ID GBRA2_HUMAN Reviewed; 451 AA. AC P47869; A8K0U7; B7Z1H8; Q59G14; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 20-FEB-2007, sequence version 2. DT 24-JAN-2024, entry version 205. DE RecName: Full=Gamma-aminobutyric acid receptor subunit alpha-2; DE AltName: Full=GABA(A) receptor subunit alpha-2; DE Flags: Precursor; GN Name=GABRA2; 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). RC TISSUE=Brain; RX PubMed=8391122; RA Hadingham K.L., Wingrove P., le Bourdelles B., Palmer K.J., Ragan C.I., RA Whiting P.J.; RT "Cloning of cDNA sequences encoding human alpha 2 and alpha 3 gamma- RT aminobutyric acidA receptor subunits and characterization of the RT benzodiazepine pharmacology of recombinant alpha 1-, alpha 2-, alpha 3-, RT and alpha 5-containing human gamma-aminobutyric acidA receptors."; RL Mol. Pharmacol. 43:970-975(1993). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Amygdala, Brain, and Cerebellum; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP INVOLVEMENT IN SUSCEPTIBILITY TO ALCOHOLISM. RX PubMed=15024690; DOI=10.1086/383283; RA Edenberg H.J., Dick D.M., Xuei X., Tian H., Almasy L., Bauer L.O., RA Crowe R.R., Goate A., Hesselbrock V., Jones K., Kwon J., Li T.-K., RA Nurnberger J.I. Jr., O'Connor S.J., Reich T., Rice J., Schuckit M.A., RA Porjesz B., Foroud T., Begleiter H.; RT "Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) RT receptor, are associated with alcohol dependence and with brain RT oscillations."; RL Am. J. Hum. Genet. 74:705-714(2004). RN [7] RP FUNCTION, INVOLVEMENT IN DEE78, VARIANT DEE78 LYS-292, CHARACTERIZATION OF RP VARIANT DEE78 LYS-292, AND VARIANT LYS-377. RX PubMed=29961870; DOI=10.1093/brain/awy171; RA Butler K.M., Moody O.A., Schuler E., Coryell J., Alexander J.J., RA Jenkins A., Escayg A.; RT "De novo variants in GABRA2 and GABRA5 alter receptor function and RT contribute to early-onset epilepsy."; RL Brain 141:2392-2405(2018). RN [8] RP INVOLVEMENT IN DEE78, AND VARIANT DEE78 HIS-335. RX PubMed=29422393; DOI=10.1016/j.ejpn.2017.12.017; RA Orenstein N., Goldberg-Stern H., Straussberg R., Bazak L., RA Weisz Hubshman M., Kropach N., Gilad O., Scheuerman O., Dory Y., Kraus D., RA Tzur S., Magal N., Kilim Y., Shkalim Zemer V., Basel-Salmon L.; RT "A de novo GABRA2 missense mutation in severe early-onset epileptic RT encephalopathy with a choreiform movement disorder."; RL Eur. J. Paediatr. Neurol. 22:516-524(2018). RN [9] RP FUNCTION, INVOLVEMENT IN DEE78, VARIANTS DEE78 THR-263; ALA-284; VAL-291 RP AND LEU-325, AND CHARACTERIZATION OF VARIANTS DEE78 THR-263; ALA-284; RP VAL-291 AND LEU-325. RX PubMed=31032849; DOI=10.1093/brain/awz079; RA Maljevic S., Keren B., Aung Y.H., Forster I.C., Mignot C., Buratti J., RA Lafitte A., Freihuber C., Rodan L.H., Bergin A., Hubert L., Poirier K., RA Munnich A., Besmond C., Hauser N., Miller R., McWalter K., Nabbout R., RA Heron D., Leguern E., Depienne C., Petrou S., Nava C.; RT "Novel GABRA2 variants in epileptic encephalopathy and intellectual RT disability with seizures."; RL Brain 142:E15-E15(2019). 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:29961870, PubMed:31032849). 