ID   GBRA3_RAT               Reviewed;         493 AA.
AC   P20236; F1LNZ5;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   18-JUL-2018, sequence version 2.
DT   02-SEP-2026, entry version 189.
DE   RecName: Full=Gamma-aminobutyric acid receptor subunit alpha-3 {ECO:0000250|UniProtKB:P26049};
DE   AltName: Full=GABA(A) receptor subunit alpha-3 {ECO:0000250|UniProtKB:P26049};
DE            Short=GABAAR subunit alpha-3;
DE   Flags: Precursor;
GN   Name=Gabra3 {ECO:0000312|RGD:2648}; Synonyms=Gabra-3;
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 [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC   TISSUE=Brain;
RX   PubMed=2153588; DOI=10.1016/0014-5793(90)80118-3;
RA   Malherbe P., Sigel E., Baur R., Persohn E., Richards J.G., Moehler H.;
RT   "Functional expression and sites of gene transcription of a novel alpha
RT   subunit of the GABAA receptor in rat brain.";
RL   FEBS Lett. 260:261-265(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [4]
RP   TISSUE SPECIFICITY.
RX   PubMed=17003036; DOI=10.1074/jbc.m606895200;
RA   Jin N., Kolliputi N., Gou D., Weng T., Liu L.;
RT   "A novel function of ionotropic gamma-aminobutyric acid receptors involving
RT   alveolar fluid homeostasis.";
RL   J. Biol. Chem. 281:36012-36020(2006).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
RN   [6]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-163, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
RX   PubMed=24090084; DOI=10.1021/pr400783j;
RA   Parker B.L., Thaysen-Andersen M., Solis N., Scott N.E., Larsen M.R.,
RA   Graham M.E., Packer N.H., Cordwell S.J.;
RT   "Site-specific glycan-peptide analysis for determination of N-glycoproteome
RT   heterogeneity.";
RL   J. Proteome Res. 12:5791-5800(2013).
CC   -!- FUNCTION: Alpha subunit of the heteropentameric ligand-gated chloride
CC       channel gated by gamma-aminobutyric acid (GABA), a major inhibitory
CC       neurotransmitter in the brain (PubMed:2153588). GABA-gated chloride
CC       channels, also named GABA(A) receptors (GABAAR), consist of five
CC       subunits arranged around a central pore and contain GABA active binding
CC       site(s) located at the alpha and beta subunit interface(s) (By
CC       similarity). When activated by GABA, GABAARs selectively allow the flow
CC       of chloride anions across the cell membrane down their electrochemical
CC       gradient (By similarity). Chloride influx into the postsynaptic neuron
CC       following GABAAR opening decreases the neuron ability to generate a new
CC       action potential, thereby reducing nerve transmission (By similarity).
CC       {ECO:0000250|UniProtKB:P14867, ECO:0000250|UniProtKB:P34903,
CC       ECO:0000269|PubMed:2153588}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823,
CC         ChEBI:CHEBI:17996; Evidence={ECO:0000250|UniProtKB:P34903};
CC   -!- SUBUNIT: Heteropentamer, formed by a combination of alpha (GABRA1-6),
CC       beta (GABRB1-3), gamma (GABRG1-3), delta (GABRD), epsilon (GABRE), rho
CC       (GABRR1-3), pi (GABRP) and theta (GABRQ) chains, each subunit
CC       exhibiting distinct physiological and pharmacological properties (By
CC       similarity). Binds UBQLN1 (By similarity). Interacts with GPHN (By
CC       similarity). {ECO:0000250|UniProtKB:P26049,
CC       ECO:0000250|UniProtKB:P34903}.
CC   -!- INTERACTION:
CC       P20236; Q03555-6: Gphn; NbExp=5; IntAct=EBI-5273284, EBI-5273276;
CC   -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC       {ECO:0000250|UniProtKB:P14867}; Multi-pass membrane protein. Cell
CC       membrane {ECO:0000250|UniProtKB:P14867}; Multi-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Expressed in most brain regions. Expressed in
CC       lungs, in alveolar epithelium (PubMed:17003036).
CC       {ECO:0000269|PubMed:17003036, ECO:0000269|PubMed:2153588}.
CC   -!- DOMAIN: GABAARs subunits share a common topological structure: a
CC       peptide sequence made up of a long extracellular N-terminal, four
CC       transmembrane domains, intracellular or cytoplasmic domain located
CC       between the third and the fourth transmembrane domains.
