Gamma-aminobutyric acid receptor subunit alpha-1

Details

Name
Gamma-aminobutyric acid receptor subunit alpha-1
Synonyms
  • GABA(A) receptor subunit alpha-1
  • GABAAR subunit alpha-1
Gene Name
GABRA1
UniProtKB Entry
P14867Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0010561|Gamma-aminobutyric acid receptor subunit alpha-1
MRKSPGLSDCLWAWILLLSTLTGRSYGQPSLQDELKDNTTVFTRILDRLLDGYDNRLRPG
LGERVTEVKTDIFVTSFGPVSDHDMEYTIDVFFRQSWKDERLKFKGPMTVLRLNNLMASK
IWTPDTFFHNGKKSVAHNMTMPNKLLRITEDGTLLYTMRLTVRAECPMHLEDFPMDAHAC
PLKFGSYAYTRAEVVYEWTREPARSVVVAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVVM
TTHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNRESVPARTVFGVTTVLTMTTLSISA
RNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVNYFTKRGYAWDGKSVVPEKPKKVKDP
LIKKNNTYAPTATSYTPNLARGDPGLATIAKSATIEPKEVKPETKPPEPKKTFNSVSKID
RLSRIAFPLLFGIFNLVYWATYLNREPQLKAPTPHQ
Number of residues
456
Molecular Weight
51801.395
Theoretical pI
9.61
GO Classification
Functions
GABA-gated chloride ion channel activity / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
Processes
inhibitory synapse assembly / regulation of postsynaptic membrane potential
Components
cytoplasmic vesicle membrane / dendrite membrane / dendritic spine / GABA-ergic synapse / postsynapse / postsynaptic specialization membrane / transmembrane transporter complex
General Function
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)
Specific Function
GABA-A receptor activity
Pfam Domain Function
Signal Regions
1-27
Transmembrane Regions
254-274 280-301 312-333 422-441
Cellular Location
Postsynaptic cell membrane
Gene sequence
>lcl|BSEQ0010562|Gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1)
ATGAGGAAAAGTCCAGGTCTGTCTGACTGTCTTTGGGCCTGGATCCTCCTTCTGAGCACA
CTGACTGGAAGAAGCTATGGACAGCCGTCATTACAAGATGAACTTAAAGACAATACCACT
GTCTTCACCAGGATTTTGGACAGACTCCTAGATGGTTATGACAATCGCCTGAGACCAGGA
TTGGGAGAGCGTGTAACCGAAGTGAAGACTGATATCTTCGTCACCAGTTTCGGACCCGTT
TCAGACCATGATATGGAATATACAATAGATGTATTTTTCCGTCAAAGCTGGAAGGATGAA
AGGTTAAAATTTAAAGGACCTATGACAGTCCTCCGGTTAAATAACCTAATGGCAAGTAAA
ATCTGGACTCCGGACACATTTTTCCACAATGGAAAGAAGTCAGTGGCCCACAACATGACC
ATGCCCAACAAACTCCTGCGGATCACAGAGGATGGCACCTTGCTGTACACCATGAGGCTG
ACAGTGAGAGCTGAATGTCCGATGCATTTGGAGGACTTCCCTATGGATGCCCATGCTTGC
CCACTAAAATTTGGAAGTTATGCTTATACAAGAGCAGAAGTTGTTTATGAATGGACCAGA
GAGCCAGCACGCTCAGTGGTTGTAGCAGAAGATGGATCACGTCTAAACCAGTATGACCTT
CTTGGACAAACAGTAGACTCTGGAATTGTCCAGTCAAGTACAGGAGAATATGTTGTTATG
ACCACTCATTTCCACTTGAAGAGAAAGATTGGCTACTTTGTTATTCAAACATACCTGCCA
TGCATAATGACAGTGATTCTCTCACAAGTCTCCTTCTGGCTCAACAGAGAGTCTGTACCA
GCAAGAACTGTCTTTGGAGTAACAACTGTGCTCACCATGACAACATTGAGCATCAGTGCC
AGAAACTCCCTCCCTAAGGTGGCTTATGCAACAGCTATGGATTGGTTTATTGCCGTGTGC
TATGCCTTTGTGTTCTCAGCTCTGATTGAGTTTGCCACAGTAAACTATTTCACTAAGAGA
GGTTATGCATGGGATGGCAAAAGTGTGGTTCCAGAAAAGCCAAAGAAAGTAAAGGATCCT
CTTATTAAGAAAAACAACACTTACGCTCCAACAGCAACCAGCTACACCCCTAATTTGGCC
AGGGGCGACCCGGGCTTAGCCACCATTGCTAAAAGTGCAACCATAGAACCTAAAGAGGTC
AAGCCCGAAACAAAACCACCAGAACCCAAGAAAACCTTTAACAGTGTCAGCAAAATTGAC
CGACTGTCAAGAATAGCCTTCCCGCTGCTATTTGGAATCTTTAACTTAGTCTACTGGGCT
ACGTATTTAAACAGAGAGCCTCAGCTAAAAGCCCCCACACCACATCAATAG
Chromosome Location
5
Locus
5q34
External Identifiers
ResourceLink
UniProtKB IDP14867
UniProtKB Entry NameGBRA1_HUMAN
GenBank Protein ID31631
GenBank Gene IDX13584
GeneCard IDGABRA1
GenAtlas IDGABRA1
HGNC IDHGNC:4075
