GBRG2_HUMAN
ID GBRG2_HUMAN Reviewed; 467 AA.
AC P18507; F5HB82; Q6GRL6; Q6PCC3; Q9UDB3; Q9UN15;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 224.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP SUBUNIT, AND ACTIVITY REGULATION.
RC TISSUE=Brain;
RX PubMed=2538761; DOI=10.1038/338582a0;
RA Pritchett D.B., Sontheimer H., Shivers B.D., Ymer S., Kettenmann H.,
RA Schofield P.R., Seeburg P.H.;
RT "Importance of a novel GABAA receptor subunit for benzodiazepine
RT pharmacology.";
RL Nature 338:582-585(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11328646; DOI=10.3109/10425170009033988;
RA Jiang S., Yu J., Wang J., Tan Z., Xue H., Feng G., He L., Yang H.;
RT "Complete genomic sequence of 195 Kb of human DNA containing the gene
RT GABRG2.";
RL DNA Seq. 11:373-382(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP ARG-357.
RC TISSUE=Brain;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 357-443 (ISOFORM 1).
RC TISSUE=Brain cortex;
RX PubMed=8382267; DOI=10.1111/j.1471-4159.1993.tb03243.x;
RA Khan Z.U., Fernando L.P., Escriba P., Busquets X., Mallet J.,
RA Miralles C.P., Filla M., De Blas A.L.;
RT "Antibodies to the human gamma 2 subunit of the gamma-aminobutyric
RT acidA/benzodiazepine receptor.";
RL J. Neurochem. 60:961-971(1993).
RN [6]
RP INTERACTION WITH GABARAP.
RX PubMed=9892355; DOI=10.1038/16264;
RA Wang H., Bedford F.K., Brandon N.J., Moss S.J., Olsen R.W.;
RT "GABA(A)-receptor-associated protein links GABA(A) receptors and the
RT cytoskeleton.";
RL Nature 397:69-72(1999).
RN [7]
RP FUNCTION.
RX PubMed=23909897; DOI=10.1111/ejn.12331;
RA Fuchs C., Abitbol K., Burden J.J., Mercer A., Brown L., Iball J.,
RA Anne Stephenson F., Thomson A.M., Jovanovic J.N.;
RT "GABA(A) receptors can initiate the formation of functional inhibitory
RT GABAergic synapses.";
RL Eur. J. Neurosci. 38:3146-3158(2013).
RN [8]
RP FUNCTION.
RX PubMed=25489750; DOI=10.3791/52115;
RA Brown L.E., Fuchs C., Nicholson M.W., Stephenson F.A., Thomson A.M.,
RA Jovanovic J.N.;
RT "Inhibitory synapse formation in a co-culture model incorporating GABAergic
RT medium spiny neurons and HEK293 cells stably expressing GABAA receptors.";
RL J. Vis. Exp. 2014:E52115-E52115(2014).
RN [9]
RP VARIANTS DEE74 THR-106; THR-107; SER-282; GLN-323; TRP-323 AND LEU-343,
RP CHARACTERIZATION OF VARIANTS DEE74 THR-106; THR-107; SER-282; GLN-323;
RP TRP-323 AND LEU-343, SUBCELLULAR LOCATION, FUNCTION, AND ACTIVITY
RP REGULATION.
RX PubMed=27864268; DOI=10.1093/brain/aww272;
RA Shen D., Hernandez C.C., Shen W., Hu N., Poduri A., Shiedley B.,
RA Rotenberg A., Datta A.N., Leiz S., Patzer S., Boor R., Ramsey K.,
RA Goldberg E., Helbig I., Ortiz-Gonzalez X.R., Lemke J.R., Marsh E.D.,
RA Macdonald R.L.;
RT "De novo GABRG2 mutations associated with epileptic encephalopathies.";
RL Brain 140:49-67(2017).
RN [10] {ECO:0007744|PDB:6D6T, ECO:0007744|PDB:6D6U}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS) OF 8-326 IN COMPLEX WITH
RP GABA AND FLUMAZENIL, FUNCTION, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=29950725; DOI=10.1038/s41586-018-0255-3;
RA Zhu S., Noviello C.M., Teng J., Walsh R.M. Jr., Kim J.J., Hibbs R.E.;
RT "Structure of a human synaptic GABAA receptor.";
RL Nature 559:67-72(2018).
RN [11]
RP VARIANT GEFS+3 MET-328.
