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 Mg(2+) (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). Heterotetramer. Forms heterotetrameric channels composed of two zeta subunits (GRIN1), and two epsilon subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) (in vitro) (PubMed:8768735, PubMed:26919761, PubMed:26875626, PubMed:28126851, PubMed:26912815). Can also form heterotetrameric channels that contain at least one zeta subunit (GRIN1), at least one epsilon subunit, plus GRIN3A or GRIN3B (By similarity). In vivo, the subunit composition may depend on the expression levels of the different subunits (Probable). Found in a complex with GRIN1 and GRIN3B. Found in a complex with GRIN1, GRIN3A and PPP2CB. Interacts with PDZ domains of PATJ, DLG3 and DLG4. Interacts with HIP1 and NETO1 (By similarity). Interacts with MAGI3 (PubMed:10748157). Interacts with DAPK1 (By similarity). Found in a complex with GRIN1 and PRR7 (PubMed:27458189). Interacts with PRR7 (PubMed:27458189). Interacts with CAMK2A (PubMed:28130356). Interacts with ARC; preventing ARC oligomerization (By similarity). Interacts with TMEM25 (By similarity). Co-localizes with the motor protein KIF17 along microtubules. Primarily found in the fronto-parieto-temporal cortex and hippocampus pyramidal cells, lower expression in the basal ganglia. A hydrophobic region that gives rise to the prediction of a transmembrane span does not cross the membrane, but is part of a discontinuously helical region that dips into the membrane and is probably part of the pore and of the selectivity filter. Phosphorylated on tyrosine residues (By similarity). Phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity (By similarity). The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberrations involving GRIN2B has been found in patients with intellectual disability. Translocations t(9;12)(p23;p13.1) and t(10;12)(q21.1;p13.1) with a common breakpoint in 12p13.1. Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2B/GRIN2B subfamily.