GBRB3_MOUSE
ID GBRB3_MOUSE Reviewed; 473 AA.
AC P63080; P15433; Q3UHR3;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Gamma-aminobutyric acid receptor subunit beta-3;
DE AltName: Full=GABA(A) receptor subunit beta-3;
DE Flags: Precursor;
GN Name=Gabrb3; Synonyms=Gabrb-3;
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=DBA/2J; TISSUE=Brain;
RX PubMed=7893750; DOI=10.1016/0167-4781(95)00009-6;
RA Kamatchi G.L., Kofuji P., Wang J.B., Fernando J.C., Liu Z., Mathura J.R.,
RA Burt D.R.;
RT "GABAA receptor beta 1, beta 2, and beta 3 subunits: comparisons in DBA/2J
RT and C57BL/6J mice.";
RL Biochim. Biophys. Acta 1261:134-142(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Hypothalamus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=9108119; DOI=10.1073/pnas.94.8.4143;
RA Homanics G.E., DeLorey T.M., Firestone L.L., Quinlan J.J., Handforth A.,
RA Harrison N.L., Krasowski M.D., Rick C.E., Korpi E.R., Makela R.,
RA Brilliant M.H., Hagiwara N., Ferguson C., Snyder K., Olsen R.W.;
RT "Mice devoid of gamma-aminobutyrate type A receptor beta3 subunit have
RT epilepsy, cleft palate, and hypersensitive behavior.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:4143-4148(1997).
RN [4]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=10670447; DOI=10.1016/s0306-4522(99)00481-9;
RA Ugarte S.D., Homanics G.E., Firestone L.L., Hammond D.L.;
RT "Sensory thresholds and the antinociceptive effects of GABA receptor
RT agonists in mice lacking the beta3 subunit of the GABA(A) receptor.";
RL Neuroscience 95:795-806(2000).
RN [5]
RP FUNCTION.
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 [6]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH LHFLP4.
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).
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:9108119). Plays an important role
CC 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/beta3/gamma2 receptor exhibits synatogenic activity whereas the
CC alpha2/beta3/gamma2 receptor shows very little or no synaptogenic
CC activity (PubMed:27129275). Functions also as histamine receptor and
CC mediates cellular responses to histamine (By similarity). Plays an
CC important role in somatosensation and in the production of
CC antinociception (PubMed:10670447). {ECO:0000250|UniProtKB:P28472,
CC ECO:0000269|PubMed:10670447, ECO:0000269|PubMed:27129275,
CC ECO:0000269|PubMed:9108119}.
CC -!- SUBUNIT: Heteropentamer, formed by a combination of alpha, beta, gamma,
CC delta and rho chains (By similarity). Can form functional homopentamers
CC (in vitro) (By similarity). Interacts with UBQLN1 (By similarity). May
CC interact with KIF21B (By similarity). Identified in a complex of 720
CC kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By
CC similarity). Interacts with LHFPL4 (PubMed:28978485). Interacts with
CC GIT1; this interaction is required for synaptic GABRB3 surface
CC stability and inhibitory synapse strength (By similarity).
CC {ECO:0000250|UniProtKB:P28472, ECO:0000250|UniProtKB:P63079,
CC ECO:0000269|PubMed:28978485}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000250|UniProtKB:P28472}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:28978485}; Multi-pass
CC membrane protein {ECO:0000255}. Cytoplasmic vesicle membrane
CC {ECO:0000250|UniProtKB:P63079}.
CC -!- DISRUPTION PHENOTYPE: Important perinatal lethality. About 57% of the
CC pups have a cleft palate. About 90% of the pups die within 24 hours
CC after birth, including 30% of those that do not have a cleft palate.
CC Surviving mice are runted until weaning, but attain normal body weight
CC in adulthood. They are hyperactive and display behavorial
CC abnormalities. They do not display jerky gait, but have difficulty with
CC swimming, walking on grids, and avoiding to fall from rotarods. Mutant
CC mice are fertile, but females do not display normal nurturing behavior.