RX PubMed=11326274; DOI=10.1038/ng0501-46;
RA Baulac S., Huberfeld G., Gourfinkel-An I., Mitropoulou G., Beranger A.,
RA Prud'homme J.-F., Baulac M., Brice A., Bruzzone R., LeGuern E.;
RT "First genetic evidence of GABA(A) receptor dysfunction in epilepsy: a
RT mutation in the gamma2-subunit gene.";
RL Nat. Genet. 28:46-48(2001).
RN [12]
RP VARIANT ECA2/FEB8 GLN-82.
RX PubMed=11326275; DOI=10.1038/ng0501-49;
RA Wallace R.H., Marini C., Petrou S., Harkin L.A., Bowser D.N., Panchal R.G.,
RA Williams D.A., Sutherland G.R., Mulley J.C., Scheffer I.E., Berkovic S.F.;
RT "Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and
RT febrile seizures.";
RL Nat. Genet. 28:49-52(2001).
RN [13]
RP VARIANT FEB8 GLY-177.
RX PubMed=16924025; DOI=10.1212/01.wnl.0000230145.73496.a2;
RA Audenaert D., Schwartz E., Claeys K.G., Claes L., Deprez L., Suls A.,
RA Van Dyck T., Lagae L., Van Broeckhoven C., Macdonald R.L., De Jonghe P.;
RT "A novel GABRG2 mutation associated with febrile seizures.";
RL Neurology 67:687-690(2006).
RN [14]
RP VARIANT SER-79.
RX PubMed=20485450; DOI=10.1038/jhg.2010.47;
RA Shi X., Huang M.C., Ishii A., Yoshida S., Okada M., Morita K., Nagafuji H.,
RA Yasumoto S., Kaneko S., Kojima T., Hirose S.;
RT "Mutational analysis of GABRG2 in a Japanese cohort with childhood
RT epilepsies.";
RL J. Hum. Genet. 55:375-378(2010).
RN [15]
RP VARIANT SER-83, AND CHARACTERIZATION OF VARIANT SER-83.
RX PubMed=21714819; DOI=10.1111/j.1460-9568.2011.07767.x;
RA Lachance-Touchette P., Brown P., Meloche C., Kinirons P., Lapointe L.,
RA Lacasse H., Lortie A., Carmant L., Bedford F., Bowie D., Cossette P.;
RT "Novel alpha1 and gamma2 GABAA receptor subunit mutations in families with
RT idiopathic generalized epilepsy.";
RL Eur. J. Neurosci. 34:237-249(2011).
RN [16]
RP VARIANT GEFS+3 GLN-323.
RX PubMed=23708187; DOI=10.1038/ng.2646;
RA Carvill G.L., Heavin S.B., Yendle S.C., McMahon J.M., O'Roak B.J., Cook J.,
RA Khan A., Dorschner M.O., Weaver M., Calvert S., Malone S., Wallace G.,
RA Stanley T., Bye A.M., Bleasel A., Howell K.B., Kivity S., Mackay M.T.,
RA Rodriguez-Casero V., Webster R., Korczyn A., Afawi Z., Zelnick N.,
RA Lerman-Sagie T., Lev D., Moeller R.S., Gill D., Andrade D.M., Freeman J.L.,
RA Sadleir L.G., Shendure J., Berkovic S.F., Scheffer I.E., Mefford H.C.;
RT "Targeted resequencing in epileptic encephalopathies identifies de novo
RT mutations in CHD2 and SYNGAP1.";
RL Nat. Genet. 45:825-830(2013).
RN [17]
RP VARIANT CYS-274.
RX PubMed=27864847; DOI=10.1002/humu.23149;
RG Clinical Study Group;
RA Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D.,
RA Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S.,
RA Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.;
RT "Diagnostic targeted resequencing in 349 patients with drug-resistant
RT pediatric epilepsies identifies causative mutations in 30 different
RT genes.";
RL Hum. Mutat. 38:216-225(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:2538761, PubMed:29950725). Plays
CC an important role in the formation of functional inhibitory GABAergic
CC synapses in addition to mediating synaptic inhibition as a GABA-gated
CC ion channel (PubMed:23909897, PubMed:25489750, PubMed:27864268). The
CC gamma2 subunit is necessary but not sufficient for a rapid formation of
CC active 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
CC (PubMed:23909897, PubMed:25489750). The alpha2/beta2/gamma2 receptor
CC exhibits synatogenic activity whereas the alpha2/beta3/gamma2 receptor
CC shows very little or no synaptogenic activity (By similarity).
