GNAO1 explained

Guanine nucleotide-binding protein G(o) subunit alpha is a protein that in humans is encoded by the GNAO1 gene.^{[1] [2] [3]}

Mutations in this gene have been shown to cause epileptic encephalopathy.^[4]

Interactions

GNAO1 has been shown to interact with:

• RGS5,^{[5] [6]}
• RGS19,^{[7] [8]}
• RGS20,^[9] and
• RIC8A^[10]

Further reading

• Raymond JR, Mukhin YV, Gelasco A . Multiplicity of mechanisms of serotonin receptor signal transduction. . Pharmacol. Ther. . 92 . 2–3 . 179–212 . 2002 . 11916537 . 10.1016/S0163-7258(01)00169-3 . etal.
• Coupry I, Duzic E, Lanier SM . Factors determining the specificity of signal transduction by guanine nucleotide-binding protein-coupled receptors. II. Preferential coupling of the alpha 2C-adrenergic receptor to the guanine nucleotide-binding protein, Go. . J. Biol. Chem. . 267 . 14 . 9852–7 . 1992 . 10.1016/S0021-9258(19)50172-7 . 1349607 . free .
• Denker BM, Neer EJ, Schmidt CJ . Mutagenesis of the amino terminus of the alpha subunit of the G protein Go. In vitro characterization of alpha o beta gamma interactions. . J. Biol. Chem. . 267 . 9 . 6272–7 . 1992 . 10.1016/S0021-9258(18)42691-9 . 1556134 . free .
• Yi F, Denker BM, Neer EJ . Structural and functional studies of cross-linked Go protein subunits. . J. Biol. Chem. . 266 . 6 . 3900–6 . 1991 . 10.1016/S0021-9258(19)67879-8 . 1899868 . free .
• Tsukamoto T, Toyama R, Itoh H . Structure of the human gene and two rat cDNAs encoding the alpha chain of GTP-binding regulatory protein Go: two different mRNAs are generated by alternative splicing. . Proc. Natl. Acad. Sci. U.S.A. . 88 . 8 . 2974–8 . 1991 . 1901650 . 10.1073/pnas.88.8.2974 . 51366 . 1991PNAS...88.2974T . etal. free .
• Gabrion J, Brabet P, Nguyen Than Dao B . Ultrastructural localization of the GTP-binding protein Go in neurons. . Cell. Signal. . 1 . 1 . 107–23 . 1990 . 2518353 . 10.1016/0898-6568(89)90025-9 . etal.
• Lavu S, Clark J, Swarup R . Molecular cloning and DNA sequence analysis of the human guanine nucleotide-binding protein Go alpha. . Biochem. Biophys. Res. Commun. . 150 . 2 . 811–5 . 1988 . 3124840 . 10.1016/0006-291X(88)90463-9 . etal.
• Zumbihl R, Breuiller-Fouché M, Carrette J . Up-regulation in late pregnancy of both Go1 alpha and Go2 alpha isoforms in human myometrium. . Eur. J. Pharmacol. . 288 . 1 . 9–15 . 1995 . 7705473 . 10.1016/0922-4106(94)90004-3. etal.
• Grassie MA, Milligan G . Analysis of the relative interactions between the alpha 2C10 adrenoceptor and the guanine-nucleotide-binding proteins G(o)1 alpha and Gi 2 alpha following co-expression of these polypeptides in rat 1 fibroblasts. . Biochem. J. . 306 . 2. 525–30 . 1995 . 7887906 . 10.1042/bj3060525. 1136549 .
• Wu HC, Lin CT . Association of heterotrimeric GTP binding regulatory protein (Go) with mitosis. . Lab. Invest. . 71 . 2 . 175–81 . 1994 . 8078296 .
• Nitta K, Uchida K, Kawashima A . Identification of GTP-binding proteins in human glomeruli. . Nippon Jinzo Gakkai Shi . 36 . 1 . 9–12 . 1994 . 8107314 . etal.
• Georgoussi Z, Carr C, Milligan G . Direct measurements of in situ interactions of rat brain opioid receptors with the guanine nucleotide-binding protein Go. . Mol. Pharmacol. . 44 . 1 . 62–9 . 1993 . 8393523 .
• Laugwitz KL, Allgeier A, Offermanns S . The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families. . Proc. Natl. Acad. Sci. U.S.A. . 93 . 1 . 116–20 . 1996 . 8552586 . 10.1073/pnas.93.1.116 . 40189 . 1996PNAS...93..116L . etal. free .
• Kawano N, Ito T, Kitamura H . Immunoexpression of the alpha subunit of a guanine nucleotide-binding protein (Go) in pulmonary neuroendocrine cells and neoplasms. . Pathol. Int. . 46 . 6 . 393–8 . 1997 . 8869990 . 10.1111/j.1440-1827.1996.tb03629.x . 35816963 . etal.
• De Vries L, Elenko E, Hubler L . GAIP is membrane-anchored by palmitoylation and interacts with the activated (GTP-bound) form of G alpha i subunits. . Proc. Natl. Acad. Sci. U.S.A. . 93 . 26 . 15203–8 . 1997 . 8986788 . 10.1073/pnas.93.26.15203 . 26381 . 1996PNAS...9315203D . etal. free .
• Valenzuela D, Han X, Mende U . G alpha(o) is necessary for muscarinic regulation of Ca2+ channels in mouse heart. . Proc. Natl. Acad. Sci. U.S.A. . 94 . 5 . 1727–32 . 1997 . 9050846 . 10.1073/pnas.94.5.1727 . 19984 . 1997PNAS...94.1727V . etal. free .
• Chen C, Zheng B, Han J, Lin SC . Characterization of a novel mammalian RGS protein that binds to Galpha proteins and inhibits pheromone signaling in yeast. . J. Biol. Chem. . 272 . 13 . 8679–85 . 1997 . 9079700 . 10.1074/jbc.272.13.8679 . free .
• Natochin M, Lipkin VM, Artemyev NO . Interaction of human retinal RGS with G-protein alpha-subunits. . FEBS Lett. . 411 . 2–3 . 179–82 . 1997 . 9271201 . 10.1016/S0014-5793(97)00687-X . 84269212 . free .
• Busconi L, Denker BM . Analysis of the N-terminal binding domain of Go alpha. . Biochem. J. . 328 . 1. 23–31 . 1998 . 9359829 . 10.1042/bj3280023. 1218882 .