CC       {ECO:0000250|UniProtKB:P14867}.
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. GABRA3 sub-
CC       subfamily. {ECO:0000305}.
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DR   EMBL; X51991; CAA36247.1; -; mRNA.
DR   EMBL; L08492; AAC42031.1; -; Genomic_DNA.
DR   EMBL; AABR07042312; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR07042313; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR07042314; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR07042315; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR07042316; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR07042317; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR07042318; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   PIR; A34130; A34130.
DR   RefSeq; NP_058765.3; NM_017069.3.
DR   RefSeq; XP_017457405.1; XM_017601916.3.
DR   PDB; 4TK1; X-ray; 2.70 A; C/D=396-406.
DR   PDB; 4TK2; X-ray; 4.10 A; C/D=396-406.
DR   PDB; 4TK3; X-ray; 2.70 A; C/D=396-406.
DR   PDB; 4TK4; X-ray; 3.60 A; C/D=396-406.
DR   PDB; 4U90; X-ray; 2.00 A; D/E=396-404.
DR   PDB; 6HSN; X-ray; 1.55 A; D/E=396-405.
DR   AlphaFoldDB; P20236; -.
DR   MDRepo; P20236; -.
DR   SMR; P20236; -.
DR   ComplexPortal; CPX-409; GABA-A receptor, alpha3-beta3-gamma2.
DR   CORUM; P20236; -.
DR   FunCoup; P20236; 229.
DR   IntAct; P20236; 1.
DR   STRING; 10116.ENSRNOP00000075419; -.
DR   BindingDB; P20236; -.
DR   ChEMBL; CHEMBL328; -.
DR   DrugCentral; P20236; -.
DR   GlyCosmos; P20236; 4 sites, 9 glycans.
DR   GlyGen; P20236; 5 sites, 9 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR   iPTMnet; P20236; -.
DR   PhosphoSitePlus; P20236; -.
DR   PaxDb; 10116-ENSRNOP00000075419; -.
DR   GeneID; 24947; -.
DR   KEGG; rno:24947; -.
DR   AGR; RGD:2648; -.
DR   CTD; 2556; -.
DR   RGD; 2648; Gabra3.
DR   VEuPathDB; HostDB:ENSRNOG00000056558; -.
DR   eggNOG; KOG3642; Eukaryota.
DR   HOGENOM; CLU_010920_2_1_1; -.
DR   InParanoid; P20236; -.
DR   OrthoDB; 45532at9989; -.
DR   PhylomeDB; P20236; -.
DR   Reactome; R-RNO-977443; GABA receptor activation.
DR   CD-CODE; A7E9CBB4; Postsynaptic density.
DR   EvolutionaryTrace; P20236; -.
DR   PRO; PR:P20236; -.
DR   Proteomes; UP000002494; Chromosome X.
DR   Bgee; ENSRNOG00000056558; Expressed in frontal cortex and 4 other cell types or tissues.
DR   GO; GO:0032590; C:dendrite membrane; IBA:GO_Central.
DR   GO; GO:1902711; C:GABA-A receptor complex; IBA:GO_Central.
DR   GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0098794; C:postsynapse; IBA:GO_Central.
DR   GO; GO:0045211; C:postsynaptic membrane; ISS:UniProtKB.
DR   GO; GO:0099634; C:postsynaptic specialization membrane; IDA:SynGO.
DR   GO; GO:0048787; C:presynaptic active zone membrane; IDA:SynGO.
DR   GO; GO:0045202; C:synapse; IDA:SynGO.
DR   GO; GO:0004890; F:GABA-A receptor activity; IDA:UniProtKB.
DR   GO; GO:0022851; F:GABA-gated chloride ion channel activity; IDA:UniProtKB.
DR   GO; GO:0099507; F:ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential; IDA:SynGO.
DR   GO; GO:1904315; F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential; IDA:SynGO.
DR   GO; GO:0031223; P:auditory behavior; IEP:RGD.
DR   GO; GO:0007268; P:chemical synaptic transmission; IMP:RGD.
DR   GO; GO:1902476; P:chloride transmembrane transport; IBA:GO_Central.
DR   GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IEA:InterPro.
DR   GO; GO:1904862; P:inhibitory synapse assembly; IBA:GO_Central.
DR   GO; GO:0010288; P:response to lead ion; IEP:RGD.
DR   GO; GO:0051932; P:synaptic transmission, GABAergic; IBA:GO_Central.
