ID GBRA1_HUMAN Reviewed; 456 AA. AC P14867; D3DQK6; Q8N629; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 17-JAN-2003, sequence version 3. DT 27-MAR-2024, entry version 232. DE RecName: Full=Gamma-aminobutyric acid receptor subunit alpha-1; DE AltName: Full=GABA(A) receptor subunit alpha-1; DE Flags: Precursor; GN Name=GABRA1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION. RX PubMed=2465923; DOI=10.1016/0014-5793(89)80563-0; RA Schofield P.R., Pritchett D.B., Sontheimer H., Kettenmann H., Seeburg P.H.; RT "Sequence and expression of human GABAA receptor alpha 1 and beta 1 RT subunits."; RL FEBS Lett. 244:361-364(1989). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-365. RC TISSUE=Cerebellum; RX PubMed=2847710; DOI=10.1016/s0006-291x(88)80949-5; RA Garrett K.M., Duman R.S., Saito N., Blume A.J., Vitek M.P., Tallman J.F.; RT "Isolation of a cDNA clone for the alpha subunit of the human GABA-A RT receptor."; RL Biochem. Biophys. Res. Commun. 156:1039-1045(1988). RN [5] RP FUNCTION. RX PubMed=23909897; DOI=10.1111/ejn.12331; RA Fuchs C., Abitbol K., Burden J.J., Mercer A., Brown L., Iball J., RA Anne Stephenson F., Thomson A.M., Jovanovic J.N.; RT "GABA(A) receptors can initiate the formation of functional inhibitory RT GABAergic synapses."; RL Eur. J. Neurosci. 38:3146-3158(2013). RN [6] RP FUNCTION. RX PubMed=25489750; DOI=10.3791/52115; RA Brown L.E., Fuchs C., Nicholson M.W., Stephenson F.A., Thomson A.M., RA Jovanovic J.N.; RT "Inhibitory synapse formation in a co-culture model incorporating GABAergic RT medium spiny neurons and HEK293 cells stably expressing GABAA receptors."; RL J. Vis. Exp. 2014:E52115-E52115(2014). RN [7] {ECO:0007744|PDB:6CDU, ECO:0007744|PDB:6D1S} RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 249-444 OF APOPROTEIN AND IN RP COMPLEX WITH AGONIST ALPHAXALONE, ACTIVITY REGULATION, BINDING TO AGONIST RP ALPHAXALONE, SUBUNIT, AND MUTAGENESIS OF GLN-269; TRP-273 AND THR-333. RX PubMed=30266951; DOI=10.1038/s41467-018-06361-4; RA Chen Q., Wells M.M., Arjunan P., Tillman T.S., Cohen A.E., Xu Y., Tang P.; RT "Structural basis of neurosteroid anesthetic action on GABAA receptors."; RL Nat. Commun. 9:3972-3972(2018). RN [8] {ECO:0007744|PDB:6D6T, ECO:0007744|PDB:6D6U} RP STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS) OF 28-456 IN COMPLEX WITH RP GABA AND FLUMAZENIL, FUNCTION, ACTIVITY REGULATION, AND SUBUNIT. RX PubMed=29950725; DOI=10.1038/s41586-018-0255-3; RA Zhu S., Noviello C.M., Teng J., Walsh R.M. Jr., Kim J.J., Hibbs R.E.; RT "Structure of a human synaptic GABAA receptor."; RL Nature 559:67-72(2018). RN [9] RP INVOLVEMENT IN EIG13, VARIANT EIG13 ASN-219, AND CHARACTERIZATION OF RP VARIANT EIG13 ASN-219. RX PubMed=21714819; DOI=10.1111/j.1460-9568.2011.07767.x; RA Lachance-Touchette P., Brown P., Meloche C., Kinirons P., Lapointe L., RA Lacasse H., Lortie A., Carmant L., Bedford F., Bowie D., Cossette P.; RT "Novel alpha1 and gamma2 GABAA receptor subunit mutations in families with RT idiopathic generalized epilepsy."; RL Eur. J. Neurosci. 34:237-249(2011). RN [10] RP INVOLVEMENT IN DEE19, AND VARIANTS DEE19 GLN-112; SER-251 AND THR-306. RX PubMed=24623842; DOI=10.1212/wnl.0000000000000291; RA Carvill G.L., Weckhuysen S., McMahon J.M., Hartmann C., Moller R.S., RA Hjalgrim H., Cook J., Geraghty E., O'Roak B.J., Petrou S., Clarke A., RA Gill D., Sadleir L.G., Muhle H., von Spiczak S., Nikanorova M., RA Hodgson B.L., Gazina E.V., Suls A., Shendure J., Dibbens L.M., RA De Jonghe P., Helbig I., Berkovic S.F., Scheffer I.E., Mefford H.C.; RT "GABRA1 and STXBP1: novel genetic causes of Dravet syndrome."; RL Neurology 82:1245-1253(2014). RN [11] RP VARIANT EJM5 ASP-322. RX PubMed=11992121; DOI=10.1038/ng885; RA Cossette P., Liu L., Brisebois K., Dong H., Lortie A., Vanasse M., RA Saint-Hilaire J.