Gamma-aminobutyric acid receptor subunit gamma-2 explained

Gamma-aminobutyric acid receptor subunit gamma-2 is a protein that in humans is encoded by the GABRG2 gene.

Function

Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain, mediates neuronal inhibition by binding to GABA receptors. The type A GABA receptors are pentameric chloride channels assembled from among many genetic variants of GABA(A) subunits. This gene encodes the gamma 2 subunit of GABA(A) receptor. Mutations in this gene have been associated with epilepsy and febrile seizures. Alternative splicing of this gene results in transcript variants encoding different isoforms.^[1]

Interactions

GABRG2 has been shown to interact with GABARAP^{[2] [3] [4]} and Dopamine receptor D5.^[5]

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 . The Journal of Biological Chemistry . 267 . 20 . 14470–14476 . July 1992 . 10.1016/S0021-9258(19)49736-6 . 1321150 . free .
• Wilcox AS, Warrington JA, Gardiner K, Berger R, Whiting P, Altherr MR, Wasmuth JJ, Patterson D, Sikela JM . Human chromosomal localization of genes encoding the gamma 1 and gamma 2 subunits of the gamma-aminobutyric acid receptor indicates that members of this gene family are often clustered in the genome . Proceedings of the National Academy of Sciences of the United States of America . 89 . 13 . 5857–5861 . July 1992 . 1321425 . 49396 . 10.1073/pnas.89.13.5857 . 1992PNAS...89.5857W . free .
• Pritchett DB, Sontheimer H, Shivers BD, Ymer S, Kettenmann H, Schofield PR, Seeburg PH . Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology . Nature . 338 . 6216 . 582–585 . April 1989 . 2538761 . 10.1038/338582a0 . 1989Natur.338..582P . 4241689 .
• Russek SJ, Farb DH . Mapping of the beta 2 subunit gene (GABRB2) to microdissected human chromosome 5q34-q35 defines a gene cluster for the most abundant GABAA receptor isoform . Genomics . 23 . 3 . 528–533 . October 1994 . 7851879 . 10.1006/geno.1994.1539 . free .
• Kostrzewa M, Köhler A, Eppelt K, Hellam L, Fairweather ND, Levy ER, Monaco AP, Müller U . Assignment of genes encoding GABAA receptor subunits alpha 1, alpha 6, beta 2, and gamma 2 to a YAC contig of 5q33 . European Journal of Human Genetics . 4 . 4 . 199–204 . 1997 . 8875185 . 10.1159/000472199. 33974711 .
• Wang H, Bedford FK, Brandon NJ, Moss SJ, Olsen RW . GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton . Nature . 397 . 6714 . 69–72 . January 1999 . 9892355 . 10.1038/16264 . 204990449 .
• Bonnert TP, McKernan RM, Farrar S, le Bourdellès B, Heavens RP, Smith DW, Hewson L, Rigby MR, Sirinathsinghji DJ, Brown N, Wafford KA, Whiting PJ . theta, a novel gamma-aminobutyric acid type A receptor subunit . Proceedings of the National Academy of Sciences of the United States of America . 96 . 17 . 9891–9896 . August 1999 . 10449790 . 22306 . 10.1073/pnas.96.17.9891 . 1999PNAS...96.9891B . free .
• Liu F, Wan Q, Pristupa ZB, Yu XM, Wang YT, Niznik HB . Direct protein-protein coupling enables cross-talk between dopamine D5 and gamma-aminobutyric acid A receptors . Nature . 403 . 6767 . 274–280 . January 2000 . 10659839 . 10.1038/35002014 . 2000Natur.403..274L . 4415918 .
• Baulac S, Huberfeld G, Gourfinkel-An I, Mitropoulou G, Beranger A, Prud'homme JF, Baulac M, Brice A, Bruzzone R, LeGuern E . First genetic evidence of GABA(A) receptor dysfunction in epilepsy: a mutation in the gamma2-subunit gene . Nature Genetics . 28 . 1 . 46–48 . May 2001 . 11326274 . 10.1038/88254 .
• Wallace RH, Marini C, Petrou S, Harkin LA, Bowser DN, Panchal RG, Williams DA, Sutherland GR, Mulley JC, Scheffer IE, Berkovic SF . Grant Robert Sutherland . Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and febrile seizures . Nature Genetics . 28 . 1 . 49–52 . May 2001 . 11326275 . 10.1038/88259 .
• Jiang S, Yu J, Wang J, Tan Z, Xue H, Feng G, He L, Yang H . Complete genomic sequence of 195 Kb of human DNA containing the gene GABRG2 . DNA Sequence . 11 . 5 . 373–382 . 2001 . 11328646 . 10.3109/10425170009033988 . 43206605 .
• Harkin LA, Bowser DN, Dibbens LM, Singh R, Phillips F, Wallace RH, Richards MC, Williams DA, Mulley JC, Berkovic SF, Scheffer IE, Petrou S . Truncation of the GABA(A)-receptor gamma2 subunit in a family with generalized epilepsy with febrile seizures plus . American Journal of Human Genetics . 70 . 2 . 530–536 . February 2002 . 11748509 . 384926 . 10.1086/338710 .
• Nymann-Andersen J, Wang H, Chen L, Kittler JT, Moss SJ, Olsen RW . Subunit specificity and interaction domain between GABA(A) receptor-associated protein (GABARAP) and GABA(A) receptors . Journal of Neurochemistry . 80 . 5 . 815–823 . March 2002 . 11948245 . 10.1046/j.0022-3042.2002.00762.x . 38049055 .
• Kananura C, Haug K, Sander T, Runge U, Gu W, Hallmann K, Rebstock J, Heils A, Steinlein OK . A splice-site mutation in GABRG2 associated with childhood absence epilepsy and febrile convulsions . Archives of Neurology . 59 . 7 . 1137–1141 . July 2002 . 12117362 . 10.1001/archneur.59.7.1137 .
• Trudell J . Unique assignment of inter-subunit association in GABA(A) alpha 1 beta 3 gamma 2 receptors determined by molecular modeling . Biochimica et Biophysica Acta (BBA) - Biomembranes . 1565 . 1 . 91–96 . September 2002 . 12225856 . 10.1016/S0005-2736(02)00512-6 . free .
• Nymann-Andersen J, Wang H, Olsen RW . Biochemical identification of the binding domain in the GABA(A) receptor-associated protein (GABARAP) mediating dimer formation . Neuropharmacology . 43 . 4 . 476–481 . September 2002 . 12367594 . 10.1016/S0028-3908(02)00165-X . 38995093 .
• Sarto I, Wabnegger L, Dögl E, Sieghart W . Homologous sites of GABA(A) receptor alpha(1), beta(3) and gamma(2) subunits are important for assembly . Neuropharmacology . 43 . 4 . 482–491 . September 2002 . 12367595 . 10.1016/S0028-3908(02)00160-0 . 140209788 .
• Lu J, Chen Y, Zhang Y, Pan H, Wu H, Xu K, Liu X, Jiang Y, Bao X, Ding K, Shen Y, Wu X . Mutation screen of the GABA(A) receptor gamma 2 subunit gene in Chinese patients with childhood absence epilepsy . Neuroscience Letters . 332 . 2 . 75–78 . October 2002 . 12384214 . 10.1016/S0304-3940(02)00805-4 . 54375872 .
• Wang J, Liu S, Haditsch U, Tu W, Cochrane K, Ahmadian G, Tran L, Paw J, Wang Y, Mansuy I, Salter MM, Lu YM . Interaction of calcineurin and type-A GABA receptor gamma 2 subunits produces long-term depression at CA1 inhibitory synapses . The Journal of Neuroscience . 23 . 3 . 826–836 . February 2003 . 12574411 . 10.1523/JNEUROSCI.23-03-00826.2003. 6741901 . free .
• Phillips WD, Froehner SC . GABARAP and GABA(A) receptor clustering . Neuron . 33 . 1 . 4–6 . January 2002 . 11779472 . 10.1016/s0896-6273(01)00569-4 . 17051192 . free .