PDB ID(s)6CDU, 6D1S, 6D6T, 6D6U, 6HUG, 6HUJ, 6HUK, 6HUO, 6HUP, 6I53, 6X3S, 6X3T, 6X3U, 6X3V, 6X3W, 6X3X, 6X3Z, 6X40, 7PBD, 7PBZ, 7PC0, 7QNE, 7T0W, 7T0Z, 8DD2, 8DD3, 8SGO, 8SI9, 8SID
KEGG IDhsa:2554
IUPHAR/Guide To Pharmacology ID404
NCBI Gene ID2554
General References
  1. Schofield PR, Pritchett DB, Sontheimer H, Kettenmann H, Seeburg PH: Sequence and expression of human GABAA receptor alpha 1 and beta 1 subunits. FEBS Lett. 1989 Feb 27;244(2):361-4. [Article]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  3. Garrett KM, Duman RS, Saito N, Blume AJ, Vitek MP, Tallman JF: Isolation of a cDNA clone for the alpha subunit of the human GABA-A receptor. Biochem Biophys Res Commun. 1988 Oct 31;156(2):1039-45. [Article]
  4. Lachance-Touchette P, Brown P, Meloche C, Kinirons P, Lapointe L, Lacasse H, Lortie A, Carmant L, Bedford F, Bowie D, Cossette P: Novel alpha1 and gamma2 GABAA receptor subunit mutations in families with idiopathic generalized epilepsy. Eur J Neurosci. 2011 Jul;34(2):237-49. doi: 10.1111/j.1460-9568.2011.07767.x. Epub 2011 Jun 30. [Article]
  5. Carvill GL, Weckhuysen S, McMahon JM, Hartmann C, Moller RS, Hjalgrim H, Cook J, Geraghty E, O'Roak BJ, Petrou S, Clarke A, Gill D, Sadleir LG, Muhle H, von Spiczak S, Nikanorova M, Hodgson BL, Gazina EV, Suls A, Shendure J, Dibbens LM, De Jonghe P, Helbig I, Berkovic SF, Scheffer IE, Mefford HC: GABRA1 and STXBP1: novel genetic causes of Dravet syndrome. Neurology. 2014 Apr 8;82(14):1245-53. doi: 10.1212/WNL.0000000000000291. Epub 2014 Mar 12. [Article]
  6. Cossette P, Liu L, Brisebois K, Dong H, Lortie A, Vanasse M, Saint-Hilaire JM, Carmant L, Verner A, Lu WY, Wang YT, Rouleau GA: Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy. Nat Genet. 2002 Jun;31(2):184-9. Epub 2002 May 6. [Article]
  7. Maljevic S, Krampfl K, Cobilanschi J, Tilgen N, Beyer S, Weber YG, Schlesinger F, Ursu D, Melzer W, Cossette P, Bufler J, Lerche H, Heils A: A mutation in the GABA(A) receptor alpha(1)-subunit is associated with absence epilepsy. Ann Neurol. 2006 Jun;59(6):983-7. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Gamma-aminobutyric acid receptor subunit alpha-1 (Humans)protein
primary
GABA(A) Receptor (Humans)protein
GABA(A) Receptor Benzodiazepine Binding Site (Humans)protein
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Butalbitalapproved, illicityestargetpotentiatorDetails
TopiramateapprovedyestargetagonistDetails
EtomidateapprovedyestargetagonistDetails
Talbutalapproved, illicityestargetpotentiatorDetails
Pentobarbitalapproved, investigational, vet_approvedyestargetpotentiatorDetails
Secobarbitalapproved, vet_approvedyestargetpotentiatorDetails
MetharbitalwithdrawnyestargetpotentiatorDetails
MethohexitalapprovedyestargetantagonistDetails
Thiopentalapproved, vet_approvedyestargetpotentiatorDetails
Primidoneapproved, vet_approvedyestargetpotentiatorDetails
ProgabideexperimentalyestargetagonistDetails
MethylphenobarbitalapprovedyestargetpotentiatorDetails
EthanolapprovedyestargetagonistDetails
Methyprylonapproved, illicit, withdrawnyestargetagonistDetails
Thiamylalapproved, vet_approvedyestargetagonistDetails
Phenobarbitalapproved, investigationalyestargetpotentiatorDetails
FlumazenilapprovedyestargetantagonistDetails
ZolpidemapprovedyestargetagonistDetails
PicrotoxinexperimentalyestargetantagonistDetails
Isofluraneapproved, vet_approvedyestargetagonistDetails