DR   CDD; cd19036; LGIC_ECD_GABAAR_A3; 1.
DR   CDD; cd19052; LGIC_TM_GABAAR_alpha; 1.
DR   FunFam; 2.70.170.10:FF:000001; Gamma-aminobutyric acid A receptor subunit alpha-2; 1.
DR   FunFam; 1.20.58.390:FF:000002; Putative gamma-aminobutyric acid receptor subunit alpha-5; 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; IPR005433; GABBAa3_rcpt.
DR   InterPro; IPR047024; Gabra-1-6_TM.
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; 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; PR01616; GABAARALPHA3.
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   PDBsum; 4TK1; -.
DR   PDBsum; 4TK2; -.
DR   PDBsum; 4TK3; -.
DR   PDBsum; 4TK4; -.
DR   PDBsum; 4U90; -.
DR   PDBsum; 6HSN; -.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Chloride; Chloride channel; Disulfide bond;
KW   Glycoprotein; Ion channel; Ion transport; Ligand-gated ion channel;
KW   Membrane; Phosphoprotein; Postsynaptic cell membrane; Receptor;
KW   Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix;
KW   Transport.
FT   SIGNAL          1..28
FT                   /evidence="ECO:0000255"
FT   CHAIN           29..493
FT                   /note="Gamma-aminobutyric acid receptor subunit alpha-3"
FT                   /id="PRO_0000000439"
FT   TOPO_DOM        29..276
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        277..298
FT                   /note="Helical"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        304..325
FT                   /note="Helical"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        338..359
FT                   /note="Helical"
FT                   /evidence="ECO:0000305"
FT   TOPO_DOM        360..458
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        459..480
FT                   /note="Helical"
FT                   /evidence="ECO:0000305"
FT   REGION          27..54
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        31..42
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         119
FT                   /ligand="4-aminobutanoate"
FT                   /ligand_id="ChEBI:CHEBI:59888"
FT                   /ligand_note="ligand shared with the neighboring beta
FT                   subunit"
FT                   /evidence="ECO:0000250|UniProtKB:P14867"
FT   BINDING         182
FT                   /ligand="4-aminobutanoate"
FT                   /ligand_id="ChEBI:CHEBI:59888"
FT                   /ligand_note="ligand shared with the neighboring beta
FT                   subunit"
FT                   /evidence="ECO:0000250|UniProtKB:P62813"
FT   MOD_RES         427
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P26049"
FT   MOD_RES         428
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P26049"
FT   MOD_RES         434
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P26049"
FT   MOD_RES         443
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P26049"
FT   CARBOHYD        63
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        163
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0007744|PubMed:24090084"
FT   CARBOHYD        176
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        228
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        191..205
FT                   /evidence="ECO:0000250|UniProtKB:P14867"
FT   CONFLICT        160
FT                   /note="V -> M (in Ref. 2; AAC42031)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        324
FT                   /note="S -> T (in Ref. 2; AAC42031)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        342
FT                   /note="I -> M (in Ref. 1; CAA36247 and 2; AAC42031)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        409
FT                   /note="K -> L (in Ref. 1; CAA36247)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   493 AA;  55430 MW;  4A685D5E05D76B41 CRC64;
     MITTQMWHFY VTRVGLLLLI SILPGTTGQG ESRRQEPGDF VKQDIGGLSP KHAPDIPDDS
     TDNITIFTRI LDRLLDGYDN RLRPGLGDAV TEVKTDIYVT SFGPVSDTDM EYTIDVFFRQ
     TWHDERLKFD GPMKILPLNN LLASKIWTPD TFFHNGKKSV AHNMTTPNKL LRLVDNGTLL
     YTMRLTIHAE CPMHLEDFPM DVHACPLKFG SYAYTKAEVI YSWTLGKNKS VEVAQDGSRL
     NQYDLLGHVV GTEIIRSSTG EYVVMTTHFH LKRKIGYFVI QTYLPCIMTV ILSQVSFWLN
     RESVPARTVF GVTTVLTMTT LSISARNSLP KVAYATAMDW FIAVCYAFVF SALIEFATVN
     YFTKRSWAWE GKKVPEALEM KKKTPAAPTK KTSTTFNIVG TTYPINLAKD TEFSTISKAA
     AAPSASSTPT VIASPKTTYV QDSPAETKTY NSVSKVDKIS RIIFPVLFAI FNLVYWATYV
     NRESAIKGMI RKQ
//