-M., Carmant L., Verner A., Lu W.-Y., Tian Wang Y., RA Rouleau G.A.; RT "Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic RT epilepsy."; RL Nat. Genet. 31:184-189(2002). RN [12] RP INVOLVEMENT IN ECA4. RX PubMed=16718694; DOI=10.1002/ana.20874; RA Maljevic S., Krampfl K., Cobilanschi J., Tilgen N., Beyer S., Weber Y.G., RA Schlesinger F., Ursu D., Melzer W., Cossette P., Bufler J., Lerche H., RA Heils A.; RT "A mutation in the GABA(A) receptor alpha(1)-subunit is associated with RT absence epilepsy."; RL Ann. Neurol. 59:983-987(2006). RN [13] RP INTERACTION WITH LHFPL4. RX PubMed=28978485; DOI=10.1016/j.celrep.2017.09.025; RA Davenport E.C., Pendolino V., Kontou G., McGee T.P., Sheehan D.F., RA Lopez-Domenech G., Farrant M., Kittler J.T.; RT "An essential role for the tetraspanin LHFPL4 in the cell-type-specific RT targeting and clustering of synaptic GABAA ceceptors."; RL Cell Rep. 21:70-83(2017). RN [14] RP INTERACTION WITH LHFLP4. RX PubMed=29742426; DOI=10.1016/j.celrep.2018.04.015; RA Wu M., Tian H.L., Liu X., Lai J.H.C., Du S., Xia J.; RT "Impairment of inhibitory synapse formation and motor behavior in mice RT lacking the NL2 binding partner LHFPL4/GARLH4."; RL Cell Rep. 23:1691-1705(2018). RN [15] RP VARIANT DEE19 MET-146. RX PubMed=27864847; DOI=10.1002/humu.23149; RG Clinical Study Group; RA Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D., RA Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S., RA Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.; RT "Diagnostic targeted resequencing in 349 patients with drug-resistant RT pediatric epilepsies identifies causative mutations in 30 different RT genes."; RL Hum. Mutat. 38:216-225(2017). CC -!- FUNCTION: Ligand-gated chloride channel which is a component of the CC heteropentameric receptor for GABA, the major inhibitory CC neurotransmitter in the brain (PubMed:23909897, PubMed:25489750, CC PubMed:29950725). Plays an important role in the formation of CC functional inhibitory GABAergic synapses in addition to mediating CC synaptic inhibition as a GABA-gated ion channel (PubMed:23909897, CC PubMed:25489750). The gamma2 subunit is necessary but not sufficient CC for a rapid formation of active synaptic contacts and the synaptogenic CC effect of this subunit is influenced by the type of alpha and beta CC subunits present in the receptor pentamer (By similarity). The CC alpha1/beta2/gamma2 receptor and the alpha1/beta3/gamma2 receptor CC exhibit synaptogenic activity (PubMed:23909897, PubMed:25489750). CC GABRA1-mediated plasticity in the orbitofrontal cortex regulates CC context-dependent action selection (By similarity). Functions also as CC histamine receptor and mediates cellular responses to histamine (By CC similarity). {ECO:0000250|UniProtKB:P62812, CC ECO:0000250|UniProtKB:P62813, ECO:0000269|PubMed:23909897, CC ECO:0000269|PubMed:25489750, ECO:0000269|PubMed:29950725}. CC -!- ACTIVITY REGULATION: Allosterically activated by benzodiazepines and CC the anesthetic alphaxalone (PubMed:30266951, PubMed:29950725). CC Allosterically activated by pentobarbital (By similarity). Inhibited by CC the antagonist bicuculline (PubMed:29950725). CC {ECO:0000250|UniProtKB:P62813, ECO:0000269|PubMed:29950725, CC ECO:0000269|PubMed:30266951}. CC -!