CC Functions also as histamine receptor and mediates cellular responses to
CC histamine (By similarity). {ECO:0000250|UniProtKB:P22723,
CC ECO:0000269|PubMed:23909897, ECO:0000269|PubMed:2538761,
CC ECO:0000269|PubMed:25489750, ECO:0000269|PubMed:27864268,
CC ECO:0000269|PubMed:29950725}.
CC -!- ACTIVITY REGULATION: Allosterically activated by benzodiazepines
CC (PubMed:2538761, PubMed:29950725). Activated by pentobarbitol (By
CC similarity). Inhibited by the antagonist bicuculline (PubMed:29950725).
CC Inhibited by zinc ions (PubMed:27864268).
CC {ECO:0000250|UniProtKB:P18508, ECO:0000269|PubMed:2538761,
CC ECO:0000269|PubMed:27864268, ECO:0000269|PubMed:29950725}.
CC -!- SUBUNIT: Heteropentamer, formed by a combination of alpha, beta, gamma,
CC delta and rho chains (PubMed:2538761, PubMed:29950725). Interacts with
CC GABARAP (PubMed:9892355). Interacts with KIF21B (By similarity).
CC Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1,
CC GABRB2, GABRG2 and GABRB3 (By similarity). Interacts with LHFPL4 (By
CC similarity). Interacts with SHISA7; interaction leads to the regulation
CC of GABA(A) receptor trafficking, channel deactivation kinetics and
CC pharmacology (By similarity). {ECO:0000250|UniProtKB:P18508,
CC ECO:0000250|UniProtKB:P22723, ECO:0000269|PubMed:2538761,
CC ECO:0000269|PubMed:29950725, ECO:0000269|PubMed:9892355}.
CC -!- INTERACTION:
CC P18507; P51513: NOVA1; NbExp=2; IntAct=EBI-9008430, EBI-726123;
CC P18507-2; O95166: GABARAP; NbExp=3; IntAct=EBI-15096952, EBI-712001;
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000269|PubMed:2538761}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:2538761,
CC ECO:0000269|PubMed:27864268}; Multi-pass membrane protein
CC {ECO:0000255}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P22723}. Cytoplasmic vesicle membrane
CC {ECO:0000250|UniProtKB:P18508}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P18507-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P18507-2; Sequence=VSP_041124;
CC Name=3;
CC IsoId=P18507-3; Sequence=VSP_047323, VSP_041124;
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 -!- DISEASE: Developmental and epileptic encephalopathy 74 (DEE74)
CC [MIM:618396]: A form of epileptic encephalopathy, a heterogeneous group
CC of severe early-onset epilepsies characterized by refractory seizures,
CC neurodevelopmental impairment, and poor prognosis. Development is
CC normal prior to seizure onset, after which cognitive and motor delays
CC become apparent. DEE74 is an autosomal dominant form with onset in the
CC first year of life. {ECO:0000269|PubMed:27864268}. Note=The gene
CC represented in this entry is involved in disease pathogenesis.
CC -!- DISEASE: Epilepsy, childhood absence 2 (ECA2) [MIM:607681]: A subtype
CC of idiopathic generalized epilepsy characterized by an onset at age 6-7
CC years, frequent absence seizures (several per day) and bilateral,
CC synchronous, symmetric 3-Hz spike waves on EEG. Tonic-clonic seizures
CC often develop in adolescence. Some individuals manifest febrile
CC seizures. Absence seizures may either remit or persist into adulthood.
CC {ECO:0000269|PubMed:11326275}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- DISEASE: Febrile seizures, familial, 8 (FEB8) [MIM:607681]: Seizures
CC associated with febrile episodes in childhood without any evidence of
CC intracranial infection or defined pathologic or traumatic cause. It is
CC a common condition, affecting 2-5% of children aged 3 months to 5
CC years. The majority are simple febrile seizures (generally defined as
CC generalized onset, single seizures with a duration of less than 30
CC minutes). Complex febrile seizures are characterized by focal onset,
CC duration greater than 30 minutes, and/or more than one seizure in a 24
CC hour period. The likelihood of developing epilepsy following simple
CC febrile seizures is low. Complex febrile seizures are associated with a
CC moderately increased incidence of epilepsy.