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:29961870, PubMed:31032849). The gamma2 subunit is CC necessary but not sufficient for a rapid formation of active synaptic CC contacts and the synaptogenic effect of this subunit is influenced by CC the type of alpha and beta subunits present in the receptor pentamer CC (By similarity). The alpha2/beta2/gamma2 receptor exhibits synaptogenic CC activity whereas the alpha2/beta3/gamma2 receptor shows very little or CC no synaptogenic activity (By similarity). CC {ECO:0000250|UniProtKB:P26048, ECO:0000269|PubMed:29961870, CC ECO:0000269|PubMed:31032849}. CC -!- ACTIVITY REGULATION: Activated by pentobarbital (By similarity). CC Inhibited by the antagonist bicuculline (By similarity). CC {ECO:0000250|UniProtKB:P10063}. CC -!- SUBUNIT: Heteropentamer, formed by a combination of alpha, beta, gamma, CC delta and rho chains. Interacts with UBQLN1 (By similarity). Interacts CC with KIF21B (By similarity). 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:P23576, CC ECO:0000250|UniProtKB:P26048}. CC -!- INTERACTION: CC P47869; P00533: EGFR; NbExp=2; IntAct=EBI-2685723, EBI-297353; CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane CC {ECO:0000250|UniProtKB:P26048}; Multi-pass membrane protein CC {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:P26048}; Multi-pass CC membrane protein {ECO:0000255}. Cytoplasmic vesicle membrane CC {ECO:0000250|UniProtKB:P23576}. Cell projection, dendrite CC {ECO:0000250|UniProtKB:P26048}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P47869-1; Sequence=Displayed; CC Name=2; CC IsoId=P47869-2; Sequence=VSP_054277, VSP_054278; CC -!- DOMAIN: The extracellular domain contributes to synaptic contact CC formation. {ECO:0000250|UniProtKB:P26048}. CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:P26048}. CC -!- POLYMORPHISM: Genetic variations in GABRA2 determine the genetic CC susceptibility to alcoholism [MIM:103780]. CC -!- DISEASE: Developmental and epileptic encephalopathy 78 (DEE78) CC [MIM:618557]: 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. DEE78 is an autosomal dominant form characterized by CC onset of refractory seizures in the first days or months of life. CC Clinical features include severe developmental delay, hypotonia, CC microcephaly, cortical visual impairment and profound intellectual CC disability. Some patients manifest a less severe phenotype CC characterized by pharmacoresponsive epilepsy, autism spectrum disorder CC and moderate intellectual disability. {ECO:0000269|PubMed:29422393, CC ECO:0000269|PubMed:29961870, ECO:0000269|PubMed:31032849}. 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. GABRA2 sub- CC subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD92532.1; Type=Erroneous initiation; Evidence={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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; S62907; AAB27278.1; -; mRNA. DR EMBL; AK125179; BAG54159.1; -; mRNA. DR EMBL; AK289662; BAF82351.1; -; mRNA. DR EMBL; AK293466; BAH11514.1; -; mRNA. DR EMBL; AB209295; BAD92532.1; ALT_INIT; mRNA. DR EMBL; AC084352; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC093745; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC095060; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC104072; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471069; EAW93022.1; -; Genomic_DNA. DR