ID   GBRA6_HUMAN             Reviewed;         453 AA.
AC   Q16445; A8K096; Q4VAV2;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   20-FEB-2007, sequence version 2.
DT   27-MAR-2024, entry version 199.
DE   RecName: Full=Gamma-aminobutyric acid receptor subunit alpha-6;
DE   AltName: Full=GABA(A) receptor subunit alpha-6;
DE   Flags: Precursor;
GN   Name=GABRA6;
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].
RC   TISSUE=Cerebellum;
RX   PubMed=8632757;
RA   Hadingham K.L., Garrett E.M., Wafford K.A., Bain C., Heavens R.P.,
RA   Sirinathsinghji D.J., Whiting P.J.;
RT   "Cloning of cDNAs encoding the human gamma-aminobutyric acid type A
RT   receptor alpha 6 subunit and characterization of the pharmacology of alpha
RT   6-containing receptors.";
RL   Mol. Pharmacol. 49:253-259(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=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   [3]
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   VARIANT [LARGE SCALE ANALYSIS] HIS-180.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: GABA, the major inhibitory neurotransmitter in the vertebrate
CC       brain, mediates neuronal inhibition by binding to the
CC       GABA/benzodiazepine receptor and opening an integral chloride channel.
CC   -!- SUBUNIT: Binds UBQLN1 (By similarity). Generally pentameric. There are
CC       five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and
CC       rho. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane; Multi-pass membrane
CC       protein. Cell membrane; Multi-pass membrane protein.
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. GABRA6 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; S81944; AAB36480.1; -; mRNA.
DR   EMBL; AK289461; BAF82150.1; -; mRNA.
DR   EMBL; CH471062; EAW61542.1; -; Genomic_DNA.
DR   EMBL; BC096241; AAH96241.1; -; mRNA.
DR   EMBL; BC096242; AAH96242.1; -; mRNA.
DR   EMBL; BC099640; AAH99640.1; -; mRNA.
DR   EMBL; BC099641; AAH99641.1; -; mRNA.
DR   CCDS; CCDS4356.1; -.
DR   RefSeq; NP_000802.2; NM_000811.2.
DR   AlphaFoldDB; Q16445; -.
DR   SMR; Q16445; -.
DR   BioGRID; 108833; 20.
DR   ComplexPortal; CPX-2164; GABA-A receptor, alpha-6/beta-3/gamma-2.
DR   ComplexPortal; CPX-2951; GABA-A receptor, alpha-6/beta-3/delta.
DR   ComplexPortal; CPX-2952; GABA-A receptor, alpha-6/beta-2/delta.
DR   IntAct; Q16445; 11.
DR   STRING; 9606.ENSP00000274545; -.
DR   BindingDB; Q16445; -.
DR   ChEMBL; CHEMBL2579; -.
DR   DrugBank; DB12537; 1,2-Benzodiazepine.
DR   DrugBank; DB00546; Adinazolam.
DR   DrugBank; DB00404; Alprazolam.
DR   DrugBank; DB01351; Amobarbital.
DR   DrugBank; DB00543; Amoxapine.
DR   DrugBank; DB11901; Apalutamide.
DR   DrugBank; DB01352; Aprobarbital.
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; 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; 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; 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   DrugCentral; Q16445; -.
DR   GuidetoPHARMACOLOGY; 409; -.
DR   GlyCosmos; Q16445; 3 sites, No reported glycans.
DR   GlyGen; Q16445; 3 sites.
DR   iPTMnet; Q16445; -.
DR   PhosphoSitePlus; Q16445; -.
DR   BioMuta; GABRA6; -.
DR   DMDM; 126302548; -.
DR   MassIVE; Q16445; -.
DR   PaxDb; 9606-ENSP00000274545; -.
DR   PeptideAtlas; Q16445; -.
DR   ProteomicsDB; 60871; -.
DR   Antibodypedia; 28560; 237 antibodies from 34 providers.
DR   DNASU; 2559; -.
DR   Ensembl; ENST00000274545.10; ENSP00000274545.5; ENSG00000145863.11.
DR   GeneID; 2559; -.
DR   KEGG; hsa:2559; -.
DR   MANE-Select; ENST00000274545.10; ENSP00000274545.5; NM_000811.3; NP_000802.2.
DR   UCSC; uc003lyu.3; human.
DR   AGR; HGNC:4080; -.
DR   CTD; 2559; -.
DR   DisGeNET; 2559; -.
DR   GeneCards; GABRA6; -.
DR   HGNC; HGNC:4080; GABRA6.
DR   HPA; ENSG00000145863; Tissue enriched (brain).
DR   MIM; 137143; gene.
DR   neXtProt; NX_Q16445; -.
DR   OpenTargets; ENSG00000145863; -.
DR   PharmGKB; PA28494; -.
DR   VEuPathDB; HostDB:ENSG00000145863; -.
DR   eggNOG; KOG3642; Eukaryota.
DR   GeneTree; ENSGT00940000156722; -.
DR   HOGENOM; CLU_010920_2_2_1; -.
DR   InParanoid; Q16445; -.
