GBRB2_HUMAN
ID GBRB2_HUMAN Reviewed; 512 AA.
AC P47870; A8K115; A8K1A0; D1LYT0; D1LYT1; Q16323; Q4FZB2;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-MAR-2010, sequence version 2.
DT 03-AUG-2022, entry version 201.
DE RecName: Full=Gamma-aminobutyric acid receptor subunit beta-2;
DE AltName: Full=GABA(A) receptor subunit beta-2;
DE Flags: Precursor;
GN Name=GABRB2;
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 2), FUNCTION, SUBCELLULAR LOCATION, AND
RP SUBUNIT.
RC TISSUE=Brain;
RX PubMed=8264558;
RA Hadingham K.L., Wingrove P.B., Wafford K.A., Bain C., Kemp J.A.,
RA Palmer K.J., Wilson A.W., Wilcox A.S., Sikela J.M., Ragan C.I.;
RT "Role of the beta subunit in determining the pharmacology of human gamma-
RT aminobutyric acid type A receptors.";
RL Mol. Pharmacol. 44:1211-1218(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
RX PubMed=7707873; DOI=10.1016/0169-328x(94)00228-7;
RA McKinley D.D., Lennon D.J., Carter D.B.;
RT "Cloning, sequence analysis and expression of two forms of mRNA coding for
RT the human beta 2 subunit of the GABAA receptor.";
RL Brain Res. Mol. Brain Res. 28:175-179(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), TISSUE SPECIFICITY,
RP MUTAGENESIS OF THR-389, FUNCTION, SUBCELLULAR LOCATION, AND ALTERNATIVE
RP SPLICING.
RC TISSUE=Brain;
RX PubMed=19763268; DOI=10.1371/journal.pone.0006977;
RA Zhao C., Xu Z., Wang F., Chen J., Ng S.K., Wong P.W., Yu Z., Pun F.W.,
RA Ren L., Lo W.S., Tsang S.Y., Xue H.;
RT "Alternative-splicing in the exon-10 region of GABA(A) receptor beta(2)
RT subunit gene: relationships between novel isoforms and psychotic
RT disorders.";
RL PLoS ONE 4:E6977-E6977(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 TISSUE SPECIFICITY.
RX PubMed=16983389; DOI=10.1038/sj.mp.4001899;
RA Zhao C., Xu Z., Chen J., Yu Z., Tong K.L., Lo W.S., Pun F.W., Ng S.K.,
RA Tsang S.Y., Xue H.;
RT "Two isoforms of GABA(A) receptor beta2 subunit with different
RT electrophysiological properties: Differential expression and genotypical
RT correlations in schizophrenia.";
RL Mol. Psychiatry 11:1092-1105(2006).
RN [8]
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 [9]
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 [10] {ECO:0007744|PDB:6D6T, ECO:0007744|PDB:6D6U}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS) OF 25-331 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 IECEE2 THR-79.
RX PubMed=25124326; DOI=10.1002/ajmg.a.36714;
RA Srivastava S., Cohen J., Pevsner J., Aradhya S., McKnight D., Butler E.,
RA Johnston M., Fatemi A.;
RT "A novel variant in GABRB2 associated with intellectual disability and
RT epilepsy.";
RL Am. J. Med. Genet. A 164A:2914-2921(2014).
RN [12]
RP INVOLVEMENT IN IECEE2, AND VARIANTS IECEE2 THR-79; HIS-244; SER-277;
RP LYS-284; PRO-293; ARG-303; VAL-304 AND ILE-316.