- SUBUNIT: Heteropentamer, formed by a combination of alpha, beta, gamma, CC delta and rho chains (PubMed:29950725, PubMed:30266951). Interacts with CC UBQLN1 (By similarity). Interacts with TRAK1 (By similarity). Interacts CC with KIF21B (By similarity). Identified in a complex of 720 kDa CC composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By CC similarity). Interacts with LHFPL4 (PubMed:28978485, PubMed:29742426). CC Interacts with NLGN2 (By similarity). Interacts with SHISA7; CC interaction leads regulation of GABA(A) receptor trafficking, channel CC deactivation kinetics and pharmacology (By similarity). CC {ECO:0000250|UniProtKB:P62812, ECO:0000250|UniProtKB:P62813, CC ECO:0000269|PubMed:28978485, ECO:0000269|PubMed:29742426, CC ECO:0000269|PubMed:29950725, ECO:0000269|PubMed:30266951}. CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane CC {ECO:0000250|UniProtKB:P08219}; Multi-pass membrane protein CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:2465923}; Multi-pass CC membrane protein {ECO:0000255}. Cytoplasmic vesicle membrane CC {ECO:0000250|UniProtKB:P62813}. CC -!- DOMAIN: The extracellular domain contributes to synaptic contact CC formation. {ECO:0000250|UniProtKB:P62812}. CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P62812}. CC -!- DISEASE: Epilepsy, childhood absence 4 (ECA4) [MIM:611136]: A subtype CC of idiopathic generalized epilepsy characterized by an onset at age 6-7 CC years, frequent absence seizures (several per day) and bilateral, CC synchronous, symmetric 3-Hz spike waves on EEG. Tonic-clonic seizures CC often develop in adolescence. Absence seizures may either remit or CC persist into adulthood. {ECO:0000269|PubMed:16718694}. Note=Disease CC susceptibility is associated with variants affecting the gene CC represented in this entry. CC -!- DISEASE: Epilepsy, idiopathic generalized 13 (EIG13) [MIM:611136]: A CC disorder characterized by recurring generalized seizures in the absence CC of detectable brain lesions and/or metabolic abnormalities. Generalized CC seizures arise diffusely and simultaneously from both hemispheres of CC the brain. Seizure types include juvenile myoclonic seizures, absence CC seizures, and generalized tonic-clonic seizures. CC {ECO:0000269|PubMed:21714819}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC -!- DISEASE: Juvenile myoclonic epilepsy 5 (EJM5) [MIM:611136]: A subtype CC of idiopathic generalized epilepsy. Patients have afebrile seizures CC only, with onset in adolescence (rather than in childhood) and CC myoclonic jerks which usually occur after awakening and are triggered CC by sleep deprivation and fatigue. {ECO:0000269|PubMed:11992121}. CC Note=Disease susceptibility is associated with variants affecting the CC gene represented in this entry. CC -!- DISEASE: Developmental and epileptic encephalopathy 19 (DEE19) CC [MIM:615744]: A severe neurologic disorder characterized by onset of CC seizures in the first months of life and usually associated with EEG CC abnormalities. Affected infants have convulsive seizures (hemiclonic or CC generalized) that are often prolonged and triggered by fever. Other CC seizure types include focal, myoclonic, absence seizures, and drop CC attacks. Development is normal in the first year of life with later CC slowing and intellectual disability. {ECO:0000269|PubMed:24623842, CC ECO:0000269|PubMed:27864847}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family. CC Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA1 sub- CC subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Forbidden fruit - Issue 56 CC of March 2005; CC