Gamma-aminobutyric acid receptor subunit alpha-1
Also known as: GABRA1
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 interface(s). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient. Alpha-1/GABRA1-containing GABAARs are largely synaptic (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. GABAARs function also as histamine receptor where histamine binds at the interface of two neighboring beta subunits and potentiates GABA response (By similarity). GABAARs containing alpha, beta and epsilon subunits also permit spontaneous chloride channel activity while preserving the structural information required for GABA-gated openings (By similarity). Alpha-1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection (By similarity). Together with rho subunits, may also control neuronal and glial GABAergic transmission in the cerebellum (By similarity).
Classification
- Family (Pfam)
- PF02931 Neur_chan_LBD, PF02932 Neur_chan_memb
- InterPro
- GABAA/Glycine_rcpt, GABAAa_rcpt, GABBAa1_rcpt, Gabra-1-6_TM, GABRA1_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 · 86
- 6CDU X-ray 3.45A
- 6D1S X-ray 3.20A
- 6D6T EM 3.80A
- 6D6U EM 3.80A
- 6HUG EM 3.10A
- 6HUJ EM 3.04A
- 6HUK EM 3.69A
- 6HUO EM 3.26A
- 6HUP EM 3.58A
- 6I53 EM 3.20A
- 6X3S EM 3.12A
- 6X3T EM 2.55A
- … and 74 more
A predicted model is available from AlphaFold.
Gene Ontology · 18
- GO:0034707 chloride channel complex
- GO:0030659 cytoplasmic vesicle membrane
- GO:0032590 dendrite membrane
- GO:0043197 dendritic spine
- GO:1902710 GABA receptor complex
- GO:1902711 GABA-A receptor complex
- GO:0098982 GABA-ergic synapse
- GO:0005886 plasma membrane
- GO:0098794 postsynapse
- GO:0099634 postsynaptic specialization membrane
- 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:1902476 chloride transmembrane transport
- GO:0160001 extrasynaptic signaling via GABA
- GO:0007214 gamma-aminobutyric acid signaling pathway
- GO:1904862 inhibitory synapse assembly
- GO:0051932 synaptic transmission, GABAergic
Disease associations
- epilepsy, idiopathic generalized, susceptibility to, 13 MONDO:0012627
- developmental and epileptic encephalopathy, 19 MONDO:0014328
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
- ZALEPLON 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
- INDIPLON 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
- ZOLPIDEM TARTRATE 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-1 1.00
- Gamma-aminobutyric acid receptor subunit alpha-1 1.00
- Gamma-aminobutyric acid receptor subunit alpha-1 1.00
- Gamma-aminobutyric acid receptor subunit alpha-1 1.00
- Gamma-aminobutyric acid receptor subunit alpha-1 1.00
- Gamma-aminobutyric acid receptor subunit alpha-1 1.00
- Gamma-aminobutyric acid receptor subunit alpha-3 0.98
- Gamma-aminobutyric acid receptor subunit alpha-3 0.97
- Gamma-aminobutyric acid receptor subunit alpha-3 0.97
- Gamma-aminobutyric acid receptor subunit alpha-3 0.97
- Gamma-aminobutyric acid receptor subunit alpha-5 0.97
- Gamma-aminobutyric acid receptor subunit alpha-5 0.97
Co-cited proteins · studied together in the literature
- Gamma-aminobutyric acid receptor subunit gamma-2 6 shared papers
- Gamma-aminobutyric acid receptor subunit beta-2 3 shared papers
- Gamma-aminobutyric acid receptor subunit beta-1 1 shared papers
- Syntaxin-binding protein 1 2 shared papers
- Gamma-aminobutyric acid receptor subunit beta-3 3 shared papers
- LHFPL tetraspan subfamily member 4 protein 2 shared papers
- LHFPL tetraspan subfamily member 4 protein 2 shared papers
- LHFPL tetraspan subfamily member 4 protein 1 shared papers
- Gamma-aminobutyric acid receptor subunit gamma-2 2 shared papers
- Gamma-aminobutyric acid receptor subunit beta-3 1 shared papers
- Gamma-aminobutyric acid receptor subunit alpha-2 1 shared papers
- Neuroligin-2 1 shared papers
Literature · 15 cited papers
- Cryo-EM structure of the human alpha1beta3gamma2 GABAA receptor in a lipid bilayer. Nature · 2019
- Structural basis of neurosteroid anesthetic action on GABAA receptors. Nat. Commun. · 2018
- Structure of a human synaptic GABAA receptor. Nature · 2018
- Impairment of inhibitory synapse formation and motor behavior in mice lacking the NL2 binding partner LHFPL4/GARLH4. Cell Rep. · 2018
- An essential role for the tetraspanin LHFPL4 in the cell-type-specific targeting and clustering of synaptic GABAA ceceptors. Cell Rep. · 2017
- Diagnostic targeted resequencing in 349 patients with drug-resistant pediatric epilepsies identifies causative mutations in 30 different genes. Hum. Mutat. · 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
- GABRA1 and STXBP1: novel genetic causes of Dravet syndrome. Neurology · 2014
- GABA(A) receptors can initiate the formation of functional inhibitory GABAergic synapses. Eur. J. Neurosci. · 2013
- Novel alpha1 and gamma2 GABAA receptor subunit mutations in families with idiopathic generalized epilepsy. Eur. J. Neurosci. · 2011
- A mutation in the GABA(A) receptor alpha(1)-subunit is associated with absence epilepsy. Ann. Neurol. · 2006
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- … and 3 more in the literature graph