GBRA1_MOUSE
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 03-AUG-2022, entry version 158.
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 PDBsum; 5OSA; -.
DR PDBsum; 5OSB; -.
DR PDBsum; 5OSC; -.
DR AlphaFoldDB; P62812; -.
DR SMR; P62812; -.
DR BioGRID; 199797; 20.
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 GlyConnect; 2320; 7 N-Linked glycans (1 site).
DR GlyGen; P62812; 2 sites, 7 N-linked glycans (1 site).
DR iPTMnet; P62812; -.
DR PhosphoSitePlus; P62812; -.
DR PaxDb; P62812; -.
DR PeptideAtlas; P62812; -.
DR PRIDE; P62812; -.
DR ProteomicsDB; 272940; -.
DR ABCD; P62812; 2 sequenced antibodies.
DR Antibodypedia; 4533; 507 antibodies from 44 providers.
DR DNASU; 14394; -.
DR Ensembl; ENSMUST00000020707; ENSMUSP00000020707; ENSMUSG00000010803.
DR Ensembl; ENSMUST00000205546; ENSMUSP00000146133; ENSMUSG00000010803.
DR GeneID; 14394; -.
DR KEGG; mmu:14394; -.
DR UCSC; uc007imf.2; mouse.
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; ELHKPAM; -.
DR OrthoDB; 1057372at2759; -.
DR PhylomeDB; P62812; -.
DR TreeFam; TF315453; -.
DR Reactome; R-MMU-977443; GABA receptor activation.
DR BioGRID-ORCS; 14394; 2 hits in 72 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 170 other tissues.
DR ExpressionAtlas; P62812; baseline and differential.
DR Genevisible; P62812; MM.
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; 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:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
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:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0050809; F:diazepam binding; ISO:MGI.
DR GO; GO:0005231; F:excitatory extracellular ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0016917; F:GABA receptor activity; 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 ion channel activity; IBA:GO_Central.
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 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:0007268; P:chemical synaptic transmission; IBA:GO_Central.
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: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; IMP:SynGO.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0051932; P:synaptic transmission, GABAergic; ISO:MGI.
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; 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 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
