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Gria2

Developmental stage

Detected at low levels in newborns. Levels increase strongly and are highest in hippocampus from 8 to 14 day old animals. Detected at intermediate levels at day 42 (at protein level).

Domain

The M4 transmembrane segment mediates tetramerization and is required for cell surface expression.

Function

Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid (PubMed:12015593, PubMed:12730367, PubMed:15591246, PubMed:2166337, PubMed:21846932, PubMed:9351977). L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system and plays an important role in fast excitatory synaptic transmission (By similarity). Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse upon entry of monovalent and divalent cations such as sodium and calcium (PubMed:11773314, PubMed:12501192, PubMed:12730367, PubMed:12872125, PubMed:16483599, PubMed:1653450, PubMed:17018279, PubMed:19946266). The receptor then desensitizes rapidly and enters in a transient inactive state, characterized by the presence of bound agonist (PubMed:12015593, PubMed:16192394, PubMed:17018279, PubMed:19946266). In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of L-glutamate (PubMed:21172611). Through complex formation with NSG1, GRIP1 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (PubMed:16037816).

Post-translational modifications

Palmitoylated (By similarity). Depalmitoylated upon L-glutamate stimulation (By similarity). Cys-610 palmitoylation leads to Golgi retention and decreased cell surface expression (By similarity). In contrast, Cys-836 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis (By similarity).

Phosphorylation at Tyr-876 is required for interaction with IQSEC1 and ARF6 activation, which in turn triggers AMPAR internalization for persistent synaptic depression.

Ubiquitinated by RNF167, leading to its degradation.

N-glycosylated.

Sequence Similarities

Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIA2 subfamily.

Tissue Specificity

Detected in forebrain (PubMed:14687553). Detected in dendrites of neuronal cells (PubMed:9697855). Expressed in the pyramidal cell layers of CA1 and CA3 and in the granule cell layer of the dentate gyrus (PubMed:12657670).

Cellular localization

Alternative names

GluA2, Glur2, Gria2, Glutamate receptor 2, GluR-2, AMPA-selective glutamate receptor 2, GluR-B, GluR-K2

swissprot:P19491 entrezGene:29627