ID   GBRA1_MOUSE             Reviewed;         455 AA.
AC   P62812; P18504;
DT   16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT   16-AUG-2004, sequence version 1.
DT   27-MAR-2024, entry version 167.
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; Synonyms=Gabra-1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6J, and DBA/2J; TISSUE=Brain;
RX   PubMed=1356407;
RA   Wang J.B., Kofuji P., Fernando J.C., Moss S.J., Huganir R.L., Burt D.R.;
RT   "The alpha 1, alpha 2, and alpha 3 subunits of GABAA receptors: comparison
RT   in seizure-prone and -resistant mice and during development.";
RL   J. Mol. Neurosci. 3:177-184(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1848528; DOI=10.1016/0888-7543(91)90272-g;
RA   Keir W.J., Kozak C.A., Chakraborti A., Deitrich R.A., Sikela J.M.;
RT   "The cDNA sequence and chromosomal location of the murine GABAA alpha 1
RT   receptor gene.";
RL   Genomics 9:390-395(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=BALB/cJ;
RX   PubMed=12106288; DOI=10.1111/j.1460-9568.1990.tb00460.x;
RA   Kato K.;
RT   "A collection of cDNA clones with specific expression patterns in mouse
RT   brain.";
RL   Eur. J. Neurosci. 2:704-711(1990).
RN   [4]
RP   INTERACTION WITH TRAK1, AND SUBCELLULAR LOCATION.
RX   PubMed=16380713; DOI=10.1038/ng1715;
RA   Gilbert S.L., Zhang L., Forster M.L., Anderson J.R., Iwase T., Soliven B.,
RA   Donahue L.R., Sweet H.O., Bronson R.T., Davisson M.T., Wollmann R.L.,
RA   Lahn B.T.;
RT   "Trak1 mutation disrupts GABA(A) receptor homeostasis in hypertonic mice.";
RL   Nat. Genet. 38:245-250(2006).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [6]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=25348603; DOI=10.1038/npp.2014.292;
RA   Swanson A.M., Allen A.G., Shapiro L.P., Gourley S.L.;
RT   "GABAAalpha1-mediated plasticity in the orbitofrontal cortex regulates
RT   context-dependent action selection.";
RL   Neuropsychopharmacology 40:1027-1036(2015).
RN   [7]
RP   SUBCELLULAR LOCATION.
RX   PubMed=25579817; DOI=10.1016/j.str.2014.11.016;
RA   Delto C.F., Heisler F.F., Kuper J., Sander B., Kneussel M., Schindelin H.;
RT   "The LisH motif of muskelin is crucial for oligomerization and governs
RT   intracellular localization.";
RL   Structure 23:364-373(2015).
RN   [8]
RP   FUNCTION, GLYCOSYLATION, AND DOMAIN EXTRACELLULAR.
RX   PubMed=27129275; DOI=10.1074/jbc.m116.714790;
RA   Brown L.E., Nicholson M.W., Arama J.E., Mercer A., Thomson A.M.,
RA   Jovanovic J.N.;
RT   "Gamma-aminobutyric acid type A (GABAA) receptor subunits play a direct
RT   structural role in synaptic contact formation via their N-terminal
RT   extracellular domains.";
RL   J. Biol. Chem. 291:13926-13942(2016).
RN   [9]
RP   INTERACTION WITH SHISA7.
RX   PubMed=31601770; DOI=10.1126/science.aax5719;
RA   Han W., Li J., Pelkey K.A., Pandey S., Chen X., Wang Y.X., Wu K., Ge L.,
RA   Li T., Castellano D., Liu C., Wu L.G., Petralia R.S., Lynch J.W.,
RA   McBain C.J., Lu W.;
RT   "Shisa7 is a GABAA receptor auxiliary subunit controlling benzodiazepine
RT   actions.";
RL   Science 366:246-250(2019).
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:27129275). Plays an important
CC       role in the formation of functional inhibitory GABAergic synapses in
CC       addition to mediating synaptic inhibition as a GABA-gated ion channel
CC       (PubMed:27129275). 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 (PubMed:27129275). The
CC       alpha1/beta2/gamma2 receptor and the alpha1/beta3/gamma2 receptor
CC       exhibit synaptogenic activity (PubMed:27129275). GABRA1-mediated
CC       plasticity in the orbitofrontal cortex regulates context-dependent
CC       action selection (PubMed:25348603). Functions also as histamine
CC       receptor and mediates cellular responses to histamine (By similarity).