CCDS; CCDS3471.1; -. [P47869-1] DR PIR; I57947; I57947. DR RefSeq; NP_000798.2; NM_000807.3. [P47869-1] DR RefSeq; NP_001107647.1; NM_001114175.2. [P47869-1] DR RefSeq; NP_001273756.1; NM_001286827.2. [P47869-2] DR RefSeq; NP_001317619.1; NM_001330690.1. DR RefSeq; XP_016863471.1; XM_017007982.1. DR RefSeq; XP_016863472.1; XM_017007983.1. DR AlphaFoldDB; P47869; -. DR SMR; P47869; -. DR BioGRID; 108829; 4. DR ComplexPortal; CPX-2174; GABA-A receptor, alpha-2/beta-3/gamma-2. DR IntAct; P47869; 3. DR MINT; P47869; -. DR STRING; 9606.ENSP00000427603; -. DR BindingDB; P47869; -. DR ChEMBL; CHEMBL4956; -. DR DrugBank; DB12537; 1,2-Benzodiazepine. DR DrugBank; DB00546; Adinazolam. DR DrugBank; DB06579; Adipiplon. DR DrugBank; DB00404; Alprazolam. DR DrugBank; DB01351; Amobarbital. DR DrugBank; DB00543; Amoxapine. DR DrugBank; DB11901; Apalutamide. DR DrugBank; DB01352; Aprobarbital. DR DrugBank; DB13994; AZD-7325. DR DrugBank; DB01483; Barbital. 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; DB01353; Butobarbital. DR DrugBank; DB01489; Camazepam. 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; DB01496; Dihydro-2-thioxo-5-((5-(2-(trifluoromethyl)phenyl)-2-furanyl)methyl)-4,6(1H,5H)-pyrimidinedione. 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; DB05087; Ganaxolone. DR DrugBank; DB01437; Glutethimide. DR DrugBank; DB00801; Halazepam. DR DrugBank; DB01159; Halothane. DR DrugBank; DB01354; Heptabarbital. DR DrugBank; DB01355; Hexobarbital. 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; DB00849; Methylphenobarbital. DR DrugBank; DB01107; Methyprylon. DR DrugBank; DB15489; Mexazolam. DR DrugBank; DB00683; Midazolam. DR DrugBank; DB01595; Nitrazepam. DR DrugBank; DB14028; Nordazepam. DR DrugBank; DB00334; Olanzapine. DR DrugBank; DB00842; Oxazepam. DR DrugBank; DB14672; Oxazepam acetate. DR DrugBank; DB04903; Pagoclone. 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; DB01346; Quinidine barbiturate. DR DrugBank; DB12404; Remimazolam. DR DrugBank; DB00418; Secobarbital. 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; DB00599; Thiopental. DR DrugBank; DB00897; Triazolam. DR DrugBank; DB00425; Zolpidem. DR DrugBank; DB00909; Zonisamide. DR DrugBank; DB01198; Zopiclone. DR DrugCentral; P47869; -. DR GuidetoPHARMACOLOGY; 405; -. DR TCDB; 1.A.9.5.2; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family. DR GlyCosmos; P47869; 2 sites, No reported glycans. DR GlyGen; P47869; 2 sites. DR iPTMnet; P47869; -. DR PhosphoSitePlus; P47869; -. DR BioMuta; GABRA2; -. DR DMDM; 126302547; -. DR MassIVE; P47869; -. DR PaxDb; 9606-ENSP00000421828; -. DR PeptideAtlas; P47869; -. DR ProteomicsDB; 55800; -. [P47869-1] DR ProteomicsDB; 6330; -. DR Antibodypedia; 12030; 396 antibodies from 33 providers. DR DNASU; 2555; -. DR Ensembl; ENST00000356504.5; ENSP00000348897.1; ENSG00000151834.16. [P47869-1] DR Ensembl; ENST00000381620.9; ENSP00000371033.4; ENSG00000151834.16. [P47869-1] DR Ensembl; ENST00000510861.5; ENSP00000421828.1; ENSG00000151834.16. [P47869-1] DR Ensembl; ENST00000514090.5; ENSP00000421300.1; ENSG00000151834.16. [P47869-1] DR GeneID; 2555; -. DR KEGG; hsa:2555; -. DR