Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT6KMPN)

• DTT Name: Excitatory amino acid transporter 4 (SLC1A6)
• Synonyms: Solute carrier family 1 member 6; Sodium-dependent glutamate/aspartate transporter; EAAT4
• Gene Name: SLC1A6
• DTT Type: Literature-reported target; [1]
• UniProt ID: EAA4_HUMAN
• TTD ID: T30163
• Sequence:
  MSSHGNSLFLRESGQRLGRVGWLQRLQESLQQRALRTRLRLQTMTLEHVLRFLRRNAFIL
  LTVSAVVIGVSLAFALRPYQLTYRQIKYFSFPGELLMRMLQMLVLPLIVSSLVTGMASLD
  NKATGRMGMRAAVYYMVTTIIAVFIGILMVTIIHPGKGSKEGLHREGRIETIPTADAFMD
  LIRNMFPPNLVEACFKQFKTQYSTRVVTRTMVRTENGSEPGASMPPPFSVENGTSFLENV
  TRALGTLQEMLSFEETVPVPGSANGINALGLVVFSVAFGLVIGGMKHKGRVLRDFFDSLN
  EAIMRLVGIIIWYAPVGILFLIAGKILEMEDMAVLGGQLGMYTLTVIVGLFLHAGIVLPL
  IYFLVTHRNPFPFIGGMLQALITAMGTSSSSATLPITFRCLEEGLGVDRRITRFVLPVGA
  TVNMDGTALYEALAAIFIAQVNNYELNLGQITTISITATAASVGAAGIPQAGLVTMVIVL
  TSVGLPTEDITLIIAVDWFLDRLRTMTNVLGDSIGAAVIEHLSQRELELQEAELTLPSLG
  KPYKSLMAQEKGASRGRGGNESAM
• 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 (By similarity). 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 (Probable).
• KEGG Pathway:
  Synaptic vesicle cycle (hsa04721)
  Glutamatergic synapse (hsa04724)
  Spinocerebellar ataxia (hsa05017)
• Reactome Pathway:
  Transport of inorganic cations/anions and amino acids/oligopeptides (R-HSA-425393)
  Glutamate Neurotransmitter Release Cycle (R-HSA-210500)

Molecular Interaction Atlas (MIA) of This DTT

4 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]
Threo-3-methylglutamate	DMOE3IJ	Discovery agent	N.A.	Investigative	[1]
[3H]ETB-TBOA	DMWGY61	Discovery agent	N.A.	Investigative	[4]

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Excitatory amino acid transporter 4 (SLC1A6) DTP Info
• Gene Name: SLC1A6

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	[5]

References

• [1] Pharmacological characterization of threo-3-methylglutamic acid with excitatory amino acid transporters in native and recombinant systems. J Neurochem. 2001 Apr;77(2):550-7.
• [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: 871).
• [3] Effects of threo-beta-hydroxyaspartate derivatives on excitatory amino acid transporters (EAAT4 and EAAT5). J Neurochem. 2001 Oct;79(2):297-302.
• [4] Characterization of the tritium-labeled analog of L-threo-beta-benzyloxyaspartate binding to glutamate transporters. Mol Pharmacol. 2007 Jan;71(1):294-302.
• [5] The SLC1 high-affinity glutamate and neutral amino acid transporter family. Mol Aspects Med. 2013 Apr-Jun;34(2-3):108-20.