RX PubMed=29100083; DOI=10.1016/j.ajhg.2017.09.008;
RG Deciphering Developmental Disorders Study;
RA Hamdan F.F., Myers C.T., Cossette P., Lemay P., Spiegelman D.,
RA Laporte A.D., Nassif C., Diallo O., Monlong J., Cadieux-Dion M.,
RA Dobrzeniecka S., Meloche C., Retterer K., Cho M.T., Rosenfeld J.A., Bi W.,
RA Massicotte C., Miguet M., Brunga L., Regan B.M., Mo K., Tam C.,
RA Schneider A., Hollingsworth G., FitzPatrick D.R., Donaldson A., Canham N.,
RA Blair E., Kerr B., Fry A.E., Thomas R.H., Shelagh J., Hurst J.A.,
RA Brittain H., Blyth M., Lebel R.R., Gerkes E.H., Davis-Keppen L., Stein Q.,
RA Chung W.K., Dorison S.J., Benke P.J., Fassi E., Corsten-Janssen N.,
RA Kamsteeg E.J., Mau-Them F.T., Bruel A.L., Verloes A., Ounap K.,
RA Wojcik M.H., Albert D.V.F., Venkateswaran S., Ware T., Jones D., Liu Y.C.,
RA Mohammad S.S., Bizargity P., Bacino C.A., Leuzzi V., Martinelli S.,
RA Dallapiccola B., Tartaglia M., Blumkin L., Wierenga K.J., Purcarin G.,
RA O'Byrne J.J., Stockler S., Lehman A., Keren B., Nougues M.C., Mignot C.,
RA Auvin S., Nava C., Hiatt S.M., Bebin M., Shao Y., Scaglia F., Lalani S.R.,
RA Frye R.E., Jarjour I.T., Jacques S., Boucher R.M., Riou E., Srour M.,
RA Carmant L., Lortie A., Major P., Diadori P., Dubeau F., D'Anjou G.,
RA Bourque G., Berkovic S.F., Sadleir L.G., Campeau P.M., Kibar Z.,
RA Lafreniere R.G., Girard S.L., Mercimek-Mahmutoglu S., Boelman C.,
RA Rouleau G.A., Scheffer I.E., Mefford H.C., Andrade D.M., Rossignol E.,
RA Minassian B.A., Michaud J.L.;
RT "High rate of recurrent de novo mutations in developmental and epileptic
RT encephalopathies.";
RL Am. J. Hum. Genet. 101:664-685(2017).
RN [13]
RP VARIANT IECEE2 PRO-287, CHARACTERIZATION OF VARIANT IECEE2 PRO-287, AND
RP FUNCTION.
RX PubMed=27789573; DOI=10.1136/jmedgenet-2016-104083;
RA Ishii A., Kang J.Q., Schornak C.C., Hernandez C.C., Shen W., Watkins J.C.,
RA Macdonald R.L., Hirose S.;
RT "A de novo missense mutation of GABRB2 causes early myoclonic
RT encephalopathy.";
RL J. Med. Genet. 54:202-211(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:8264558, PubMed:19763268,
CC PubMed:27789573, PubMed:29950725). Plays an important role in the
CC formation of functional inhibitory GABAergic synapses in addition to
CC mediating synaptic inhibition as a GABA-gated ion channel
CC (PubMed:23909897, PubMed:25489750). The gamma2 subunit is necessary but
CC not sufficient for a rapid formation of active synaptic contacts and
CC the synaptogenic effect of this subunit is influenced by the type of
CC alpha and beta subunits present in the receptor pentamer (By
CC similarity). The alpha1/beta2/gamma2 receptor and the
CC alpha2/beta2/gamma2 receptor exhibit synaptogenic activity
CC (PubMed:23909897, PubMed:25489750). Functions also as histamine
CC receptor and mediates cellular responses to histamine (By similarity).
CC {ECO:0000250|UniProtKB:P63137, ECO:0000250|UniProtKB:P63138,
CC ECO:0000269|PubMed:19763268, ECO:0000269|PubMed:23909897,
CC ECO:0000269|PubMed:25489750, ECO:0000269|PubMed:27789573,
CC ECO:0000269|PubMed:29950725, ECO:0000269|PubMed:8264558}.
CC -!- ACTIVITY REGULATION: Allosterically activated by benzodiazepines
CC (PubMed:29950725). Allosterically activated by the anesthetic etomidate
CC (By similarity). Inhibited by the antagonist bicuculline
CC (PubMed:29950725). {ECO:0000250|UniProtKB:P0C2W5,
CC ECO:0000269|PubMed:29950725}.
