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
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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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

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas 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]
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]
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⏷ Show the Full List of 6 Investigative Drug(s)

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]
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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.