CC Mutant mice have abnormal electroencephalograms (EEGs) and tend to
CC suffer from seizures. Brains from mutant mice show strongly reduced
CC numbers of GABA and benzodiazepine receptors. Neurons from dorsal root
CC ganglion show a decrease of about 80% of GABA-induced chloride
CC currents. In addition, mutant mice have an average lifespan of about 18
CC weeks, instead of the expected 127 weeks (PubMed:9108119). Mutant mice
CC display a lowered threshold to nociception and are abnormally sensitive
CC to touch and heat stimuli. GABA receptor agonists have decreased
CC antinociceptive effects in mutant mice (PubMed:10670447).
CC {ECO:0000269|PubMed:10670447, ECO:0000269|PubMed:9108119}.
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. GABRB3 sub-
CC subfamily. {ECO:0000305}.
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DR EMBL; U14420; AAB60502.1; -; mRNA.
DR EMBL; AK039070; BAC30230.1; -; mRNA.
DR EMBL; AK147247; BAE27794.1; -; mRNA.
DR CCDS; CCDS21324.1; -.
DR PIR; S53532; S53532.
DR RefSeq; NP_032097.1; NM_008071.3.
DR AlphaFoldDB; P63080; -.
DR SMR; P63080; -.
DR BioGRID; 199804; 2.
DR ComplexPortal; CPX-2981; GABA-A receptor, alpha-6/beta-3/gamma-2.
DR ComplexPortal; CPX-2982; GABA-A receptor, alpha-3/beta-3/gamma-2.
DR ComplexPortal; CPX-2983; GABA-A receptor, alpha-1/beta-3/gamma-2.
DR ComplexPortal; CPX-2984; GABA-A receptor, alpha-5/beta-3/gamma-2.
DR ComplexPortal; CPX-2985; GABA-A receptor, alpha-2/beta-3/gamma-2.
DR ComplexPortal; CPX-2986; GABA-A receptor, alpha-6/beta-3/delta.
DR ComplexPortal; CPX-2989; GABA-A receptor, alpha-4/beta-3/delta.
DR STRING; 10090.ENSMUSP00000038051; -.
DR ChEMBL; CHEMBL4296058; -.
DR DrugCentral; P63080; -.
DR GlyConnect; 2326; 3 N-Linked glycans (1 site).
DR GlyGen; P63080; 3 sites, 3 N-linked glycans (1 site).
DR iPTMnet; P63080; -.
DR PhosphoSitePlus; P63080; -.
DR MaxQB; P63080; -.
DR PaxDb; P63080; -.
DR PeptideAtlas; P63080; -.
DR PRIDE; P63080; -.
DR ProteomicsDB; 273425; -.
DR ABCD; P63080; 2 sequenced antibodies.
DR Antibodypedia; 22323; 344 antibodies from 39 providers.
DR DNASU; 14402; -.
DR Ensembl; ENSMUST00000039697; ENSMUSP00000038051; ENSMUSG00000033676.
DR GeneID; 14402; -.
DR KEGG; mmu:14402; -.
DR UCSC; uc009hee.1; mouse.
DR CTD; 2562; -.
DR MGI; MGI:95621; Gabrb3.
DR VEuPathDB; HostDB:ENSMUSG00000033676; -.
DR eggNOG; KOG3643; Eukaryota.
DR GeneTree; ENSGT00940000154713; -.
DR InParanoid; P63080; -.
DR OMA; MYWKDTP; -.
DR PhylomeDB; P63080; -.
DR Reactome; R-MMU-977443; GABA receptor activation.
DR BioGRID-ORCS; 14402; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Gabrb3; mouse.
DR PRO; PR:P63080; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P63080; protein.
DR Bgee; ENSMUSG00000033676; Expressed in olfactory tubercle and 148 other tissues.
DR ExpressionAtlas; P63080; baseline and differential.
DR Genevisible; P63080; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
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:1902711; C:GABA-A receptor complex; IMP:UniProtKB.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0060077; C:inhibitory synapse; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; ISO:MGI.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0043195; C:terminal bouton; ISO:MGI.
DR GO; GO:0035612; F:AP-2 adaptor complex binding; ISO:MGI.
DR GO; GO:0005254; F:chloride channel 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; IMP:UniProtKB.