CC -!- SUBUNIT: Heteropentamer, formed by a combination of alpha, beta, gamma,
CC delta and rho chains (PubMed:8264558, PubMed:29950725). Interacts with
CC UBQLN1 (By similarity). Interacts with KCTD8, KCTD12 and KCTD16; this
CC interaction determines the pharmacology and kinetics of the receptor
CC response, the KCTD proteins markedly accelerating the GABA-B response,
CC although to different extents (By similarity). May interact with KIF21B
CC (By similarity). Identified in a complex of 720 kDa composed of LHFPL4,
CC NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity).
CC {ECO:0000250|UniProtKB:P63138, ECO:0000269|PubMed:29950725,
CC ECO:0000269|PubMed:8264558}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000250|UniProtKB:P63137}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:19763268,
CC ECO:0000269|PubMed:8264558}; Multi-pass membrane protein {ECO:0000255}.
CC Cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P63138}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Long, Beta-2L;
CC IsoId=P47870-2; Sequence=Displayed;
CC Name=2; Synonyms=Short, Beta-2S;
CC IsoId=P47870-1; Sequence=VSP_038825;
CC Name=3; Synonyms=Beta-2S1;
CC IsoId=P47870-3; Sequence=VSP_038823, VSP_038824, VSP_038828;
CC Name=4; Synonyms=Beta-2S2;
CC IsoId=P47870-4; Sequence=VSP_038825, VSP_038826, VSP_038827;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 2 show reduced expression in
CC schizophrenic brain. Isoform 3 shows increased expression in
CC schizophrenic and bipolar disorder brains while isoform 4 shows reduced
CC expression. {ECO:0000269|PubMed:16983389, ECO:0000269|PubMed:19763268}.
CC -!- DOMAIN: The extracellular domain contributes to synaptic contact
CC formation. {ECO:0000250|UniProtKB:P63137}.
CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P63137}.
CC -!- DISEASE: Epileptic encephalopathy, infantile or early childhood, 2
CC (IECEE2) [MIM:617829]: A form of epileptic encephalopathy, a
CC heterogeneous group of severe childhood onset epilepsies characterized
CC by refractory seizures, neurodevelopmental impairment, and poor
CC prognosis. Development is normal prior to seizure onset, after which
CC cognitive and motor delays become apparent. IECEE2 is an autosomal
CC dominant condition with variable age at seizure onset, ranging from
CC early infancy to 6 years. {ECO:0000269|PubMed:25124326,
CC ECO:0000269|PubMed:27789573, ECO:0000269|PubMed:29100083}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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. GABRB2 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; S67368; AAB29370.1; -; mRNA.
DR EMBL; S77554; AAB33983.1; -; mRNA.
DR EMBL; S77553; AAB33982.1; -; mRNA.
DR EMBL; GU086163; ACY69094.1; -; mRNA.
DR EMBL; GU086164; ACY69095.1; -; mRNA.
DR EMBL; AK289730; BAF82419.1; -; mRNA.
DR EMBL; AK289815; BAF82504.1; -; mRNA.
DR EMBL; CH471062; EAW61543.1; -; Genomic_DNA.
DR EMBL; BC099705; AAH99705.1; -; mRNA.
DR EMBL; BC099719; AAH99719.1; -; mRNA.
DR EMBL; BC105639; AAI05640.1; -; mRNA.
DR CCDS; CCDS4354.1; -. [P47870-1]
DR CCDS; CCDS4355.1; -. [P47870-2]
DR PIR; I52656; I52656.
DR RefSeq; NP_000804.1; NM_000813.2. [P47870-1]
DR RefSeq; NP_068711.1; NM_021911.2. [P47870-2]
DR PDB; 6D6T; EM; 3.80 A; A/C=25-331.
DR PDB; 6D6U; EM; 3.80 A; A/C=25-331.
DR PDB; 6X3S; EM; 3.12 A; A/C=25-331, A/C=487-512.
DR PDB; 6X3T; EM; 2.55 A; A/C=25-331, A/C=487-512.
DR PDB; 6X3U; EM; 3.49 A; A/C=25-331, A/C=487-512.
DR PDB; 6X3V; EM; 3.50 A; A/C=25-331, A/C=487-512.
