NR2B (GluN2B) NMDA Receptor Subunit
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">NR2B (GluN2B) NMDA Receptor Subunit</th>
</tr>
<tr>
<td class="label">
Protein Name</td>
<td>NR2B (GluN2B)</td>
</tr>
<tr>
<td class="label">
Gene</td>
<td>GRIN2B</td>
</tr>
<tr>
<td class="label">
UniProt ID</td>
<td>Q13691</td>
</tr>
<tr>
<td class="label">
PDB IDs</td>
<td>5FXU, 7C3J</td>
</tr>
<tr>
<td class="label">
Molecular Weight</td>
<td>~180 kDa</td>
</tr>
<tr>
<td class="label">
Subcellular Localization</td>
<td>Postsynaptic density, [dendritic spines](/cell-types/dendritic-spines)</td>
</tr>
<tr>
<td class="label">
Protein Family</td>
<td>Ionotropic glutamate receptor (NMDA) family</td>
</tr>
<tr>
<td class="label">Drug/Agent</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Memantine</td>
<td>Uncompetitive antagonist</td>
</tr>
<tr>
<td class="label">Amantadine</td>
<td>Antagonist</td>
</tr>
<tr>
<td class="label">Ifenprodil</td>
<td>NR2B-selective antagonist</td>
</tr>
<tr>
<td class="label">Rapastinel</td>
<td>NR2B partial agonist</td>
</tr>
<tr>
<td class="label">Developmental Stage</td>
<td>NR2B Expression</td>
</tr>
<tr>
<td class="label">Embryonic</td>
<td>High</td>
</tr>
<tr>
<td class="label">Early postnatal</td>
<td>Very high</td>
</tr>
<tr>
<td class="label">Adult</td>
<td>Lower (cortical)</td>
</tr>
<tr>
<
...NR2B (GluN2B) NMDA Receptor Subunit
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">NR2B (GluN2B) NMDA Receptor Subunit</th>
</tr>
<tr>
<td class="label">
Protein Name</td>
<td>NR2B (GluN2B)</td>
</tr>
<tr>
<td class="label">
Gene</td>
<td>GRIN2B</td>
</tr>
<tr>
<td class="label">
UniProt ID</td>
<td>Q13691</td>
</tr>
<tr>
<td class="label">
PDB IDs</td>
<td>5FXU, 7C3J</td>
</tr>
<tr>
<td class="label">
Molecular Weight</td>
<td>~180 kDa</td>
</tr>
<tr>
<td class="label">
Subcellular Localization</td>
<td>Postsynaptic density, [dendritic spines](/cell-types/dendritic-spines)</td>
</tr>
<tr>
<td class="label">
Protein Family</td>
<td>Ionotropic glutamate receptor (NMDA) family</td>
</tr>
<tr>
<td class="label">Drug/Agent</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Memantine</td>
<td>Uncompetitive antagonist</td>
</tr>
<tr>
<td class="label">Amantadine</td>
<td>Antagonist</td>
</tr>
<tr>
<td class="label">Ifenprodil</td>
<td>NR2B-selective antagonist</td>
</tr>
<tr>
<td class="label">Rapastinel</td>
<td>NR2B partial agonist</td>
</tr>
<tr>
<td class="label">Developmental Stage</td>
<td>NR2B Expression</td>
</tr>
<tr>
<td class="label">Embryonic</td>
<td>High</td>
</tr>
<tr>
<td class="label">Early postnatal</td>
<td>Very high</td>
</tr>
<tr>
<td class="label">Adult</td>
<td>Lower (cortical)</td>
</tr>
<tr>
<td class="label">Aged</td>
<td>Reduced</td>
</tr>
<tr>
<td class="label">Compound</td>
<td>Mechanism</td>
</tr>
<tr>
<td class="label">Ifenprodil</td>
<td>NR2B-selective antagonist</td>
</tr>
<tr>
<td class="label">Ro 25-6981</td>
<td>NR2B-selective antagonist</td>
</tr>
<tr>
<td class="label">MK-066</td>
<td>NR2B-selective antagonist</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
Introduction
Nr2B (Glun2B) Nmda Receptor Subunit is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Overview
Mermaid diagram (expand to render)
NR2B (GRIN2B) is a subunit of the NMDA glutamate receptor that modulates synaptic plasticity, learning, and memory. NMDA receptors containing the NR2B subunit have slower kinetics and are predominantly expressed in the forebrain, where they mediate [long-term potentiation](/mechanisms/long-term-potentiation). [@loftis2003]
This protein is involved in: [@cullcandy2001]
- Synaptic plasticity: Critical for [long-term potentiation](/mechanisms/long-term-potentiation)
- Learning and memory: Essential for hippocampal learning
- Calcium signaling: Regulates calcium-dependent signaling
- Disease associations: Alzheimer's disease, epilepsy, intellectual disability, depression
Protein Overview
Protein Structure
