Glutamate receptor 1
Also known as: GLUA1, GLUH1, GLUR1, GRIA1
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. 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 CACNG2 or CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of L-glutamate. Resensitization is blocked by CNIH2 through interaction with CACNG8 in the CACNG8-containing AMPA receptors complex. Calcium (Ca(2+)) permeability depends on subunits composition and, heteromeric channels containing edited GRIA2 subunit are calcium-impermeable. Also permeable to other divalents cations such as strontium(2+) and magnesium(2+) and monovalent cations such as potassium(1+) and lithium(1+) (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 · 1
- 6X5Q X-ray 2.14A
A predicted model is available from AlphaFold.
Gene Ontology · 92
- GO:0032281 AMPA glutamate receptor complex
- GO:0044308 axonal spine
- GO:0009986 cell surface
- GO:0005911 cell-cell junction
- GO:0005829 cytosol
- GO:0030425 dendrite
- GO:0043198 dendritic shaft
- GO:0043197 dendritic spine
- GO:0032591 dendritic spine membrane
- GO:0031901 early endosome membrane
- GO:0030666 endocytic vesicle membrane
- GO:0005789 endoplasmic reticulum membrane
- GO:0033116 endoplasmic reticulum-Golgi intermediate compartment membrane
- GO:0012507 ER to Golgi transport vesicle membrane
- GO:0060076 excitatory synapse
- GO:0009897 external side of plasma membrane
- GO:0098978 glutamatergic synapse
- GO:0031594 neuromuscular junction
- GO:0044309 neuron spine
- GO:0043025 neuronal cell body
- GO:0032809 neuronal cell body membrane
- GO:0099544 perisynaptic space
- GO:0005886 plasma membrane
- GO:0014069 postsynaptic density
- GO:0098839 postsynaptic density membrane
- GO:0099092 postsynaptic density, intracellular component
- GO:0045211 postsynaptic membrane
- GO:0098793 presynapse
- GO:0048787 presynaptic active zone membrane
- GO:1990635 proximal dendrite
- GO:0055037 recycling endosome
- GO:0055038 recycling endosome membrane
- GO:0098685 Schaffer collateral - CA1 synapse
- GO:0097060 synaptic membrane
- GO:0030672 synaptic vesicle membrane
- GO:0008179 adenylate cyclase binding
- GO:0004971 AMPA glutamate receptor activity
- GO:0001540 amyloid-beta binding
- GO:0031698 beta-2 adrenergic receptor binding
- GO:0001965 G-protein alpha-subunit binding
- GO:0031681 G-protein beta-subunit binding
- GO:0035254 glutamate receptor binding
- GO:0022849 glutamate-gated calcium ion channel activity
- GO:0042802 identical protein binding
- GO:0019865 immunoglobulin binding
- GO:0099507 ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential
- GO:0031489 myosin V binding
- GO:0030165 PDZ domain binding
- GO:0051428 peptide hormone receptor binding
- GO:0051018 protein kinase A binding
- GO:0019901 protein kinase binding
- GO:0097110 scaffold protein binding
- GO:0031267 small GTPase binding
- GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
- GO:0048266 behavioral response to pain
- GO:0071418 cellular response to amine stimulus
- GO:1990416 cellular response to brain-derived neurotrophic factor stimulus
- GO:0071359 cellular response to dsRNA
- GO:1905430 cellular response to glycine
- GO:1905232 cellular response to L-glutamate
- GO:0071375 cellular response to peptide hormone stimulus
- GO:0021987 cerebral cortex development
- GO:0007268 chemical synaptic transmission
- GO:1990708 conditioned place preference
- GO:0035235 ionotropic glutamate receptor signaling pathway
- GO:0007616 long-term memory
- GO:0060291 long-term synaptic potentiation
- GO:0050804 modulation of chemical synaptic transmission
- GO:0019228 neuronal action potential
- GO:2000463 positive regulation of excitatory postsynaptic potential
- GO:0010628 positive regulation of gene expression
- GO:0090326 positive regulation of locomotion involved in locomotory behavior
- GO:0045838 positive regulation of membrane potential
- GO:0031623 receptor internalization
- GO:0034765 regulation of monoatomic ion transmembrane transport
- GO:0001919 regulation of receptor recycling
- GO:0046685 response to arsenic-containing substance
- GO:0042220 response to cocaine
- GO:0051602 response to electrical stimulus
- GO:0032355 response to estradiol
- GO:0045471 response to ethanol
- GO:0060992 response to fungicide
- GO:0010226 response to lithium ion
- GO:0043278 response to morphine
- GO:0031667 response to nutrient levels
- GO:1990911 response to psychosocial stress
- GO:0009744 response to sucrose
- GO:0009410 response to xenobiotic stimulus
- GO:0007165 signal transduction
- GO:0021510 spinal cord development
- GO:0007416 synapse assembly
- 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 1 1.00
- Glutamate receptor 1 1.00
- Glutamate receptor 1 1.00
- Glutamate receptor 4 0.98
- Glutamate receptor 4 0.98
- Glutamate receptor 4 0.98
- Glutamate receptor 3 0.98
- Glutamate receptor 4 0.98
- Glutamate receptor 3 0.98
- Glutamate receptor 3 0.98
- Glutamate receptor 3 0.98
- Glutamate receptor 2 0.98
Co-cited proteins · studied together in the literature
- Glutamate receptor 2 1 shared papers
- Palmitoyl thioesterase CPT1C 1 shared papers
- Palmitoyl thioesterase CPT1C 1 shared papers
- Protein cornichon homolog 2 2 shared papers
- Glutamate receptor 4 1 shared papers
- Voltage-dependent calcium channel gamma-8 subunit 2 shared papers
- Protein cornichon homolog 2 1 shared papers
- Protein cornichon homolog 2 1 shared papers
- Protein cornichon homolog 3 1 shared papers
- Voltage-dependent calcium channel gamma-2 subunit 1 shared papers
- Voltage-dependent calcium channel gamma-4 subunit 1 shared papers
- Voltage-dependent calcium channel gamma-8 subunit 1 shared papers
Literature · 13 cited papers
- Identification and functional evaluation of GRIA1 missense and truncation variants in individuals with ID: An emerging neurodevelopmental syndrome. Am. J. Hum. Genet. · 2022
- Mechanisms of CPT1C-Dependent AMPAR Trafficking Enhancement. Front. Mol. Neurosci. · 2018
- Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains. Nat. Neurosci. · 2017
- A eukaryotic specific transmembrane segment is required for tetramerization in AMPA receptors. J. Neurosci. · 2013
- Diagnostic exome sequencing in persons with severe intellectual disability. N. Engl. J. Med. · 2012
- Hippocampal AMPA receptor gating controlled by both TARP and cornichon proteins. Neuron · 2010
- Functional comparison of the effects of TARPs and cornichons on AMPA receptor trafficking and gating. Proc. Natl. Acad. Sci. U.S.A. · 2010
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- The DNA sequence and comparative analysis of human chromosome 5. Nature · 2004
- Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
- Molecular cloning and chromosomal localization of one of the human glutamate receptor genes. Proc. Natl. Acad. Sci. U.S.A. · 1991
- The human glutamate receptor cDNA GluR1: cloning, sequencing, expression and localization to chromosome 5. DNA Seq. · 1992
- … and 1 more in the literature graph