Grin2B Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Protein Name | Glutamate [NMDA] Receptor Subunit 2B |
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| Gene | GRIN2B |
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| UniProt ID | Q8VHX6 |
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| PDB ID | 3APF, 3O4F, 5EWJ |
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| Molecular Weight | 180.3 kDa |
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| Subcellular Localization | Postsynaptic membrane |
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| Protein Family | Ionotropic glutamate receptor family |
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The NMDAR subunit 2B (NR2B) is a ~180 kDa transmembrane protein forming ionotropic glutamate receptors:
- Extracellular domain: Ligand-binding domain (LBD) for glutamate and glycine
- Transmembrane domain: Four helices (M1-M4), forming the channel pore
- C-terminal domain: Intracellular, involved in trafficking and signaling interactions
- Assembly: Forms heterotetrameric receptors with GRIN1 subunits
Key features:
- High conductance calcium channel
- Voltage-dependent Mg²⁺ block
- Multiple phosphorylation sites
NR2B-containing NMDA receptors are critical for synaptic plasticity and excitatory neurotransmission:
Channel properties:
- Requires glutamate + glycine co-activation
- Voltage-dependent Mg²⁺ block at resting membrane potential
- Highly permeable to Ca²⁺ and Na⁺
Physiological roles:
- Synaptic plasticity: LTP and LTD induction
- Learning and memory: Critical for hippocampal-dependent learning
- Neuronal development: Dendritic spine formation
- Gene transcription: Ca²⁺ influx activates signaling cascades
Distribution:
- Forebrain (hippocampus, cortex)
- Expressed during development, declines with age
- NMDAR function is altered in AD
- Excitotoxicity contributes to neuronal death
- NR2B-containing receptors may be particularly vulnerable
- Synaptic NR2B loss correlates with cognitive decline
- NMDAR dysregulation in dopaminergic pathways
- Contributes to L-DOPA-induced dyskinesias
- NR2B antagonists may have therapeutic potential
¶ Stroke and Ischemia
- Excessive NMDAR activation causes excitotoxic cell death
- NR2B-selective antagonists are neuroprotective in ischemia
¶ Intellectual Disability and Autism
- GRIN2B mutations cause ID and autism spectrum disorders
- Gain-of-function and loss-of-function variants identified
- Ketamine: Non-selective NMDAR antagonist (rapid antidepressant)
- Memantine: Low-affinity NMDAR antagonist (approved for AD)
- Ifenprodil: NR2B-selective antagonist
- Glycine site agonists
- Allosteric modulators
- NR2B antagonists have been tested in clinical trials for AD, PD, stroke
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Liu L, et al. (2007). "Role of NMDA receptor subtypes in the pathogenesis of Alzheimer's disease." Neuropharmacology. 53(6):783-791.
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Loftis JM, et al. (2003). "N-methyl-D-aspartate receptor subunit NR2B: molecular features and therapeutic implications." Pharmacol Rev. 55(1):103-123.
3.Cull-Candy SG, et al. (2001). "NMDA receptor subunits: diversity, development and disease." Curr Opin Neurobiol. 11(3):327-335.
The study of Grin2B Protein 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.
- Neurodegenerative Disease Research - Comprehensive reviews on disease mechanisms
- Alzheimer's Association - Disease information and current research
- NIH National Institute on Aging - Research updates and clinical trials
GRIN2B encodes the GluN2B subunit of the NMDA receptor, a critical ionotropic glutamate receptor involved in synaptic plasticity, learning, and memory. Dysfunction is implicated in neurodegenerative diseases.