CC       {ECO:0000250|UniProtKB:P62813, ECO:0000269|PubMed:25348603,
CC       ECO:0000269|PubMed:27129275}.
CC   -!- ACTIVITY REGULATION: Allosterically activated by benzodiazepines, the
CC       neuroanesthetic alphaxalone and pentobarbital (By similarity).
CC       Inhibited by the antagonist bicuculline (By similarity).
CC       {ECO:0000250|UniProtKB:P14867, ECO:0000250|UniProtKB:P62813}.
CC   -!- SUBUNIT: Heteropentamer, formed by a combination of alpha, beta, gamma,
CC       delta and rho chains (By similarity). Interacts with UBQLN1 (By
CC       similarity). Interacts with TRAK1 (PubMed:16380713). Interacts with
CC       KIF21B (By similarity). Identified in a complex of 720 kDa composed of
CC       LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity).
CC       Interacts with LHFPL4 (By similarity). Interacts with NLGN2 (By
CC       similarity). Interacts with SHISA7; interaction leads to the regulation
CC       of GABA(A) receptor trafficking, channel deactivation kinetics and
CC       pharmacology (PubMed:31601770). {ECO:0000250|UniProtKB:P14867,
CC       ECO:0000250|UniProtKB:P62813, ECO:0000269|PubMed:16380713,
CC       ECO:0000269|PubMed:31601770}.
CC   -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC       {ECO:0000250|UniProtKB:P08219}; Multi-pass membrane protein
CC       {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:16380713,
CC       ECO:0000269|PubMed:25579817}; Multi-pass membrane protein
CC       {ECO:0000255}. Cytoplasmic vesicle membrane
CC       {ECO:0000250|UniProtKB:P62813}.
CC   -!- DOMAIN: The extracellular domain contributes to synaptic contact
CC       formation. {ECO:0000269|PubMed:27129275}.
CC   -!- PTM: Glycosylated. {ECO:0000269|PubMed:27129275}.
CC   -!- DISRUPTION PHENOTYPE: Gene knockdown in orbitofrontal prefrontal cortex
CC       results in an inability of mice to select actions based on their
CC       consequences, developing instead habit-like behavioral inflexibility.
CC       {ECO:0000269|PubMed:25348603}.
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}.
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DR   EMBL; M86566; AAB59634.1; -; mRNA.
DR   EMBL; M63436; AAA37654.1; -; mRNA.
DR   EMBL; X61430; CAA43672.1; -; mRNA.
DR   CCDS; CCDS24553.1; -.
DR   PIR; A39062; A39062.
DR   RefSeq; NP_034380.1; NM_010250.5.
DR   RefSeq; XP_006532259.1; XM_006532196.3.
DR   RefSeq; XP_017169748.1; XM_017314259.1.
DR   RefSeq; XP_017169749.1; XM_017314260.1.
DR   PDB; 5OSA; X-ray; 2.75 A; A/B/C/D/E=250-338, A/B/C/D/E=417-455.
DR   PDB; 5OSB; X-ray; 3.80 A; A/B/C/D/E=250-338, A/B/C/D/E=417-455.
DR   PDB; 5OSC; X-ray; 3.10 A; A/B/C/D/E=250-338, A/B/C/D/E=417-455.
DR   PDB; 8FOI; EM; 2.50 A; A/C=1-455.
DR   PDB; 8G4N; EM; 2.67 A; A/C=1-455.
DR   PDB; 8G4O; EM; 3.06 A; A/C=1-455.
DR   PDB; 8G4X; EM; 2.56 A; A=1-455.
DR   PDB; 8G5F; EM; 2.64 A; C=1-455.
DR   PDB; 8G5G; EM; 2.94 A; A=1-455.
DR   PDB; 8G5H; EM; 2.89 A; C=1-455.
DR   PDBsum; 5OSA; -.
DR   PDBsum; 5OSB; -.
DR   PDBsum; 5OSC; -.
DR   PDBsum; 8FOI; -.
DR   PDBsum; 8G4N; -.
DR   PDBsum; 8G4O; -.
