Glutamate receptor 2
Also known as: GLUR2, GRIA2, GluA2
Function
Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system and plays an important role in fast excitatory synaptic transmission. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse upon entry of monovalent and divalent cations such as sodium and calcium. The receptor then desensitizes rapidly and enters in a transient inactive state, characterized by the presence of bound agonist (By similarity). In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of L-glutamate (By similarity). Through complex formation with NSG1, GRIP1 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (By similarity).
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
- Secreted Hydrolases & Toxins
Experimental structures · PDB · 16
- 2WJW X-ray 1.80A
- 2WJX X-ray 4.10A
- 2XHD X-ray 1.80A
- 3R7X X-ray 2.10A
- 3RN8 X-ray 1.70A
- 3RNN X-ray 1.75A
- 3UA8 X-ray 1.90A
- 5H8S X-ray 1.70A
- 5YBF X-ray 1.50A
- 5YBG X-ray 1.52A
- 5ZG0 X-ray 1.58A
- 5ZG1 X-ray 1.32A
- … and 4 more
A predicted model is available from AlphaFold.
Gene Ontology · 23
- GO:0032281 AMPA glutamate receptor complex
- GO:0032279 asymmetric synapse
- GO:0030425 dendrite
- GO:0043197 dendritic spine
- GO:0030666 endocytic vesicle membrane
- GO:0060076 excitatory synapse
- GO:0009897 external side of plasma membrane
- GO:0043025 neuronal cell body
- GO:0005886 plasma membrane
- GO:0098794 postsynapse
- GO:0014069 postsynaptic density
- GO:0098839 postsynaptic density membrane
- GO:0098843 postsynaptic endocytic zone
- GO:0045211 postsynaptic membrane
- GO:0098685 Schaffer collateral - CA1 synapse
- GO:0004971 AMPA glutamate receptor activity
- GO:0001540 amyloid-beta binding
- GO:0004970 glutamate-gated receptor activity
- GO:0099094 ligand-gated monoatomic cation channel activity
- GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
- GO:0035235 ionotropic glutamate receptor signaling pathway
- GO:0050804 modulation of chemical synaptic transmission
- GO:0035249 synaptic transmission, glutamatergic
Disease associations
Drugs targeting this protein · 13
- ZONAMPANEL antagonist
- PERAMPANEL antagonist
- FARAMPATOR positive allosteric modulator
- MIBAMPATOR positive allosteric modulator
- DASOLAMPANEL antagonist
- TOPIRAMATE antagonist
- IRAMPANEL antagonist
- SELURAMPANEL antagonist
- BECAMPANEL antagonist
- TEZAMPANEL antagonist
- OSAVAMPATOR positive allosteric modulator
- PESAMPATOR positive allosteric modulator
- TALAMPANEL antagonist
Related proteins · sequence + function similarity
- Glutamate receptor 2 1.00
- Glutamate receptor 2 1.00
- Glutamate receptor 2 1.00
- Glutamate receptor 2 1.00
- Glutamate receptor 3 0.98
- Glutamate receptor 3 0.98
- Glutamate receptor 4 0.98
- Glutamate receptor 3 0.98
- Glutamate receptor 3 0.98
- Glutamate receptor 1 0.98
- Glutamate receptor 1 0.98
- Glutamate receptor 4 0.98
Co-cited proteins · studied together in the literature
- Glutamate receptor 1 1 shared papers
- E3 ubiquitin-protein ligase RNF167 1 shared papers
- Glutamate receptor ionotropic, kainate 2 1 shared papers
- PRKCA-binding protein 1 shared papers
- Glutamate receptor 2 1 shared papers
- Protein kinase C alpha type 1 shared papers
- Glutamate receptor 2 1 shared papers
Literature · 12 cited papers
- AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders. Nat. Commun. · 2019
- A eukaryotic specific transmembrane segment is required for tetramerization in AMPA receptors. J. Neurosci. · 2013
- Ubiquitin ligase RNF167 regulates AMPA receptor-mediated synaptic transmission. Proc. Natl. Acad. Sci. U.S.A. · 2012
- Quinazolinedione sulfonamides: a novel class of competitive AMPA receptor antagonists with oral activity. Bioorg. Med. Chem. Lett. · 2011
- Discovery of N-[(2S)-5-(6-fluoro-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfonamide, a novel clinical AMPA receptor positive modulator. J. Med. Chem. · 2010
- Crystal structure of the GluR2 amino-terminal domain provides insights into the architecture and assembly of ionotropic glutamate receptors. J. Mol. Biol. · 2009
- Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature · 2005
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- The PDZ domain of PICK1 differentially accepts protein kinase C-alpha and GluR2 as interacting ligands. J. Biol. Chem. · 2004
- Glutamatergic plasticity by synaptic delivery of GluR-B(long)-containing AMPA receptors. Neuron · 2003
- Primary structure and functional expression of the AMPA/kainate receptor subunit 2 from human brain. NeuroReport · 1994
- RNA editing of the glutamate receptor subunits GluR2 and GluR6 in human brain tissue. J. Neurochem. · 1994