Zaleplonapproved, illicit, investigationalyestargetpotentiatorDetails
Methoxyfluraneapproved, investigational, vet_approved, withdrawnyestargetagonistDetails
Halothaneapproved, vet_approvedunknowntargetother/unknownDetails
HexobarbitalexperimentalyestargetpotentiatorDetails
Butobarbitalapproved, illicityestargetpotentiatorDetails
Meprobamateapproved, illicityestargetagonistDetails
ClomethiazoleinvestigationalunknowntargetDetails
AmoxapineapprovedunknowntargetantagonistDetails
Eszopicloneapproved, investigationalyestargetpotentiatorDetails
ZopicloneapprovedyestargetpotentiatorDetails
Ginkgo bilobaapproved, investigational, nutraceuticalunknowntargetnegative modulatorDetails
Fludiazepamexperimental, illicityestargetpotentiatorDetails
Dihydroquinidine barbiturateexperimentalyestargetpotentiatorDetails
Amobarbitalapproved, illicityestargetpotentiatorDetails
HeptabarbitalexperimentalyestargetpotentiatorDetails
Aprobarbitalexperimental, illicityestargetpotentiatorDetails
BarbitalillicityestargetpotentiatorDetails
Dihydro-2-thioxo-5-((5-(2-(trifluoromethyl)phenyl)-2-furanyl)methyl)-4,6(1H,5H)-pyrimidinedioneexperimental, illicityestargetpotentiatorDetails
Glutethimideapproved, illicityestargetagonistDetails
Quinidine barbiturateapprovedyestargetpotentiatorDetails
CarisoprodolapprovedyestargetactivatormodulatorDetails
MuscimolinvestigationalunknowntargetDetails
ClozapineapprovedunknowntargetantagonistDetails
Flavoneapproved, experimentalyestargetinhibitorDetails
EltanoloneinvestigationalyestargetinhibitorDetails
gamma-Aminobutyric acidapproved, investigationalyestargetinhibitorDetails
EVT 201investigationalyestargetmodulatorDetails
ZK-93423investigationalyestargetinhibitorDetails
Ethchlorvynolapproved, illicit, withdrawnyestargetantagonistDetails
IndiploninvestigationalyestargetagonistDetails
Butabarbitalapproved, illicityestargetantagonistDetails
Clobazamapproved, illicityestargetantagonistDetails
NitrazepamapprovedyestargetantagonistDetails
ThiocolchicosideexperimentalyestargetinhibitorDetails
Brexanoloneapproved, investigationalyestargetinhibitorDetails
Desfluraneapprovedyestargetpositive allosteric modulatorDetails
Alprazolamapproved, illicit, investigationalyestargetpositive allosteric modulatorDetails
Butabarbitalapproved, illicityestargetpositive allosteric modulatorDetails
Chlordiazepoxideapproved, illicit, investigationalyestargetpositive allosteric modulatorDetails
Clobazamapproved, illicityestargetpositive allosteric modulatorDetails
Clonazepamapproved, illicityestargetpositive allosteric modulatorDetails
Clorazepic acidapproved, illicityestargetpositive allosteric modulatorDetails
Lorazepamapprovedyestargetpositive allosteric modulatorDetails
Ethchlorvynolapproved, illicit, withdrawnyestargetpositive allosteric modulatorDetails
Enfluraneapproved, investigational, vet_approvedyestargetpotentiatorDetails
Temazepamapproved, investigationalyestargetpositive allosteric modulatorDetails
Butalbitalapproved, illicityestargetpositive allosteric modulatorDetails
Etomidateapprovedyestargetpositive allosteric modulatorDetails
Talbutalapproved, illicityestargetpositive allosteric modulatorDetails
Pentobarbitalapproved, investigational, vet_approvedyestargetpositive allosteric modulatorDetails
Meprobamateapproved, illicityestargetpositive allosteric modulatorDetails
