Gamma-aminobutyric acid receptor subunit alpha-4
Also known as: GABRA4
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. GABAARs containing alpha-4 are predominantly extrasynaptic, contributing to tonic inhibition in dentate granule cells and thalamic relay neurons (By similarity). Extrasynaptic alpha-4-containing GABAARs control levels of excitability and network activity (By similarity). GABAAR containing alpha-4-beta-3-delta subunits 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.
Classification
- Family (Pfam)
- PF02931 Neur_chan_LBD, PF02932 Neur_chan_memb
- InterPro
- GABAA/Glycine_rcpt, GABAAa_rcpt, GABBAa4_rcpt, Gabra-1-6_TM, 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
- Cytochrome c Oxidase & Mito Import Proteins
Experimental structures · PDB · 5
A predicted model is available from AlphaFold.
Gene Ontology · 17
- GO:0034707 chloride channel complex
- GO:0032590 dendrite membrane
- GO:1902711 GABA-A receptor complex
- GO:0098982 GABA-ergic synapse
- GO:0005886 plasma membrane
- GO:0098794 postsynapse
- GO:0099634 postsynaptic specialization membrane
- GO:0008503 benzodiazepine receptor 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:1902476 chloride transmembrane transport
- GO:0160001 extrasynaptic signaling via GABA
- GO:0007214 gamma-aminobutyric acid signaling pathway
- GO:1904862 inhibitory synapse assembly
- GO:0032229 negative regulation of synaptic transmission, GABAergic
- GO:0051932 synaptic transmission, GABAergic
Drugs targeting this protein · 68
- 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
- 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-4 0.99
- Gamma-aminobutyric acid receptor subunit alpha-4 0.99
- Gamma-aminobutyric acid receptor subunit alpha-4 0.99
- Gamma-aminobutyric acid receptor subunit alpha-6 0.94
- Gamma-aminobutyric acid receptor subunit alpha-3 0.94
- Gamma-aminobutyric acid receptor subunit alpha-3 0.93
- Gamma-aminobutyric acid receptor subunit alpha-3 0.93
- Gamma-aminobutyric acid receptor subunit alpha-3 0.93
- Gamma-aminobutyric acid receptor subunit alpha-1 0.92
- Gamma-aminobutyric acid receptor subunit alpha-6 0.92
- Gamma-aminobutyric acid receptor subunit alpha-1 0.92
- Gamma-aminobutyric acid receptor subunit alpha-1 0.92
Co-cited proteins · studied together in the literature
- Gamma-aminobutyric acid receptor subunit delta 1 shared papers
- Gamma-aminobutyric acid receptor subunit beta-3 1 shared papers
Literature · 7 cited papers
- Differential assembly diversifies GABAA receptor structures and signalling. Nature · 2022
- The consensus coding sequences of human breast and colorectal cancers. Science · 2006
- Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature · 2005
- 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
- Cloning and characterization of the human GABAA receptor alpha 4 subunit: identification of a unique diazepam-insensitive binding site. Eur. J. Pharmacol. · 1995
- Mapping of the alpha 4 subunit gene (GABRA4) to human chromosome 4 defines an alpha 2-alpha 4-beta 1-gamma 1 gene cluster: further evidence that modern GABAA receptor gene clusters are derived from an ancestral cluster. Genomics · 1995