GBRG2_RAT
ID GBRG2_RAT Reviewed; 466 AA.
AC P18508;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Gamma-aminobutyric acid receptor subunit gamma-2;
DE AltName: Full=GABA(A) receptor subunit gamma-2;
DE Flags: Precursor;
GN Name=Gabrg2;
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, SUBUNIT,
RP AND ACTIVITY REGULATION.
RC TISSUE=Brain;
RX PubMed=2561970; DOI=10.1016/0896-6273(89)90257-2;
RA Shivers B.D., Killisch I., Sprengel R., Sontheimer H., Koehler M.,
RA Schofield P.R., Seeburg P.H.;
RT "Two novel GABAA receptor subunits exist in distinct neuronal
RT subpopulations.";
RL Neuron 3:327-337(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2165521; DOI=10.1523/jneurosci.10-07-02330.1990;
RA Malherbe P., Sigel E., Baur R., Persohn E., Richards J.G., Mohler H.;
RT "Functional characteristics and sites of gene expression of the alpha 1,
RT beta 1, gamma 2-isoform of the rat GABAA receptor.";
RL J. Neurosci. 10:2330-2337(1990).
RN [3]
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN A COMPLEX WITH
RP NLGN2; LHFPL4; GABRA1; GABRB2 AND GABRB3.
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:2561970). 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 (By similarity). The gamma2 subunit is necessary but not sufficient for
CC 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 (By similarity). The
CC alpha1/beta2/gamma2 receptor, alpha2/beta2/gamma2 receptor and the
CC alpha1/beta3/gamma2 receptor exhibit synaptogenic activity whereas the
CC alpha2/beta3/gamma2 receptor shows very little or no synaptogenic
CC activity (By similarity). Functions also as histamine receptor and
CC mediates cellular responses to histamine (By similarity).
CC {ECO:0000250|UniProtKB:P22723, ECO:0000269|PubMed:2561970}.
CC -!- ACTIVITY REGULATION: Allosterically activated by benzodiazepines (By
CC similarity). Activated by pentobarbitol (PubMed:2561970). Inhibited by
CC the antagonist bicuculline (PubMed:2561970). Inhibited by zinc ions (By
CC similarity). {ECO:0000250|UniProtKB:P18507,
CC ECO:0000269|PubMed:2561970}.
CC -!- SUBUNIT: Heteropentamer, formed by a combination of alpha, beta, gamma,
CC delta and rho chains (PubMed:2561970).Interacts with GABARAP (By
CC similarity). Interacts with KIF21B (PubMed:25172774). Identified in a
CC complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2
CC and GABRB3 (PubMed:28279354). Interacts with LHFPL4 (By similarity).
CC Interacts with SHISA7; interaction leads to the regulation of GABA(A)
CC receptor trafficking, channel deactivation kinetics and pharmacology
CC (By similarity). {ECO:0000250|UniProtKB:P18507,
CC ECO:0000250|UniProtKB:P22723, ECO:0000269|PubMed:25172774,
CC ECO:0000269|PubMed:2561970, ECO:0000269|PubMed:28279354}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000269|PubMed:2561970}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:2561970}; Multi-pass
CC membrane protein {ECO:0000255}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P22723}. 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:P22723}.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P22723}.
CC -!- PTM: Palmitoylated by ZDHHC3/GODZ; required for the accumulation of
CC GABA(A) receptors at the postsynaptic membrane of inhibitory GABAergic
CC synapses. {ECO:0000250|UniProtKB:P22723}.
CC -!- MISCELLANEOUS: This subunit carries the benzodiazepine binding site.
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. GABRG2 sub-
CC subfamily. {ECO:0000305}.
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DR EMBL; L08497; AAC42036.1; -; Genomic_DNA.
DR PIR; JQ0077; JQ0077.
DR RefSeq; NP_899156.1; NM_183327.1.
DR PDB; 2PR9; X-ray; 2.51 A; P=400-409.
DR PDB; 6DW0; EM; 3.80 A; D=1-466.
DR PDB; 6DW1; EM; 3.10 A; D=1-466.
DR PDBsum; 2PR9; -.
DR PDBsum; 6DW0; -.
DR PDBsum; 6DW1; -.
DR AlphaFoldDB; P18508; -.
DR SMR; P18508; -.
DR BioGRID; 248326; 2.
DR ComplexPortal; CPX-250; GABA-A receptor, alpha-1/beta-2/gamma-2.
DR ComplexPortal; CPX-405; GABA-A receptor, alpha-6/beta-3/gamma-2.
DR ComplexPortal; CPX-409; GABA-A receptor, alpha-3/beta-3/gamma-2.
DR ComplexPortal; CPX-410; GABA-A receptor, alpha-1/beta-3/gamma-2.
DR ComplexPortal; CPX-411; GABA-A receptor, alpha-5/beta-3/gamma-2.
DR ComplexPortal; CPX-412; GABA-A receptor, alpha-2/beta-3/gamma-2.
DR CORUM; P18508; -.
DR IntAct; P18508; 3.
DR MINT; P18508; -.
DR STRING; 10116.ENSRNOP00000004619; -.
DR BindingDB; P18508; -.
DR ChEMBL; CHEMBL2095167; -.
DR ChEMBL; CHEMBL2111327; -.
DR ChEMBL; CHEMBL2111343; -.
DR ChEMBL; CHEMBL2111365; -.
DR ChEMBL; CHEMBL2111374; -.
