Ionotropic Glutamate receptor 2

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

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:20614889, PubMed:31300657, PubMed:8003671). 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 (PubMed:14687553). 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:20614889, PubMed:8003671). The receptor then desensitizes rapidly and enters in a transient inactive state, characterized by the presence of bound agonist (By similarity). 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 (By similarity). 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 (By similarity).

Neurodevelopmental disorder with language impairment and behavioral abnormalities

NEDLIB

A neurodevelopmental disorder characterized by global developmental delay, impaired intellectual development, poor or absent speech, and behavioral abnormalities, such as autism spectrum disorder, repetitive behaviors, and hyperactivity. Some patients develop seizures and manifest developmental regression.

None

The disease is caused by variants affecting the gene represented in this entry. The genetic variation producing the missense variant p.Q607E, associated with NEDLIB, is predicted to deeply affect RNA editing. In a physiological context, the adenosine (A) residue of the original glutamine (Q) codon CAG is post-transcriptionaly edited to inosine (I) by ADAR2, leading to a codon recognized by the ribosome as arginine (R). The glutamate (E) codon GAG, resulting from the genetic variation, is predicted to be edited 90% less than the normal CAG codon. If edited, the codon GIG would be translated as p.Q607G.

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

Ubiquitinated by RNF167, leading to its degradation.

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

N-glycosylated.

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

• Cell membrane
• Multi-pass membrane protein
• Postsynaptic cell membrane
• Multi-pass membrane protein
• Postsynaptic density membrane
• Multi-pass membrane protein
• Interaction with CACNG2, CNIH2 and CNIH3 promotes cell surface expression (By similarity). Displays a somatodendritic localization and is excluded from axons in neurons (By similarity).

GluA2, GLUR2, GRIA2, Glutamate receptor 2, GluR-2, AMPA-selective glutamate receptor 2, GluR-B, GluR-K2

• entrezGene:2891
• entrezGene:2892
• omim:138247
• omim:305915
• swissprot:P42262
• swissprot:P42263

Proteins

Neuroscience

98821Da