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glutamate receptor 1; GluR-1; GluR-A; GluR-K1; glutamate receptor ionotropic, AMPA 1; AMPA-selective glutamate receptor 1 (GRIA1, GLUH1, GLUR1)
Function:
- ionotropic glutamate receptor
- role in hippocampal consolidation & reconsolidation of memories
- 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, & thereby converts the chemical signal to an electrical impulse
- the receptor then desensitizes rapidly & enters a transient inactive state, characterized by the presence of boundagonist
- palmitoylated, depalmitoylated upon glutamate stimulation
- Cys-603 palmitoylation leads to Golgi retention & decreased cell surface expression
- in contrast, Cys-829 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis (putative)
- interacts with DLG1 via its C-terminus
- interacts with CACNG2 & RASGRF2 (putative)
- binds AMPA (quisqualate) > glutamate > kainate
- Ser831 & S845 in the C-terminal domain involved in phosphorylation-dependent regulation of activity
- hosphorylation of S831 by CAM kinase 2 or protein kinase C is associated with long-term potentiation
- dephosphorylation* of S845 is associated with long-term depression
- S845 is phosphorylated by protein kinase A
Structure:
- homotetramer or heterotetramer of pore-forming glutamate receptor subunits
- tetramers may be formed by the dimerization of dimers
- belongs to the glutamate-gated ion channel (TC 1.A.10) family
Compartment:
- cell membrane
- endoplasmic reticulum membrane
- cell junction, synapse, postsynaptic cell membrane
- interaction with CACNG2 promotes cell surface expression (putative)
Alternative splicing: named isoforms=2
Expression:
- widely expressed in brain
- together with GluR2 comprise the majority of AMPA receptors in the hippocampus & neocortex.
Note:
- postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists
General
ionotropic receptor subunit
Properties
SIZE: entity length = 906 aa
MW = 102 kD
COMPARTMENT: endoplasmic reticulum
MOTIF: exoplasmic domain {19-536}
MOTIF: signal sequence {1-18}
N-glycosylation site {N63}
N-glycosylation site {N249}
N-glycosylation site {N257}
N-glycosylation site {N363}
N-glycosylation site {N401}
N-glycosylation site {N406}
Glutamate binding {492-494}
binding site
SITE: 499-499
FOR-BINDING-OF: Glutamate
transmembrane domain {537-557}
cytoplasmic loop {558-617}
MOTIF: cysteine residue {C603}
MODIFICATION: palmitate
COMPARTMENT: membrane
transmembrane domain {618-638}
exoplasmic loop {639-805}
MOTIF: Ser phosphorylation site {S645}
Glutamate binding {668-669}
Ser phosphorylation site {S710}
binding site
SITE: 719-719
FOR-BINDING-OF: Glutamate
transmembrane domain {806-826}
cytoplasmic domain {827-906}
MOTIF: cysteine residue {C829}
MODIFICATION: palmitate
COMPARTMENT: membrane
Ser phosphorylation site {S849}
Ser phosphorylation site {S863}
Database Correlations
OMIM 138248
UniProt P42261
PFAM correlations
Entrez Gene 2890
Kegg hsa:2890
References
- UniProt :accession P42261
- Castellani GC, Quinlan EM, Bersani F, Cooper LN, Shouval HZ.
A model of bidirectional synaptic plasticity: From signaling
network to channel conductance.
Learn Mem. 2005 Jul 18; [Epub ahead of print]
PMID: 16027175
Component-of
AMPA receptor or alpha glutamate receptor