CC {ECO:0000269|PubMed:16924025}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Generalized epilepsy with febrile seizures plus 3 (GEFS+3)
CC [MIM:607681]: A rare autosomal dominant, familial condition with
CC incomplete penetrance and large intrafamilial variability. Patients
CC display febrile seizures persisting sometimes beyond the age of 6 years
CC and/or a variety of afebrile seizure types. This disease combines
CC febrile seizures, generalized seizures often precipitated by fever at
CC age 6 years or more, and partial seizures, with a variable degree of
CC severity. {ECO:0000269|PubMed:11326274, ECO:0000269|PubMed:23708187}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
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}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Forbidden fruit - Issue 56
CC of March 2005;
CC URL="https://web.expasy.org/spotlight/back_issues/056";
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DR EMBL; X15376; CAA33437.1; -; mRNA.
DR EMBL; AF165124; AAD50273.1; -; Genomic_DNA.
DR EMBL; AC008611; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC091926; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC091984; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC059389; AAH59389.1; -; mRNA.
DR EMBL; BC069348; AAH69348.1; -; mRNA.
DR EMBL; BC074795; AAH74795.1; -; mRNA.
DR CCDS; CCDS4358.1; -. [P18507-1]
DR CCDS; CCDS4359.1; -. [P18507-2]
DR CCDS; CCDS47333.1; -. [P18507-3]
DR PIR; S03905; S03905.
DR RefSeq; NP_000807.2; NM_000816.3. [P18507-1]
DR RefSeq; NP_944493.2; NM_198903.2. [P18507-3]
DR RefSeq; NP_944494.1; NM_198904.2. [P18507-2]
DR PDB; 6D6T; EM; 3.80 A; E=8-326.
DR PDB; 6D6U; EM; 3.80 A; E=40-361, E=439-467.
DR PDB; 6HUG; EM; 3.10 A; C=1-467.
DR PDB; 6HUJ; EM; 3.04 A; C=1-467.
DR PDB; 6HUK; EM; 3.69 A; C=1-467.
DR PDB; 6HUO; EM; 3.26 A; C=1-467.
DR PDB; 6HUP; EM; 3.58 A; C=1-467.
DR PDB; 6I53; EM; 3.20 A; C=1-467.
DR PDB; 6X3S; EM; 3.12 A; E=8-361, E=440-467.
DR PDB; 6X3T; EM; 2.55 A; E=8-361, E=440-467.
DR PDB; 6X3U; EM; 3.49 A; E=8-361, E=440-467.
DR PDB; 6X3V; EM; 3.50 A; E=8-361, E=440-467.
DR PDB; 6X3W; EM; 3.30 A; E=8-361, E=440-467.
DR PDB; 6X3X; EM; 2.92 A; E=8-361, E=440-467.
DR PDB; 6X3Z; EM; 3.23 A; E=8-361, E=440-467.
DR PDB; 6X40; EM; 2.86 A; E=8-361, E=440-467.
DR PDBsum; 6D6T; -.
DR PDBsum; 6D6U; -.
DR PDBsum; 6HUG; -.
DR PDBsum; 6HUJ; -.
DR PDBsum; 6HUK; -.
DR PDBsum; 6HUO; -.
DR PDBsum; 6HUP; -.
DR PDBsum; 6I53; -.
DR PDBsum; 6X3S; -.
DR PDBsum; 6X3T; -.
DR PDBsum; 6X3U; -.
DR PDBsum; 6X3V; -.
DR PDBsum; 6X3W; -.
DR PDBsum; 6X3X; -.
DR PDBsum; 6X3Z; -.
DR PDBsum; 6X40; -.
DR AlphaFoldDB; P18507; -.
DR SMR; P18507; -.
DR BioGRID; 108840; 18.
DR ComplexPortal; CPX-2159; GABA-A receptor, alpha-1/beta-2/gamma-2.
DR ComplexPortal; CPX-2164; GABA-A receptor, alpha-6/beta-3/gamma-2.
DR ComplexPortal; CPX-2166; GABA-A receptor, alpha-3/beta-3/gamma-2.
DR ComplexPortal; CPX-2167; GABA-A receptor, alpha-1/beta-3/gamma-2.
DR ComplexPortal; CPX-2168; GABA-A receptor, alpha-5/beta-3/gamma-2.
DR ComplexPortal; CPX-2174; GABA-A receptor, alpha-2/beta-3/gamma-2.
DR CORUM; P18507; -.
DR IntAct; P18507; 15.
DR MINT; P18507; -.
DR STRING; 9606.ENSP00000410732; -.
DR BindingDB; P18507; -.
DR ChEMBL; CHEMBL2094120; -.
DR ChEMBL; CHEMBL2094121; -.
DR ChEMBL; CHEMBL2094122; -.
DR ChEMBL; CHEMBL2094130; -.