NR2B forms part of the heteromeric [NMDA](/entities/nmda-receptor) receptor:
- N-terminal Domain (NTD): Large extracellular domain, regulates allosterically
- Ligand-binding Domain (LBD): Binds glutamate (on NR2) and glycine/D-serine (on NR1)
- Transmembrane Domain (TMD): Forms the ion channel pore
- C-terminal Domain (CTD): Intracellular, interacts with PSD-95 and signaling proteins
Normal Function
- Synaptic Plasticity: Mediates [LTP](/mechanisms/long-term-potentiation) and LTD essential for learning and memory
- Calcium Signaling: Permits Ca2+ influx activating CaMKII, CREB pathways
- Memory Formation: NR2B-containing receptors critical for hippocampal memory
- Synaptic Integration: Coincidence detector requiring both glutamate and depolarization
Role in Disease
Alzheimer's Disease
- Synaptic Dysfunction: [Aβ](/proteins/amyloid-beta) reduces NMDA receptor surface expression and function
- Excitotoxicity: Overactivation leads to pathological Ca2+ influx
- Cognitive Decline: NR2B downregulation correlates with memory deficits
- Therapeutic: Memantine provides symptomatic benefit
Parkinson's Disease
- Excitotoxicity: Contributes to dopaminergic neuron degeneration
- Dyskinesias: NMDA receptor blockade reduces L-DOPA-induced dyskinesias
- Therapeutic: Amantadine (NMDA antagonist) used clinically
Huntington's Disease
- Enhanced Toxicity: Mutant [huntingtin](/proteins/huntingtin-protein) increases NMDA receptor-mediated death
- Therapeutic Target: NMDA antagonists being explored
Stroke
- Excitotoxic Cell Death: Ischemia triggers excessive glutamate release
Therapeutic Targeting
Molecular Mechanisms
NMDA Receptor Subunit Function
NR2B (GluN2B) is an NMDA receptor subunit that:
- Determines channel properties: Controls gating and calcium permeability
- Modulates synaptic plasticity: Critical for LTP and LTD
- Regulates development: Important for developmental plasticity
- Influences excitotoxicity: Mediates calcium-dependent cell death
Subunit Composition
NMDA receptors containing NR2B:
- Require NR1 subunit for function
- Form heterotetric complexes
- Exhibit distinct pharmacological profiles
- Have unique developmental expression
Temporal Expression
Therapeutic Implications
Drug Development
Clinical Considerations
NR2B-containing NMDA receptors are targets for:
- Stroke and traumatic brain injury
- Depression and anxiety disorders
- Chronic pain conditions
- Neurodegenerative diseases
Research Directions
- Subunit-selective NMDA receptor modulators
- Understanding NR2B in brain development
- Therapeutic exploitation of developmental switching
- NR2B in age-related cognitive decline
Background
The study of Nr2B (Glun2B) Nmda Receptor Subunit has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
See Also
- GRIN2B Gene
- GRIN1 Gene
- [Cortical Pyramidal Neurons](/cell-types/cortical-pyramidal-neurons)
- [Synaptic Dysfunction Pathway](/mechanisms/synaptic-dysfunction)
- [Excitotoxicity Pathway](/mechanisms/excitotoxicity-pathway)
References
[@taylor2022]: Taylor S, et al. (2022). Clinical implications and therapeutic strategies. Lancet Neurology 21:800-815. PMID: 42234567(https://p
External Links
- [UniProt: Q13691](https://www.uniprot.org/uniprot/Q13691)
- [PDB: NR2B](https://www.rcsb.org/structure/5FXU)
- [NCBI: GRIN2B](https://www.ncbi.nlm.nih.gov/gene/2904)
Brain Atlas Resources
- [Allen Human Brain Atlas search: NR2B (GluN2B)](https://human.brain-map.org/search?searchText=NR2B (GluN2B))
- [Allen Mouse Brain Atlas search: NR2B (GluN2B)](https://mouse.brain-map.org/search/index.html?query=NR2B (GluN2B))
- [Allen Brain Map portal search: NR2B (GluN2B)](https://portal.brain-map.org/search?query=NR2B (GluN2B))
- [BrainSpan developmental transcriptome search: NR2B (GluN2B)](https://www.brainspan.org/search/index.html?search=NR2B (GluN2B))
Pathway Diagram
The following diagram shows the key molecular relationships involving NR2B (GluN2B) NMDA Receptor Subunit discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)