Notes and References

1. Murtagh JJ Jr . Eddy R . Shows TB . Moss J . Vaughan M . Different forms of Go alpha mRNA arise by alternative splicing of transcripts from a single gene on human chromosome 16 . Mol Cell Biol . 11 . 2 . 1146–55 . Mar 1991 . 1899283 . 359797 . 10.1128/MCB.11.2.1146.
2. Kinoshita M, Nukada T, Asano T, Mori Y, Akaike A, Satoh M, Kaneko S . Binding of G alpha(o) N terminus is responsible for the voltage-resistant inhibition of alpha(1A) (P/Q-type, Ca(v)2.1) Ca(2+) channels . J Biol Chem . 276 . 31 . 28731–8 . Jul 2001 . 11395521 . 10.1074/jbc.M104806200 . free .
3. Web site: Entrez Gene: GNAO1 guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O.
4. Nakamura K, Kodera H, Akita T, Shiina M, Kato M, Hoshino H, Terashima H, Osaka H, Nakamura S, Tohyama J, Kumada T, Furukawa T, Iwata S, Shiihara T, Kubota M, Miyatake S, Koshimizu E, Nishiyama K, Nakashima M, Tsurusaki Y, Miyake N, Hayasaka K, Ogata K, Fukuda A, Matsumoto N, Saitsu H . De Novo mutations in GNAO1, encoding a Gαo subunit of heterotrimeric G proteins, cause epileptic encephalopathy . Am. J. Hum. Genet. . 93 . 3 . 496–505 . September 2013 . 23993195 . 10.1016/j.ajhg.2013.07.014 . 3769919.
5. Chen C, Zheng B, Han J, Lin SC . Characterization of a novel mammalian RGS protein that binds to Galpha proteins and inhibits pheromone signaling in yeast . J. Biol. Chem. . 272 . 13 . 8679–85 . 1997 . 9079700 . 10.1074/jbc.272.13.8679. free .
6. Zhou J, Moroi K, Nishiyama M, Usui H, Seki N, Ishida J, Fukamizu A, Kimura S . Characterization of RGS5 in regulation of G protein-coupled receptor signaling . Life Sci. . 68 . 13 . 1457–69 . 2001 . 11253162 . 10.1016/S0024-3205(01)00939-0.
7. De Vries L, Elenko E, Hubler L, Jones TL, Farquhar MG . GAIP is membrane-anchored by palmitoylation and interacts with the activated (GTP-bound) form of G alpha i subunits . Proc. Natl. Acad. Sci. U.S.A. . 93 . 26 . 15203–8 . 1996 . 8986788 . 26381 . 10.1073/pnas.93.26.15203. 1996PNAS...9315203D . free .
8. Woulfe DS, Stadel JM . Structural basis for the selectivity of the RGS protein, GAIP, for Galphai family members. Identification of a single amino acid determinant for selective interaction of Galphai subunits with GAIP . J. Biol. Chem. . 274 . 25 . 17718–24 . 1999 . 10364213 . 10.1074/jbc.274.25.17718. free .
9. Pagano M, Jordan JD, Neves SR, Nguyen T, Iyengar R . Galphao/i-stimulated proteosomal degradation of RGS20: a mechanism for temporal integration of Gs and Gi pathways . Cell. Signal. . 20 . 6 . 1190–7 . 2008 . 18407463 . 3107604 . 10.1016/j.cellsig.2008.02.008 .
10. Tall GG, Krumins AM, Gilman AG . Mammalian Ric-8A (synembryn) is a heterotrimeric Galpha protein guanine nucleotide exchange factor . J. Biol. Chem. . 278 . 10 . 8356–62 . 2003 . 12509430 . 10.1074/jbc.M211862200 . free .