Glutamate receptor ionotropic, NMDA 2C
Also known as: GRIN2C, NMDAR2C
Function
Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+). Participates in synaptic plasticity for learning and memory formation by contributing to the slow phase of excitatory postsynaptic current and long-term synaptic potentiation (By similarity). Channel activation requires binding of the neurotransmitter L-glutamate to the GluN2 subunit, glycine or D-serine binding to the GluN1 subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+). NMDARs mediate simultaneously the potassium efflux and the influx of calcium and sodium (By similarity). Each GluN2 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators.
Classification
- Family (Pfam)
- PF01094 ANF_receptor, PF00060 Lig_chan, PF10613 Lig_chan-Glu_bd, PF10565 NMDAR2_C
- InterPro
- ANF_lig-bd_rcpt, Glu/Gly-bd, Iono_Glu_rcpt_met, Ionotropic_Glu_rcpt, Iontro_rcpt_C, NMDAR2_C, Peripla_BP_I
- Functional cluster
- Nucleic Acid Metabolism & Repair Enzymes
Experimental structures · PDB · 6
A predicted model is available from AlphaFold.
Gene Ontology · 23
- GO:0005789 endoplasmic reticulum membrane
- GO:0098978 glutamatergic synapse
- GO:0017146 NMDA selective glutamate receptor complex
- GO:0005886 plasma membrane
- GO:0098839 postsynaptic density membrane
- GO:0045211 postsynaptic membrane
- GO:0005261 monoatomic cation channel activity
- GO:0004972 NMDA glutamate receptor activity
- GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
- GO:0007420 brain development
- GO:0097553 calcium ion transmembrane import into cytosol
- GO:0098976 excitatory chemical synaptic transmission
- GO:0060079 excitatory postsynaptic potential
- GO:0007215 glutamate receptor signaling pathway
- GO:0035235 ionotropic glutamate receptor signaling pathway
- GO:0060291 long-term synaptic potentiation
- GO:0098655 monoatomic cation transmembrane transport
- GO:2000463 positive regulation of excitatory postsynaptic potential
- GO:0051968 positive regulation of synaptic transmission, glutamatergic
- GO:1904062 regulation of monoatomic cation transmembrane transport
- GO:0048168 regulation of neuronal synaptic plasticity
- GO:0048167 regulation of synaptic plasticity
- GO:0035249 synaptic transmission, glutamatergic
Drugs targeting this protein · 20
- FELBAMATE antagonist
- ORPHENADRINE CITRATE antagonist
- ORPHENADRINE HYDROCHLORIDE antagonist
- GW468816 antagonist
- NEBOGLAMINE positive allosteric modulator
- AMANTADINE HYDROCHLORIDE antagonist
- MEMANTINE HYDROCHLORIDE negative allosteric modulator
- KETAMINE HYDROCHLORIDE negative allosteric modulator
- ACAMPROSATE CALCIUM antagonist
- NERAMEXANE MESYLATE antagonist
- RALFINAMIDE antagonist
- DELUCEMINE antagonist
- ESKETAMINE HYDROCHLORIDE negative allosteric modulator
- RAPASTINEL partial agonist
- AV-101 antagonist
- ESKETAMINE negative allosteric modulator
- APIMOSTINEL partial agonist
- CNS-5161 blocker
- PERZINFOTEL antagonist
- LANICEMINE blocker
Related proteins · sequence + function similarity
- Glutamate receptor ionotropic, NMDA 2C 0.99
- Glutamate receptor ionotropic, NMDA 2C 0.99
- Glutamate receptor ionotropic, NMDA 2D 0.90
- Glutamate receptor ionotropic, NMDA 2D 0.89
- Glutamate receptor ionotropic, NMDA 2D 0.89
- Glutamate receptor ionotropic, NMDA 3A 0.86
- Glutamate receptor ionotropic, NMDA 3A 0.86
- Glutamate receptor ionotropic, NMDA 3A 0.85
- Glutamate receptor ionotropic, NMDA 3B 0.85
- Glutamate receptor ionotropic, NMDA 3B 0.84
- Glutamate receptor ionotropic, NMDA 3B 0.83
- Semaphorin-6B 0.70
Co-cited proteins · studied together in the literature
- Glutamate receptor ionotropic, NMDA 1 3 shared papers
- Sorting nexin-27 1 shared papers
- Glutamate receptor ionotropic, NMDA 2D 2 shared papers
- Sorting nexin-27 1 shared papers
- Glutamate receptor ionotropic, NMDA 2A 2 shared papers
- Glutamate receptor ionotropic, NMDA 2B 2 shared papers
- Glutamate receptor ionotropic, NMDA 3B 1 shared papers
- Glutamate receptor ionotropic, NMDA 3A 1 shared papers
Literature · 7 cited papers
- Structural insights into assembly and function of GluN1-2C, GluN1-2A-2C, and GluN1-2D NMDARs. Mol. Cell · 2022
- Positive Allosteric Modulators of GluN2A-Containing NMDARs with Distinct Modes of Action and Impacts on Circuit Function. Neuron · 2016
- Rare mutations in N-methyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia. Transl. Psychiatry · 2011
- Deficiency of sorting nexin 27 (SNX27) leads to growth retardation and elevated levels of N-methyl-D-aspartate receptor 2C (NR2C). Mol. Cell. Biol. · 2011
- DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature · 2006
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- Cloning of the cDNA for the human NMDA receptor NR2C subunit and its expression in the central nervous system and periphery. Brain Res. Mol. Brain Res. · 1996