Gamma-aminobutyric acid receptor subunit delta
Also known as: GABRD
Function
Delta 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 delta/GABRD subunits are predominantly located in extrasynaptic or perisynaptic positions on hippocampus and cerebellar granule cells, and contribute to the tonic GABAergic inhibition (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, GABAAd_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
- Cytochrome P450 & Heme Enzymes
Experimental structures · PDB · 7
A predicted model is available from AlphaFold.
Gene Ontology · 17
- GO:0030424 axon
- GO:0034707 chloride channel complex
- GO:0030425 dendrite
- GO:1902711 GABA-A receptor complex
- GO:0098982 GABA-ergic synapse
- GO:0098978 glutamatergic synapse
- GO:0043025 neuronal cell body
- GO:0005886 plasma membrane
- GO:0045211 postsynaptic membrane
- GO:0005254 chloride channel activity
- GO:0004890 GABA-A receptor 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:0007165 signal transduction
- GO:0051932 synaptic transmission, GABAergic
Disease associations
- epilepsy, idiopathic generalized, susceptibility to, 10 MONDO:0013103
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
- 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 delta 0.98
- Gamma-aminobutyric acid receptor subunit delta 0.98
- Gamma-aminobutyric acid receptor subunit pi 0.89
- Gamma-aminobutyric acid receptor subunit pi 0.88
- Gamma-aminobutyric acid receptor subunit pi 0.88
- Gamma-aminobutyric acid receptor subunit pi 0.87
- Glycine receptor subunit alpha-4 0.86
- Glutamate-gated chloride channel subunit beta 0.86
- Glycine receptor subunit alphaZ1 0.85
- Glycine receptor subunit alpha-1 0.85
- Glycine receptor subunit alpha-1 0.85
- Glycine receptor subunit alpha-3 0.84
Co-cited proteins · studied together in the literature
- Gamma-aminobutyric acid receptor subunit alpha-4 1 shared papers
- Kinectin 1 shared papers
- Zinc finger protein ZIC 5 1 shared papers
- Gamma-aminobutyric acid receptor subunit beta-3 2 shared papers
- SKI family transcriptional corepressor 1 1 shared papers
- Colorectal mutant cancer protein 1 shared papers
- Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 1 shared papers
- DNA repair protein RAD51 homolog 4 1 shared papers
- Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 1 shared papers
- Pyridoxine-5'-phosphate oxidase 1 shared papers
- Ras/Rap GTPase-activating protein SynGAP 1 shared papers
- Protocadherin-19 1 shared papers
Literature · 6 cited papers
- Differential assembly diversifies GABAA receptor structures and signalling. Nature · 2022
- MAGI2 mutations cause congenital nephrotic syndrome. J. Am. Soc. Nephrol. · 2017
- Diagnostic targeted resequencing in 349 patients with drug-resistant pediatric epilepsies identifies causative mutations in 30 different genes. Hum. Mutat. · 2017
- The DNA sequence and biological annotation of human chromosome 1. Nature · 2006
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies. Hum. Mol. Genet. · 2004