GBRA1_RAT
ID GBRA1_RAT Reviewed; 455 AA.
AC P62813; P18504; Q53YK4;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 144.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION, AND
RP SUBUNIT.
RX PubMed=2540033; DOI=10.1016/0014-5793(89)80271-6;
RA Lolait S.J., O'Carroll A.-M., Kusano K., Muller J.-M., Brownstein M.J.,
RA Mahan L.C.;
RT "Cloning and expression of a novel rat GABAA receptor.";
RL FEBS Lett. 246:145-148(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2561977; DOI=10.1016/0896-6273(89)90243-2;
RA Khrestchatisky M., Maclennan A.J., Chiang M.Y., Xu W., Jackson M.B.,
RA Brecha N., Sternini C., Olsen R.W., Tobin A.J.;
RT "A novel alpha subunit in rat brain GABAA receptors.";
RL Neuron 3:745-753(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=1977069; DOI=10.1016/0169-328x(90)90017-8;
RA Malherbe P., Draguhn A., Multhaup G., Beyreuther K., Mohler H.;
RT "GABAA-receptor expressed from rat brain alpha- and beta-subunit cDNAs
RT displays potentiation by benzodiazepine receptor ligands.";
RL Brain Res. Mol. Brain Res. 8:199-208(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Brain;
RX PubMed=1966765; DOI=10.1101/sqb.1990.055.01.006;
RA Seeburg P.H., Wisden W., Verdoorn T., Pritchett D., Werner P., Herb A.,
RA Lueddens H., Sprengel R., Sakmann B.;
RT "The GABAA receptor family: molecular and functional diversity.";
RL Cold Spring Harb. Symp. Quant. Biol. 55:29-40(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Groot-Kormelink P.J.;
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [7]
RP MUTAGENESIS OF PHE-91, FUNCTION, SUBCELLULAR LOCATION, AND ACTIVITY
RP REGULATION.
RX PubMed=1376242; DOI=10.1002/j.1460-2075.1992.tb05258.x;
RA Sigel E., Baur R., Kellenberger S., Malherbe P.;
RT "Point mutations affecting antagonist affinity and agonist dependent gating
RT of GABAA receptor channels.";
RL EMBO J. 11:2017-2023(1992).
RN [8]
RP INTERACTION WITH UBQLN1.
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 [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=18281286; DOI=10.1074/jbc.m709993200;
RA Saras A., Gisselmann G., Vogt-Eisele A.K., Erlkamp K.S., Kletke O.,
RA Pusch H., Hatt H.;
RT "Histamine action on vertebrate GABAA receptors: direct channel gating and
RT potentiation of GABA responses.";
RL J. Biol. Chem. 283:10470-10475(2008).
RN [10]
RP INTERACTION WITH KIF21B, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=25172774; DOI=10.1016/j.ejcb.2014.07.007;
RA Labonte D., Thies E., Kneussel M.;
RT "The kinesin KIF21B participates in the cell surface delivery of gamma2
RT subunit-containing GABAA receptors.";
RL Eur. J. Cell Biol. 93:338-346(2014).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN A COMPLEX WITH
RP NLGN2; LHFPL4; GABRB2; GABRG2 AND GABRB3, AND INTERACTION WITH LHFLP4 AND
RP NLGN2.
RX PubMed=28279354; DOI=10.1016/j.neuron.2017.02.023;
RA Yamasaki T., Hoyos-Ramirez E., Martenson J.S., Morimoto-Tomita M.,
RA Tomita S.;
RT "GARLH family proteins stabilize GABAA receptors at synapses.";
RL Neuron 93:1138-1152(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:2540033, PubMed:1977069,
CC PubMed:1376242). Plays an important role in the formation of functional
CC inhibitory GABAergic synapses in addition to mediating synaptic
CC inhibition as a GABA-gated ion channel (By similarity). The gamma2
CC subunit is necessary but not sufficient for a rapid formation of active
CC synaptic contacts and the synaptogenic effect of this subunit is
CC influenced by the type of alpha and beta subunits present in the
CC receptor pentamer (By similarity). The alpha1/beta2/gamma2 receptor and
CC the alpha1/beta3/gamma2 receptor exhibit synaptogenic activity (By
CC similarity). GABRA1-mediated plasticity in the orbitofrontal cortex
CC regulates context-dependent action selection (By similarity). Functions
CC also as histamine receptor and mediates cellular responses to histamine
CC (PubMed:18281286). {ECO:0000250|UniProtKB:P62812,
CC ECO:0000269|PubMed:1376242, ECO:0000269|PubMed:18281286,
CC ECO:0000269|PubMed:1977069, ECO:0000269|PubMed:2540033}.
CC -!- ACTIVITY REGULATION: Allosterically activated by benzodiazepines and
CC pentobarbital (PubMed:1977069). Allosterically activated by the
CC neuroanesthetic alphaxalone (By similarity). Inhibited by the
CC antagonist bicuculline (PubMed:1977069, PubMed:1376242).
CC {ECO:0000250|UniProtKB:P14867, ECO:0000269|PubMed:1376242,
CC ECO:0000269|PubMed:1977069}.
CC -!- SUBUNIT: Heteropentamer, formed by a combination of alpha, beta, gamma,
CC delta and rho chains (PubMed:18281286, PubMed:2540033). Interacts with
CC UBQLN1 (PubMed:11528422). Interacts with TRAK1 (By similarity).
CC Interacts with KIF21B (PubMed:25172774). Identified in a complex of 720
CC kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3
CC (PubMed:28279354). Interacts with LHFPL4 (PubMed:28279354). Interacts
CC with NLGN2 (PubMed:28279354). Interacts with SHISA7; interaction leads
CC to the regulation of GABA(A) receptor trafficking, channel deactivation
CC kinetics and pharmacology (By similarity).