DR PDB; 6X3W; EM; 3.30 A; A/C=25-331, A/C=487-512.
DR PDB; 6X3X; EM; 2.92 A; A/C=25-331, A/C=487-512.
DR PDB; 6X3Z; EM; 3.23 A; A/C=25-331, A/C=487-512.
DR PDB; 6X40; EM; 2.86 A; A/C=25-331, A/C=487-512.
DR PDBsum; 6D6T; -.
DR PDBsum; 6D6U; -.
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; P47870; -.
DR SMR; P47870; -.
DR BioGRID; 108835; 7.
DR ComplexPortal; CPX-2159; GABA-A receptor, alpha-1/beta-2/gamma-2.
DR ComplexPortal; CPX-2952; GABA-A receptor, alpha-6/beta-2/delta.
DR ComplexPortal; CPX-2953; GABA-A receptor, alpha-4/beta-2/delta.
DR CORUM; P47870; -.
DR IntAct; P47870; 4.
DR MINT; P47870; -.
DR STRING; 9606.ENSP00000274547; -.
DR BindingDB; P47870; -.
DR ChEMBL; CHEMBL1920; -.
DR DrugBank; DB12537; 1,2-Benzodiazepine.
DR DrugBank; DB00546; Adinazolam.
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; DB00898; Ethanol.
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; DB06716; Fospropofol.
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; DB01595; Nitrazepam.
DR DrugBank; DB14028; Nordazepam.
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 DrugCentral; P47870; -.
DR TCDB; 1.A.9.5.2; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.
DR GlyGen; P47870; 3 sites.
DR iPTMnet; P47870; -.
DR PhosphoSitePlus; P47870; -.
DR BioMuta; GABRB2; -.
DR DMDM; 292495010; -.
DR MassIVE; P47870; -.
DR PaxDb; P47870; -.
DR PeptideAtlas; P47870; -.
DR PRIDE; P47870; -.
DR ProteomicsDB; 55801; -. [P47870-2]
DR ProteomicsDB; 55802; -. [P47870-1]
DR ProteomicsDB; 55803; -. [P47870-3]
DR ProteomicsDB; 55804; -. [P47870-4]
DR Antibodypedia; 4534; 335 antibodies from 34 providers.
DR DNASU; 2561; -.
DR Ensembl; ENST00000274547.7; ENSP00000274547.2; ENSG00000145864.14. [P47870-2]
DR Ensembl; ENST00000353437.10; ENSP00000274546.6; ENSG00000145864.14. [P47870-1]
DR Ensembl; ENST00000393959.6; ENSP00000377531.1; ENSG00000145864.14. [P47870-2]
DR Ensembl; ENST00000520240.5; ENSP00000429320.1; ENSG00000145864.14. [P47870-1]
DR Ensembl; ENST00000675303.1; ENSP00000502748.1; ENSG00000145864.14. [P47870-1]
DR Ensembl; ENST00000675773.1; ENSP00000502701.1; ENSG00000145864.14. [P47870-1]
DR GeneID; 2561; -.
DR KEGG; hsa:2561; -.
DR MANE-Select; ENST00000393959.6; ENSP00000377531.1; NM_001371727.1; NP_001358656.1.
DR UCSC; uc003lyr.2; human. [P47870-2]
DR CTD; 2561; -.
DR DisGeNET; 2561; -.
DR GeneCards; GABRB2; -.
DR HGNC; HGNC:4082; GABRB2.
DR HPA; ENSG00000145864; Tissue enriched (brain).
DR MalaCards; GABRB2; -.
DR MIM; 600232; gene.
DR MIM; 617829; phenotype.
DR neXtProt; NX_P47870; -.
DR OpenTargets; ENSG00000145864; -.
DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR PharmGKB; PA28496; -.
DR VEuPathDB; HostDB:ENSG00000145864; -.
DR eggNOG; KOG3643; Eukaryota.
DR GeneTree; ENSGT00940000154245; -.
DR HOGENOM; CLU_010920_1_4_1; -.
DR InParanoid; P47870; -.
DR OMA; INKMDPH; -.
DR OrthoDB; 480926at2759; -.
