovery agent	N.A.	Investigative	[1], [2]
Threo-3-methylglutamate	DMOE3IJ	Discovery agent	N.A.	Investigative	[1]
WAY-213613	DMMXL4E	Discovery agent	N.A.	Investigative	[4]
[3H]ETB-TBOA	DMWGY61	Discovery agent	N.A.	Investigative	[5]

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Excitatory amino acid transporter 2 (SLC1A2) DTP Info
• Gene Name: SLC1A2

1 Approved Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-glutamic acid	DM4PUDW	Schizophrenia	6A20	Approved	[6]

References

• [1] Contrasting modes of action of methylglutamate derivatives on the excitatory amino acid transporters, EAAT1 and EAAT2. Mol Pharmacol. 1997 May;51(5):809-15.
• [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: 869).
• [3] DL-threo-beta-benzyloxyaspartate, a potent blocker of excitatory amino acid transporters. Mol Pharmacol. 1998 Feb;53(2):195-201.
• [4] Characterization of novel aryl-ether, biaryl, and fluorene aspartic acid and diaminopropionic acid analogs as potent inhibitors of the high-affinit... Mol Pharmacol. 2005 Oct;68(4):974-82.
• [5] Characterization of the tritium-labeled analog of L-threo-beta-benzyloxyaspartate binding to glutamate transporters. Mol Pharmacol. 2007 Jan;71(1):294-302.
• [6] EAAT2 (GLT-1; slc1a2) glutamate transporters reconstituted in liposomes argues against heteroexchange being substantially faster than net uptake. J Neurosci. 2014 Oct 1;34(40):13472-85.