Eszopicloneapproved, investigationalyestargetpositive allosteric modulatorDetails
Metharbitalwithdrawnyestargetpositive allosteric modulatorDetails
Isofluraneapproved, vet_approvedyestargetpositive allosteric modulatorDetails
Primidoneapproved, vet_approvedyestargetpositive allosteric modulatorDetails
Halazepamapproved, illicit, withdrawnyestargetpositive allosteric modulatorDetails
Propofolapproved, investigational, vet_approvedyestargetpositive allosteric modulatorDetails
Diazepamapproved, illicit, investigational, vet_approvedyestargetpositive allosteric modulatorDetails
Oxazepamapprovedyestargetpositive allosteric modulatorDetails
Methoxyfluraneapproved, investigational, vet_approved, withdrawnyestargetpositive allosteric modulatorDetails
Methyprylonapproved, illicit, withdrawnyestargetpositive allosteric modulatorDetails
Halothaneapproved, vet_approvedyestargetpositive allosteric modulatorDetails
Flumazenilapprovedyestargetpositive allosteric modulatorDetails
Estazolamapproved, illicityestargetpositive allosteric modulatorDetails
Sevofluraneapproved, vet_approvedyestargetagonistDetails
Glutethimideapproved, illicityestargetpositive allosteric modulatorDetails
Prazepamapproved, illicityestargetpositive allosteric modulatorDetails
Quazepamapproved, illicityestargetpositive allosteric modulatorDetails
AmoxapineapprovedunknowntargetbinderDetails
Prasteroneapproved, investigational, nutraceuticalunknowntargetantagonistDetails
ThiocolchicosideexperimentalyestargetantagonistDetails
Stiripentolapprovedyestargetagonistpositive allosteric modulatorDetails
Taurineapproved, nutraceuticalyestargetagonistDetails
Lamotrigineapproved, investigationalunknowntargetantagonistinducerDetails
Apalutamideapproved, investigationalnotargetantagonistDetails
Brexanoloneapproved, investigationalyestargetpositive allosteric modulatorDetails
Memantineapproved, investigationalunknowntargetbinderDetails
Medroxyprogesterone acetateapproved, investigationalunknowntargetinhibitorDetails
Phenytoinapproved, vet_approvedunknowntargetDetails
Midazolamapproved, illicityestargetpositive allosteric modulatorDetails
Flurazepamapproved, illicit, investigationalyestargetpositive allosteric modulatorDetails
Triazolamapproved, investigationalyestargetpositive allosteric modulatorDetails
Bromazepamapproved, illicit, investigationalyestargetpositive allosteric modulatorDetails
Nitrazepamapprovedyestargetpositive allosteric modulatorDetails
Camazepamexperimental, illicityestargetpositive allosteric modulatorDetails
Delorazepamexperimental, illicityestargetpositive allosteric modulatorDetails
Flunitrazepamapproved, illicityestargetpositive allosteric modulatorDetails
Etizolamexperimentalyestargetpositive allosteric modulatorDetails
Medazepamexperimentalyestargetpositive allosteric modulatorDetails
Doxefazepamexperimentalyestargetpositive allosteric modulatorDetails
Lormetazepamapprovedyestargetpositive allosteric modulatorDetails
Nordazepamexperimentalyestargetpositive allosteric modulatorDetails
Adinazolamexperimentalyestargetpositive allosteric modulatorDetails
Ethyl loflazepateexperimental, illicityestargetpositive allosteric modulatorDetails
Cloxazolamexperimentalyestargetpositive allosteric modulatorDetails
Clotiazepamapproved, illicityestargetpositive allosteric modulatorDetails
Ketazolamapprovedyestargetpositive allosteric modulatorDetails