DR PhylomeDB; P47870; -.
DR TreeFam; TF315453; -.
DR PathwayCommons; P47870; -.
DR Reactome; R-HSA-1236394; Signaling by ERBB4.
DR Reactome; R-HSA-977443; GABA receptor activation.
DR SignaLink; P47870; -.
DR SIGNOR; P47870; -.
DR BioGRID-ORCS; 2561; 7 hits in 1070 CRISPR screens.
DR ChiTaRS; GABRB2; human.
DR GeneWiki; GABRB2; -.
DR GenomeRNAi; 2561; -.
DR Pharos; P47870; Tclin.
DR PRO; PR:P47870; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P47870; protein.
DR Bgee; ENSG00000145864; Expressed in Brodmann (1909) area 23 and 140 other tissues.
DR ExpressionAtlas; P47870; baseline and differential.
DR Genevisible; P47870; HS.
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:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:1902711; C:GABA-A receptor complex; IPI:ComplexPortal.
DR GO; GO:0098982; C:GABA-ergic 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; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
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:BHF-UCL.
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; IEA:Ensembl.
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: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:0090102; P:cochlea development; IEA:Ensembl.
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:0060119; P:inner ear receptor cell development; IEA:Ensembl.
DR GO; GO:0060384; P:innervation; IEA:Ensembl.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
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:0007605; P:sensory perception of sound; IEA:Ensembl.
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; 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 3D-structure; Alternative splicing; Cell membrane; Chloride;
KW Chloride channel; Cytoplasmic vesicle; Disease variant; Disulfide bond;
KW Epilepsy; Glycoprotein; Ion channel; Ion transport;
KW Ligand-gated ion channel; Membrane; Phosphoprotein;
KW Postsynaptic cell membrane; Receptor; Reference proteome; Signal; Synapse;
KW Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..25
FT /evidence="ECO:0000250"
FT CHAIN 26..512
FT /note="Gamma-aminobutyric acid receptor subunit beta-2"
FT /id="PRO_0000000459"
FT TOPO_DOM 26..244
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 245..266
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TRANSMEM 270..292
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TRANSMEM 304..326
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 327..489
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 490..511
FT /note="Helical"
FT /evidence="ECO:0000305"
FT MOD_RES 441
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P63137"
FT CARBOHYD 32
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 104
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 160..174
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..63
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:19763268"
FT /id="VSP_038823"
FT VAR_SEQ 360..397
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:19763268,
FT ECO:0000303|PubMed:7707873, ECO:0000303|PubMed:8264558"
FT /id="VSP_038825"
FT VAR_SEQ 360..376
FT /note="IFYKDIKQNGTQYRSLW -> VNSEGKPSLLLKLMEEC (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:19763268"
FT /id="VSP_038824"
FT VAR_SEQ 377..512
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:19763268"
FT /id="VSP_038828"
FT VAR_SEQ 410
FT /note="E -> D (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:19763268"
FT /id="VSP_038826"
FT VAR_SEQ 411..512
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:19763268"
FT /id="VSP_038827"
FT VARIANT 79
FT /note="M -> T (in IECEE2; unknown pathological
FT significance; dbSNP:rs606231468)"
FT /evidence="ECO:0000269|PubMed:25124326,
FT ECO:0000269|PubMed:29100083"
FT /id="VAR_080712"
FT VARIANT 244
FT /note="Y -> H (in IECEE2; unknown pathological
FT significance; dbSNP:rs1554094149)"
FT /evidence="ECO:0000269|PubMed:29100083"
FT /id="VAR_080713"
FT VARIANT 277
FT /note="L -> S (in IECEE2; unknown pathological
FT significance; dbSNP:rs1554094145)"
FT /evidence="ECO:0000269|PubMed:29100083"
FT /id="VAR_080714"
FT VARIANT 284
FT /note="T -> K (in IECEE2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:29100083"
FT /id="VAR_080715"
FT VARIANT 287
FT /note="T -> P (in IECEE2; loss of localization to the cell
FT membrane; retained intracellularly it affects the cell
FT surface expression of the GABA receptor; decreased GABA
FT receptor activity; dbSNP:rs1554093894)"
FT /evidence="ECO:0000269|PubMed:27789573"
FT /id="VAR_080716"
FT VARIANT 293
FT /note="R -> P (in IECEE2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:29100083"
FT /id="VAR_080717"
FT VARIANT 303
FT /note="K -> R (in IECEE2; unknown pathological
FT significance; dbSNP:rs1554093885)"
FT /evidence="ECO:0000269|PubMed:29100083"
FT /id="VAR_080718"
FT VARIANT 304
FT /note="A -> V (in IECEE2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:29100083"
FT /id="VAR_080719"
FT VARIANT 316
FT /note="V -> I (in IECEE2; unknown pathological
FT significance; dbSNP:rs1554093884)"
FT /evidence="ECO:0000269|PubMed:29100083"
FT /id="VAR_080720"
FT MUTAGEN 389
FT /note="T->A: Displays reduced current rundown following
FT repeated receptor activation."