DR   PDBsum; 8G4X; -.
DR   PDBsum; 8G5F; -.
DR   PDBsum; 8G5G; -.
DR   PDBsum; 8G5H; -.
DR   AlphaFoldDB; P62812; -.
DR   EMDB; EMD-29350; -.
DR   EMDB; EMD-29727; -.
DR   EMDB; EMD-29728; -.
DR   EMDB; EMD-29733; -.
DR   EMDB; EMD-29741; -.
DR   EMDB; EMD-29742; -.
DR   EMDB; EMD-29743; -.
DR   SMR; P62812; -.
DR   BioGRID; 199797; 32.
DR   ComplexPortal; CPX-2979; GABA-A receptor, alpha-1/beta-2/gamma-2.
DR   ComplexPortal; CPX-2983; GABA-A receptor, alpha-1/beta-3/gamma-2.
DR   DIP; DIP-32219N; -.
DR   IntAct; P62812; 1.
DR   STRING; 10090.ENSMUSP00000020707; -.
DR   BindingDB; P62812; -.
DR   ChEMBL; CHEMBL3139; -.
DR   DrugCentral; P62812; -.
DR   TCDB; 1.A.9.5.16; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.
DR   GlyConnect; 2320; 7 N-Linked glycans (1 site).
DR   GlyCosmos; P62812; 2 sites, 7 glycans.
DR   GlyGen; P62812; 3 sites, 7 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR   iPTMnet; P62812; -.
DR   PhosphoSitePlus; P62812; -.
DR   SwissPalm; P62812; -.
DR   PaxDb; 10090-ENSMUSP00000020707; -.
DR   PeptideAtlas; P62812; -.
DR   ProteomicsDB; 272940; -.
DR   ABCD; P62812; 2 sequenced antibodies.
DR   Antibodypedia; 4533; 557 antibodies from 44 providers.
DR   DNASU; 14394; -.
DR   Ensembl; ENSMUST00000020707.12; ENSMUSP00000020707.6; ENSMUSG00000010803.14.
DR   Ensembl; ENSMUST00000205546.2; ENSMUSP00000146133.2; ENSMUSG00000010803.14.
DR   GeneID; 14394; -.
DR   KEGG; mmu:14394; -.
DR   UCSC; uc007imf.2; mouse.
DR   AGR; MGI:95613; -.
DR   CTD; 2554; -.
DR   MGI; MGI:95613; Gabra1.
DR   VEuPathDB; HostDB:ENSMUSG00000010803; -.
DR   eggNOG; KOG3642; Eukaryota.
DR   GeneTree; ENSGT00940000159136; -.
DR   HOGENOM; CLU_010920_2_1_1; -.
DR   InParanoid; P62812; -.
DR   OMA; YLWAYLF; -.
DR   OrthoDB; 4265336at2759; -.
DR   PhylomeDB; P62812; -.
DR   TreeFam; TF315453; -.
DR   Reactome; R-MMU-977443; GABA receptor activation.
DR   BioGRID-ORCS; 14394; 2 hits in 77 CRISPR screens.
DR   ChiTaRS; Gabra1; mouse.
DR   PRO; PR:P62812; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; P62812; Protein.
DR   Bgee; ENSMUSG00000010803; Expressed in cerebellum lobe and 172 other cell types or tissues.
DR   ExpressionAtlas; P62812; 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; ISO:MGI.
DR   GO; GO:1902711; C:GABA-A receptor complex; ISS:UniProtKB.
DR   GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR   GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0098794; C:postsynapse; IBA:GO_Central.
DR   GO; GO:0099634; C:postsynaptic specialization membrane; ISO:MGI.
DR   GO; GO:0045202; C:synapse; IBA:GO_Central.
DR   GO; GO:0050809; F:diazepam binding; ISO:MGI.
DR   GO; GO:0004890; F:GABA-A receptor activity; IEA:InterPro.
DR   GO; GO:0022851; F:GABA-gated chloride ion channel activity; ISO:MGI.
DR   GO; GO:0005237; F:inhibitory extracellular ligand-gated monoatomic ion channel activity; IBA:GO_Central.
DR   GO; GO:0099507; F:ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential; ISO:MGI.
DR   GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR   GO; GO:0097159; F:organic cyclic compound binding; ISO:MGI.
