Glutamate receptor ionotropic, NMDA 2B
Also known as: GRIN2B, NMDAR2B
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 long-term depression (LTD) of hippocampus membrane currents (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. 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 (By similarity).
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
- DNA-Directed RNA Polymerase Subunits
Experimental structures · PDB · 27
- 5EWJ X-ray 2.77A
- 5EWL X-ray 2.98A
- 5EWM X-ray 2.76A
- 7EU8 EM 4.07A
- 7KL0 X-ray 2.40A
- 7KL1 X-ray 2.40A
- 7KL2 X-ray 2.56A
- 7UIS X-ray 2.58A
- 7UJP X-ray 2.56A
- 7UJQ X-ray 2.25A
- 7UJR X-ray 1.95A
- 7UJS X-ray 2.75A
- … and 15 more
A predicted model is available from AlphaFold.
Gene Ontology · 44
- GO:0009986 cell surface
- GO:0097542 ciliary tip
- GO:0035869 ciliary transition zone
- GO:0005929 cilium
- GO:0005737 cytoplasm
- GO:0005856 cytoskeleton
- GO:0030425 dendrite
- GO:0005789 endoplasmic reticulum membrane
- GO:0005770 late endosome
- GO:0005764 lysosome
- GO:0043005 neuron projection
- GO:0017146 NMDA selective glutamate receptor complex
- GO:0005886 plasma membrane
- GO:0014069 postsynaptic density
- GO:0098839 postsynaptic density membrane
- GO:0045211 postsynaptic membrane
- GO:0097060 synaptic membrane
- GO:0001540 amyloid-beta binding
- GO:0016595 glutamate binding
- GO:0022849 glutamate-gated calcium ion channel activity
- GO:0016594 glycine binding
- 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:0008270 zinc ion binding
- GO:0007420 brain development
- GO:0097553 calcium ion transmembrane import into cytosol
- GO:0007268 chemical synaptic transmission
- 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:0007611 learning or memory
- GO:0060291 long-term synaptic potentiation
- GO:0098655 monoatomic cation transmembrane transport
- GO:1902951 negative regulation of dendritic spine maintenance
- GO:2000463 positive regulation of excitatory postsynaptic potential
- GO:0051968 positive regulation of synaptic transmission, glutamatergic
- GO:0051290 protein heterotetramerization
- GO:1904062 regulation of monoatomic cation transmembrane transport
- GO:0048168 regulation of neuronal synaptic plasticity
- GO:0048167 regulation of synaptic plasticity
- GO:0045471 response to ethanol
- GO:0035249 synaptic transmission, glutamatergic
Disease associations
- intellectual disability, autosomal dominant 6 MONDO:0013509
- developmental and epileptic encephalopathy, 27 MONDO:0014505
Drugs targeting this protein · 24
- 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
- TRAXOPRODIL antagonist
- RADIPRODIL antagonist
- ACAMPROSATE CALCIUM antagonist
- RISLENEMDAZ antagonist
- NERAMEXANE MESYLATE antagonist
- RALFINAMIDE antagonist
- DELUCEMINE antagonist
- ESKETAMINE HYDROCHLORIDE negative allosteric modulator
- RAPASTINEL partial agonist
- EVT-101 antagonist
- 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 2B 1.00
- Glutamate receptor ionotropic, NMDA 2B 1.00
- Glutamate receptor ionotropic, NMDA 2B 1.00
- Glutamate receptor ionotropic, NMDA 2B 0.99
- Glutamate receptor ionotropic, NMDA 2A 0.94
- Glutamate receptor ionotropic, NMDA 2A 0.93
- Glutamate receptor ionotropic, NMDA 2A 0.93
- Glutamate receptor ionotropic, NMDA 2A 0.93
- Glutamate receptor ionotropic, NMDA 2A 0.93
- Glutamate [NMDA] receptor subunit 1 0.85
- Glutamate [NMDA] receptor subunit 1 0.85
- Glutamate [NMDA] receptor subunit 1 0.85
Co-cited proteins · studied together in the literature
- Glutamate receptor ionotropic, NMDA 2A 10 shared papers
- Glutamate receptor ionotropic, NMDA 1 8 shared papers
- Glutamate receptor ionotropic, NMDA 2D 4 shared papers
- Phosphoenolpyruvate carboxykinase, cytosolic [GTP] 1 shared papers
- Retinoic acid-induced protein 1 1 shared papers
- Glutamate receptor ionotropic, NMDA 2C 2 shared papers
- Glutamate receptor ionotropic, NMDA 2C 2 shared papers
- Phosphoenolpyruvate carboxykinase, cytosolic [GTP] 1 shared papers
- Myelin transcription factor 1-like protein 1 shared papers
- Glutamate receptor ionotropic, NMDA 1 1 shared papers
- Leucine-rich repeat-containing protein 7 1 shared papers
- Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 3 1 shared papers
Literature · 24 cited papers
- De novo GRIN variants in M3 helix associated with neurological disorders control channel gating of NMDA receptor. Cell. Mol. Life Sci. · 2024
- Structural basis of ketamine action on human NMDA receptors. Nature · 2021
- Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and Causes ASD-Related Behaviors. J. Neurosci. · 2017
- 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
- Diagnostic targeted resequencing in 349 patients with drug-resistant pediatric epilepsies identifies causative mutations in 30 different genes. Hum. Mutat. · 2017
- Mechanistic insight into NMDA receptor dysregulation by rare variants in the GluN2A and GluN2B agonist binding domains. Am. J. Hum. Genet. · 2016
- Synaptonuclear messenger PRR7 inhibits c-Jun ubiquitination and regulates NMDA-mediated excitotoxicity. EMBO J. · 2016
- Discovery of GluN2A-Selective NMDA Receptor Positive Allosteric Modulators (PAMs): Tuning Deactivation Kinetics via Structure-Based Design. J. Med. Chem. · 2016
- A Novel Binding Mode Reveals Two Distinct Classes of NMDA Receptor GluN2B-selective Antagonists. Mol. Pharmacol. · 2016
- Positive Allosteric Modulators of GluN2A-Containing NMDARs with Distinct Modes of Action and Impacts on Circuit Function. Neuron · 2016
- De novo mutations in moderate or severe intellectual disability. PLoS Genet. · 2014
- … and 12 more in the literature graph