DR ChEMBL; CHEMBL2095172; -.
DR ChEMBL; CHEMBL2095190; -.
DR ChEMBL; CHEMBL2111339; -.
DR ChEMBL; CHEMBL2111366; -.
DR ChEMBL; CHEMBL2111370; -.
DR ChEMBL; CHEMBL2111392; -.
DR ChEMBL; CHEMBL2111413; -.
DR ChEMBL; CHEMBL4523638; -.
DR ChEMBL; CHEMBL4523640; -.
DR ChEMBL; CHEMBL4523641; -.
DR DrugBank; DB12537; 1,2-Benzodiazepine.
DR DrugBank; DB00546; Adinazolam.
DR DrugBank; DB06579; Adipiplon.
DR DrugBank; DB00404; Alprazolam.
DR DrugBank; DB00543; Amoxapine.
DR DrugBank; DB11901; Apalutamide.
DR DrugBank; DB14719; Bentazepam.
DR DrugBank; DB11859; Brexanolone.
DR DrugBank; DB01558; Bromazepam.
DR DrugBank; DB09017; Brotizolam.
DR DrugBank; DB00237; Butabarbital.
DR DrugBank; DB00241; Butalbital.
DR DrugBank; DB01489; Camazepam.
DR DrugBank; DB00395; Carisoprodol.
DR DrugBank; DB00475; Chlordiazepoxide.
DR DrugBank; DB14715; Cinazepam.
DR DrugBank; DB01594; Cinolazepam.
DR DrugBank; DB00349; Clobazam.
DR DrugBank; DB01068; Clonazepam.
DR DrugBank; DB00628; Clorazepic acid.
DR DrugBank; DB01559; Clotiazepam.
DR DrugBank; DB01553; Cloxazolam.
DR DrugBank; DB01511; Delorazepam.
DR DrugBank; DB01189; Desflurane.
DR DrugBank; DB00829; Diazepam.
DR DrugBank; DB13837; Doxefazepam.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB01215; Estazolam.
DR DrugBank; DB00402; Eszopiclone.
DR DrugBank; DB00189; Ethchlorvynol.
DR DrugBank; DB01545; Ethyl loflazepate.
DR DrugBank; DB09166; Etizolam.
DR DrugBank; DB00292; Etomidate.
DR DrugBank; DB01567; Fludiazepam.
DR DrugBank; DB01205; Flumazenil.
DR DrugBank; DB01544; Flunitrazepam.
DR DrugBank; DB00690; Flurazepam.
DR DrugBank; DB01381; Ginkgo biloba.
DR DrugBank; DB01437; Glutethimide.
DR DrugBank; DB00801; Halazepam.
DR DrugBank; DB01159; Halothane.
DR DrugBank; DB00753; Isoflurane.
DR DrugBank; DB01587; Ketazolam.
DR DrugBank; DB00555; Lamotrigine.
DR DrugBank; DB13643; Loprazolam.
DR DrugBank; DB00186; Lorazepam.
DR DrugBank; DB13872; Lormetazepam.
DR DrugBank; DB13437; Medazepam.
DR DrugBank; DB00603; Medroxyprogesterone acetate.
DR DrugBank; DB01043; Memantine.
DR DrugBank; DB00371; Meprobamate.
DR DrugBank; DB00463; Metharbital.
DR DrugBank; DB01028; Methoxyflurane.
DR DrugBank; DB01107; Methyprylon.
DR DrugBank; DB15489; Mexazolam.
DR DrugBank; DB00683; Midazolam.
DR DrugBank; DB12458; Muscimol.
DR DrugBank; DB01595; Nitrazepam.
DR DrugBank; DB14028; Nordazepam.
DR DrugBank; DB00334; Olanzapine.
DR DrugBank; DB00842; Oxazepam.
DR DrugBank; DB14672; Oxazepam acetate.
DR DrugBank; DB00312; Pentobarbital.
DR DrugBank; DB00252; Phenytoin.
DR DrugBank; DB13335; Pinazepam.
DR DrugBank; DB01708; Prasterone.
DR DrugBank; DB01588; Prazepam.
DR DrugBank; DB00794; Primidone.
DR DrugBank; DB00818; Propofol.
DR DrugBank; DB01589; Quazepam.
DR DrugBank; DB12404; Remimazolam.
DR DrugBank; DB01236; Sevoflurane.
DR DrugBank; DB09118; Stiripentol.
DR DrugBank; DB00306; Talbutal.
