Gamma-aminobutyric acid receptor subunit beta-2
Also known as: GABRB2
Function
Beta 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). 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. 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).
Classification
- Family (Pfam)
- PF02931 Neur_chan_LBD, PF02932 Neur_chan_memb
- InterPro
- GABAA/Glycine_rcpt, GABAAb_rcpt, Neur_chan_lig-bd, Neur_chan_lig-bd_sf, Neur_channel, Neuro-gated_channel_TM_sf, Neuro_actylchol_rec, Neurotrans-gated_channel_TM, Neurotransmitter_ion_chnl_CS
- Functional cluster
- Mixed Regulatory & Membrane Proteins
Experimental structures · PDB · 31
- 6D6T EM 3.80A
- 6D6U EM 3.80A
- 6X3S EM 3.12A
- 6X3T EM 2.55A
- 6X3U EM 3.49A
- 6X3V EM 3.50A
- 6X3W EM 3.30A
- 6X3X EM 2.92A
- 6X3Z EM 3.23A
- 6X40 EM 2.86A
- 7T0W EM 3.00A
- 7T0Z EM 3.00A
- … and 19 more
A predicted model is available from AlphaFold.
Gene Ontology · 24
- GO:0034707 chloride channel complex
- GO:0030659 cytoplasmic vesicle membrane
- GO:0043197 dendritic spine
- GO:0070062 extracellular exosome
- GO:1902711 GABA-A receptor complex
- GO:0098982 GABA-ergic synapse
- GO:0005886 plasma membrane
- GO:0045211 postsynaptic membrane
- GO:0099634 postsynaptic specialization membrane
- GO:0005254 chloride channel activity
- GO:0004890 GABA-A receptor activity
- GO:0022851 GABA-gated chloride ion channel activity
- GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
- GO:0071420 cellular response to histamine
- GO:0007268 chemical synaptic transmission
- GO:1902476 chloride transmembrane transport
- GO:0090102 cochlea development
- GO:0160001 extrasynaptic signaling via GABA
- GO:0007214 gamma-aminobutyric acid signaling pathway
- GO:1904862 inhibitory synapse assembly
- GO:0060119 inner ear receptor cell development
- GO:0060384 innervation
- GO:0032229 negative regulation of synaptic transmission, GABAergic
- GO:0051932 synaptic transmission, GABAergic
Disease associations
- developmental and epileptic encephalopathy 92 MONDO:0020631
Drugs targeting this protein · 67
- GLUTETHIMIDE positive modulator
- DIAZEPAM positive allosteric modulator
- MIDAZOLAM HYDROCHLORIDE positive allosteric modulator
- QUAZEPAM positive allosteric modulator
- SEVOFLURANE positive allosteric modulator
- CHLORDIAZEPOXIDE HYDROCHLORIDE positive allosteric modulator
- DESFLURANE positive allosteric modulator
- TRICLOFOS SODIUM positive modulator
- METHYPRYLON positive allosteric modulator
- TALBUTAL positive allosteric modulator
- SECOBARBITAL SODIUM positive allosteric modulator
- BUTABARBITAL SODIUM positive allosteric modulator
- THIAMYLAL SODIUM positive allosteric modulator
- ISOFLURANE positive allosteric modulator
- ENFLURANE positive modulator
- FLUNITRAZEPAM positive allosteric modulator
- METHOXYFLURANE positive modulator
- ZOPICLONE positive allosteric modulator
- ESZOPICLONE positive allosteric modulator
- GANAXOLONE positive allosteric modulator
- CLOTIAZEPAM positive allosteric modulator
- ACAMPROSATE CALCIUM positive modulator
- BREXANOLONE positive allosteric modulator
- CLORAZEPATE DIPOTASSIUM positive allosteric modulator
- ADIPIPLON partial agonist
- PAGOCLONE positive allosteric modulator
- TETRAZEPAM positive allosteric modulator
- ETIFOXINE antagonist
- METHAQUALONE HYDROCHLORIDE positive allosteric modulator
- RESEQUINIL inverse agonist
- TOPIRAMATE positive modulator
- METHAQUALONE positive allosteric modulator
- ESTAZOLAM positive allosteric modulator
- METHOHEXITAL SODIUM positive allosteric modulator
- CLOMETHIAZOLE positive allosteric modulator
- DARIGABAT agonist
- FLURAZEPAM HYDROCHLORIDE positive allosteric modulator
- CENOBAMATE positive allosteric modulator
- FLUMAZENIL allosteric antagonist
- CIPEPOFOL agonist
