Gamma-aminobutyric acid receptor subunit alpha-4

Details

Name
Gamma-aminobutyric acid receptor subunit alpha-4
Kind
protein
Synonyms
  • GABA(A) receptor subunit alpha-4
  • GABAAR subunit alpha-4
Gene Name
GABRA4
UniProtKB Entry
P48169Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0018959|Gamma-aminobutyric acid receptor subunit alpha-4
MVSAKKVPAIALSAGVSFALLRFLCLAVCLNESPGQNQKEEKLCTENFTRILDSLLDGYD
NRLRPGFGGPVTEVKTDIYVTSFGPVSDVEMEYTMDVFFRQTWIDKRLKYDGPIEILRLN
NMMVTKVWTPDTFFRNGKKSVSHNMTAPNKLFRIMRNGTILYTMRLTISAECPMRLVDFP
MDGHACPLKFGSYAYPKSEMIYTWTKGPEKSVEVPKESSSLVQYDLIGQTVSSETIKSIT
GEYIVMTVYFHLRRKMGYFMIQTYIPCIMTVILSQVSFWINKESVPARTVFGITTVLTMT
TLSISARHSLPKVSYATAMDWFIAVCFAFVFSALIEFAAVNYFTNIQMEKAKRKTSKPPQ
EVPAAPVQREKHPEAPLQNTNANLNMRKRTNALVHSESDVGNRTEVGNHSSKSSTVVQES
SKGTPRSYLASSPNPFSRANAAETISAARALPSASPTSIRTGYMPRKASVGSASTRHVFG
SRLQRIKTTVNTIGATGKLSATPPPSAPPPSGSGTSKIDKYARILFPVTFGAFNMVYWVV
YLSKDTMEKSESLM
Number of residues
554
Molecular Weight
61622.645
Theoretical pI
10.0
GO Classification
Functions
benzodiazepine receptor activity / GABA-A receptor activity
Processes
chloride transmembrane transport / gamma-aminobutyric acid signaling pathway
Components
chloride channel complex / GABA-A receptor complex / neuron projection / plasma membrane / synapse
General Function
Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:35355020). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (PubMed:35355020). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:35355020). GABAARs containing alpha-4 are predominantly extrasynaptic, contributing to tonic inhibition in dentate granule cells and thalamic relay neurons (By similarity). Extrasynaptic alpha-4-containing GABAARs control levels of excitability and network activity (By similarity). GABAAR containing alpha-4-beta-3-delta subunits can simultaneously bind GABA and histamine where histamine binds at the interface of two neighboring beta subunits, which may be involved in the regulation of sleep and wakefulness (PubMed:35355020)
Specific Function
benzodiazepine receptor activity
Pfam Domain Function
Signal Regions
1-35
Transmembrane Regions
260-280 285-305 319-341 518-540
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0018960|Gamma-aminobutyric acid receptor subunit alpha-4 (GABRA4)
ATGGTTTCTGCCAAGAAGGTACCCGCGATCGCTCTGTCCGCCGGGGTCAGTTTCGCCCTC
CTGCGCTTCCTGTGCCTGGCGGTTTGTTTAAACGAATCCCCAGGACAGAACCAAAAGGAG
GAGAAATTGTGCACAGAAAATTTCACCCGCATCCTGGACAGTTTGCTCGATGGTTATGAC
AACAGGCTGCGTCCTGGATTTGGGGGTCCTGTTACAGAAGTGAAAACTGACATATATGTC
ACCAGCTTTGGACCTGTTTCTGATGTTGAAATGGAATACACAATGGATGTGTTCTTCAGG
CAGACATGGATTGACAAAAGATTAAAATATGACGGCCCCATTGAAATTTTGAGATTGAAC
AATATGATGGTAACGAAAGTGTGGACCCCTGATACTTTCTTCAGGAATGGAAAGAAATCT
GTCTCACATAATATGACAGCTCCAAATAAGCTTTTTAGAATTATGAGAAATGGTACTATT
TTATACACAATGAGACTCACCATAAGTGCGGAGTGTCCCATGAGATTGGTGGATTTTCCC
ATGGATGGTCATGCATGCCCTTTGAAATTCGGGAGTTATGCCTATCCAAAGAGTGAGATG
ATCTATACCTGGACAAAAGGTCCTGAGAAATCAGTTGAAGTTCCGAAGGAGTCTTCCAGC
TTAGTTCAATATGATTTGATTGGGCAAACCGTATCAAGTGAAACCATCAAATCAATTACG
GGTGAATATATTGTTATGACGGTTTACTTCCACCTCAGACGGAAGATGGGTTATTTTATG