DR DrugBank; DB01956; Taurine.
DR DrugBank; DB00231; Temazepam.
DR DrugBank; DB11582; Thiocolchicoside.
DR DrugBank; DB00897; Triazolam.
DR DrugBank; DB00425; Zolpidem.
DR DrugCentral; P18507; -.
DR TCDB; 1.A.9.5.4; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.
DR GlyGen; P18507; 3 sites.
DR iPTMnet; P18507; -.
DR PhosphoSitePlus; P18507; -.
DR SwissPalm; P18507; -.
DR BioMuta; GABRG2; -.
DR DMDM; 116242488; -.
DR EPD; P18507; -.
DR MassIVE; P18507; -.
DR PeptideAtlas; P18507; -.
DR PRIDE; P18507; -.
DR ProteomicsDB; 27833; -.
DR ProteomicsDB; 53569; -. [P18507-1]
DR ProteomicsDB; 53570; -. [P18507-2]
DR TopDownProteomics; P18507-2; -. [P18507-2]
DR ABCD; P18507; 4 sequenced antibodies.
DR Antibodypedia; 28585; 397 antibodies from 38 providers.
DR DNASU; 2566; -.
DR Ensembl; ENST00000414552.6; ENSP00000410732.2; ENSG00000113327.17. [P18507-3]
DR Ensembl; ENST00000639111.2; ENSP00000492125.2; ENSG00000113327.17. [P18507-1]
DR Ensembl; ENST00000639213.2; ENSP00000491909.2; ENSG00000113327.17. [P18507-2]
DR GeneID; 2566; -.
DR KEGG; hsa:2566; -.
DR MANE-Select; ENST00000639213.2; ENSP00000491909.2; NM_198904.4; NP_944494.1. [P18507-2]
DR UCSC; uc003lyy.5; human. [P18507-1]
DR CTD; 2566; -.
DR DisGeNET; 2566; -.
DR GeneCards; GABRG2; -.
DR HGNC; HGNC:4087; GABRG2.
DR HPA; ENSG00000113327; Tissue enhanced (brain, retina).
DR MalaCards; GABRG2; -.
DR MIM; 137164; gene.
DR MIM; 604233; phenotype.
DR MIM; 607681; phenotype.
DR MIM; 618396; phenotype.
DR neXtProt; NX_P18507; -.
DR OpenTargets; ENSG00000113327; -.
DR Orphanet; 64280; Childhood absence epilepsy.
DR Orphanet; 33069; Dravet syndrome.
DR Orphanet; 36387; Generalized epilepsy with febrile seizures-plus.
DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR Orphanet; 1945; Rolandic epilepsy.
DR PharmGKB; PA28501; -.
DR VEuPathDB; HostDB:ENSG00000113327; -.
DR eggNOG; KOG3642; Eukaryota.
DR GeneTree; ENSGT00940000156685; -.
DR HOGENOM; CLU_010920_2_0_1; -.
DR InParanoid; P18507; -.
DR OMA; PMDVHSC; -.
DR OrthoDB; 1057372at2759; -.
DR PhylomeDB; P18507; -.
DR TreeFam; TF315453; -.
DR PathwayCommons; P18507; -.
DR Reactome; R-HSA-1236394; Signaling by ERBB4.
DR Reactome; R-HSA-977443; GABA receptor activation.
DR SignaLink; P18507; -.
DR SIGNOR; P18507; -.
DR BioGRID-ORCS; 2566; 14 hits in 1074 CRISPR screens.
DR ChiTaRS; GABRG2; human.
DR GeneWiki; GABRG2; -.
DR GenomeRNAi; 2566; -.
DR Pharos; P18507; Tclin.
DR PRO; PR:P18507; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P18507; protein.
DR Bgee; ENSG00000113327; Expressed in middle temporal gyrus and 137 other tissues.
DR ExpressionAtlas; P18507; baseline and differential.
DR Genevisible; P18507; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
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; ISS:BHF-UCL.
DR GO; GO:1902711; C:GABA-A receptor complex; IPI:ComplexPortal.
DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0060077; C:inhibitory synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; IEA:Ensembl.
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:0008503; F:benzodiazepine receptor activity; TAS:ProtInc.
DR GO; GO:0005254; F:chloride channel activity; ISS:UniProtKB.
DR GO; GO:0005231; F:excitatory extracellular ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0004890; F:GABA-A receptor activity; ISS:UniProtKB.
DR GO; GO:0022851; F:GABA-gated chloride ion channel activity; IEA:Ensembl.
