Gamma-aminobutyric acid receptor subunit alpha-5
Also known as: GABRA5
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-5/GABRA5 subunits are mainly extrasynaptic and contribute to the tonic GABAergic inhibition in the hippocampus (By similarity). Extrasynaptic alpha-5-containing GABAARs in CA1 pyramidal neurons play a role in learning and memory processes (By similarity).
Classification
- Family (Pfam)
- PF02931 Neur_chan_LBD, PF02932 Neur_chan_memb
- InterPro
- GABAA/Glycine_rcpt, GABAAa_rcpt, GABBAa5_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
- Mixed Regulatory & Membrane Proteins
Experimental structures · PDB · 21
- 5O8F X-ray 3.20A
- 5OJM X-ray 3.30A
- 6A96 EM 3.51A
- 8BEJ EM 3.24A
- 8BGI X-ray 2.56A
- 8BHA EM 2.67A
- 8BHB EM 2.54A
- 8BHG X-ray 2.39A
- 8BHI EM 2.67A
- 8BHK EM 3.30A
- 8BHM EM 2.95A
- 8BHO EM 2.93A
- … and 9 more
A predicted model is available from AlphaFold.
Gene Ontology · 23
- GO:0034707 chloride channel complex
- GO:0032590 dendrite membrane
- GO:1902711 GABA-A receptor complex
- GO:0098982 GABA-ergic synapse
- GO:0032809 neuronal cell body membrane
- GO:0005886 plasma membrane
- GO:0098794 postsynapse
- GO:0099634 postsynaptic specialization membrane
- GO:0042734 presynaptic membrane
- GO:0050811 GABA receptor binding
- 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:0038023 signaling receptor activity
- GO:1904315 transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
- GO:1902476 chloride transmembrane transport
- GO:0090102 cochlea development
- GO:0007214 gamma-aminobutyric acid signaling pathway
- GO:1904862 inhibitory synapse assembly
- GO:0060119 inner ear receptor cell development
- GO:0060384 innervation
- GO:0007165 signal transduction
- GO:0051932 synaptic transmission, GABAergic
Disease associations
- developmental and epileptic encephalopathy, 79 MONDO:0032813
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 alpha-5 1.00
- Gamma-aminobutyric acid receptor subunit alpha-5 1.00
- Gamma-aminobutyric acid receptor subunit alpha-5 1.00
- Gamma-aminobutyric acid receptor subunit alpha-2 0.98
- Gamma-aminobutyric acid receptor subunit alpha-2 0.98
- Gamma-aminobutyric acid receptor subunit alpha-2 0.97
- Gamma-aminobutyric acid receptor subunit alpha-2 0.97
- Gamma-aminobutyric acid receptor subunit alpha-2 0.97
- Gamma-aminobutyric acid receptor subunit alpha-1 0.97
- Gamma-aminobutyric acid receptor subunit alpha-3 0.97
- Gamma-aminobutyric acid receptor subunit alpha-1 0.97
- Gamma-aminobutyric acid receptor subunit alpha-1 0.97
Co-cited proteins · studied together in the literature
- Gamma-aminobutyric acid receptor subunit alpha-2 1 shared papers
- Gamma-aminobutyric acid receptor subunit beta-3 2 shared papers
- Gamma-aminobutyric acid receptor subunit alpha-5 1 shared papers
- 2-oxoglutarate dehydrogenase complex component E1 1 shared papers
- Biorientation of chromosomes in cell division protein 1-like 1 1 shared papers
- Gamma-aminobutyric acid receptor subunit gamma-2 1 shared papers
- Sodium/hydrogen exchanger 6 1 shared papers
- Protein RIC-3 1 shared papers
- 26S proteasome regulatory subunit 4 1 shared papers
Literature · 10 cited papers
- Altered inhibitory synapses in de novo GABRA5 and GABRA1 mutations associated with early onset epileptic encephalopathies. Brain · 2019
- Cryo-EM structure of the human alpha5beta3 GABAA receptor. Cell Res. · 2018
- De novo variants in GABRA2 and GABRA5 alter receptor function and contribute to early-onset epilepsy. Brain · 2018
- Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry. Proteomics · 2007
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- Tonic inhibition in mouse hippocampal CA1 pyramidal neurons is mediated by alpha5 subunit-containing gamma-aminobutyric acid type A receptors. Proc. Natl. Acad. Sci. U.S.A. · 2004
- Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
- Human gamma-aminobutyric acid-type A receptor alpha5 subunit gene (GABRA5): characterization and structural organization of the 5' flanking region. Genomics · 1997
- FISH ordering of reference markers and of the gene for the alpha 5 subunit of the gamma-aminobutyric acid receptor (GABRA5) within the Angelman and Prader-Willi syndrome chromosomal regions. Hum. Mol. Genet. · 1993
- Cloning and expression of a cDNA encoding the human GABA-A receptor alpha 5 subunit. Biochem. Soc. Trans. · 1992