Glutamate receptor ionotropic, NMDA 2D
Also known as: GRIN2D, GluN2D, NMDAR2D
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 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
- InterPro
- ANF_lig-bd_rcpt, Glu/Gly-bd, Iono_Glu_rcpt_met, Ionotropic_Glu_rcpt, Iontro_rcpt_C, Peripla_BP_I
- Functional cluster
- Nucleic Acid Metabolism & Repair Enzymes
Experimental structures · PDB · 13
- 7YFF EM 3.60A
- 7YFL EM 3.90A
- 7YFM EM 5.10A
- 7YFO EM 6.40A
- 7YFR EM 5.10A
- 8E96 EM 3.38A
- 8Y1V EM 4.20A
- 9D37 EM 3.34A
- 9D38 EM 3.95A
- 9D39 EM 3.65A
- 9D3A EM 3.78A
- 9D3B EM 3.71A
- … and 1 more
A predicted model is available from AlphaFold.
Gene Ontology · 29
- GO:0005789 endoplasmic reticulum membrane
- GO:0098978 glutamatergic synapse
- GO:0098686 hippocampal mossy fiber to CA3 synapse
- GO:0017146 NMDA selective glutamate receptor complex
- GO:0005886 plasma membrane
- GO:0098839 postsynaptic density membrane
- GO:0045211 postsynaptic membrane
- GO:0048787 presynaptic active zone membrane
- GO:0016595 glutamate binding
- GO:0022849 glutamate-gated calcium ion channel activity
- GO:0004970 glutamate-gated receptor activity
- GO:0099507 ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential
- GO:0004972 NMDA glutamate receptor activity
- GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
- GO:0022843 voltage-gated monoatomic cation channel activity
- GO:0007420 brain development
- GO:0097553 calcium ion transmembrane import into cytosol
- GO:1905232 cellular response to L-glutamate
- GO:0098976 excitatory chemical synaptic transmission
- GO:0060079 excitatory postsynaptic potential
- 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
Disease associations
- developmental and epileptic encephalopathy, 46 MONDO:0014947
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 2D 1.00
- Glutamate receptor ionotropic, NMDA 2D 1.00
- Glutamate receptor ionotropic, NMDA 3B 0.91
- Glutamate receptor ionotropic, NMDA 2C 0.90
- Glutamate receptor ionotropic, NMDA 3B 0.90
- Glutamate receptor ionotropic, NMDA 3B 0.90
- Glutamate receptor ionotropic, NMDA 2C 0.89
- Glutamate receptor ionotropic, NMDA 2C 0.89
- Glutamate receptor ionotropic, NMDA 3A 0.77
- Metabotropic glutamate receptor 6 0.77
- Glutamate receptor ionotropic, NMDA 3A 0.76
- Glutamate receptor ionotropic, NMDA 3A 0.76
Co-cited proteins · studied together in the literature
- Glutamate receptor ionotropic, NMDA 2C 3 shared papers
- Glutamate receptor ionotropic, NMDA 1 5 shared papers
- Glutamate receptor ionotropic, NMDA 2A 4 shared papers
- Glutamate receptor ionotropic, NMDA 2B 4 shared papers
- Glutamate receptor ionotropic, NMDA 2C 2 shared papers
- Glutamate receptor ionotropic, NMDA 3B 1 shared papers
- Glutamate receptor ionotropic, NMDA 3A 1 shared papers
Literature · 9 cited papers
- Distinct structure and gating mechanism in diverse NMDA receptors with GluN2C and GluN2D subunits. Nat. Struct. Mol. Biol. · 2023
- Functional evaluation of a de novo GRIN2A mutation identified in a patient with profound global developmental delay and refractory epilepsy. Mol. Pharmacol. · 2017
- Molecular mechanism of disease-associated mutations in the pre-M1 helix of NMDA receptors and potential rescue pharmacology. PLoS Genet. · 2017
- GRIN2D recurrent de novo dominant mutation causes a severe epileptic encephalopathy treatable with NMDA receptor channel blockers. Am. J. Hum. Genet. · 2016
- 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
- The consensus coding sequences of human breast and colorectal cancers. Science · 2006
- The DNA sequence and biology of human chromosome 19. Nature · 2004
- Functional characterization of human N-methyl-D-aspartate subtype 1A/2D receptors. J. Neurochem. · 1998