URL="https://web.expasy.org/spotlight/back_issues/056"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X14766; CAA32874.1; -; mRNA. DR EMBL; CH471062; EAW61538.1; -; Genomic_DNA. DR EMBL; CH471062; EAW61539.1; -; Genomic_DNA. DR EMBL; BC030696; AAH30696.1; -; mRNA. DR EMBL; X13584; CAA31925.1; -; mRNA. DR CCDS; CCDS4357.1; -. DR PIR; A31588; A31588. DR PIR; A60652; A60652. DR RefSeq; NP_000797.2; NM_000806.5. DR RefSeq; NP_001121115.1; NM_001127643.1. DR RefSeq; NP_001121116.1; NM_001127644.1. DR RefSeq; NP_001121117.1; NM_001127645.1. DR RefSeq; NP_001121120.1; NM_001127648.1. DR PDB; 6CDU; X-ray; 3.45 A; A/B/C/D/E/F/G/H/I/J=249-340, A/B/C/D/E/F/G/H/I/J=415-444. DR PDB; 6D1S; X-ray; 3.20 A; A/B/C/D/E/F/G/H/I/J=249-340, A/B/C/D/E/F/G/H/I/J=415-444. DR PDB; 6D6T; EM; 3.80 A; B/D=28-339, B/D=418-456. DR PDB; 6D6U; EM; 3.80 A; B/D=28-339, B/D=418-456. DR PDB; 6HUG; EM; 3.10 A; A/D=28-456. DR PDB; 6HUJ; EM; 3.04 A; A/D=1-456. DR PDB; 6HUK; EM; 3.69 A; A/D=1-456. DR PDB; 6HUO; EM; 3.26 A; A/D=1-456. DR PDB; 6HUP; EM; 3.58 A; A/D=1-456. DR PDB; 6I53; EM; 3.20 A; A/D=1-456. DR PDB; 6X3S; EM; 3.12 A; B/D=28-339, B/D=418-456. DR PDB; 6X3T; EM; 2.55 A; B/D=28-339, B/D=419-456. DR PDB; 6X3U; EM; 3.49 A; B/D=28-339, B/D=419-456. DR PDB; 6X3V; EM; 3.50 A; B/D=28-339, B/D=418-456. DR PDB; 6X3W; EM; 3.30 A; B/D=28-339, B/D=418-456. DR PDB; 6X3X; EM; 2.92 A; B/D=28-339, B/D=418-456. DR PDB; 6X3Z; EM; 3.23 A; B/D=28-339, B/D=418-456. DR PDB; 6X40; EM; 2.86 A; B/D=28-339, B/D=418-456. DR PDB; 7PBD; EM; 3.04 A; A/D=32-339, A/D=418-456. DR PDB; 7PBZ; EM; 2.79 A; A/D=32-339, A/D=418-456. DR PDB; 7PC0; EM; 3.00 A; A/D=32-339, A/D=418-456. DR PDB; 7QNE; EM; 2.70 A; A/D=1-456. DR PDB; 7T0W; EM; 3.00 A; B/D=28-339, B/D=418-445. DR PDB; 7T0Z; EM; 3.00 A; B/D=28-339, B/D=418-445. DR PDB; 8DD2; EM; 2.90 A; B/D=28-339. DR PDB; 8DD3; EM; 2.90 A; B/D=28-339. DR PDB; 8SGO; EM; 2.65 A; B/D=28-339, B/D=418-456. DR PDB; 8SI9; EM; 2.98 A; B/D=28-339, B/D=418-456. DR PDB; 8SID; EM; 2.71 A; B/D=28-339, B/D=418-456. DR PDBsum; 6CDU; -. DR PDBsum; 6D1S; -. DR PDBsum; 6D6T; -. DR PDBsum; 6D6U; -. DR PDBsum; 6HUG; -. DR PDBsum; 6HUJ; -. DR PDBsum; 6HUK; -. DR PDBsum; 6HUO; -. DR PDBsum; 6HUP; -. DR PDBsum; 6I53; -. DR PDBsum; 6X3S; -. DR PDBsum; 6X3T; -. DR PDBsum; 6X3U; -. DR PDBsum; 6X3V; -. DR PDBsum; 6X3W; -. DR PDBsum; 6X3X; -. DR PDBsum; 6X3Z; -. DR PDBsum; 6X40; -. DR PDBsum; 7PBD; -. DR PDBsum; 7PBZ; -. DR PDBsum; 7PC0; -. DR PDBsum; 7QNE; -. DR PDBsum; 7T0W; -. DR PDBsum; 7T0Z; -. DR PDBsum; 8DD2; -. DR PDBsum; 8DD3; -. DR PDBsum; 8SGO; -. DR PDBsum; 8SI9; -. DR PDBsum; 8SID; -. DR AlphaFoldDB; P14867; -. DR EMDB; EMD-0275; -. DR EMDB; EMD-0279; -. DR EMDB; EMD-0280; -. DR EMDB; EMD-0282; -. DR EMDB; EMD-0283; -. DR EMDB; EMD-13290; -. DR EMDB; EMD-13314; -. DR EMDB; EMD-13315; -. DR EMDB; EMD-22031; -. DR EMDB; EMD-22032; -. DR EMDB; EMD-22033; -. DR EMDB; EMD-22034; -. DR EMDB; EMD-22035; -. DR EMDB; EMD-22036; -. DR EMDB; EMD-22037; -. DR EMDB; EMD-22038; -. DR EMDB; EMD-25583; -. DR EMDB; EMD-25585; -. DR EMDB; EMD-27332; -. DR EMDB; EMD-27333; -. DR EMDB; EMD-40462; -. DR EMDB; EMD-40503; -. DR EMDB; EMD-40506; -. DR EMDB; EMD-4411; -. DR EMDB; EMD-7816; -. DR EMDB; EMD-7817; -. DR SMR; P14867; -. DR BioGRID; 108828; 134. DR ComplexPortal; CPX-2159; GABA-A receptor, alpha-1/beta-2/gamma-2. DR ComplexPortal; CPX-2167; GABA-A receptor, alpha-1/beta-3/gamma-2. DR CORUM; P14867; -. DR IntAct; P14867; 5. DR MINT; P14867; -. DR STRING; 9606.ENSP00000393097; -. DR BindingDB; P14867; -. DR ChEMBL; CHEMBL1962; -. DR DrugBank; DB12537; 1,2-Benzodiazepine. DR