Gamma-aminobutyric acid receptor subunit gamma-2
Also known as: GABRG2
Function
Gamma 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. Gamma-2/GABRG2-containing GABAARs are found at both synaptic and extrasynaptic sites (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. Extrasynaptic gamma-2-containing receptors contribute to the tonic GABAergic inhibition (By similarity). GABAARs function also as histamine receptor where histamine binds at the interface of two neighboring beta subunits and potentiates GABA response in a gamma-2 subunit-controlled manner (By similarity).
Classification
- Family (Pfam)
- PF02931 Neur_chan_LBD, PF02932 Neur_chan_memb
- InterPro
- GABAA/Glycine_rcpt, GABBAg2_rcpt, GABRG-1/4, 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
- RNA Polymerase & tRNA Deacylases
Experimental structures · PDB · 75
- 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
- 6X3U EM 3.49A
- 6X3V EM 3.50A
- … and 63 more
A predicted model is available from AlphaFold.
Gene Ontology · 23
- GO:0030424 axon
- GO:0034707 chloride channel complex
- GO:0030659 cytoplasmic vesicle membrane
- GO:0032590 dendrite membrane
- GO:0043197 dendritic spine
- GO:1902711 GABA-A receptor complex
- GO:0098982 GABA-ergic synapse
- GO:0005886 plasma membrane
- GO:0098794 postsynapse
- GO:0045211 postsynaptic membrane
- GO:0099634 postsynaptic specialization membrane
- GO:0008503 benzodiazepine receptor activity
- GO:0005254 chloride channel 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:0071420 cellular response to histamine
- 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
Disease associations
- febrile seizures, familial, 8 MONDO:0011891
- developmental and epileptic encephalopathy, 74 MONDO:0032725
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
- 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
- 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 gamma-2 1.00
- Gamma-aminobutyric acid receptor subunit gamma-2 1.00
- Gamma-aminobutyric acid receptor subunit gamma-2 1.00
- Gamma-aminobutyric acid receptor subunit gamma-2 1.00
- Gamma-aminobutyric acid receptor subunit gamma-2 1.00
- Gamma-aminobutyric acid receptor subunit gamma-1 0.98
- Gamma-aminobutyric acid receptor subunit gamma-1 0.98
- Gamma-aminobutyric acid receptor subunit gamma-1 0.98
- Gamma-aminobutyric acid receptor subunit gamma-3 0.94
- Gamma-aminobutyric acid receptor subunit gamma-3 0.94
- Gamma-aminobutyric acid receptor subunit gamma-4 0.92
- Gamma-aminobutyric acid receptor subunit gamma-3 0.90
Co-cited proteins · studied together in the literature
- Gamma-aminobutyric acid receptor subunit alpha-1 6 shared papers
- Gamma-aminobutyric acid receptor subunit beta-2 3 shared papers
- Gamma-aminobutyric acid receptor subunit alpha-5 1 shared papers
- Gamma-aminobutyric acid receptor subunit beta-3 4 shared papers
- Gamma-aminobutyric acid receptor subunit epsilon 1 shared papers
- Gamma-aminobutyric acid receptor-associated protein 1 shared papers
- Gamma-aminobutyric acid receptor subunit alpha-5 1 shared papers
- Gamma-aminobutyric acid receptor subunit theta 1 shared papers
- Gamma-aminobutyric acid receptor subunit alpha-3 1 shared papers
- Gamma-aminobutyric acid receptor subunit beta-1 1 shared papers
- Pyridoxine-5'-phosphate oxidase 2 shared papers
- Ras/Rap GTPase-activating protein SynGAP 2 shared papers
Literature · 20 cited papers
- Cryo-EM structure of the human alpha1beta3gamma2 GABAA receptor in a lipid bilayer. Nature · 2019
- Structure of a human synaptic GABAA receptor. Nature · 2018
- Diagnostic targeted resequencing in 349 patients with drug-resistant pediatric epilepsies identifies causative mutations in 30 different genes. Hum. Mutat. · 2017
- De novo GABRG2 mutations associated with epileptic encephalopathies. Brain · 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
- GABA(A) receptors can initiate the formation of functional inhibitory GABAergic synapses. Eur. J. Neurosci. · 2013
- Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. Nat. Genet. · 2013
- Novel alpha1 and gamma2 GABAA receptor subunit mutations in families with idiopathic generalized epilepsy. Eur. J. Neurosci. · 2011
- Mutational analysis of GABRG2 in a Japanese cohort with childhood epilepsies. J. Hum. Genet. · 2010
- A novel GABRG2 mutation associated with febrile seizures. Neurology · 2006
- Impact of epsilon and theta subunits on pharmacological properties of alpha3beta1 GABAA receptors expressed in Xenopus oocytes. BMC Pharmacol. · 2006
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- … and 8 more in the literature graph