DR   OMA; WTDPRRR; -.
DR   OrthoDB; 4265336at2759; -.
DR   PhylomeDB; Q16445; -.
DR   TreeFam; TF315453; -.
DR   PathwayCommons; Q16445; -.
DR   Reactome; R-HSA-977443; GABA receptor activation.
DR   SignaLink; Q16445; -.
DR   SIGNOR; Q16445; -.
DR   BioGRID-ORCS; 2559; 5 hits in 1152 CRISPR screens.
DR   ChiTaRS; GABRA6; human.
DR   GeneWiki; GABRA6; -.
DR   GenomeRNAi; 2559; -.
DR   Pharos; Q16445; Tclin.
DR   PRO; PR:Q16445; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; Q16445; Protein.
DR   Bgee; ENSG00000145863; Expressed in cerebellar vermis and 84 other cell types or tissues.
DR   ExpressionAtlas; Q16445; baseline and differential.
DR   GO; GO:0099192; C:cerebellar Golgi cell to granule cell synapse; 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; ISO:ComplexPortal.
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:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0045202; C:synapse; IBA:GO_Central.
DR   GO; GO:0008503; F:benzodiazepine receptor activity; TAS:ProtInc.
DR   GO; GO:0004890; F:GABA-A receptor activity; IEA:InterPro.
DR   GO; GO:0022851; F:GABA-gated chloride ion channel activity; IBA:GO_Central.
DR   GO; GO:0005237; F:inhibitory extracellular ligand-gated monoatomic ion channel activity; IBA:GO_Central.
DR   GO; GO:1904315; F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential; IEA:Ensembl.
DR   GO; GO:1902476; P:chloride transmembrane transport; IBA:GO_Central.
DR   GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IBA:GO_Central.
DR   GO; GO:0060078; P:regulation of postsynaptic membrane potential; IBA:GO_Central.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   GO; GO:0051932; P:synaptic transmission, GABAergic; IBA:GO_Central.
DR   CDD; cd19039; LGIC_ECD_GABAAR_A6; 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; IPR005436; GABBAa6_rcpt.
DR   InterPro; IPR047024; Gabra-1-6_TM.
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:SF335; GAMMA-AMINOBUTYRIC ACID RECEPTOR SUBUNIT ALPHA-6; 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; PR01619; GABAARALPHA6.
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; Q16445; HS.
PE   2: Evidence at transcript level;
KW   Cell membrane; Chloride; Chloride channel; Disulfide bond; Glycoprotein;
KW   Ion channel; Ion transport; Ligand-gated ion channel; Membrane;
KW   Phosphoprotein; Postsynaptic cell membrane; Receptor; Reference proteome;
KW   Signal; Synapse; Transmembrane; Transmembrane helix; Transport.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000255"
FT   CHAIN           20..453
FT                   /note="Gamma-aminobutyric acid receptor subunit alpha-6"
FT                   /id="PRO_0000000447"
FT   TOPO_DOM        20..242
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        243..264
FT                   /note="Helical"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        269..290
FT                   /note="Helical"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        301..324
FT                   /note="Helical"
FT                   /evidence="ECO:0000305"
FT   TOPO_DOM        325..419
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        420..441
FT                   /note="Helical"
FT                   /evidence="ECO:0000305"
FT   MOD_RES         403
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P30191"
FT   CARBOHYD        31
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        128
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        141
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        156..170
FT                   /evidence="ECO:0000250"
FT   VARIANT         180
FT                   /note="P -> H (in a colorectal cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036033"
FT   VARIANT         187
FT                   /note="T -> M (in dbSNP:rs3811993)"
FT                   /id="VAR_036782"
FT   VARIANT         404
FT                   /note="P -> S (in dbSNP:rs34907804)"
FT                   /id="VAR_036783"
FT   CONFLICT        408
FT                   /note="S -> P (in Ref. 1; AAB36480)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   453 AA;  51024 MW;  5C9F85845BC8E3B0 CRC64;
     MASSLPWLCI ILWLENALGK LEVEGNFYSE NVSRILDNLL EGYDNRLRPG FGGAVTEVKT
     DIYVTSFGPV SDVEMEYTMD VFFRQTWTDE RLKFGGPTEI LSLNNLMVSK IWTPDTFFRN
     GKKSIAHNMT TPNKLFRIMQ NGTILYTMRL TINADCPMRL VNFPMDGHAC PLKFGSYAYP
     KSEIIYTWKK GPLYSVEVPE ESSSLLQYDL IGQTVSSETI KSNTGEYVIM TVYFHLQRKM
     GYFMIQIYTP CIMTVILSQV SFWINKESVP ARTVFGITTV LTMTTLSISA RHSLPKVSYA
     TAMDWFIAVC FAFVFSALIE FAAVNYFTNL QTQKAKRKAQ FAAPPTVTIS KATEPLEAEI
     VLHPDSKYHL KKRITSLSLP IVSSSEANKV LTRAPILQST PVTPPPLSPA FGGTSKIDQY
     SRILFPVAFA GFNLVYWVVY LSKDTMEVSS SVE
//