SLC1A2

This gene encodes a member of a family of solute transporter proteins. The membrane-bound protein is the principal transporter that clears the excitatory neurotransmitter glutamate from the extracellular space at synapses in the central nervous system. Glutamate clearance is necessary for proper synaptic activation and to prevent neuronal damage from excessive activation of glutamate receptors. Mutations in and decreased expression of this protein are associated with amyotrophic lateral sclerosis. Alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq]

Full Name

solute carrier family 1 (glial high affinity glutamate transporter), member 2

Function

Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:7521911, PubMed:14506254, PubMed:15265858, PubMed:26690923).
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 (PubMed:14506254).
Mediates Cl- flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na+ symport (PubMed:14506254).
Essential for the rapid removal of released glutamate from the synaptic cleft, and for terminating the postsynaptic action of glutamate (By similarity).

Biological Process

Biological Process adult behaviorIEA:Ensembl
Biological Process cellular response to cocaineIEA:Ensembl
Biological Process cellular response to extracellular stimulusIEA:Ensembl
Biological Process chemical synaptic transmissionManual Assertion Based On ExperimentTAS:ProtInc
Biological Process D-aspartate import across plasma membraneManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process glutathione biosynthetic processIEA:Ensembl
Biological Process ion transportTAS:Reactome
Biological Process L-aspartate import across plasma membraneManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process L-aspartate transmembrane transportISS:ARUK-UCL
Biological Process L-glutamate import across plasma membraneManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process L-glutamate transmembrane transportManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process multicellular organism agingIEA:Ensembl
Biological Process multicellular organism growthIEA:Ensembl
Biological Process neurotransmitter reuptakeIEA:Ensembl
Biological Process neurotransmitter transportTAS:Reactome
Biological Process positive regulation of glucose importIEA:Ensembl
Biological Process protein homotrimerizationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process response to amino acidIEA:Ensembl
Biological Process response to woundingIEA:Ensembl
Biological Process response to xenobiotic stimulusIEA:Ensembl
Biological Process telencephalon developmentIEA:Ensembl
Biological Process transepithelial transportISS:ARUK-UCL
Biological Process transport across blood-brain barrierISS:ARUK-UCL
Biological Process visual behaviorIEA:Ensembl

Cellular Location

Cell membrane

Involvement in disease

Developmental and epileptic encephalopathy 41 (DEE41):
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE41 inheritance is autosomal dominant.

Topology

Cytoplasmic: 1-44
Helical: 45-64
Extracellular: 65-87
Helical: 88-108
Cytoplasmic: 109-120
Helical: 121-142
Extracellular: 143-235
Helical: 236-259
Cytoplasmic: 260-268
Helical: 269-296
Extracellular: 297-317
Helical: 318-339
Cytoplasmic: 340-344
Helical: 345-375
Extracellular: 376-384
Helical: 385-411
Cytoplasmic: 412-424
Helical: 425-458
Extracellular: 459-471
Helical: 472-493
Cytoplasmic: 494-574

PTM

Glycosylated.
Palmitoylation at Cys-38 is not required for correct subcellular localization, but is important for glutamate uptake activity.