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:1377365). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:1377365). Plays a role in regulating the balance between excitatory and inhibitory activity of pyramidal neurons in the prefrontal cortex (PubMed:27922130). Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (PubMed:8987814). Heterotetramer. Forms heterotetrameric channels composed of two zeta subunits (GRIN1), and two epsilon subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) (in vitro) (PubMed:1377365). 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). Interacts with PDZ domains of PATJ and DLG4 (By similarity). Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes (By similarity). Detected in cerebellum (at protein level) (PubMed:8987814). Detected in the granule cell layer of the cerebellum (PubMed:1377365). 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. Mutant mice appear grossly normal (PubMed:8987814). Mossy fiber granule cells from mutant mice present a decrease of the slow component of the excitatory postsynaptic current (PubMed:8987814). Pyramidal neurons in the prefrontal cortex display a reduced dendritic spine density (PubMed:27922130). Besides, the prefrontal cortex has an altered pattern of excitatory and inhibitory synapses (PubMed:27922130). Pyramidal neurons in the prefrontal cortex display a reduced frequency of miniature excitatory postsynaptic currents (mEPSC), together with an increased frequency of miniature inhibitory postsynaptic currents (mIPSC), indicative of a shift in the balance between excitatory and inhibitory membrane currents (PubMed:27922130). The slow component of the excitatory postsynaptic current is nearly abolished in mossy fiber cells from mice lacking both Grin2a and Grin2c (PubMed:8987814). Mice lacking both Grin2a and Grin2c display subtle motor deficits; they have no visible phenotype when performing simple tasks, but have decreased ability to walk across a narrow wooden bar, and are unable to stay on a rapidly rotating rod (PubMed:8987814). Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2C/GRIN2C subfamily.