GBRA1_HUMAN
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 03-AUG-2022, entry version 223.
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";
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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 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 AlphaFoldDB; P14867; -.
DR SMR; P14867; -.
DR BioGRID; 108828; 12.
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; 4.
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; 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 GlyGen; P14867; 2 sites.
DR iPTMnet; P14867; -.
DR PhosphoSitePlus; P14867; -.
DR BioMuta; GABRA1; -.
DR DMDM; 27808653; -.
DR MassIVE; P14867; -.
DR MaxQB; P14867; -.
DR PaxDb; P14867; -.
DR PeptideAtlas; P14867; -.
DR PRIDE; P14867; -.
DR ProteomicsDB; 53091; -.
DR ABCD; P14867; 4 sequenced antibodies.
DR Antibodypedia; 4533; 507 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 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; DICTIQY; -.
DR OrthoDB; 1057372at2759; -.
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; 7 hits in 1066 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 106 other tissues.
DR ExpressionAtlas; P14867; baseline and differential.
DR Genevisible; P14867; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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:0005887; C:integral component of plasma membrane; ISS:BHF-UCL.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
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:0005231; F:excitatory extracellular ligand-gated ion channel activity; 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 ion channel activity; IBA:GO_Central.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:1904315; F:transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential; IBA:GO_Central.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
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:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0050877; P:nervous system process; IBA:GO_Central.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:0060078; P:regulation of postsynaptic membrane potential; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0051932; P:synaptic transmission, GABAergic; ISS:BHF-UCL.
DR Gene3D; 1.20.58.390; -; 1.
DR Gene3D; 2.70.170.10; -; 1.
DR InterPro; IPR006028; GABAA/Glycine_rcpt.
DR InterPro; IPR001390; GABAAa_rcpt.
DR InterPro; IPR005431; GABBAa1_rcpt.
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 PANTHER; PTHR18945; PTHR18945; 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; SSF63712; SSF63712; 1.
DR SUPFAM; SSF90112; SSF90112; 1.
DR TIGRFAMs; TIGR00860; LIC; 1.
DR PROSITE; PS00236; NEUROTR_ION_CHANNEL; 1.
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:6X40"
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
