Recombinant Human Gamma-aminobutyric acid receptor subunit beta-2 (GABRB2), partial

Function

Beta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:19763268, PubMed:27789573, PubMed:29950725, PubMed:8264558). 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). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (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 beta-2 receptors contribute to the tonic GABAergic inhibition (By similarity). Beta-containing GABAARs can simultaneously bind GABA and histamine where histamine binds at the interface of two neighboring beta subunits, which may be involved in the regulation of sleep and wakefulness (By similarity)

Subcellular Location

Postsynaptic cell membrane (Multi-pass membrane protein); Cell membrane (Multi-pass membrane protein); Cytoplasmic vesicle membrane

Disease Association

Epileptic encephalopathy, infantile or early childhood, 2 (IECEE2) : A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. IECEE2 is an autosomal dominant condition with variable age at seizure onset, ranging from early infancy to 6 years. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Isoform 1 and isoform 2 show reduced expression in schizophrenic brain. Isoform 3 shows increased expression in schizophrenic and bipolar disorder brains while isoform 4 shows reduced expression

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:29950725, PubMed:8264558). Interacts with UBQLN1 (By similarity). May interact with KIF21B (By similarity). Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity)

• Hadingham K.L. et al. Role of the beta subunit in determining the pharmacology of human gamma-aminobutyric acid type A receptors. — Mol. Pharmacol. (1993)
• McKinley D.D. et al. Cloning, sequence analysis and expression of two forms of mRNA coding for the human beta 2 subunit of the GABAA receptor. — Brain Res. Mol. Brain Res. (1995)
• Zhao C. et al. Alternative-splicing in the exon-10 region of GABA(A) receptor beta(2) subunit gene: relationships between novel isoforms and psychotic disorders. — PLoS ONE (2009)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Zhao C. et al. Two isoforms of GABA(A) receptor beta2 subunit with different electrophysiological properties: Differential expression and genotypical correlations in schizophrenia. — Mol. Psychiatry (2006)
• Fuchs C. et al. GABA(A) receptors can initiate the formation of functional inhibitory GABAergic synapses. — Eur. J. Neurosci. (2013)