ID GBRA4_HUMAN Reviewed; 554 AA.
AC P48169; Q8IYR7;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 2.
DT 01-MAY-2013, entry version 130.
DE RecName: Full=Gamma-aminobutyric acid receptor subunit alpha-4;
DE AltName: Full=GABA(A) receptor subunit alpha-4;
DE Flags: Precursor;
GN Name=GABRA4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RC TISSUE=Brain cortex;
RX PubMed=8719416; DOI=10.1016/0922-4106(95)90072-1;
RA Yang W., Drewe J.A., Lan N.C.;
RT "Cloning and characterization of the human GABAA receptor alpha 4
RT subunit: identification of a unique diazepam-insensitive binding
RT site.";
RL Eur. J. Pharmacol. 291:319-325(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA 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.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA 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.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-57.
RX PubMed=7607683; DOI=10.1016/0888-7543(95)80178-O;
RA McLean P.J., Farb D.H., Russek S.J.;
RT "Mapping of the alpha 4 subunit gene (GABRA4) to human chromosome 4
RT defines an alpha 2-alpha 4-beta 1-gamma 1 gene cluster: further
RT evidence that modern GABAA receptor gene clusters are derived from an
RT ancestral cluster.";
RL Genomics 26:580-586(1995).
RN [7]
RP VARIANT [LARGE SCALE ANALYSIS] ARG-516.
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.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: GABA, the major inhibitory neurotransmitter in the
CC vertebrate brain, mediates neuronal inhibition by binding to the
CC GABA/benzodiazepine receptor and opening an integral chloride
CC channel.
CC -!- SUBUNIT: Generally pentameric. There are five types of GABA(A)
CC receptor chains: alpha, beta, gamma, delta, and rho.
CC -!- SUBCELLULAR LOCATION: Cell junction, synapse, postsynaptic cell
CC membrane; Multi-pass membrane protein. Cell membrane; Multi-pass
CC membrane protein.
CC -!- INDUCTION: The alpha4 beta2 gamma 2L receptor is not repressed by
CC diazepam.
CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9)
CC family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily.
CC GABRA4 sub-subfamily.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Forbidden fruit - Issue
CC 56 of March 2005;
CC URL="http://web.expasy.org/spotlight/back_issues/sptlt056.shtml";
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DR EMBL; U30461; AAB52519.1; -; mRNA.
DR EMBL; AK090780; BAG52228.1; -; mRNA.
DR EMBL; AC107383; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471069; EAW93029.1; -; Genomic_DNA.
DR EMBL; BC035055; AAH35055.1; -; mRNA.
DR EMBL; U20166; AAA74743.1; -; Genomic_DNA.
DR IPI; IPI00008225; -.
DR PIR; G01928; G01928.
DR RefSeq; NP_000800.2; NM_000809.3.
DR RefSeq; NP_001191195.1; NM_001204266.1.
DR RefSeq; NP_001191196.1; NM_001204267.1.
DR UniGene; Hs.248112; -.
DR ProteinModelPortal; P48169; -.
DR IntAct; P48169; 1.
DR STRING; 9606.ENSP00000264318; -.
DR PhosphoSite; P48169; -.
DR DMDM; 206729865; -.
DR PaxDb; P48169; -.
DR PRIDE; P48169; -.
DR DNASU; 2557; -.
DR Ensembl; ENST00000264318; ENSP00000264318; ENSG00000109158.
DR GeneID; 2557; -.
DR KEGG; hsa:2557; -.
DR UCSC; uc003gxg.3; human.
DR CTD; 2557; -.
DR GeneCards; GC04M046836; -.
DR HGNC; HGNC:4078; GABRA4.
DR MIM; 137141; gene.
DR neXtProt; NX_P48169; -.
DR PharmGKB; PA28492; -.
DR eggNOG; NOG238757; -.
DR HOGENOM; HOG000231337; -.
DR HOVERGEN; HBG051707; -.
DR InParanoid; P48169; -.
DR KO; K05175; -.
DR OMA; THANLNM; -.
DR OrthoDB; EOG4MPHQ4; -.
DR PhylomeDB; P48169; -.
DR Reactome; REACT_13685; Neuronal System.
DR Reactome; REACT_15518; Transmembrane transport of small molecules.
DR BindingDB; P48169; -.
DR ChEMBL; CHEMBL2472; -.
DR DrugBank; DB00404; Alprazolam.
DR DrugBank; DB00189; Ethchlorvynol.
DR DrugBank; DB01544; Flunitrazepam.
DR DrugBank; DB00690; Flurazepam.
DR DrugBank; DB00186; Lorazepam.
DR DrugBank; DB00371; Meprobamate.
DR DrugBank; DB00683; Midazolam.
DR GenomeRNAi; 2557; -.