DrugBank; DB00546; Adinazolam. DR DrugBank; DB06579; Adipiplon. DR DrugBank; DB00404; Alprazolam. DR DrugBank; DB01351; Amobarbital. DR DrugBank; DB00543; Amoxapine. DR DrugBank; DB11901; Apalutamide. DR DrugBank; DB01352; Aprobarbital. DR DrugBank; DB01483; Barbital. DR DrugBank; DB14719; Bentazepam. DR DrugBank; DB11859; Brexanolone. DR DrugBank; DB01558; Bromazepam. DR DrugBank; DB09017; Brotizolam. DR DrugBank; DB00237; Butabarbital. DR DrugBank; DB00241; Butalbital. DR DrugBank; DB01353; Butobarbital. DR DrugBank; DB01489; Camazepam. DR DrugBank; DB00395; Carisoprodol. DR DrugBank; DB00475; Chlordiazepoxide. DR DrugBank; DB14715; Cinazepam. DR DrugBank; DB01594; Cinolazepam. DR DrugBank; DB00349; Clobazam. DR DrugBank; DB06470; Clomethiazole. DR DrugBank; DB01068; Clonazepam. DR DrugBank; DB00628; Clorazepic acid. DR DrugBank; DB01559; Clotiazepam. DR DrugBank; DB01553; Cloxazolam. DR DrugBank; DB01511; Delorazepam. DR DrugBank; DB01189; Desflurane. DR DrugBank; DB00829; Diazepam. DR DrugBank; DB01496; Dihydro-2-thioxo-5-((5-(2-(trifluoromethyl)phenyl)-2-furanyl)methyl)-4,6(1H,5H)-pyrimidinedione. DR DrugBank; DB01341; Dihydroquinidine barbiturate. DR DrugBank; DB13837; Doxefazepam. DR DrugBank; DB00228; Enflurane. DR DrugBank; DB01215; Estazolam. DR DrugBank; DB00402; Eszopiclone. DR DrugBank; DB00898; Ethanol. DR DrugBank; DB00189; Ethchlorvynol. DR DrugBank; DB01545; Ethyl loflazepate. DR DrugBank; DB09166; Etizolam. DR DrugBank; DB00292; Etomidate. DR DrugBank; DB01567; Fludiazepam. DR DrugBank; DB01205; Flumazenil. DR DrugBank; DB01544; Flunitrazepam. DR DrugBank; DB00690; Flurazepam. DR DrugBank; DB05087; Ganaxolone. DR DrugBank; DB01381; Ginkgo biloba. DR DrugBank; DB01437; Glutethimide. DR DrugBank; DB00801; Halazepam. DR DrugBank; DB01159; Halothane. DR DrugBank; DB01354; Heptabarbital. DR DrugBank; DB01355; Hexobarbital. DR DrugBank; DB00753; Isoflurane. DR DrugBank; DB01587; Ketazolam. DR DrugBank; DB00555; Lamotrigine. DR DrugBank; DB13643; Loprazolam. DR DrugBank; DB00186; Lorazepam. DR DrugBank; DB13872; Lormetazepam. DR DrugBank; DB13437; Medazepam. DR DrugBank; DB00603; Medroxyprogesterone acetate. DR DrugBank; DB01043; Memantine. DR DrugBank; DB00371; Meprobamate. DR DrugBank; DB00463; Metharbital. DR DrugBank; DB00474; Methohexital. DR DrugBank; DB01028; Methoxyflurane. DR DrugBank; DB00849; Methylphenobarbital. DR DrugBank; DB01107; Methyprylon. DR DrugBank; DB15489; Mexazolam. DR DrugBank; DB00683; Midazolam. DR DrugBank; DB12458; Muscimol. DR DrugBank; DB01595; Nitrazepam. DR DrugBank; DB14028; Nordazepam. DR DrugBank; DB00334; Olanzapine. DR DrugBank; DB00842; Oxazepam. DR DrugBank; DB14672; Oxazepam acetate. DR DrugBank; DB00312; Pentobarbital. DR DrugBank; DB01174; Phenobarbital. DR DrugBank; DB00252; Phenytoin. DR DrugBank; DB00466; Picrotoxin. DR DrugBank; DB13335; Pinazepam. DR DrugBank; DB01708; Prasterone. DR DrugBank; DB01588; Prazepam. DR DrugBank; DB00794; Primidone. DR DrugBank; DB00837; Progabide. DR DrugBank; DB00818; Propofol. DR DrugBank; DB01589; Quazepam. DR DrugBank; DB01346; Quinidine barbiturate. DR DrugBank; DB12404; Remimazolam. DR DrugBank; DB00418; Secobarbital. DR DrugBank; DB01236; Sevoflurane. DR DrugBank; DB09118; Stiripentol. DR DrugBank; DB00306; Talbutal. DR DrugBank; DB01956; Taurine. DR DrugBank; DB00231; Temazepam. DR DrugBank; DB01154; Thiamylal. DR DrugBank; DB11582; Thiocolchicoside. DR DrugBank; DB00599; Thiopental. DR DrugBank; DB00273; Topiramate. DR DrugBank; DB00897; Triazolam. DR DrugBank; DB00962; Zaleplon. DR DrugBank; DB00425; Zolpidem. DR