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:0030534; P:adult behavior; IEA:Ensembl.
DR GO; GO:0071420; P:cellular response to histamine; ISS:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:1902476; P:chloride transmembrane transport; IDA:ComplexPortal.
DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IDA:ComplexPortal.
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:0009791; P:post-embryonic development; IEA:Ensembl.
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; ISS:BHF-UCL.
DR Gene3D; 1.20.58.390; -; 1.
DR Gene3D; 2.70.170.10; -; 1.
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; Alternative splicing; Cell membrane; Cell projection;
KW Chloride; Chloride channel; Cytoplasmic vesicle; Disease variant;
KW Disulfide bond; Epilepsy; Glycoprotein; Ion channel; Ion transport;
KW Lipoprotein; Membrane; Palmitate; Postsynaptic cell membrane;
KW Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix;
KW Transport.
FT SIGNAL 1..39
FT /evidence="ECO:0000255"
FT CHAIN 40..467
FT /note="Gamma-aminobutyric acid receptor subunit gamma-2"
FT /id="PRO_0000000477"
FT TOPO_DOM 40..273
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 274..296
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TRANSMEM 300..322
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TRANSMEM 334..356
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 357..443
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 444..466
FT /note="Helical"
FT /evidence="ECO:0000305"
FT REGION 425..442
FT /note="Interaction with GABARAP"
FT /evidence="ECO:0000255"
FT CARBOHYD 52
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 129
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 247
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 190..204
FT /evidence="ECO:0000250"
FT VAR_SEQ 211
FT /note="Y -> WSRSIAQAGMCSGVISAHYSLRFWGSTDPPTLASRVAGISD (in
FT isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_047323"
FT VAR_SEQ 376
FT /note="P -> PLLRMFSFK (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_041124"
FT VARIANT 79
FT /note="N -> S (found in a patient with generalized tonic-
FT clonic seizures; dbSNP:rs112894280)"
FT /evidence="ECO:0000269|PubMed:20485450"
FT /id="VAR_065226"
FT VARIANT 82
FT /note="R -> Q (in ECA2 and FEB8; abolishes in vitro
FT sensitivity to diazepam; dbSNP:rs121909673)"
FT /evidence="ECO:0000269|PubMed:11326275"
FT /id="VAR_014265"
FT VARIANT 83
FT /note="P -> S (found in a patient with idiopathic
FT generalized epilepsy; unknown pathological significance;
FT the currents elicited by mutant receptors are
FT indistinguishable from wild-type; no difference in
FT sensitivity of the mutant receptors to the allosteric
FT regulators zinc and benzodiazepine diazepam compared to
FT wild-type; dbSNP:rs587777365)"
FT /evidence="ECO:0000269|PubMed:21714819"
FT /id="VAR_071813"
FT VARIANT 106
FT /note="A -> T (in DEE74; does not affect protein abundance;
FT decreases cell surface expression; decreases current
FT amplitude in response to GABA; does not affect zinc
FT sensitivity; accelerates activation and prolonges
FT deactivation; dbSNP:rs796052505)"
FT /evidence="ECO:0000269|PubMed:27864268"
FT /id="VAR_082266"
FT VARIANT 107
FT /note="I -> T (in DEE74; increases protein abundance;
FT retained in the endoplasmic reticulum; decreases cell
FT surface expression; decreases current amplitude in response
FT to GABA; increases zinc sensitivity; accelerates activation
FT and prolonges deactivation)"
FT /evidence="ECO:0000269|PubMed:27864268"
FT /id="VAR_082267"
FT VARIANT 177
FT /note="R -> G (in FEB8; dbSNP:rs267606837)"
FT /evidence="ECO:0000269|PubMed:16924025"
FT /id="VAR_038602"
FT VARIANT 274
FT /note="Y -> C (probable disease-associated variant found in
FT a patient with generalized epilepsy with myoclonic atonic
FT seizures, cognitive impairment and behavioral disorder)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078226"
FT VARIANT 282
FT /note="P -> S (in DEE74; increases protein abundance;
