GBRA2_HUMAN
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 03-AUG-2022, entry version 197.
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 -!- 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";
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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; 3.
DR ComplexPortal; CPX-2174; GABA-A receptor, alpha-2/beta-3/gamma-2.
DR IntAct; P47869; 2.
DR MINT; P47869; -.
DR STRING; 9606.ENSP00000421828; -.
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; 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 GlyGen; P47869; 2 sites.
DR iPTMnet; P47869; -.
DR PhosphoSitePlus; P47869; -.
DR BioMuta; GABRA2; -.
DR DMDM; 126302547; -.
DR MassIVE; P47869; -.
DR PaxDb; P47869; -.
DR PeptideAtlas; P47869; -.
DR PRIDE; P47869; -.
DR ProteomicsDB; 55800; -. [P47869-1]
DR ProteomicsDB; 6330; -.
DR Antibodypedia; 12030; 348 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 CTD; 2555; -.
DR DisGeNET; 2555; -.
DR GeneCards; GABRA2; -.
DR HGNC; HGNC:4076; GABRA2.
DR HPA; ENSG00000151834; Tissue enhanced (brain, epididymis).
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; 1057372at2759; -.
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; 15 hits in 1072 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 137 other tissues.
DR ExpressionAtlas; P47869; baseline and differential.
DR Genevisible; P47869; 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: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:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; IEA:Ensembl.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; IDA:UniProtKB.
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:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0008503; F:benzodiazepine receptor activity; IMP: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; 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 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:0007268; P:chemical synaptic transmission; IBA:GO_Central.
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:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0050877; P:nervous system process; IBA:GO_Central.
DR GO; GO:0006836; P:neurotransmitter transport; IMP:UniProtKB.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:0001505; P:regulation of neurotransmitter levels; IMP:UniProtKB.
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; IBA:GO_Central.
DR Gene3D; 1.20.58.390; -; 1.
DR Gene3D; 2.70.170.10; -; 1.
DR InterPro; IPR006028; GABAA/Glycine_rcpt.
DR InterPro; IPR001390; GABAAa_rcpt.
DR InterPro; IPR005432; GABBAa2_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 PANTHER; PTHR18945:SF218; PTHR18945:SF218; 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; 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 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; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:29422393"
FT /id="VAR_083191"
FT VARIANT 377
FT /note="N -> K (found in a patient with epilepsy; unknown
FT pathological 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
