Gamma-aminobutyric acid receptor subunit alpha-2
Also known as: GABRA2
Function
Alpha 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 interfaces (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 (By similarity). The alpha-2 subunit exhibits synaptogenic activity together with beta-2 and very little to no activity together with beta-3, the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation (By similarity).
Classification
- Family (Pfam)
- PF02931 Neur_chan_LBD, PF02932 Neur_chan_memb
- InterPro
- GABAA/Glycine_rcpt, GABAAa_rcpt, GABBAa2_rcpt, Gabra-1-6_TM, Gabra-2_ECD, 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 · 8
- 9CRV EM 3.18A
- 9CSB EM 3.34A
- 9CT0 EM 3.19A
- 9CTJ EM 3.74A
- 9CTV EM 3.36A
- 9CX7 EM 3.30A
- 9CXB EM 3.33A
- 9CXC EM 3.30A
A predicted model is available from AlphaFold.
Gene Ontology · 20
- GO:0030424 axon
- GO:0034707 chloride channel complex
- GO:0032590 dendrite membrane
- GO:1902711 GABA-A receptor complex
- GO:0098982 GABA-ergic synapse
- GO:0060077 inhibitory synapse
- GO:0043025 neuronal cell body
- GO:0005886 plasma membrane
- GO:0098794 postsynapse
- GO:0099634 postsynaptic specialization membrane
- GO:0030672 synaptic vesicle membrane
- GO:0008503 benzodiazepine receptor activity
- GO:0004890 GABA-A receptor activity
- GO:0022851 GABA-gated chloride ion channel activity
- GO:0099507 ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential
- GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
- GO:1902476 chloride transmembrane transport
- GO:0007214 gamma-aminobutyric acid signaling pathway
- GO:1904862 inhibitory synapse assembly
- GO:0051932 synaptic transmission, GABAergic
Disease associations
- alcohol dependence MONDO:0007079
- developmental and epileptic encephalopathy, 78 MONDO:0032812
Drugs targeting this protein · 70
- 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
- AZD6280 positive allosteric modulator
- AZD7325 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
- BROMAZEPAM positive allosteric 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 alpha-2 1.00
- Gamma-aminobutyric acid receptor subunit alpha-2 1.00
- Gamma-aminobutyric acid receptor subunit alpha-2 1.00
- Gamma-aminobutyric acid receptor subunit alpha-2 1.00
- Gamma-aminobutyric acid receptor subunit alpha-5 0.97
- Gamma-aminobutyric acid receptor subunit alpha-5 0.97
- Gamma-aminobutyric acid receptor subunit alpha-5 0.97
- Gamma-aminobutyric acid receptor subunit alpha-5 0.97
- Gamma-aminobutyric acid receptor subunit alpha-1 0.96
- Gamma-aminobutyric acid receptor subunit alpha-1 0.96
- Gamma-aminobutyric acid receptor subunit alpha-1 0.96
- Gamma-aminobutyric acid receptor subunit alpha-1 0.96
Co-cited proteins · studied together in the literature
- Gamma-aminobutyric acid receptor subunit alpha-5 1 shared papers
- Gamma-aminobutyric acid receptor subunit alpha-3 1 shared papers
- Gamma-aminobutyric acid receptor subunit gamma-1 1 shared papers
- Gamma-aminobutyric acid receptor subunit theta 1 shared papers
- Gamma-aminobutyric acid receptor subunit beta-1 1 shared papers
Literature · 8 cited papers
- Novel GABRA2 variants in epileptic encephalopathy and intellectual disability with seizures. Brain · 2019
- De novo variants in GABRA2 and GABRA5 alter receptor function and contribute to early-onset epilepsy. Brain · 2018
- A de novo GABRA2 missense mutation in severe early-onset epileptic encephalopathy with a choreiform movement disorder. Eur. J. Paediatr. Neurol. · 2018
- Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature · 2005
- Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations. Am. J. Hum. Genet. · 2004
- Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
- Theta, a novel gamma-aminobutyric acid type A receptor subunit. Proc. Natl. Acad. Sci. U.S.A. · 1999
- Cloning of cDNA sequences encoding human alpha 2 and alpha 3 gamma-aminobutyric acidA receptor subunits and characterization of the benzodiazepine pharmacology of recombinant alpha 1-, alpha 2-, alpha 3-, and alpha 5-containing human gamma-aminobutyric acidA receptors. Mol. Pharmacol. · 1993