- ZURANOLONE positive allosteric modulator
- ABP-700 agonist
- PADSEVONIL partial agonist
- LOREDIPLON positive allosteric modulator
- PENTOBARBITAL positive allosteric modulator
- METHARBITAL positive allosteric modulator
- CHLORDIAZEPOXIDE positive allosteric modulator
- CLONAZEPAM positive allosteric modulator
- BUTALBITAL positive allosteric modulator
- REMIMAZOLAM BESYLATE positive allosteric modulator
- PROPOFOL positive allosteric modulator
- OXAZEPAM positive allosteric modulator
- LORAZEPAM positive allosteric modulator
- ETHCHLORVYNOL positive modulator
- TRIAZOLAM positive allosteric modulator
- MIDAZOLAM positive allosteric modulator
- ALPRAZOLAM positive allosteric modulator
- ETOMIDATE positive modulator
- CLOBAZAM positive allosteric modulator
- THIOPENTAL SODIUM positive allosteric modulator
- PRIMIDONE positive allosteric modulator
- HALOTHANE positive allosteric modulator
- TEMAZEPAM positive allosteric modulator
- PRAZEPAM positive allosteric modulator
- HALAZEPAM positive allosteric modulator
- PENTOBARBITAL SODIUM positive allosteric modulator
- MEPROBAMATE agonist
Related proteins · sequence + function similarity
- Gamma-aminobutyric acid receptor subunit beta-2 1.00
- Gamma-aminobutyric acid receptor subunit beta-2 0.99
- Gamma-aminobutyric acid receptor subunit beta-2 0.99
- Gamma-aminobutyric acid receptor subunit beta-3 0.97
- Gamma-aminobutyric acid receptor subunit beta-3 0.97
- Gamma-aminobutyric acid receptor subunit beta-3 0.97
- Gamma-aminobutyric acid receptor subunit beta-3 0.97
- Gamma-aminobutyric acid receptor subunit beta-1 0.97
- Gamma-aminobutyric acid receptor subunit beta-1 0.97
- Gamma-aminobutyric acid receptor subunit beta-1 0.96
- Gamma-aminobutyric acid receptor subunit beta-1 0.96
- Gamma-aminobutyric acid receptor subunit beta-4 0.92
Co-cited proteins · studied together in the literature
- Gamma-aminobutyric acid receptor subunit beta-2 1 shared papers
- Gamma-aminobutyric acid receptor subunit gamma-2 3 shared papers
- Gamma-aminobutyric acid receptor subunit alpha-1 3 shared papers
- Gamma-aminobutyric acid receptor subunit beta-2 1 shared papers
- Gamma-aminobutyric acid receptor subunit beta-3 1 shared papers
- BDNF/NT-3 growth factors receptor 1 shared papers
- Dehydrodolichyl diphosphate synthase complex subunit DHDDS 1 shared papers
- Dehydrodolichyl diphosphate synthase complex subunit NUS1 1 shared papers
- Gamma-aminobutyric acid type B receptor subunit 2 1 shared papers
- Clathrin heavy chain 1 1 shared papers
Literature · 12 cited papers
- Structure of a human synaptic GABAA receptor. Nature · 2018
- High rate of recurrent de novo mutations in developmental and epileptic encephalopathies. Am. J. Hum. Genet. · 2017
- A de novo missense mutation of GABRB2 causes early myoclonic encephalopathy. J. Med. Genet. · 2017
- Inhibitory synapse formation in a co-culture model incorporating GABAergic medium spiny neurons and HEK293 cells stably expressing GABAA receptors. J. Vis. Exp. · 2014
- A novel variant in GABRB2 associated with intellectual disability and epilepsy. Am. J. Med. Genet. A · 2014
- GABA(A) receptors can initiate the formation of functional inhibitory GABAergic synapses. Eur. J. Neurosci. · 2013
- 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
- Two isoforms of GABA(A) receptor beta2 subunit with different electrophysiological properties: Differential expression and genotypical correlations in schizophrenia. Mol. Psychiatry · 2006
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
- Role of the beta subunit in determining the pharmacology of human gamma-aminobutyric acid type A receptors. Mol. Pharmacol. · 1993
- 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