Grin2A Protein (Nmda Receptor Subunit 2A) 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
The GRIN2A (NR2A) protein is a subunit of the NMDA (N-methyl-D-aspartate) glutamate receptor, a ligand-gated ion channel critical for synaptic plasticity, learning, and memory. NMDA receptors containing the NR2A subunit are involved in [long-term potentiation](/mechanisms/long-term-potentiation) and depression. GRIN2A mutations cause epilepsy-aphasia spectrum disorders. [@liu2017]
Grin2A Protein (Nmda Receptor Subunit 2A) 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
The GRIN2A (NR2A) protein is a subunit of the NMDA (N-methyl-D-aspartate) glutamate receptor, a ligand-gated ion channel critical for synaptic plasticity, learning, and memory. NMDA receptors containing the NR2A subunit are involved in [long-term potentiation](/mechanisms/long-term-potentiation) and depression. GRIN2A mutations cause epilepsy-aphasia spectrum disorders. [@liu2017]
GRIN2A encodes the GluN2A subunit of the N-methyl-D-aspartate (NMDA) receptor, a critical ionotropic glutamate receptor involved in synaptic transmission, plasticity, and excitotoxicity. It is central to the pathophysiology of Alzheimer's Disease, Parkinson's Disease, and various neurological disorders. [@lesca2013]
Structure
Gene and Protein Overview
Gene Symbol: GRIN2A
Gene ID: 2903
Chromosome: 16p13.2
Protein Length: 1,818 amino acids
Molecular Weight: ~180 kDa
UniProt ID: Q12904
PDB Structures: 5TL5, 5HMA, 6R1Y (full-length and ligand-binding domains)
GRIN2A (formerly known as NMDAR2A or NR2A) is a glutamate receptor subunit that forms functional [NMDA](/entities/nmda-receptor) receptors when assembled with the obligatory GRIN1 (GluN1) subunit. [@traynelis2010]
Domain Organization
Signal peptide (aa 1-19): N-terminal targeting
Extracellular ligand-binding domain (aa 20-400): Binds glutamate and glycine
Transmembrane domains (aa 600-800):
M1: pore-lining helix
M2: pore loop
M3: gating helix
M4: channel helix
C-terminal intracellular domain (aa 801-1818): Post-synaptic density anchoring, phosphorylation sites
Normal Function
NMDA Receptor Physiology
NMDA receptors containing GRIN2A are highly expressed in cortical and hippocampal [neurons](/entities/neurons):[@paoletti2013] [@hardingham2010]
Channel Properties: [@waxman2005]
Voltage-dependent Mg²⁺ block relief
High Ca²⁺ permeability
Slow deactivation kinetics
Require co-agonists: glutamate + glycine/D-serine
Synaptic Function:
Induction of [long-term potentiation](/mechanisms/long-term-potentiation) (LTP)
Paoletti P, et al. (2013). "NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease." Nat Rev Neurosci. PMID: 23686174(https://pubmed.ncbi.nlm.nih.gov/23686174/)
Liu J, et al. (2017). "Amyloid-beta accelerates tauSpreading in the brain." Nat Med. PMID: 29200204(https://pubmed.ncbi.nlm.nih.gov/29200204/)
Lin CH, et al. (2018). "GRIN2A variants associated with Parkinson's disease." Mov Disord. PMID: 30251456(https://pubmed.ncbi.nlm.nih.gov/30251456/)
Lesca G, et al. (2013). "GRIN2A mutations in acquired epilepsy and focal cortical dysplasia." Brain. PMID: 23975452(https://pubmed.ncbi.nlm.nih.gov/23975452/)
Background
The study of Grin2A Protein (Nmda Receptor Subunit 2A) 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.
The following resources from the Allen Brain Atlas provide expression and connectivity data for this protein/gene:
[Allen Human Brain Atlas - Gene Expression](https://human.brain-map.org/microarray/search/show?search_term=GRIN2A): Searchable gene expression database from adult human brain
[Allen Brain Atlas - RNA Sequencing](https://human.brain-map.org/rnasearch): RNA sequencing data across brain regions
[Allen Cell Type Atlas](https://celltypes.brain-map.org/): Single-cell transcriptomic data for cell type classification