Cinolazepamexperimentalyestargetpositive allosteric modulatorDetails
Brotizolaminvestigational, withdrawnyestargetpositive allosteric modulatorDetails
Pinazepamexperimentalyestargetpositive allosteric modulatorDetails
Loprazolamexperimentalyestargetpositive allosteric modulatorDetails
Oxazepam acetateexperimentalyestargetpositive allosteric modulatorDetails
1,2-Benzodiazepineapproved, investigationalunknowntargetpositive allosteric modulatorDetails
Cinazepamexperimentalyestargetpositive allosteric modulatorDetails
Bentazepamexperimentalyestargetpositive allosteric modulatorDetails
Mexazolamexperimentalyestargetpositive allosteric modulatorDetails
Remimazolamapproved, investigationalyestargetpositive allosteric modulatorDetails
Ganaxoloneapproved, investigationalyestargetpositive allosteric modulatorDetails
Zuranoloneapproved, experimentalyestargetpositive allosteric modulatorDetails
Adipiploninvestigationalyestargetpartial agonistDetails
5,7,2′-trihydroxy-6,8-dimethoxyflavoneexperimentalunknowntargetligandDetails
Lamotrigineapproved, investigationalunknowntargetinhibitorDetails
Olanzapineapproved, investigationalnotargetinhibitorDetails
MexazolamexperimentalyestargetligandDetails
OxazepamapprovedyestargetligandDetails
Alprazolamapproved, illicit, investigationalyestargetligandDetails
LorazepamapprovedyestargetligandDetails
Temazepamapproved, investigationalunknowntargetligandDetails
Chlordiazepoxideapproved, illicit, investigationalyestargetligandDetails
Clorazepic acidapproved, illicityestargetligandDetails
Midazolamapproved, illicityestargetligandDetails
Flurazepamapproved, illicit, investigationalyestargetligandDetails
Diazepamapproved, illicit, investigational, vet_approvedyestargetligandDetails
Triazolamapproved, investigationalyestargetligandDetails
Clonazepamapproved, illicityestargetligandDetails
Estazolamapproved, illicityestargetligandDetails
Bromazepamapproved, illicit, investigationalyestargetligandDetails
NitrazepamapprovedyestargetligandDetails
Clobazamapproved, illicityestargetligandDetails
Camazepamexperimental, illicityestargetligandDetails
Delorazepamexperimental, illicityestargetligandDetails
Flunitrazepamapproved, illicityestargetligandDetails
Prazepamapproved, illicityestargetligandDetails
EtizolamexperimentalyestargetligandDetails
MedazepamexperimentalyestargetligandDetails
DoxefazepamexperimentalyestargetligandDetails
LormetazepamapprovedyestargetligandDetails
NordazepamexperimentalyestargetligandDetails
AdinazolamexperimentalyestargetligandDetails
Halazepamapproved, illicit, withdrawnunknowntargetligandDetails
Ethyl loflazepateexperimental, illicityestargetligandDetails
CloxazolamexperimentalyestargetligandDetails
Clotiazepamapproved, illicityestargetligandDetails
KetazolamapprovedyestargetligandDetails
CinolazepamexperimentalyestargetligandDetails
Brotizolaminvestigational, withdrawnyestargetligandDetails
PinazepamexperimentalyestargetligandDetails
LoprazolamexperimentalunknowntargetligandDetails
Quazepamapproved, illicityestargetligandDetails
Oxazepam acetateexperimentalyestargetligandDetails
1,2-Benzodiazepineapproved, investigationalunknowntargetligandDetails
CinazepamexperimentalyestargetligandDetails
BentazepamexperimentalyestargetligandDetails
Remimazolamapproved, investigationalyestargetligandDetails
Zonisamideapproved, investigationalunknowntargetbinderDetails