{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P14867","secondaryAccessions":["D3DQK6","Q8N629"],"uniProtkbId":"GBRA1_HUMAN","entryAudit":{"firstPublicDate":"1990-04-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2003-01-17","entryVersion":242,"sequenceVersion":3},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Gamma-aminobutyric acid receptor subunit alpha-1"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"23909897"}],"value":"GABA(A) receptor subunit alpha-1"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"25489750"}],"value":"GABAAR subunit alpha-1"}]}],"flag":"Precursor"},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:4075"}],"value":"GABRA1"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P08219"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P62812"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P62813"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23909897"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25489750"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29950725"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30602789"}],"value":"Alpha subunit of the heteropentameric ligand-gated chloride channel gated by Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:23909897, PubMed:25489750, PubMed:29950725, PubMed:30602789). 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) (PubMed:29950725, PubMed:30602789). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:23909897, PubMed:29950725, PubMed:30602789). 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 (PubMed:23909897, PubMed:25489750). 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)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"chloride(in) = chloride(out)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:29823"},{"database":"ChEBI","id":"CHEBI:17996"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23909897"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29950725"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30602789"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P62813"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29950725"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30266951"}],"value":"Allosterically activated by benzodiazepines and the anesthetic alphaxalone (PubMed:29950725, PubMed:30266951). Allosterically activated by pentobarbital (By similarity). Inhibited by the antagonist bicuculline (PubMed:29950725). Potentiated by histamine (By similarity)"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P62812"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P62813"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28978485"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29742426"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29950725"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30266951"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30602789"}],"value":"Heteropentamer, formed by a combination of alpha (GABRA1-6), beta (GABRB1-3), gamma (GABRG1-3), delta (GABRD), epsilon (GABRE), rho (GABRR1-3), pi (GABRP) and theta (GABRQ) subunits, each subunit exhibiting distinct physiological and pharmacological properties (PubMed:29950725, PubMed:30266951, PubMed:30602789). Interacts with UBQLN1 (By similarity). Interacts with TRAK1 (By similarity). Interacts with KIF21B (By similarity). Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity). Interacts with LHFPL4 (PubMed:28978485, PubMed:29742426). Interacts with NLGN2 (By similarity). Interacts with SHISA7; interaction leads regulation of GABAAR trafficking, channel deactivation kinetics and pharmacology (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P62813"}],"value":"Mainly located in GABAergic synapses in granule cells, and also in the extrasynaptic membrane at a lower concentration"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P08219"}],"value":"Postsynaptic cell membrane","id":"SL-0219"},"topology":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29950725"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"2465923"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25489750"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29950725"}],"value":"Multi-pass membrane protein","id":"SL-9909"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P62813"}],"value":"Cytoplasmic vesicle membrane","id":"SL-0089"},"topology":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29950725"}],"value":"Multi-pass membrane protein","id":"SL-9909"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P62812"}],"value":"The extracellular domain contributes to synaptic contact formation"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29950725"}],"value":"The GABA-binding pockets are located at the interface between neighboring alpha and beta subunits"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29950725"}],"value":"GABAARs subunits share a common topological structure: a peptide sequence made up of a long extracellular N-terminal, four transmembrane domains, intracellular or cytoplasmic domain located between the third and the fourth transmembrane domains"}],"commentType":"DOMAIN"},{"commentType":"DISEASE","disease":{"diseaseId":"Epilepsy, childhood absence 4","diseaseAccession":"DI-00299","acronym":"ECA4","description":"A subtype of idiopathic generalized epilepsy characterized by an onset at age 6-7 years, frequent absence seizures (several per day) and bilateral, synchronous, symmetric 3-Hz spike waves on EEG. Tonic-clonic seizures often develop in adolescence. Absence seizures may either remit or persist into adulthood.","diseaseCrossReference":{"database":"MIM","id":"611136"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16718694"}]},"note":{"texts":[{"value":"Disease susceptibility is associated with variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Epilepsy, idiopathic generalized 13","diseaseAccession":"DI-04084","acronym":"EIG13","description":"A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures.","diseaseCrossReference":{"database":"MIM","id":"611136"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21714819"}]},"note":{"texts":[{"value":"Disease susceptibility is associated with variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Juvenile myoclonic epilepsy 5","diseaseAccession":"DI-03086","acronym":"EJM5","description":"A subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue.","diseaseCrossReference":{"database":"MIM","id":"611136"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11992121"}]},"note":{"texts":[{"value":"Disease susceptibility is associated with variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Developmental and epileptic encephalopathy 19","diseaseAccession":"DI-04092","acronym":"DEE19","description":"A severe neurologic disorder characterized by onset of seizures in the first months of life and usually associated with EEG abnormalities. Affected infants have convulsive seizures (hemiclonic or generalized) that are often prolonged and triggered by fever. Other seizure types include focal, myoclonic, absence seizures, and drop attacks. Development is normal in the first year of life with later slowing and intellectual disability.","diseaseCrossReference":{"database":"MIM","id":"615744"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24623842"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27864847"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29950725"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30266951"}],"value":"Functions as a receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. 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