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Glutamate transporter subfamily C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).


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Glutamate transporters present the unusual structural motif of 8TM segments and 2 re-entrant loops [25]. The crystal structure of a glutamate transporter homologue (GltPh) from Pyrococcus horikoshii supports this topology and indicates that the transporter assembles as a trimer, where each monomer is a functional unit capable of substrate permeation [6,40,54] reviewed by [28]). This structural data is in agreement with the proposed quaternary structure for EAAT2 [21] and several functional studies that propose the monomer is the functional unit [23,31,34,45]. Recent evidence suggests that EAAT3 and EAAT4 may assemble as heterotrimers [39]. The activity of glutamate transporters located upon both neurones (predominantly EAAT3, 4 and 5) and glia (predominantly EAAT 1 and 2) serves, dependent upon their location, to regulate excitatory neurotransmission, maintain low ambient extracellular concentrations of glutamate (protecting against excitotoxicity) and provide glutamate for metabolism including the glutamate-glutamine cycle. The Na+/K+-ATPase that maintains the ion gradients that drive transport has been demonstrated to co-assemble with EAAT1 and EAAT2 [42]. Recent evidence supports altered glutamate transport and novel roles in brain for splice variants of EAAT1 and EAAT2 [20,35]. Three patients with dicarboxylic aminoaciduria (DA) were recently found to have loss-of-function mutations in EAAT3 [5]. DA is characterized by excessive excretion of the acidic amino acids glutamate and aspartate and EAAT3 is the predominant glutamate/aspartate transporter in the kidney. Enhanced expression of EAAT2 resulting from administration of β-lactam antibacterials (e.g. ceftriaxone) is neuroprotective and occurs through NF-κB-mediated EAAT2 promoter activation [19,36,43] reviewed by [30]). PPARγ activation (e.g. by rosiglitazone) also leads to enhanced expression of EAAT though promoter activation [41]. In addition, several translational activators of EAAT2 have recently been described [8] along with treatments that increase the surface expression of EAAT2 (e.g. [33,58]), or prevent its down-regulation (e.g. [22]). A thermodynamically uncoupled Cl- flux, activated by Na+ and glutamate [24,29,38] (Na+ and aspartate in the case of GltPh [44]), is sufficiently large, in the instances of EAAT4 and EAAT5, to influence neuronal excitability [50,53]. Indeed, it has recently been suggested that the primary function of EAAT5 is as a slow anion channel gated by glutamate, rather than a glutamate transporter [18].


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EAAT1 (Excitatory amino acid transporter 1 / SLC1A3) C Show summary »

EAAT2 (Excitatory amino acid transporter 2 / SLC1A2) C Show summary »

EAAT3 (Excitatory amino acid transporter 3 / SLC1A1) C Show summary »

EAAT4 (Excitatory amino acid transporter 4 / SLC1A6) C Show summary »

EAAT5 (Excitatory amino acid transporter 5 / SLC1A7) C Show summary »

Target Id 872
Nomenclature Excitatory amino acid transporter 5
Systematic nomenclature SLC1A7
Common abbreviation EAAT5
Previous and unofficial names EAAT5 | excitatory amino acid transporter 5 | solute carrier family 1 (glutamate transporter), member 7 | solute carrier family 1 (glutamate transporter)
Genes SLC1A7 (Hs), Slc1a7 (Mm), Slc1a7 (Rn)
Ensembl ID ENSG00000162383 (Hs), ENSMUSG00000008932 (Mm), ENSRNOG00000011644 (Rn)
UniProtKB AC O00341 (Hs), Q8JZR4 (Mm)
Bioparadigms SLC Tables SLC1A7 (Hs)
Endogenous substrates
L-glutamic acid
L-aspartic acid
L-trans-2,4-pyrolidine dicarboxylate
D-aspartic acid
DL-TBOA pKi 5.5 [46]
Labelled ligands
[3H]ETB-TBOA (Binding) pKd 7.6 [48] - Rat
[3H]L-aspartic acid
[3H]D-aspartic acid
Stoichiometry Probably 3 Na+: 1 H+ : 1 glutamate (in): 1 K+ (out)


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How to cite this family page

Database page citation (select format):

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Transporters. Br J Pharmacol. 180 Suppl 2:S374-469.