DrugBank; DB00909; Zonisamide. DR DrugBank; DB01198; Zopiclone. DR DrugCentral; P14867; -. DR GuidetoPHARMACOLOGY; 404; -. DR TCDB; 1.A.9.5.4; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family. DR GlyCosmos; P14867; 2 sites, No reported glycans. DR GlyGen; P14867; 2 sites. DR iPTMnet; P14867; -. DR PhosphoSitePlus; P14867; -. DR BioMuta; GABRA1; -. DR DMDM; 27808653; -. DR MassIVE; P14867; -. DR MaxQB; P14867; -. DR PaxDb; 9606-ENSP00000393097; -. DR PeptideAtlas; P14867; -. DR ProteomicsDB; 53091; -. DR ABCD; P14867; 4 sequenced antibodies. DR Antibodypedia; 4533; 557 antibodies from 44 providers. DR DNASU; 2554; -. DR Ensembl; ENST00000023897.10; ENSP00000023897.6; ENSG00000022355.18. DR Ensembl; ENST00000393943.10; ENSP00000377517.4; ENSG00000022355.18. DR Ensembl; ENST00000428797.7; ENSP00000393097.2; ENSG00000022355.18. DR Ensembl; ENST00000437025.6; ENSP00000415441.2; ENSG00000022355.18. DR Ensembl; ENST00000635880.1; ENSP00000489738.1; ENSG00000022355.18. DR Ensembl; ENST00000636573.1; ENSP00000490320.1; ENSG00000022355.18. DR Ensembl; ENST00000637827.1; ENSP00000490804.1; ENSG00000022355.18. DR Ensembl; ENST00000638112.1; ENSP00000489839.1; ENSG00000022355.18. DR GeneID; 2554; -. DR KEGG; hsa:2554; -. DR MANE-Select; ENST00000393943.10; ENSP00000377517.4; NM_001127644.2; NP_001121116.1. DR UCSC; uc003lyx.5; human. DR AGR; HGNC:4075; -. DR CTD; 2554; -. DR DisGeNET; 2554; -. DR GeneCards; GABRA1; -. DR HGNC; HGNC:4075; GABRA1. DR HPA; ENSG00000022355; Group enriched (brain, retina). DR MalaCards; GABRA1; -. DR MIM; 137160; gene. DR MIM; 611136; phenotype. DR MIM; 615744; phenotype. DR neXtProt; NX_P14867; -. DR OpenTargets; ENSG00000022355; -. DR Orphanet; 64280; Childhood absence epilepsy. DR Orphanet; 33069; Dravet syndrome. DR Orphanet; 307; Juvenile myoclonic epilepsy. DR PharmGKB; PA28489; -. DR VEuPathDB; HostDB:ENSG00000022355; -. DR eggNOG; KOG3642; Eukaryota. DR GeneTree; ENSGT00940000159136; -. DR HOGENOM; CLU_010920_2_1_1; -. DR InParanoid; P14867; -. DR OMA; YLWAYLF; -. DR OrthoDB; 4265336at2759; -. DR PhylomeDB; P14867; -. DR TreeFam; TF315453; -. DR PathwayCommons; P14867; -. DR Reactome; R-HSA-1236394; Signaling by ERBB4. DR Reactome; R-HSA-977443; GABA receptor activation. DR SignaLink; P14867; -. DR SIGNOR; P14867; -. DR BioGRID-ORCS; 2554; 8 hits in 1150 CRISPR screens. DR ChiTaRS; GABRA1; human. DR GeneWiki; Gamma-aminobutyric_acid_(GABA)_A_receptor,_alpha_1; -. DR GeneWiki; Gamma-aminobutyric_acid_receptor_subunit_alpha-1; -. DR GenomeRNAi; 2554; -. DR Pharos; P14867; Tclin. DR PRO; PR:P14867; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; P14867; Protein. DR Bgee; ENSG00000022355; Expressed in lateral nuclear group of thalamus and 105 other cell types or tissues. DR ExpressionAtlas; P14867; baseline and differential. DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW. DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0032590; C:dendrite membrane; IBA:GO_Central. DR GO; GO:1902710; C:GABA receptor complex; ISS:BHF-UCL. DR GO; GO:1902711; C:GABA-A receptor complex; IDA:UniProtKB. DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl. DR GO; GO:0043005; C:neuron projection; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; ISS:BHF-UCL. DR GO; GO:0098794; C:postsynapse; IBA:GO_Central. DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell. DR GO; GO:0045202; C:synapse; IBA:GO_Central. DR GO; GO:0004890; F:GABA-A receptor activity; TAS:ProtInc. DR GO; GO:0022851; F:GABA-gated chloride ion channel activity; IDA:GO_Central. DR GO; GO:0005237; F:inhibitory extracellular