FT /evidence="ECO:0000269|PubMed:19763268"
FT CONFLICT 336
FT /note="Q -> L (in Ref. 4; BAF82419)"
FT /evidence="ECO:0000305"
FT HELIX 32..43
FT /evidence="ECO:0007829|PDB:6X3T"
FT TURN 44..46
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 55..58
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 60..75
FT /evidence="ECO:0007829|PDB:6X3T"
FT TURN 76..79
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 80..92
FT /evidence="ECO:0007829|PDB:6X3T"
FT HELIX 94..96
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:6X3T"
FT HELIX 109..114
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 125..130
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 138..142
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 146..159
FT /evidence="ECO:0007829|PDB:6X3T"
FT TURN 165..168
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 171..182
FT /evidence="ECO:0007829|PDB:6X3T"
FT TURN 185..187
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 188..192
FT /evidence="ECO:0007829|PDB:6X3T"
FT TURN 193..198
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 199..202
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 208..224
FT /evidence="ECO:0007829|PDB:6X3T"
FT STRAND 227..240
FT /evidence="ECO:0007829|PDB:6X3T"
FT HELIX 243..248
FT /evidence="ECO:0007829|PDB:6X3T"
FT HELIX 250..262
FT /evidence="ECO:0007829|PDB:6X3T"
FT HELIX 263..265
FT /evidence="ECO:0007829|PDB:6X3T"
FT HELIX 271..285
FT /evidence="ECO:0007829|PDB:6X3T"
FT TURN 286..289
FT /evidence="ECO:0007829|PDB:6X3T"
FT HELIX 290..293
FT /evidence="ECO:0007829|PDB:6X3T"
FT HELIX 304..328
FT /evidence="ECO:0007829|PDB:6X3T"
FT TURN 329..331
FT /evidence="ECO:0007829|PDB:6X40"
SQ SEQUENCE 512 AA; 59150 MW; C390A0C92815DD89 CRC64;
MWRVRKRGYF GIWSFPLIIA AVCAQSVNDP SNMSLVKETV DRLLKGYDIR LRPDFGGPPV
AVGMNIDIAS IDMVSEVNMD YTLTMYFQQA WRDKRLSYNV IPLNLTLDNR VADQLWVPDT
YFLNDKKSFV HGVTVKNRMI RLHPDGTVLY GLRITTTAAC MMDLRRYPLD EQNCTLEIES
YGYTTDDIEF YWRGDDNAVT GVTKIELPQF SIVDYKLITK KVVFSTGSYP RLSLSFKLKR
NIGYFILQTY MPSILITILS WVSFWINYDA SAARVALGIT TVLTMTTINT HLRETLPKIP
YVKAIDMYLM GCFVFVFMAL LEYALVNYIF FGRGPQRQKK AAEKAASANN EKMRLDVNKI
FYKDIKQNGT QYRSLWDPTG NLSPTRRTTN YDFSLYTMDP HENILLSTLE IKNEMATSEA
VMGLGDPRST MLAYDASSIQ YRKAGLPRHS FGRNALERHV AQKKSRLRRR ASQLKITIPD
LTDVNAIDRW SRIFFPVVFS FFNIVYWLYY VN
