GRIN2B

This gene encodes a member of the N-methyl-D-aspartate (NMDA) receptor family within the ionotropic glutamate receptor superfamily. The encoded protein is a subunit of the NMDA receptor ion channel which acts as an agonist binding site for glutamate. The NMDA receptors mediate a slow calcium-permeable component of excitatory synaptic transmission in the central nervous system. The NMDA receptors are heterotetramers of seven genetically encoded, differentially expressed subunits including NR1 (GRIN1), NR2 (GRIN2A, GRIN2B, GRIN2C, or GRIN2D) and NR3 (GRIN3A or GRIN3B). The early expression of this gene in development suggests a role in brain development, circuit formation, synaptic plasticity, and cellular migration and differentiation. Naturally occurring mutations within this gene are associated with neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, and schizophrenia. [provided by RefSeq, Aug 2017]

Glutamate Ionotropic Receptor NMDA Type Subunit 2B

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:28126851).

Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:8768735, PubMed:26875626).

In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death. Contributes to neural pattern formation in the developing brain. Plays a role in long-term depression (LTD) of hippocampus membrane currents and in synaptic plasticity (By similarity).

Brain development Source: ARUK-UCL
Calcium ion transmembrane import into cytosol Source: UniProtKB
Chemical synaptic transmission Source: ProtInc
Excitatory chemical synaptic transmission Source: ARUK-UCL
Excitatory postsynaptic potential Source: GO_Central
Glutamate receptor signaling pathway Source: ProtInc
Learning or memory Source: ARUK-UCL
Long-term synaptic potentiation Source: GO_Central
Multicellular organism development Source: ARUK-UCL
Negative regulation of dendritic spine maintenance Source: ARUK-UCL
Positive regulation of cysteine-type endopeptidase activity Source: ARUK-UCL
Positive regulation of neuron death Source: ARUK-UCL
Protein heterotetramerization Source: UniProtKB
Regulation of synaptic plasticity Source: ARUK-UCL
Response to ethanol Source: UniProtKB

Late endosome; Cell membrane; Postsynaptic cell membrane; Cytoskeleton; Lysosome. Co-localizes with the motor protein KIF17 along microtubules.

Mental retardation, autosomal dominant 6, with or without seizures (MRD6):
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD6 additional features may include seizures, hypotonia, abnormal movements, such as dystonia, and autistic features.
Developmental and epileptic encephalopathy 27 (DEE27):
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.
A chromosomal aberrations involving GRIN2B has been found in patients with mental retardation. Translocations t(9;12)(p23;p13.1) and t(10;12)(q21.1;p13.1) with a common breakpoint in 12p13.1.

Extracellular: 27-557
Helical: 558-576
Cytoplasmic: 577-603
Discontinuously helical: 604-623
Cytoplasmic: 624-630
Helical: 631-646
Extracellular: 647-817
Helical: 818-837
Cytoplasmic: 838-1484

Phosphorylated on tyrosine residues (By similarity). Phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity (By similarity).