ATTCAGACCTATATTCCGTGCATTATGACAGTGATTCTTTCTCAAGTTTCATTTTGGATA
AATAAAGAATCAGTTCCCGCTAGGACTGTATTTGGAATAACAACTGTCCTCACCATGACC
ACACTAAGCATCAGTGCACGACATTCTTTGCCCAAAGTGTCCTATGCTACCGCCATGGAC
TGGTTCATAGCTGTCTGCTTTGCTTTTGTATTTTCGGCCCTTATCGAGTTTGCTGCTGTC
AACTATTTCACCAATATTCAAATGGAAAAAGCCAAAAGGAAGACATCAAAGCCCCCTCAG
GAAGTTCCCGCTGCTCCAGTGCAGAGAGAGAAGCATCCTGAAGCCCCTCTGCAGAATACA
AATGCCAATTTGAACATGAGAAAAAGAACAAATGCTTTGGTTCACTCTGAATCTGATGTT
GGCAACAGAACTGAGGTGGGAAACCATTCAAGCAAATCTTCCACAGTTGTTCAAGAATCT
TCTAAAGGCACACCTCGGTCTTACTTAGCTTCCAGTCCAAACCCATTCAGCCGTGCAAAT
GCAGCTGAAACCATATCTGCAGCAAGAGCACTTCCATCTGCTTCTCCTACTTCTATCCGA
ACTGGATATATGCCTCGAAAGGCTTCAGTTGGATCTGCTTCTACTCGTCACGTGTTTGGA
TCAAGACTGCAGAGGATAAAGACCACAGTTAATACCATAGGGGCTACTGGGAAGTTGTCA
GCTACTCCTCCTCCATCGGCTCCACCACCTTCTGGATCTGGCACAAGTAAAATAGACAAA
TATGCCCGTATTCTCTTTCCAGTCACATTTGGGGCATTTAACATGGTTTATTGGGTTGTT
TATTTATCTAAGGACACTATGGAGAAATCAGAAAGTCTAATGTAA
Chromosome Location
4
Locus
4p12
External Identifiers
ResourceLink
UniProtKB IDP48169
UniProtKB Entry NameGBRA4_HUMAN
GenBank Protein ID905393
GenBank Gene IDU30461
GeneCard IDGABRA4
GenAtlas IDGABRA4
HGNC IDHGNC:4078
PDB ID(s)7QN5, 7QN7, 7QN9, 7QNA, 7QNC
KEGG IDhsa:2557
IUPHAR/Guide To Pharmacology ID407
NCBI Gene ID2557
General References
  1. Yang W, Drewe JA, Lan NC: Cloning and characterization of the human GABAA receptor alpha 4 subunit: identification of a unique diazepam-insensitive binding site. Eur J Pharmacol. 1995 Nov 30;291(3):319-25. [Article]
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  3. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [Article]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  5. McLean PJ, Farb DH, Russek SJ: Mapping of the alpha 4 subunit gene (GABRA4) to human chromosome 4 defines an alpha 2-alpha 4-beta 1-gamma 1 gene cluster: further evidence that modern GABAA receptor gene clusters are derived from an ancestral cluster. Genomics. 1995 Apr 10;26(3):580-6. [Article]
  6. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Meprobamateapproved, illicityestargetagonistDetails
Pentobarbitalapproved, investigational, vet_approvedyestargetpotentiatorDetails
Amobarbitalapproved, illicityestargetpotentiatorDetails
Butalbitalapproved, illicityestargetpotentiatorDetails
Talbutalapproved, illicityestargetpotentiatorDetails
Secobarbitalapproved, vet_approvedyestargetpotentiatorDetails
MetharbitalwithdrawnyestargetpotentiatorDetails
Thiopentalapproved, vet_approvedyestargetpotentiatorDetails
Primidoneapproved, vet_approvedyestargetpotentiatorDetails
MethylphenobarbitalapprovedyestargetpotentiatorDetails
Aprobarbitalexperimental, illicityestargetpotentiatorDetails
Butobarbitalapproved, illicityestargetpotentiatorDetails
HeptabarbitalexperimentalyestargetpotentiatorDetails
HexobarbitalexperimentalyestargetpotentiatorDetails
BarbitalillicityestargetpotentiatorDetails
Dihydro-2-thioxo-5-((5-(2-(trifluoromethyl)phenyl)-2-furanyl)methyl)-4,6(1H,5H)-pyrimidinedioneexperimental, illicityestargetpotentiatorDetails
EthanolapprovedunknowntargetDetails