GBRA2_MOUSE
ID GBRA2_MOUSE Reviewed; 451 AA.
AC P26048;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Gamma-aminobutyric acid receptor subunit alpha-2;
DE AltName: Full=GABA(A) receptor subunit alpha-2;
DE Flags: Precursor;
GN Name=Gabra2; Synonyms=Gabra-2;
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 INTERACTION WITH UBQLN1, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=11528422; DOI=10.1038/nn0901-908;
RA Bedford F.K., Kittler J.T., Muller E., Thomas P., Uren J.M., Merlo D.,
RA Wisden W., Triller A., Smart T.G., Moss S.J.;
RT "GABA(A) receptor cell surface number and subunit stability are regulated
RT by the ubiquitin-like protein Plic-1.";
RL Nat. Neurosci. 4:908-916(2001).
RN [3]
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 [4]
RP INTERACTION WITH LHFPL4, AND SUBCELLULAR LOCATION.
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 [5]
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 alpha2/beta2/gamma2 receptor exhibits synaptogenic activity whereas the
CC alpha2/beta3/gamma2 receptor shows very little or no synaptogenic
CC activity (PubMed:27129275). {ECO:0000269|PubMed:27129275}.
CC -!- ACTIVITY REGULATION: Activated by pentobarbital (By similarity).
CC Inhibited by the antagonist bicuculline (By similarity).
CC {ECO:0000250|UniProtKB:P10063}.
CC -!- SUBUNIT: Heteropentamer, formed by a combination of alpha, beta, gamma,
CC delta and rho chains (PubMed:11528422). Interacts with UBQLN1
CC (PubMed:11528422). Interacts with KIF21B (By similarity). Interacts
CC with LHFPL4 (PubMed:28978485, PubMed:11528422) (By similarity).
CC Interacts with SHISA7; interaction leads to the regulation of GABA(A)
CC receptor trafficking, channel deactivation kinetics and pharmacology
CC (PubMed:31601770). {ECO:0000250|UniProtKB:P23576,
CC ECO:0000269|PubMed:11528422, ECO:0000269|PubMed:28978485,
CC ECO:0000269|PubMed:31601770, ECO:0000303|PubMed:11528422}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000269|PubMed:11528422}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:11528422,
CC ECO:0000269|PubMed:28978485}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle membrane
CC {ECO:0000250|UniProtKB:P23576}. Cell projection, dendrite
CC {ECO:0000269|PubMed:28978485}.
CC -!- DOMAIN: The extracellular domain contributes to synaptic contact
CC formation. {ECO:0000269|PubMed:27129275}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:27129275}.
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. GABRA2 sub-
CC subfamily. {ECO:0000305}.
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DR EMBL; M86567; AAA37650.1; -; mRNA.
DR CCDS; CCDS19327.1; -.
DR RefSeq; NP_032092.1; NM_008066.3.
DR RefSeq; XP_006503796.1; XM_006503733.3.
DR AlphaFoldDB; P26048; -.
DR SMR; P26048; -.
DR ComplexPortal; CPX-2985; GABA-A receptor, alpha-2/beta-3/gamma-2.
DR STRING; 10090.ENSMUSP00000000572; -.
DR ChEMBL; CHEMBL2094133; -.
DR DrugCentral; P26048; -.
DR GlyConnect; 2321; 5 N-Linked glycans (1 site).
DR GlyGen; P26048; 2 sites, 5 N-linked glycans (1 site).
DR iPTMnet; P26048; -.
DR PhosphoSitePlus; P26048; -.
DR SwissPalm; P26048; -.
DR PaxDb; P26048; -.
DR PeptideAtlas; P26048; -.
DR PRIDE; P26048; -.
DR ProteomicsDB; 267772; -.
DR ABCD; P26048; 2 sequenced antibodies.
DR Antibodypedia; 12030; 348 antibodies from 33 providers.
DR DNASU; 14395; -.
DR Ensembl; ENSMUST00000197284; ENSMUSP00000142892; ENSMUSG00000000560.
DR GeneID; 14395; -.
DR KEGG; mmu:14395; -.
DR UCSC; uc008xqv.1; mouse.
DR CTD; 2555; -.
DR MGI; MGI:95614; Gabra2.
DR VEuPathDB; HostDB:ENSMUSG00000000560; -.
DR eggNOG; KOG3642; Eukaryota.
DR GeneTree; ENSGT00940000157266; -.
DR InParanoid; P26048; -.
DR OMA; AXSITEV; -.
DR OrthoDB; 1057372at2759; -.
DR PhylomeDB; P26048; -.
DR TreeFam; TF315453; -.
DR Reactome; R-MMU-977443; GABA receptor activation.
DR BioGRID-ORCS; 14395; 3 hits in 73 CRISPR screens.
DR PRO; PR:P26048; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P26048; protein.
DR Bgee; ENSMUSG00000000560; Expressed in subiculum and 92 other tissues.
DR ExpressionAtlas; P26048; baseline and differential.
DR Genevisible; P26048; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; IDA:MGI.
DR GO; GO:0032590; C:dendrite membrane; ISO:MGI.
DR GO; GO:1902711; C:GABA-A receptor complex; ISO:MGI.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0060077; C:inhibitory synapse; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; IDA:SynGO.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IDA:MGI.
DR GO; GO:0098794; C:postsynapse; IDA:MGI.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0008503; F:benzodiazepine receptor activity; ISO:MGI.
DR GO; GO:0005231; F:excitatory extracellular ligand-gated ion channel activity; IBA:GO_Central.
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: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; 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:0006836; P:neurotransmitter transport; ISO:MGI.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:0001505; P:regulation of neurotransmitter levels; ISO:MGI.
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; IBA:GO_Central.
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; IPR005432; GABBAa2_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 PANTHER; PTHR18945:SF218; PTHR18945:SF218; 1.
DR Pfam; PF02931; Neur_chan_LBD; 1.
DR Pfam; PF02932; Neur_chan_memb; 1.
DR PRINTS; PR01079; GABAARALPHA.
DR PRINTS; PR01615; GABAARALPHA2.
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 Cell membrane; Cell projection; 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..28
FT /evidence="ECO:0000255"
FT CHAIN 29..451
FT /note="Gamma-aminobutyric acid receptor subunit alpha-2"
FT /id="PRO_0000000434"
FT TOPO_DOM 29..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..419
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 420..441
FT /note="Helical"
FT /evidence="ECO:0000305"
FT REGION 389..408
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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"
SQ SEQUENCE 451 AA; 51139 MW; C5E47898963A36CF CRC64;
MKTKLSTCNV WSLLLVLLVW DPVRLVLANI QEDEAKNNIT IFTRILDRLL DGYDNRLRPG
LGDSITEVFT NIYVTSFGPV SDTDMEYTID VFFRQKWKDE RLKFKGPMNI LRLNNLMASK
IWTPDTFFHN GKKSVAHNMT MPNKLLRIQD DGTLLYTMRL TVQAECPMHL EDFPMDAHSC
PLKFGSYAYT TSEVTYIWTY NASDSVQVAP DGSRLNQYDL LGQSIGKETI KSSTGEYTVM
TAHFHLKRKI GYFVIQTYLP CIMTVILSQV SFWLNRESVP ARTVFGVTTV LTMTTLSISA
RNSLPKVAYA TAMDWFIAVC YAFVFSALIE FATVNYFTKR GWAWDGKSVV NDKKKEKGSV
MIQNNAYAVA VANYAPNLSK DPVLSTISKS ATTPEPNKKP ENKPAEAKKT FNSVSKIDRM
SRIVFPVLFG TFNLVYWATY LNREPVLGVS P
