Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTG2A6F)

• DTT Name: Excitatory amino acid transporter 3 (SLC1A1)
• Synonyms: Solute carrier family 1 member 1; Sodium-dependent glutamate/aspartate transporter 3; Neuronal and epithelial glutamate transporter; Excitatory amino-acid carrier 1; EAAT3; EAAC1
• Gene Name: SLC1A1
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Dicarboxylate/amino acid:cation symporter
• UniProt ID: EAA3_HUMAN
• TTD ID: T31721
• Sequence:
  MGKPARKGCEWKRFLKNNWVLLSTVAAVVLGITTGVLVREHSNLSTLEKFYFAFPGEILM
  RMLKLIILPLIISSMITGVAALDSNVSGKIGLRAVVYYFCTTLIAVILGIVLVVSIKPGV
  TQKVGEIARTGSTPEVSTVDAMLDLIRNMFPENLVQACFQQYKTKREEVKPPSDPEMNMT
  EESFTAVMTTAISKNKTKEYKIVGMYSDGINVLGLIVFCLVFGLVIGKMGEKGQILVDFF
  NALSDATMKIVQIIMCYMPLGILFLIAGKIIEVEDWEIFRKLGLYMATVLTGLAIHSIVI
  LPLIYFIVVRKNPFRFAMGMAQALLTALMISSSSATLPVTFRCAEENNQVDKRITRFVLP
  VGATINMDGTALYEAVAAVFIAQLNDLDLGIGQIITISITATSASIGAAGVPQAGLVTMV
  IVLSAVGLPAEDVTLIIAVDWLLDRFRTMVNVLGDAFGTGIVEKLSKKELEQMDVSSEVN
  IVNPFALESTILDNEDSDTKKSYVNGGFAVDKSDTISFTQTSQF
• Function: Can also transport L-cysteine. 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 an important role in L-glutamate and L-aspartate reabsorption in renal tubuli. 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. Negatively regulated by ARL6IP5. 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)
  Protein digestion and absorption (hsa04974)
• Reactome Pathway:
  Transport of inorganic cations/anions and amino acids/oligopeptides (R-HSA-425393)
  Defective SLC1A1 is implicated in schizophrenia 18 (SCZD18) and dicarboxylic aminoaciduria (DCBXA) (R-HSA-5619067)
  Glutamate Neurotransmitter Release Cycle (R-HSA-210500)

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	[3]
L-beta-BA	DMENM1B	Discovery agent	N.A.	Investigative	[4]
NBI-59159	DM7S5Y4	Discovery agent	N.A.	Investigative	[1]
[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 3 (SLC1A1) DTP Info
• Gene Name: SLC1A1

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] Ligands targeting the excitatory amino acid transporters (EAATs). Curr Top Med Chem. 2006;6(17):1897-906.
• [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: 870).
• [3] Syntheses of optically pure beta-hydroxyaspartate derivatives as glutamate transporter blockers. Bioorg Med Chem Lett. 2000 Nov 6;10(21):2407-10.
• [4] The substituted aspartate analogue L-beta-threo-benzyl-aspartate preferentially inhibits the neuronal excitatory amino acid transporter EAAT3. Neuropharmacology. 2005 Nov;49(6):850-61.
• [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] Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria. J Clin Invest. 2011 Jan;121(1):446-53.