GRIA4
Domain
The M4 transmembrane segment mediates tetramerization and is required for cell surface expression.
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 (By similarity). 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 (By similarity). 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 a transient inactive state, characterized by the presence of bound agonist (By similarity). In the presence of CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of L-glutamate (PubMed:21172611).
Involvement in disease
Neurodevelopmental disorder with or without seizures and gait abnormalities
NEDSGA
An autosomal dominant neurodevelopmental disorder characterized by global developmental delay apparent from infancy or early childhood, mild to profound intellectual disability, hypertonia early in life, which progresses to spasticity and impaired gait later, and behavioral abnormalities. Some patients may develop seizures of variable severity early in life.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Palmitoylated. Depalmitoylated upon L-glutamate stimulation. Cys-611 palmitoylation leads to Golgi retention and decreased cell surface expression. In contrast, Cys-837 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis.
Phosphorylated at Ser-862 by PRKCG; phosphorylation increases plasma membrane-associated GRI4 expression.
Sequence Similarities
Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIA4 subfamily.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Postsynaptic cell membrane
- Multi-pass membrane protein
- Cell projection
- Dendrite
- Postsynaptic cell membrane
- Multi-pass membrane protein
Alternative names
GluA4, GLUR4, GRIA4, Glutamate receptor 4, GluR-4, GluR4, AMPA-selective glutamate receptor 4, GluR-D