GABRB1 explained

Gamma-aminobutyric acid receptor subunit beta-1 is a protein that in humans is encoded by the GABRB1 gene.^[1]

Function

The gamma-aminobutyric acid A receptor (GABA_A receptor) is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes GABA A receptor, beta 1 subunit. It is mapped to chromosome 4p12 in a cluster of genes encoding alpha 4, alpha 2 and gamma 1 subunits of the GABA_A receptor. Alteration of this gene is implicated in the pathogenetics of schizophrenia.

Clinical significance

Mice bearing mutant copies of this gene have been shown to be vulnerable to binge drinking of alcohol.^[2]

See also

• GABAA receptor

Further reading

• Moss SJ, Doherty CA, Huganir RL . Identification of the cAMP-dependent protein kinase and protein kinase C phosphorylation sites within the major intracellular domains of the beta 1, gamma 2S, and gamma 2L subunits of the gamma-aminobutyric acid type A receptor . J. Biol. Chem. . 267 . 20 . 14470–14476 . 1992 . 10.1016/S0021-9258(19)49736-6 . 1321150 . free .
• Moss SJ, Smart TG, Blackstone CD, Huganir RL . Functional modulation of GABAA receptors by cAMP-dependent protein phosphorylation . Science . 257 . 5070 . 661–665 . 1992 . 1323140 . 10.1126/science.1323140 . 1992Sci...257..661M .
• Dean M, Lucas-Derse S, Bolos A . Genetic mapping of the beta 1 GABA receptor gene to human chromosome 4, using a tetranucleotide repeat polymorphism . Am. J. Hum. Genet. . 49 . 3 . 621–626 . 1991 . 1652891 . 1683131 . etal.
• Kirkness EF, Kusiak JW, Fleming JT . Isolation, characterization, and localization of human genomic DNA encoding the beta 1 subunit of the GABAA receptor (GABRB1) . Genomics . 10 . 4 . 985–995 . 1991 . 1655634 . 10.1016/0888-7543(91)90189-L . etal.
• Garrett KM, Saito N, Duman RS . Differential expression of gamma-aminobutyric acidA receptor subunits . Mol. Pharmacol. . 37 . 5 . 652–657 . 1990 . 2160058 . etal.
• Schofield PR, Pritchett DB, Sontheimer H . Sequence and expression of human GABAA receptor alpha 1 and beta 1 subunits . FEBS Lett. . 244 . 2 . 361–364 . 1989 . 2465923 . 10.1016/0014-5793(89)80563-0 . 84068989 . etal. free . 1989FEBSL.244..361S .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–174 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Coon H, Sobell J, Heston L . Search for mutations in the beta 1 GABAA receptor subunit gene in patients with schizophrenia . Am. J. Med. Genet. . 54 . 1 . 12–20 . 1994 . 8178835 . 10.1002/ajmg.1320540105 . etal.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–156 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 . etal.
• Russek SJ . Evolution of GABA(A) receptor diversity in the human genome . Gene . 227 . 2 . 213–222 . 1999 . 10023064 . 10.1016/S0378-1119(98)00594-0 .
• McDonald BJ, Amato A, Connolly CN . Adjacent phosphorylation sites on GABAA receptor beta subunits determine regulation by cAMP-dependent protein kinase . Nat. Neurosci. . 1 . 1 . 23–28 . 1999 . 10195104 . 10.1038/223 . 204994519 . etal.
• Bonnert TP, McKernan RM, Farrar S . theta, a novel gamma-aminobutyric acid type A receptor subunit . Proc. Natl. Acad. Sci. U.S.A. . 96 . 17 . 9891–9896 . 1999 . 10449790 . 10.1073/pnas.96.17.9891 . 22306 . 1999PNAS...96.9891B . etal. free .
• Russek SJ, Bandyopadhyay S, Farb DH . An initiator element mediates autologous downregulation of the human type A gamma -aminobutyric acid receptor beta 1 subunit gene . Proc. Natl. Acad. Sci. U.S.A. . 97 . 15 . 8600–8605 . 2000 . 10900018 . 10.1073/pnas.97.15.8600 . 26994 . 2000PNAS...97.8600R . free .
• Buckley ST, Eckert AL, Dodd PR . Expression and distribution of GABAA receptor subtypes in human alcoholic cerebral cortex . Ann. N. Y. Acad. Sci. . 914 . 58–64 . 2006 . 1 . 11085308 . 10.1111/j.1749-6632.2000.tb05183.x . 2000NYASA.914...58B . 13569188 .
• Schaerer MT, Kannenberg K, Hunziker P . Interaction between GABA(A) receptor beta subunits and the multifunctional protein gC1q-R . J. Biol. Chem. . 276 . 28 . 26597–26604 . 2001 . 11350968 . 10.1074/jbc.M102534200 . etal. free .
• Onishi-Haraikawa Y, Funaki M, Gotoh N . Unique phosphorylation mechanism of Gab1 using PI 3-kinase as an adaptor protein . Biochem. Biophys. Res. Commun. . 288 . 2 . 476–482 . 2001 . 11606067 . 10.1006/bbrc.2001.5791 . etal.
• Porjesz B, Almasy L, Edenberg HJ . Linkage disequilibrium between the beta frequency of the human EEG and a GABAA receptor gene locus . Proc. Natl. Acad. Sci. U.S.A. . 99 . 6 . 3729–3733 . 2002 . 11891318 . 10.1073/pnas.052716399 . 122592 . 2002PNAS...99.3729P . etal. free .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–16903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Brandon NJ, Jovanovic JN, Colledge M . A-kinase anchoring protein 79/150 facilitates the phosphorylation of GABA(A) receptors by cAMP-dependent protein kinase via selective interaction with receptor beta subunits . Mol. Cell. Neurosci. . 22 . 1 . 87–97 . 2003 . 12595241 . 10.1016/S1044-7431(02)00017-9 . 6172436 . etal.
• Buckley ST, Dodd PR . GABAA receptor beta subunit mRNA expression in the human alcoholic brain . Neurochem. Int. . 45 . 7 . 1011–1020 . 2004 . 15337300 . 10.1016/j.neuint.2004.05.009 . 54392069 .

Notes and References

1. Web site: Entrez Gene: GABRB1 gamma-aminobutyric acid (GABA) A receptor, beta 1.
2. Anstee QM, Knapp S, Maguire EP, Hosie AM, Thomas P, Mortensen M, Bhome R, Martinez A, Walker SE, Dixon CI, Ruparelia K, Montagnese S, Kuo YT, Herlihy A, Bell JD, Robinson I, Guerrini I, McQuillin A, Fisher EM, Ungless MA, Gurling HM, Morgan MY, Brown SD, Stephens DN, Belelli D, Lambert JJ, Smart TG, Thomas HC . Mutations in the Gabrb1 gene promote alcohol consumption through increased tonic inhibition . Nat Commun . 4 . 2816 . November 2013 . 24281383 . 10.1038/ncomms3816 . 3843143. 2013NatCo...4.2816A .