FT retained in the endoplasmic reticulum decreases; cell
FT surface expression; decreases current amplitude in response
FT to GABA; increases zinc sensitivity; accelerates activation
FT and prolonges deactivation; dbSNP:rs796052508)"
FT /evidence="ECO:0000269|PubMed:27864268"
FT /id="VAR_082268"
FT VARIANT 323
FT /note="R -> Q (in GEFS+3 and DEE74; does not affect protein
FT abundance; decreases cell surface expression; decreases
FT current amplitude in response to GABA; increases zinc
FT sensitivity; accelerates deactivation; dbSNP:rs397514737)"
FT /evidence="ECO:0000269|PubMed:23708187,
FT ECO:0000269|PubMed:27864268"
FT /id="VAR_078620"
FT VARIANT 323
FT /note="R -> W (in DEE74; does not affect protein abundance;
FT decreases cell surface expression; decreases current
FT amplitude in response to GABA; increases zinc sensitivity;
FT accelerates deactivation; dbSNP:rs796052510)"
FT /evidence="ECO:0000269|PubMed:27864268"
FT /id="VAR_082269"
FT VARIANT 328
FT /note="K -> M (in GEFS+3; dbSNP:rs121909672)"
FT /evidence="ECO:0000269|PubMed:11326274"
FT /id="VAR_014266"
FT VARIANT 343
FT /note="F -> L (in DEE74; does not affect protein abundance;
FT decreases cell surface expression; decreases current
FT amplitude in response to GABA; does not affect zinc
FT sensitivity; accelerates activation and prolonges
FT deactivation; dbSNP:rs796052511 and dbSNP:rs1554100923)"
FT /evidence="ECO:0000269|PubMed:27864268"
FT /id="VAR_082270"
FT VARIANT 357
FT /note="H -> R (in dbSNP:rs17855003)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_065163"
FT CONFLICT 120
FT /note="T -> M (in Ref. 1; CAA33437)"
FT /evidence="ECO:0000305"
FT CONFLICT 181
FT /note="T -> S (in Ref. 1; CAA33437)"
FT /evidence="ECO:0000305"
FT CONFLICT 384..385
FT /note="Missing (in Ref. 5; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 399
FT /note="E -> D (in Ref. 5; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 438..439
FT /note="IA -> RI (in Ref. 5; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT HELIX 65..73
FT /evidence="ECO:0007829|PDB:6X3T"
FT TURN 74..76
FT /evidence="ECO:0007829|PDB:6X3T"
FT TURN 83..87
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 90..105
FT /evidence="ECO:0007829|PDB:6X3T"
FT TURN 106..109
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 110..122
FT /evidence="ECO:0007829|PDB:6X3T"
FT HELIX 124..126
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:6I53"
FT STRAND 134..137
FT /evidence="ECO:0007829|PDB:6X3T"
FT HELIX 139..144
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 155..160
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 168..173
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 176..189
FT /evidence="ECO:0007829|PDB:6X3T"
FT TURN 195..198
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 201..212
FT /evidence="ECO:0007829|PDB:6X3T"
FT TURN 215..217
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 218..229
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 232..235
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 238..254
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 257..270
FT /evidence="ECO:0007829|PDB:6X3T"
FT HELIX 274..291
FT /evidence="ECO:0007829|PDB:6X3T"
FT HELIX 292..295
FT /evidence="ECO:0007829|PDB:6X3T"
FT HELIX 301..323
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 324..326
FT /evidence="ECO:0007829|PDB:6HUJ"
FT HELIX 334..359
FT /evidence="ECO:0007829|PDB:6X3T"
FT HELIX 440..465
FT /evidence="ECO:0007829|PDB:6X3T"
SQ SEQUENCE 467 AA; 54162 MW; 7450DFE1157C9224 CRC64;
MSSPNIWSTG SSVYSTPVFS QKMTVWILLL LSLYPGFTSQ KSDDDYEDYA SNKTWVLTPK
VPEGDVTVIL NNLLEGYDNK LRPDIGVKPT LIHTDMYVNS IGPVNAINME YTIDIFFAQT
WYDRRLKFNS TIKVLRLNSN MVGKIWIPDT FFRNSKKADA HWITTPNRML RIWNDGRVLY
TLRLTIDAEC QLQLHNFPMD EHSCPLEFSS YGYPREEIVY QWKRSSVEVG DTRSWRLYQF
SFVGLRNTTE VVKTTSGDYV VMSVYFDLSR RMGYFTIQTY IPCTLIVVLS WVSFWINKDA
VPARTSLGIT TVLTMTTLST IARKSLPKVS YVTAMDLFVS VCFIFVFSAL VEYGTLHYFV
SNRKPSKDKD KKKKNPAPTI DIRPRSATIQ MNNATHLQER DEEYGYECLD GKDCASFFCC
FEDCRTGAWR HGRIHIRIAK MDSYARIFFP TAFCLFNLVY WVSYLYL
