extracellular domain of gamma-aminobutyric acid receptor subunit alpha-1 (GABAAR-A1 or GABRA1)
This family contains extracellular domain of gamma-aminobutyric acid receptor subunit alpha-1 (GABAAR-A1), a protein that is encoded by the GABRA1 gene in humans. GABAAR is an anionic channel, mediating fast inhibitory synaptic transmission. Upon gamma-aminobutyric acid (GABA) binding to the ligand binding site on the ECD, Cl- ions are selectively conducted through the GABAAR pore, resulting in hyperpolarization of the neuron. GABAAR is the principal mediator of rapid inhibitory synaptic transmission in the human brain. A decline in GABAAR signaling triggers hyperactive neurological disorders such as insomnia, anxiety, and epilepsy. The alpha-1 subunits form heteropentamers with other GABAAR subunits, most broadly expressed as combination of two alpha1, beta1, gamma. Alpha1, beta2, and gamma2 subunits are clustered on the same human chromosome and may be why alpha1beta2gamma2 receptors are one of the most abundant GABAA receptor isoforms in CNS neurons. Mutations in this gene cause familial juvenile myoclonic epilepsy, sporadic childhood absence epilepsy type 4, and idiopathic familial generalized epilepsy. Polymorphisms in GABRA1 are also significantly associated with schizophrenia. GABRA1 has also been associated with methamphetamine abuse. The GABRA1 receptor is the specific target of the z-drug class of nonbenzodiazepine hypnotic agents and is responsible for their hypnotic and hallucinogenic effects.
Jiyao W et al.(2023). "The conserved domain database in 2023.",