Gamma-aminobutyric acid receptor subunit beta-3
Also known as: GABRB3
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). GABAARs containing beta-3/GABRB3 subunit are found at both synaptic and extrasynaptic sites (By similarity). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient. Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission. GABAARs containing alpha-1 and beta-3 subunits exhibit synaptogenic activity; the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation. Extrasynaptic beta-3 receptors contribute to the tonic GABAergic inhibition (By similarity). GABAARs containing alpha-1, beta-3 and epsilon subunits may also permit spontaneous chloride channel activity while preserving the structural information required for GABA-gated openings (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. Plays an important role in somatosensation and in the production of antinociception (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 · 87
- 4COF X-ray 2.97A
- 5O8F X-ray 3.20A
- 5OJM X-ray 3.30A
- 6A96 EM 3.51A
- 6HUG EM 3.10A
- 6HUJ EM 3.04A
- 6HUK EM 3.69A
- 6HUO EM 3.26A
- 6HUP EM 3.58A
- 6I53 EM 3.20A
- 6QFA EM 2.49A
- 7A5V EM 1.70A
- … and 75 more
A predicted model is available from AlphaFold.
Gene Ontology · 26
- GO:0009986 cell surface
- GO:0034707 chloride channel complex
- GO:0030659 cytoplasmic vesicle membrane
- GO:0043197 dendritic spine
- 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:0004890 GABA-A receptor activity
- GO:0022851 GABA-gated chloride ion channel activity
- GO:0042802 identical protein binding
- GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
- GO:0071420 cellular response to histamine
- GO:1902476 chloride transmembrane transport
- GO:0090102 cochlea development
- GO:0160001 extrasynaptic signaling via GABA
- GO:0007214 gamma-aminobutyric acid signaling pathway
- GO:0060080 inhibitory postsynaptic potential
- GO:1904862 inhibitory synapse assembly
- GO:0060119 inner ear receptor cell development
- GO:0060384 innervation
- GO:0032229 negative regulation of synaptic transmission, GABAergic
- GO:0060021 roof of mouth development
- GO:0007165 signal transduction
- GO:0051932 synaptic transmission, GABAergic
Disease associations
- OMIM:137192 RAW:OMIM_137192
- epilepsy, childhood absence, susceptibility to, 5 MONDO:0012843
- developmental and epileptic encephalopathy, 43 MONDO:0014921
Drugs targeting this protein · 69
- 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
- GABOXADOL agonist
- CLOMETHIAZOLE positive allosteric modulator
- ETAZOLATE 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-3 1.00
- Gamma-aminobutyric acid receptor subunit beta-3 1.00
- Gamma-aminobutyric acid receptor subunit beta-3 1.00
- Gamma-aminobutyric acid receptor subunit beta-2 0.98
- Gamma-aminobutyric acid receptor subunit beta-1 0.98
- Gamma-aminobutyric acid receptor subunit beta-1 0.98
- Gamma-aminobutyric acid receptor subunit beta-1 0.98
- Gamma-aminobutyric acid receptor subunit beta-1 0.98
- Gamma-aminobutyric acid receptor subunit beta-2 0.98
- Gamma-aminobutyric acid receptor subunit beta-2 0.97
- Gamma-aminobutyric acid receptor subunit beta-2 0.97
- Gamma-aminobutyric acid receptor subunit beta-2 0.97
Co-cited proteins · studied together in the literature
- Gamma-aminobutyric acid receptor subunit alpha-5 2 shared papers
- Gamma-aminobutyric acid receptor subunit beta-1 2 shared papers
- Gamma-aminobutyric acid receptor subunit alpha-4 1 shared papers
- Gamma-aminobutyric acid receptor subunit gamma-2 4 shared papers
- Gamma-aminobutyric acid receptor subunit alpha-5 1 shared papers
- Gamma-aminobutyric acid receptor subunit beta-3 1 shared papers
- Gamma-aminobutyric acid receptor subunit delta 2 shared papers
- Gamma-aminobutyric acid receptor subunit alpha-1 3 shared papers
- UDP-N-acetylglucosamine transferase subunit ALG13 2 shared papers
- Sodium channel protein type 1 subunit alpha 3 shared papers
- Gamma-aminobutyric acid receptor subunit beta-2 1 shared papers
- Gamma-aminobutyric acid receptor subunit beta-2 1 shared papers
Literature · 24 cited papers
- Differential assembly diversifies GABAA receptor structures and signalling. Nature · 2022
- Cryo-EM structure of the human alpha1beta3gamma2 GABAA receptor in a lipid bilayer. Nature · 2019
- Cryo-EM structure of the human alpha5beta3 GABAA receptor. Cell Res. · 2018
- A mutation in GABRB3 associated with Dravet syndrome. Am. J. Med. Genet. A · 2017
- Diagnostic targeted resequencing in 349 patients with drug-resistant pediatric epilepsies identifies causative mutations in 30 different genes. Hum. Mutat. · 2017
- De novo mutations in SLC1A2 and CACNA1A are important causes of epileptic encephalopathies. Am. J. Hum. Genet. · 2016
- Improving diagnosis and broadening the phenotypes in early-onset seizure and severe developmental delay disorders through gene panel analysis. J. Med. Genet. · 2016
- Epileptic encephalopathy de novo GABRB mutations impair GABAA receptor function. Ann. Neurol. · 2016
- Inhibitory synapse formation in a co-culture model incorporating GABAergic medium spiny neurons and HEK293 cells stably expressing GABAA receptors. J. Vis. Exp. · 2014
- De novo mutations in moderate or severe intellectual disability. PLoS Genet. · 2014
- Crystal structure of a human GABAA receptor. Nature · 2014
- De novo mutations in epileptic encephalopathies. Nature · 2013
- … and 12 more in the literature graph