GRIN2A

This gene encodes a member of the glutamate-gated ion channel protein family. The encoded protein is an N-methyl-D-aspartate (NMDA) receptor subunit. NMDA receptors are both ligand-gated and voltage-dependent, and are involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. These receptors are permeable to calcium ions, and activation results in a calcium influx into post-synaptic cells, which results in the activation of several signaling cascades. Disruption of this gene is associated with focal epilepsy and speech disorder with or without cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

Glutamate Ionotropic Receptor NMDA Type Subunit 2A

Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg2+ (PubMed:8768735, PubMed:26919761, PubMed:26875626, PubMed:28105280).

Sensitivity to glutamate and channel kinetics depend on the subunit composition; channels containing GRIN1 and GRIN2A have lower sensitivity to glutamate and faster deactivation kinetics than channels formed by GRIN1 and GRIN2B (PubMed:26919761, PubMed:26875626).

Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (By similarity).

Activation of cysteine-type endopeptidase activity Source: ARUK-UCL
Brain development Source: ARUK-UCL
Calcium ion transmembrane import into cytosol Source: UniProtKB
Chemical synaptic transmission Source: ProtInc
Directional locomotion Source: Ensembl
Dopamine metabolic process Source: Ensembl
Excitatory chemical synaptic transmission Source: ARUK-UCL
Excitatory postsynaptic potential Source: GO_Central
Glutamate receptor signaling pathway Source: ProtInc
Learning or memory Source: ProtInc
Long-term synaptic potentiation Source: GO_Central
Memory Source: Ensembl
Negative regulation of protein catabolic process Source: Ensembl
Neurogenesis Source: Ensembl
Positive regulation of apoptotic process Source: Ensembl
Protein localization to postsynaptic membrane Source: Ensembl
Regulation of synaptic plasticity Source: ARUK-UCL
Response to amphetamine Source: Ensembl
Response to drug Source: Ensembl
Response to ethanol Source: UniProtKB
Response to wounding Source: Ensembl
Sensory perception of pain Source: Ensembl
Serotonin metabolic process Source: Ensembl
Sleep Source: Ensembl
Startle response Source: Ensembl
Visual learning Source: Ensembl

Cell membrane; Postsynaptic cell membrane; Dendritic spine; Synapse; Cytoplasmic vesicle membrane. Expression at the dendrite cell membrane and at synapses is regulated by SORCS2 and the retromer complex.

Epilepsy, focal, with speech disorder and with or without mental retardation (FESD):
A highly variable neurologic disorder with features ranging from severe early-onset seizures associated with delayed psychomotor development, persistent speech difficulties, and mental retardation to a more benign entity characterized by childhood onset of mild or asymptomatic seizures associated with transient speech difficulties followed by remission of seizures in adolescence and normal psychomotor development. The disorder encompasses several clinical entities, including Landau-Kleffner syndrome, epileptic encephalopathy with continuous spike and wave during slow-wave sleep, autosomal dominant rolandic epilepsy, mental retardation and speech dyspraxia, and benign epilepsy with centrotemporal spikes.
A chromosomal aberration involving GRIN2A has been found in a family with epilepsy and neurodevelopmental defects. Translocation t(16;17)(p13.2;q11.2).
GRIN2A somatic mutations have been frequently found in cutaneous malignant melanoma, suggesting that the glutamate signaling pathway may play a role in the pathogenesis of melanoma.

Extracellular: 23-555
Helical: 556-576
Cytoplasmic: 577-600
Discontinuously helical: 601-620
Cytoplasmic: 621-625
Helical: 626-645
Extracellular: 646-816
Helical: 817-837
Cytoplasmic: 838-1464