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FUNCTION Gamma subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:14993607, PubMed:16412217, PubMed:23909897, PubMed:2538761, PubMed:25489750, PubMed:27864268, PubMed:29950725, PubMed:30602789). 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:29950725, PubMed:30602789). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:14993607, PubMed:16412217, PubMed:2538761, PubMed:27864268, PubMed:29950725, PubMed:30602789). Gamma-2/GABRG2-containing GABAARs are found at both synaptic and extrasynaptic sites (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:23909897, PubMed:25489750). Extrasynaptic gamma-2-containing receptors contribute to the tonic GABAergic inhibition (By similarity). GABAARs function also as histamine receptor where histamine binds at the interface of two neighboring beta subunits and potentiates GABA response in a gamma-2 subunit-controlled manner (By similarity).CATALYTIC ACTIVITY chloride(in) = chloride(out)ACTIVITY REGULATION Allosterically activated by benzodiazepines (PubMed:16412217, PubMed:2538761, PubMed:29950725). Activated by pentobarbital (PubMed:16412217). Potentiated by etomidate, propofol, pregnanolone (PubMed:16412217). Inhibited by the antagonist bicuculline (PubMed:29950725). Inhibited by zinc ions (PubMed:27864268). Potentiated by histamine (By similarity).SUBUNIT Heteropentamer, formed by a combination of alpha (GABRA1-6), beta (GABRB1-3), gamma (GABRG1-3), delta (GABRD), epsilon (GABRE), rho (GABRR1-3), pi (GABRP) and theta (GABRQ) chains, each subunit exhibiting distinct physiological and pharmacological properties (PubMed:14993607, PubMed:2538761, PubMed:29950725, PubMed:30602789). Interacts with GABARAP (PubMed:9892355). Interacts with KIF21B (By similarity). Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity). Interacts with LHFPL4 (By similarity). Interacts with SHISA7; interaction leads to the regulation of GABA(A) receptor trafficking, channel deactivation kinetics and pharmacology (By similarity).INTERACTION The extracellular domain contributes to synaptic contact formation.DOMAIN 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.PTM Palmitoylated by ZDHHC3/GODZ; required for the accumulation of GABA(A) receptors at the postsynaptic membrane of inhibitory GABAergic synapses.DISEASE The gene represented in this entry is involved in disease pathogenesis.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRG2 sub-subfamily.ONLINE INFORMATION Forbidden fruit - Issue 56 of March 2005
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