Gabra1
Domain
The extracellular domain contributes to synaptic contact formation.
The GABA-binding pockets are located at the interface between neighboring alpha and beta subunits.
GABAARs subunits share a common topological structure: a peptide sequence made up of a long extracellular N-terminal, four transmembrane domains, intracellular or cytoplasmic domain located between the third and the fourth transmembrane domains.
Function
Alpha subunit of the heteropentameric ligand-gated chloride channel gated by Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain. GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (PubMed:27129275). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (By similarity). Alpha-1/GABRA1-containing GABAARs are largely synaptic (By similarity). Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (By similarity). GABAARs containing alpha-1 and beta-2 or -3 subunits exhibit synaptogenic activity; the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation (PubMed:27129275). GABAARs function also as histamine receptor where histamine binds at the interface of two neighboring beta subunits and potentiates GABA response (By similarity). GABAARs containing alpha, beta and epsilon subunits also permit spontaneous chloride channel activity while preserving the structural information required for GABA-gated openings (By similarity). Alpha-1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection (PubMed:25348603). Together with rho subunits, may also control neuronal and glial GABAergic transmission in the cerebellum (PubMed:16945976, PubMed:25422464).
Post-translational modifications
Glycosylated.
Sequence Similarities
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA1 sub-subfamily.
Tissue Specificity
Expressed in the cerebellum.
Cellular localization
- Postsynaptic cell membrane
- Multi-pass membrane protein
- Cell membrane
- Multi-pass membrane protein
- Cytoplasmic vesicle membrane
- Located at the plasma membrane of astrocytes (PubMed:25422464). Located in the somatic, proximal and distal dendritic regions of cerebellar Purkinje cells and in the molecular layer (PubMed:16945976).
Alternative names
Gabra-1, Gabra1, Gamma-aminobutyric acid receptor subunit alpha-1, GABA(A) receptor subunit alpha-1, GABAAR subunit alpha-1