Notes and References

1. Web site: Entrez Gene: GABRG2 gamma-aminobutyric acid (GABA) A receptor, gamma 2.
2. Nymann-Andersen J, Wang H, Chen L, Kittler JT, Moss SJ, Olsen RW . Subunit specificity and interaction domain between GABA(A) receptor-associated protein (GABARAP) and GABA(A) receptors . Journal of Neurochemistry . 80 . 5 . 815–823 . March 2002 . 11948245 . 10.1046/j.0022-3042.2002.00762.x . 38049055 .
3. Coyle JE, Qamar S, Rajashankar KR, Nikolov DB . Structure of GABARAP in two conformations: implications for GABA(A) receptor localization and tubulin binding . Neuron . 33 . 1 . 63–74 . January 2002 . 11779480 . 10.1016/S0896-6273(01)00558-X . 14487823 . free .
4. Wang H, Bedford FK, Brandon NJ, Moss SJ, Olsen RW . GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton . Nature . 397 . 6714 . 69–72 . January 1999 . 9892355 . 10.1038/16264 . 204990449 .
5. Liu F, Wan Q, Pristupa ZB, Yu XM, Wang YT, Niznik HB . Direct protein-protein coupling enables cross-talk between dopamine D5 and gamma-aminobutyric acid A receptors . Nature . 403 . 6767 . 274–280 . January 2000 . 10659839 . 10.1038/35002014 . 2000Natur.403..274L . 4415918 .