DR GO; GO:0022851; F:GABA-gated chloride ion channel activity; IMP:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005216; F:ion channel activity; IDA:MGI.
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; IDA:SynGO.
DR GO; GO:0007420; P:brain development; IMP:MGI.
DR GO; GO:0071420; P:cellular response to histamine; ISS:UniProtKB.
DR GO; GO:0071294; P:cellular response to zinc ion; IDA:MGI.
DR GO; GO:0021549; P:cerebellum development; IMP:MGI.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:1902476; P:chloride transmembrane transport; IMP:UniProtKB.
DR GO; GO:0042747; P:circadian sleep/wake cycle, REM sleep; IMP:MGI.
DR GO; GO:0090102; P:cochlea development; IMP:DFLAT.
DR GO; GO:0035640; P:exploration behavior; IMP:MGI.
DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; ISS:UniProtKB.
DR GO; GO:0060022; P:hard palate development; IDA:MGI.
DR GO; GO:0060080; P:inhibitory postsynaptic potential; IMP:CACAO.
DR GO; GO:1904862; P:inhibitory synapse assembly; IDA:UniProtKB.
DR GO; GO:0060119; P:inner ear receptor cell development; IMP:DFLAT.
DR GO; GO:0060384; P:innervation; IMP:DFLAT.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0007612; P:learning; IMP:MGI.
DR GO; GO:0007613; P:memory; IMP:MGI.
DR GO; GO:0061744; P:motor behavior; IMP:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:DFLAT.
DR GO; GO:1901215; P:negative regulation of neuron death; IMP:DFLAT.
DR GO; GO:0007399; P:nervous system development; IMP:MGI.
DR GO; GO:0050877; P:nervous system process; IBA:GO_Central.
DR GO; GO:0048666; P:neuron development; IMP:DFLAT.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; IMP:DFLAT.
DR GO; GO:0019098; P:reproductive behavior; IMP:MGI.
DR GO; GO:0072347; P:response to anesthetic; IMP:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:MGI.
DR GO; GO:0060021; P:roof of mouth development; IMP:UniProtKB.
DR GO; GO:0007605; P:sensory perception of sound; IMP:DFLAT.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0035176; P:social behavior; IMP:MGI.
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; IPR002289; GABAAb_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; PR01160; GABAARBETA.
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; Chloride; Chloride channel; Cytoplasmic vesicle;
KW Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW Ligand-gated ion channel; Membrane; Postsynaptic cell membrane; Receptor;
KW Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix;
KW Transport.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..473
FT /note="Gamma-aminobutyric acid receptor subunit beta-3"
FT /id="PRO_0000000463"
FT TOPO_DOM 26..245
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 246..267
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 268..270
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 271..293
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 294..304
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 305..327
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 328..450
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 451..472
FT /note="Helical"
FT /evidence="ECO:0000250"
FT CARBOHYD 33
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 174
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 161..175
FT /evidence="ECO:0000250"
SQ SEQUENCE 473 AA; 54166 MW; 6A5ABD8A9143FE45 CRC64;
MWGFAGGRLF GIFSAPVLVA VVCCAQSVND PGNMSFVKET VDKLLKGYDI RLRPDFGGPP
VCVGMNIDIA SIDMVSEVNM DYTLTMYFQQ YWRDKRLAYS GIPLNLTLDN RVADQLWVPD
TYFLNDKKSF VHGVTVKNRM IRLHPDGTVL YGLRITTTAA CMMDLRRYPL DEQNCTLEIE
SYGYTTDDIE FYWRGGDKAV TGVERIELPQ FSIVEHRLVS RNVVFATGAY PRLSLSFRLK
RNIGYFILQT YMPSILITIL SWVSFWINYD ASAARVALGI TTVLTMTTIN THLRETLPKI
PYVKAIDMYL MGCFVFVFLA LLEYAFVNYI FFGRGPQRQK KLAEKTAKAK NDRSKSEINR
VDAHGNILLA PMDVHNEMNE VAGSVGDTRN SAISFDNSGI QYRKQSMPKE GHGRYMGDRS
IPHKKTHLRR RSSQLKIKIP DLTDVNAIDR WSRIVFPFTF SLFNLVYWLY YVN