CC {ECO:0000250|UniProtKB:P62812, ECO:0000269|PubMed:11528422,
CC ECO:0000269|PubMed:18281286, ECO:0000269|PubMed:25172774,
CC ECO:0000269|PubMed:2540033, ECO:0000269|PubMed:28279354}.
CC -!- INTERACTION:
CC P62813; Q63787: Pik3r1; NbExp=4; IntAct=EBI-6258192, EBI-518443;
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000250|UniProtKB:P08219}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:1376242,
CC ECO:0000269|PubMed:18281286, ECO:0000269|PubMed:2540033}; Multi-pass
CC membrane protein {ECO:0000255}. Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:25172774}.
CC -!- TISSUE SPECIFICITY: Expressed in brain (at protein level).
CC {ECO:0000269|PubMed:25172774}.
CC -!- DOMAIN: The extracellular domain contributes to synaptic contact
CC formation. {ECO:0000250|UniProtKB:P62812}.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P62812}.
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; L08490; AAC42029.1; -; Genomic_DNA.
DR EMBL; AY574250; AAS90346.1; -; mRNA.
DR EMBL; BC100061; AAI00062.1; -; mRNA.
DR PIR; JQ0158; JQ0158.
DR RefSeq; NP_899155.1; NM_183326.2.
DR RefSeq; XP_006246185.1; XM_006246123.3.
DR RefSeq; XP_006246186.1; XM_006246124.3.
DR RefSeq; XP_017452668.1; XM_017597179.1.
DR PDB; 6DW0; EM; 3.80 A; A/C=1-340, A/C=409-455.
DR PDB; 6DW1; EM; 3.10 A; A/C=1-340, A/C=409-455.
DR PDBsum; 6DW0; -.
DR PDBsum; 6DW1; -.
DR AlphaFoldDB; P62813; -.
DR SMR; P62813; -.
DR BioGRID; 248322; 1.
DR ComplexPortal; CPX-250; GABA-A receptor, alpha-1/beta-2/gamma-2.
DR ComplexPortal; CPX-410; GABA-A receptor, alpha-1/beta-3/gamma-2.
DR CORUM; P62813; -.
DR IntAct; P62813; 2.
DR MINT; P62813; -.
DR STRING; 10116.ENSRNOP00000004725; -.
DR BindingDB; P62813; -.
DR ChEMBL; CHEMBL343; -.
DR DrugCentral; P62813; -.
DR GlyGen; P62813; 2 sites.
DR iPTMnet; P62813; -.
DR PhosphoSitePlus; P62813; -.
DR PaxDb; P62813; -.
DR PRIDE; P62813; -.
DR ABCD; P62813; 2 sequenced antibodies.
DR Ensembl; ENSRNOT00000004725; ENSRNOP00000004725; ENSRNOG00000003512.
DR GeneID; 29705; -.
DR KEGG; rno:29705; -.
DR UCSC; RGD:61855; rat.
DR CTD; 2554; -.
DR RGD; 61855; Gabra1.
DR eggNOG; KOG3642; Eukaryota.
DR GeneTree; ENSGT00940000159136; -.
DR HOGENOM; CLU_010920_2_1_1; -.
DR InParanoid; P62813; -.
DR OMA; ELHKPAM; -.
DR OrthoDB; 1057372at2759; -.
DR PhylomeDB; P62813; -.
DR TreeFam; TF315453; -.
DR Reactome; R-RNO-977443; GABA receptor activation.
DR PRO; PR:P62813; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000003512; Expressed in cerebellum and 6 other tissues.
DR Genevisible; P62813; RN.
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; IDA:BHF-UCL.
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; IDA:RGD.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; IDA:SynGO.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
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; IDA:RGD.
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:RGD.
DR GO; GO:0022851; F:GABA-gated chloride ion channel activity; ISO:RGD.
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; IPI:RGD.
DR GO; GO:1904315; F:transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential; ISO:RGD.
DR GO; GO:0071420; P:cellular response to histamine; IDA:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:1902476; P:chloride transmembrane transport; ISO:RGD.
DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; ISO:RGD.
DR GO; GO:1904862; P:inhibitory synapse assembly; ISS: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; ISO:RGD.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0051932; P:synaptic transmission, GABAergic; IDA: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; 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_0000000430"
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 MUTAGEN 91
FT /note="F->L: Strongly decreases the affinity for GABA-
FT dependent channel gating."
FT /evidence="ECO:0000269|PubMed:1376242"
FT CONFLICT 91
FT /note="F -> L (in Ref. 3; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 435
FT /note="L -> I (in Ref. 1; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT HELIX 40..45
FT /evidence="ECO:0007829|PDB:6DW1"
FT TURN 46..51
FT /evidence="ECO:0007829|PDB:6DW1"
FT TURN 58..61
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 65..76
FT /evidence="ECO:0007829|PDB:6DW1"
FT TURN 81..84
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 85..95
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 108..112
FT /evidence="ECO:0007829|PDB:6DW1"
FT TURN 114..116
FT /evidence="ECO:0007829|PDB:6DW1"
FT HELIX 117..119
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 137..143
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 145..148
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 157..164
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 176..184
FT /evidence="ECO:0007829|PDB:6DW1"
FT TURN 190..192
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 193..199
FT /evidence="ECO:0007829|PDB:6DW1"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 215..225
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 228..230
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 235..247
FT /evidence="ECO:0007829|PDB:6DW1"
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