ligand-gated monoatomic ion channel activity; IBA:GO_Central. DR GO; GO:1904315; F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential; IEA:Ensembl. DR GO; GO:1902476; P:chloride transmembrane transport; IDA:GO_Central. DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IDA:ComplexPortal. DR GO; GO:1904862; P:inhibitory synapse assembly; IDA:UniProtKB. DR GO; GO:0060078; P:regulation of postsynaptic membrane potential; IBA:GO_Central. DR GO; GO:0051932; P:synaptic transmission, GABAergic; ISS:BHF-UCL. DR CDD; cd19034; LGIC_ECD_GABAAR_A1; 1. DR CDD; cd19052; LGIC_TM_GABAAR_alpha; 1. DR Gene3D; 2.70.170.10; Neurotransmitter-gated ion-channel ligand-binding domain; 1. DR Gene3D; 1.20.58.390; Neurotransmitter-gated ion-channel transmembrane domain; 1. DR InterPro; IPR006028; GABAA/Glycine_rcpt. DR InterPro; IPR001390; GABAAa_rcpt. DR InterPro; IPR005431; GABBAa1_rcpt. DR InterPro; IPR047024; Gabra-1-6_TM. DR InterPro; IPR047079; GABRA1_ECD. DR InterPro; IPR006202; Neur_chan_lig-bd. DR InterPro; IPR036734; Neur_chan_lig-bd_sf. DR InterPro; IPR006201; Neur_channel. DR InterPro; IPR036719; Neuro-gated_channel_TM_sf. DR InterPro; IPR038050; Neuro_actylchol_rec. DR InterPro; IPR006029; Neurotrans-gated_channel_TM. DR InterPro; IPR018000; Neurotransmitter_ion_chnl_CS. DR NCBIfam; TIGR00860; LIC; 1. DR PANTHER; PTHR18945:SF514; GAMMA-AMINOBUTYRIC ACID RECEPTOR SUBUNIT ALPHA-1; 1. DR PANTHER; PTHR18945; NEUROTRANSMITTER GATED ION CHANNEL; 1. DR Pfam; PF02931; Neur_chan_LBD; 1. DR Pfam; PF02932; Neur_chan_memb; 1. DR PRINTS; PR01079; GABAARALPHA. DR PRINTS; PR01614; GABAARALPHA1. DR PRINTS; PR00253; GABAARECEPTR. DR PRINTS; PR00252; NRIONCHANNEL. DR SUPFAM; SSF90112; Neurotransmitter-gated ion-channel transmembrane pore; 1. DR SUPFAM; SSF63712; Nicotinic receptor ligand binding domain-like; 1. DR PROSITE; PS00236; NEUROTR_ION_CHANNEL; 1. DR Genevisible; P14867; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Chloride; Chloride channel; KW Cytoplasmic vesicle; Disease variant; Disulfide bond; Epilepsy; KW Glycoprotein; Ion channel; Ion transport; Ligand-gated ion channel; KW Membrane; Postsynaptic cell membrane; Receptor; Reference proteome; Signal; KW Synapse; Transmembrane; Transmembrane helix; Transport. FT SIGNAL 1..27 FT /evidence="ECO:0000255" FT CHAIN 28..456 FT /note="Gamma-aminobutyric acid receptor subunit alpha-1" FT /id="PRO_0000000428" FT TOPO_DOM 28..251 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 252..273 FT /note="Helical" FT /evidence="ECO:0000305" FT TRANSMEM 279..300 FT /note="Helical" FT /evidence="ECO:0000305" FT TRANSMEM 313..334 FT /note="Helical" FT /evidence="ECO:0000305" FT TOPO_DOM 335..421 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 422..443 FT /note="Helical" FT /evidence="ECO:0000305" FT BINDING 273 FT /ligand="alphaxolone" FT /ligand_id="ChEBI:CHEBI:34531" FT /ligand_note="agonist" FT /evidence="ECO:0000269|PubMed:30266951" FT CARBOHYD 38 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 138 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 166..180 FT /evidence="ECO:0000250" FT VARIANT 112 FT /note="R -> Q (in DEE19; dbSNP:rs587777308)" FT /evidence="ECO:0000269|PubMed:24623842" FT /id="VAR_071809" FT VARIANT 146 FT /note="L -> M (in DEE19)" FT /evidence="ECO:0000269|PubMed:27864847" FT /id="VAR_078222" FT VARIANT 219 FT /note="D -> N (in EIG13; the mutant protein is partially FT retained in the endoplasmic reticulum and has decreased FT expression at the plasma membrane; causes decreased current FT amplitude in response to GABA compared to wild-type and