DR ChEMBL; CHEMBL3883322; -.
DR ChEMBL; CHEMBL4296047; -.
DR ChEMBL; CHEMBL4296048; -.
DR ChEMBL; CHEMBL4296051; -.
DR ChEMBL; CHEMBL4296054; -.
DR ChEMBL; CHEMBL4296062; -.
DR DrugCentral; P18508; -.
DR GlyGen; P18508; 3 sites.
DR iPTMnet; P18508; -.
DR SwissPalm; P18508; -.
DR PaxDb; P18508; -.
DR PRIDE; P18508; -.
DR ABCD; P18508; 3 sequenced antibodies.
DR Ensembl; ENSRNOT00000082445; ENSRNOP00000072234; ENSRNOG00000003241.
DR GeneID; 29709; -.
DR KEGG; rno:29709; -.
DR UCSC; RGD:61966; rat.
DR CTD; 2566; -.
DR RGD; 61966; Gabrg2.
DR eggNOG; KOG3642; Eukaryota.
DR HOGENOM; CLU_010920_2_0_1; -.
DR InParanoid; P18508; -.
DR Reactome; R-RNO-977443; GABA receptor activation.
DR EvolutionaryTrace; P18508; -.
DR PRO; PR:P18508; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000003241; Expressed in frontal cortex and 2 other tissues.
DR ExpressionAtlas; P18508; baseline and differential.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISO:RGD.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032590; C:dendrite membrane; IDA:BHF-UCL.
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:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0060077; C:inhibitory synapse; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; IDA:SynGO.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098794; C:postsynapse; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0005254; F:chloride channel activity; 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; IDA:RGD.
DR GO; GO:0022851; F:GABA-gated chloride ion channel activity; IBA:GO_Central.
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; ISO:RGD.
DR GO; GO:0030534; P:adult behavior; ISO:RGD.
DR GO; GO:0071420; P:cellular response to histamine; ISS:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; ISO:RGD.
DR GO; GO:1902476; P:chloride transmembrane transport; ISO:RGD.
DR GO; GO:0006821; P:chloride transport; TAS: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:0009791; P:post-embryonic development; ISO:RGD.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
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; IDA:BHF-UCL.
DR Gene3D; 1.20.58.390; -; 1.
DR Gene3D; 2.70.170.10; -; 1.
DR IDEAL; IID50125; -.
DR InterPro; IPR006028; GABAA/Glycine_rcpt.
DR InterPro; IPR005439; GABBAg2_rcpt.
DR InterPro; IPR005437; GABRG-1/4.
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; PR00253; GABAARECEPTR.
DR PRINTS; PR01620; GABAARGAMMA.
DR PRINTS; PR01622; GABAARGAMMA2.
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; Cell projection; Chloride; Chloride channel;
KW Cytoplasmic vesicle; Disulfide bond; Glycoprotein; Ion channel;
KW Ion transport; Lipoprotein; Membrane; Palmitate;
KW Postsynaptic cell membrane; Reference proteome; Signal; Synapse;
KW Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..38
FT /evidence="ECO:0000255"
FT CHAIN 39..466
FT /note="Gamma-aminobutyric acid receptor subunit gamma-2"
FT /id="PRO_0000000479"
FT TOPO_DOM 39..272
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 273..295
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TRANSMEM 299..321
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TRANSMEM 333..355
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 356..442
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 443..465
FT /note="Helical"
FT /evidence="ECO:0000305"
FT CARBOHYD 51
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 128
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 246
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 189..203
FT /evidence="ECO:0000250"
FT CONFLICT 22
FT /note="M -> I (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT HELIX 64..70
FT /evidence="ECO:0007829|PDB:6DW1"
FT TURN 71..75
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 82..87
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 90..103
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 106..121
FT /evidence="ECO:0007829|PDB:6DW1"
FT HELIX 123..125
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 129..136
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 166..172
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 175..188
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 195..198
FT /evidence="ECO:0007829|PDB:6DW1"
FT TURN 214..216
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 218..225
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 243..246
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 249..252
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 257..260
FT /evidence="ECO:0007829|PDB:6DW1"
FT STRAND 263..267
FT /evidence="ECO:0007829|PDB:6DW1"
SQ SEQUENCE 466 AA; 54077 MW; 3C60B66E0D23072F CRC64;
MSSPNTWSTG STVYSPVFSQ KMTLWILLLL SLYPGFTSQK SDDDYEDYAS NKTWVLTPKV
PEGDVTVILN NLLEGYDNKL RPDIGVKPTL IHTDMYVNSI GPVNAINMEY TIDIFFAQTW
YDRRLKFNST IKVLRLNSNM VGKIWIPDTF FRNSKKADAH WITTPNRMLR IWNDGRVLYT
LRLTIDAECQ LQLHNFPMDE HSCPLEFSSY GYPREEIVYQ WKRSSVEVGD TRSWRLYQFS
FVGLRNTTEV VKTTSGDYVV MSVYFDLSRR MGYFTIQTYI PCTLIVVLSW VSFWINKDAV
PARTSLGITT VLTMTTLSTI ARKSLPKVSY VTAMDLFVSV CFIFVFSALV EYGTLHYFVS
NRKPSKDKDK KKKNPAPTID IRPRSATIQM NNATHLQERD EEYGYECLDG KDCASFFCCF
EDCRTGAWRH GRIHIRIAKM DSYARIFFPT AFCLFNLVYW VSYLYL