MANE-Select; ENST00000381620.9; ENSP00000371033.4; NM_000807.4; NP_000798.2. DR UCSC; uc003gxc.5; human. [P47869-1] DR AGR; HGNC:4076; -. DR CTD; 2555; -. DR DisGeNET; 2555; -. DR GeneCards; GABRA2; -. DR HGNC; HGNC:4076; GABRA2. DR HPA; ENSG00000151834; Tissue enriched (brain). DR MalaCards; GABRA2; -. DR MIM; 103780; phenotype. DR MIM; 137140; gene. DR MIM; 618557; phenotype. DR neXtProt; NX_P47869; -. DR OpenTargets; ENSG00000151834; -. DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy. DR PharmGKB; PA28490; -. DR VEuPathDB; HostDB:ENSG00000151834; -. DR eggNOG; KOG3642; Eukaryota. DR GeneTree; ENSGT00940000157266; -. DR HOGENOM; CLU_010920_2_1_1; -. DR InParanoid; P47869; -. DR OMA; AXSITEV; -. DR OrthoDB; 4265336at2759; -. DR PhylomeDB; P47869; -. DR TreeFam; TF315453; -. DR PathwayCommons; P47869; -. DR Reactome; R-HSA-977443; GABA receptor activation. DR SignaLink; P47869; -. DR SIGNOR; P47869; -. DR BioGRID-ORCS; 2555; 16 hits in 1160 CRISPR screens. DR ChiTaRS; GABRA2; human. DR GeneWiki; GABRA2; -. DR GenomeRNAi; 2555; -. DR Pharos; P47869; Tclin. DR PRO; PR:P47869; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; P47869; Protein. DR Bgee; ENSG00000151834; Expressed in frontal pole and 138 other cell types or tissues. DR ExpressionAtlas; P47869; baseline and differential. DR GO; GO:0030424; C:axon; IEA:Ensembl. DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW. DR GO; GO:0032590; C:dendrite membrane; IBA:GO_Central. DR GO; GO:1902711; C:GABA-A receptor complex; IDA:GO_Central. DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl. DR GO; GO:0060077; C:inhibitory synapse; IEA:Ensembl. DR GO; GO:0043005; C:neuron projection; IBA:GO_Central. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0098794; C:postsynapse; IBA:GO_Central. DR GO; GO:0099634; C:postsynaptic specialization membrane; IEA:Ensembl. DR GO; GO:0045202; C:synapse; IBA:GO_Central. DR GO; GO:0030672; C:synaptic vesicle membrane; IDA:UniProtKB. DR GO; GO:0008503; F:benzodiazepine receptor activity; IMP:UniProtKB. DR GO; GO:0004890; F:GABA-A receptor activity; IEA:InterPro. DR GO; GO:0022851; F:GABA-gated chloride ion channel activity; IDA:GO_Central. DR GO; GO:0005237; F:inhibitory extracellular ligand-gated monoatomic ion channel activity; IBA:GO_Central. 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:1902476; P:chloride transmembrane transport; IDA:GO_Central. DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IMP:UniProtKB. DR GO; GO:1904862; P:inhibitory synapse assembly; ISS:UniProtKB. DR GO; GO:0060078; P:regulation of postsynaptic membrane potential; IBA:GO_Central. DR GO; GO:0051932; P:synaptic transmission, GABAergic; IBA:GO_Central. DR CDD; cd19035; LGIC_ECD_GABAAR_A2; 1. DR CDD; cd19052; LGIC_TM_GABAAR_alpha; 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; IPR005432; GABBAa2_rcpt. DR InterPro; IPR047024; Gabra-1-6_TM. DR InterPro; IPR047023; Gabra-2_ECD. 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:SF218; GAMMA-AMINOBUTYRIC ACID RECEPTOR SUBUNIT ALPHA-2; 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; PR01615; GABAARALPHA2. 