DR NextBio; 10099; -.
DR ArrayExpress; P48169; -.
DR Bgee; P48169; -.
DR CleanEx; HS_GABRA4; -.
DR Genevestigator; P48169; -.
DR GermOnline; ENSG00000109158; Homo sapiens.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008503; F:benzodiazepine receptor activity; TAS:ProtInc.
DR GO; GO:0005254; F:chloride channel activity; IEA:UniProtKB-KW.
DR GO; GO:0005230; F:extracellular ligand-gated ion channel activity; IEA:InterPro.
DR GO; GO:0004890; F:GABA-A receptor activity; IEA:InterPro.
DR GO; GO:0007417; P:central nervous system development; IEA:Compara.
DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; TAS:ProtInc.
DR GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR GO; GO:2001023; P:regulation of response to drug; IEA:Compara.
DR Gene3D; 2.70.170.10; -; 1.
DR InterPro; IPR006028; GABAA_rcpt.
DR InterPro; IPR001390; GABAAa_rcpt.
DR InterPro; IPR005434; GABBAa4_rcpt.
DR InterPro; IPR006202; Neur_chan_lig-bd.
DR InterPro; IPR006201; Neur_channel.
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; PR01079; GABAARALPHA.
DR PRINTS; PR01617; GABAARALPHA4.
DR PRINTS; PR00253; GABAARECEPTR.
DR PRINTS; PR00252; NRIONCHANNEL.
DR SUPFAM; SSF90112; Neu_channel_TM; 1.
DR SUPFAM; SSF63712; Neur_chan_LBD; 1.
DR TIGRFAMs; TIGR00860; LIC; 1.
DR PROSITE; PS00236; NEUROTR_ION_CHANNEL; 1.
PE 2: Evidence at transcript level;
KW Cell junction; Cell membrane; Chloride; Chloride channel;
KW Complete proteome; Disulfide bond; Glycoprotein; Ion channel;
KW Ion transport; Ligand-gated ion channel; Membrane; Polymorphism;
KW Postsynaptic cell membrane; Receptor; Reference proteome; Signal;
KW Synapse; Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1 35 Potential.
FT CHAIN 36 554 Gamma-aminobutyric acid receptor subunit
FT alpha-4.
FT /FTId=PRO_0000000441.
FT TOPO_DOM 36 258 Extracellular (Probable).
FT TRANSMEM 259 280 Helical; (Probable).
FT TRANSMEM 285 306 Helical; (Probable).
FT TRANSMEM 318 340 Helical; (Probable).
FT TOPO_DOM 341 523 Cytoplasmic (Probable).
FT TRANSMEM 524 543 Helical; (Probable).
FT CARBOHYD 47 47 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 144 144 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 157 157 N-linked (GlcNAc...) (Potential).
FT DISULFID 172 186 By similarity.
FT VARIANT 19 19 A -> T (in dbSNP:rs16859837).
FT /FTId=VAR_046552.
FT VARIANT 26 26 L -> M (in dbSNP:rs2229940).
FT /FTId=VAR_046553.
FT VARIANT 516 516 S -> R (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036032.
FT CONFLICT 316 316 A -> L (in Ref. 1; AAB52519).
FT CONFLICT 379 379 N -> D (in Ref. 1; AAB52519).
FT CONFLICT 463 463 Y -> H (in Ref. 1; AAB52519).
SQ SEQUENCE 554 AA; 61623 MW; B159F9934FB02390 CRC64;
MVSAKKVPAI ALSAGVSFAL LRFLCLAVCL NESPGQNQKE EKLCTENFTR ILDSLLDGYD
NRLRPGFGGP VTEVKTDIYV TSFGPVSDVE MEYTMDVFFR QTWIDKRLKY DGPIEILRLN
NMMVTKVWTP DTFFRNGKKS VSHNMTAPNK LFRIMRNGTI LYTMRLTISA ECPMRLVDFP
MDGHACPLKF GSYAYPKSEM IYTWTKGPEK SVEVPKESSS LVQYDLIGQT VSSETIKSIT
GEYIVMTVYF HLRRKMGYFM IQTYIPCIMT VILSQVSFWI NKESVPARTV FGITTVLTMT
TLSISARHSL PKVSYATAMD WFIAVCFAFV FSALIEFAAV NYFTNIQMEK AKRKTSKPPQ
EVPAAPVQRE KHPEAPLQNT NANLNMRKRT NALVHSESDV GNRTEVGNHS SKSSTVVQES
SKGTPRSYLA SSPNPFSRAN AAETISAARA LPSASPTSIR TGYMPRKASV GSASTRHVFG
SRLQRIKTTV NTIGATGKLS ATPPPSAPPP SGSGTSKIDK YARILFPVTF GAFNMVYWVV
YLSKDTMEKS ESLM
//