FT alters receptor gating kinetics including faster FT desensitization; dbSNP:rs587777364)" FT /evidence="ECO:0000269|PubMed:21714819" FT /id="VAR_071810" FT VARIANT 251 FT /note="G -> S (in DEE19; dbSNP:rs587777307)" FT /evidence="ECO:0000269|PubMed:24623842" FT /id="VAR_071811" FT VARIANT 306 FT /note="K -> T (in DEE19; dbSNP:rs587777309)" FT /evidence="ECO:0000269|PubMed:24623842" FT /id="VAR_071812" FT VARIANT 322 FT /note="A -> D (in EJM5; dbSNP:rs121434579)" FT /evidence="ECO:0000269|PubMed:11992121" FT /id="VAR_013642" FT MUTAGEN 269 FT /note="Q->L: Reduced potentiation and activation by the FT agonist alphaxalone." FT /evidence="ECO:0000269|PubMed:30266951" FT MUTAGEN 273 FT /note="W->L: Completely abolishes potentiation and FT activation by the agonist alphaxalone." FT /evidence="ECO:0000269|PubMed:30266951" FT MUTAGEN 333 FT /note="T->A: Reduced potentiation and activation by the FT agonist alphaxalone." FT /evidence="ECO:0000269|PubMed:30266951" FT CONFLICT 122 FT /note="W -> R (in Ref. 1; CAA32874)" FT /evidence="ECO:0000305" FT CONFLICT 128..140 FT /note="Missing (in Ref. 4; CAA31925)" FT /evidence="ECO:0000305" FT CONFLICT 204 FT /note="R -> H (in Ref. 4; CAA31925)" FT /evidence="ECO:0000305" FT CONFLICT 315 FT /note="W -> WDW (in Ref. 4; CAA31925)" FT /evidence="ECO:0000305" FT CONFLICT 362..365 FT /note="IKKN -> FPNS (in Ref. 4; CAA31925)" FT /evidence="ECO:0000305" FT HELIX 39..49 FT /evidence="ECO:0007829|PDB:6X3T" FT TURN 50..52 FT /evidence="ECO:0007829|PDB:8SGO" FT TURN 59..63 FT /evidence="ECO:0007829|PDB:6X3T" FT STRAND 66..81 FT /evidence="ECO:0007829|PDB:6X3T" FT TURN 82..85 FT /evidence="ECO:0007829|PDB:6X3T" FT STRAND 86..98 FT /evidence="ECO:0007829|PDB:6X3T" FT HELIX 100..102 FT /evidence="ECO:0007829|PDB:6X3T" FT STRAND 109..113 FT /evidence="ECO:0007829|PDB:6X3T" FT HELIX 117..119 FT /evidence="ECO:0007829|PDB:6X3T" FT STRAND 126..128 FT /evidence="ECO:0007829|PDB:6X3T" FT STRAND 131..133 FT /evidence="ECO:0007829|PDB:6X3T" FT STRAND 139..141 FT /evidence="ECO:0007829|PDB:6X3T" FT STRAND 144..149 FT /evidence="ECO:0007829|PDB:6X3T" FT STRAND 152..165 FT /evidence="ECO:0007829|PDB:6X3T" FT TURN 171..174 FT /evidence="ECO:0007829|PDB:6X3T" FT STRAND 177..188 FT /evidence="ECO:0007829|PDB:6X3T" FT TURN 191..193 FT /evidence="ECO:0007829|PDB:6X3T" FT STRAND 194..200 FT /evidence="ECO:0007829|PDB:6X3T" FT HELIX 202..204 FT /evidence="ECO:0007829|PDB:6X3T" FT STRAND 205..208 FT /evidence="ECO:0007829|PDB:6X3T" FT STRAND 216..232 FT /evidence="ECO:0007829|PDB:6X3T" FT STRAND 235..248 FT /evidence="ECO:0007829|PDB:6X3T" FT HELIX 251..256 FT /evidence="ECO:0007829|PDB:6X3T" FT HELIX 258..270 FT /evidence="ECO:0007829|PDB:6X3T" FT HELIX 271..273 FT /evidence="ECO:0007829|PDB:6X3T" FT HELIX 279..301 FT /evidence="ECO:0007829|PDB:6X3T" FT HELIX 312..336 FT /evidence="ECO:0007829|PDB:6X3T" FT TURN 337..339 FT /evidence="ECO:0007829|PDB:6X3T" FT STRAND 346..348 FT /evidence="ECO:0007829|PDB:6I53" FT HELIX 419..444 FT /evidence="ECO:0007829|PDB:6X3T" SQ SEQUENCE 456 AA; 51802 MW; F81EC9ECBE64E94D CRC64; MRKSPGLSDC LWAWILLLST LTGRSYGQPS LQDELKDNTT VFTRILDRLL DGYDNRLRPG LGERVTEVKT DIFVTSFGPV SDHDMEYTID VFFRQSWKDE RLKFKGPMTV LRLNNLMASK IWTPDTFFHN GKKSVAHNMT MPNKLLRITE DGTLLYTMRL TVRAECPMHL EDFPMDAHAC PLKFGSYAYT RAEVVYEWTR EPARSVVVAE DGSRLNQYDL LGQTVDSGIV QSSTGEYVVM TTHFHLKRKI GYFVIQTYLP CIMTVILSQV SFWLNRESVP ARTVFGVTTV LTMTTLSISA RNSLPKVAYA TAMDWFIAVC YAFVFSALIE FATVNYFTKR GYAWDGKSVV PEKPKKVKDP LIKKNNTYAP TATSYTPNLA RGDPGLATIA KSATIEPKEV KPETKPPEPK KTFNSVSKID RLSRIAFPLL FGIFNLVYWA TYLNREPQLK APTPHQ //