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 Genevisible; P47869; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Cell projection; Chloride; KW Chloride channel; Cytoplasmic vesicle; Disease variant; Disulfide bond; KW Epilepsy; Glycoprotein; Ion channel; Ion transport; KW Ligand-gated ion channel; Membrane; Postsynaptic cell membrane; Receptor; KW Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix; KW Transport. FT SIGNAL 1..28 FT /evidence="ECO:0000255" FT CHAIN 29..451 FT /note="Gamma-aminobutyric acid receptor subunit alpha-2" FT /id="PRO_0000000433" FT TOPO_DOM 29..251 FT /note="Extracellular" FT /evidence="ECO:0000305" FT TRANSMEM 252..273 FT /note="Helical" FT /evidence="ECO:0000305" FT TRANSMEM 279..300 FT /note="Helical" FT /evidence="ECO:0000305" FT TRANSMEM 313..334 FT /note="Helical" FT /evidence="ECO:0000305" FT TOPO_DOM 335..419 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 420..441 FT /note="Helical" FT /evidence="ECO:0000305" FT CARBOHYD 38 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 138 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 166..180 FT /evidence="ECO:0000250" FT VAR_SEQ 1..85 FT /note="MKTKLNIYNMQFLLFVFLVWDPARLVLANIQEDEAKNNITIFTRILDRLLDG FT YDNRLRPGLGDSITEVFTNIYVTSFGPVSDTDM -> MRLKITLPSLREFLTDFWMVTI FT IGLDQDWE (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054277" FT VAR_SEQ 353 FT /note="K -> KSPSIKAEGITLTYNSVKAILQGAKLIWSKYIAFSWPSLFQEKTLEY FT LEKWMDCLTFKQSS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054278" FT VARIANT 263 FT /note="M -> T (in DEE78; impaired GABA-gated chloride ion FT channel activity)" FT /evidence="ECO:0000269|PubMed:31032849" FT /id="VAR_083186" FT VARIANT 284 FT /note="V -> A (in DEE78; impaired GABA-gated chloride ion FT channel activity)" FT /evidence="ECO:0000269|PubMed:31032849" FT /id="VAR_083187" FT VARIANT 291 FT /note="L -> V (in DEE78; impaired GABA-gated chloride ion FT channel activity)" FT /evidence="ECO:0000269|PubMed:31032849" FT /id="VAR_083188" FT VARIANT 292 FT /note="T -> K (in DEE78; impaired GABA-gated chloride ion FT channel activity)" FT /evidence="ECO:0000269|PubMed:29961870" FT /id="VAR_083189" FT VARIANT 325 FT /note="F -> L (in DEE78; impaired GABA-gated chloride ion FT channel activity)" FT /evidence="ECO:0000269|PubMed:31032849" FT /id="VAR_083190" FT VARIANT 335 FT /note="N -> H (in DEE78; uncertain significance)" FT /evidence="ECO:0000269|PubMed:29422393" FT /id="VAR_083191" FT VARIANT 377 FT /note="N -> K (found in a patient with epilepsy; uncertain FT significance)" FT /evidence="ECO:0000269|PubMed:29961870" FT /id="VAR_083192" FT CONFLICT 10..11 FT /note="MQ -> IE (in Ref. 1; AAB27278)" FT /evidence="ECO:0000305" FT CONFLICT 343 FT /note="A -> T (in Ref. 1; AAB27278)" FT /evidence="ECO:0000305" SQ SEQUENCE 451 AA; 51326 MW; 43F9F708B5A00FFD CRC64; MKTKLNIYNM QFLLFVFLVW DPARLVLANI QEDEAKNNIT IFTRILDRLL DGYDNRLRPG LGDSITEVFT NIYVTSFGPV SDTDMEYTID VFFRQKWKDE RLKFKGPMNI LRLNNLMASK IWTPDTFFHN GKKSVAHNMT MPNKLLRIQD DGTLLYTMRL TVQAECPMHL EDFPMDAHSC PLKFGSYAYT TSEVTYIWTY NASDSVQVAP DGSRLNQYDL LGQSIGKETI KSSTGEYTVM TAHFHLKRKI GYFVIQTYLP CIMTVILSQV SFWLNRESVP ARTVFGVTTV LTMTTLSISA RNSLPKVAYA TAMDWFIAVC YAFVFSALIE FATVNYFTKR GWAWDGKSVV NDKKKEKASV MIQNNAYAVA VANYAPNLSK DPVLSTISKS ATTPEPNKKP ENKPAEAKKT FNSVSKIDRM SRIVFPVLFG TFNLVYWATY LNREPVLGVS P //