DR   GO; GO:1904315; F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential; IDA:SynGO.
DR   GO; GO:0071420; P:cellular response to histamine; ISO:MGI.
DR   GO; GO:1902476; P:chloride transmembrane transport; ISO:MGI.
DR   GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; ISO:MGI.
DR   GO; GO:1904862; P:inhibitory synapse assembly; IDA:UniProtKB.
DR   GO; GO:0060078; P:regulation of postsynaptic membrane potential; IMP:SynGO.
DR   GO; GO:0051932; P:synaptic transmission, GABAergic; ISO:MGI.
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; P62812; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Chloride; Chloride channel;
KW   Cytoplasmic vesicle; Disulfide bond; Glycoprotein; Ion channel;
KW   Ion transport; Ligand-gated ion channel; Membrane;
KW   Postsynaptic cell membrane; Receptor; Reference proteome; Signal; Synapse;
KW   Transmembrane; Transmembrane helix; Transport.
FT   SIGNAL          1..27
FT                   /evidence="ECO:0000255"
FT   CHAIN           28..455
FT                   /note="Gamma-aminobutyric acid receptor subunit alpha-1"
FT                   /id="PRO_0000000429"
FT   TOPO_DOM        28..250
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        251..272
FT                   /note="Helical"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        278..299
FT                   /note="Helical"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        312..333
FT                   /note="Helical"
FT                   /evidence="ECO:0000305"
FT   TOPO_DOM        334..420
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        421..442
FT                   /note="Helical"
FT                   /evidence="ECO:0000305"
FT   CARBOHYD        37
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        137
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        165..179
FT                   /evidence="ECO:0000250"
FT   HELIX           37..48
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   TURN            58..62
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   STRAND          65..80
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   TURN            81..84
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   STRAND          85..97
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   STRAND          99..101
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   STRAND          108..112
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   HELIX           114..117
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   STRAND          125..127
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   STRAND          130..134
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   STRAND          138..140
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   STRAND          145..148
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   STRAND          151..154
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   STRAND          157..164
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   STRAND          176..179
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   STRAND          183..187
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   TURN            190..192
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   STRAND          193..199
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   TURN            201..204
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   STRAND          205..207
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   STRAND          215..230
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   STRAND          235..247
FT                   /evidence="ECO:0007829|PDB:8G4O"
FT   HELIX           250..255
FT                   /evidence="ECO:0007829|PDB:5OSA"
FT   HELIX           257..269
FT                   /evidence="ECO:0007829|PDB:5OSA"
FT   HELIX           270..272
FT                   /evidence="ECO:0007829|PDB:5OSA"
FT   HELIX           278..284
FT                   /evidence="ECO:0007829|PDB:5OSA"
FT   HELIX           287..300
FT                   /evidence="ECO:0007829|PDB:5OSA"
FT   HELIX           311..335
FT                   /evidence="ECO:0007829|PDB:5OSA"
FT   HELIX           417..441
FT                   /evidence="ECO:0007829|PDB:5OSA"
SQ   SEQUENCE   455 AA;  51754 MW;  A270B43423B4086E CRC64;
     MKKSRGLSDY LWAWTLILST LSGRSYGQPS QDELKDNTTV FTRILDRLLD GYDNRLRPGL
     GERVTEVKTD IFVTSFGPVS DHDMEYTIDV FFRQSWKDER LKFKGPMTVL RLNNLMASKI
     WTPDTFFHNG KKSVAHNMTM PNKLLRITED GTLLYTMRLT VRAECPMHLE DFPMDAHACP
     LKFGSYAYTR AEVVYEWTRE PARSVVVAED GSRLNQYDLL GQTVDSGIVQ SSTGEYVVMT
     THFHLKRKIG YFVIQTYLPC IMTVILSQVS FWLNRESVPA RTVFGVTTVL TMTTLSISAR
     NSLPKVAYAT AMDWFIAVCY AFVFSALIEF ATVNYFTKRG YAWDGKSVVP EKPKKVKDPL
     IKKNNTYAPT ATSYTPNLAR GDPGLATIAK SATIEPKEVK PETKPPEPKK TFNSVSKIDR
     LSRIAFPLLF GIFNLVYWAT YLNREPQLKA PTPHQ
//