| |  |
| |
| | The diagram shows the general functional domains of G alpha 11 in respect to the amino acid residues and the corresponding exons. The alpha helical domain is found in all G alpha family members. Switch regions (SR), the areas that change their conformation based on if GTP or GDP is bound, are shown in orange (SR1: 182-192, SR2: 204-224, SR3: 236-247). The location of the 183 and 209 mutations are shown and affect switch regions 1 and 2 respectively. The GTPase domain is both essential for hydrolyzing bound GTP as well as binding downstream effectors. Adapted from Mizuno and Itoh, 2009. |
| |
| Description | Aminoacids: 359. Molecular weight: 42123 daltons.
GNA11 is a proto-oncogene that belongs to the Gq family of the G alpha family of G protein coupled receptors. It is highly homologous to GNAQ. |
| Expression | GNA11 is generally expressed ubiquitously, an exception being platelets, where only GNAQ is expressed. |
| Localisation | Cytoplasmic. Signaling occurs at the membrane, which requires N-terminal lipid modification (palmitoylation) of the protein. |
| Function | GNA11 is a G protein alpha unit associating with a beta and a gamma subunit. Upon ligand binding to G protein coupled receptors, GNA11 binds GTP, which leads to activation and disassociation from the beta and gamma subunits. Known downstream signaling partners are phospholipase C (PLC) beta and RhoA. PLC beta upon activation releases inositol triphosphate (IP3) and diacylglycerol (DAG) from membrane phosphatidylinositol-3-phosphate. RhoA activation is mediated through proteins such as p63 RhoGef, Duet and Trio by GNAQ, and may thus also be mediating Rho activation by GNA11. GNA11 activation has been shown to induce MAP Kinase activation, possibly via DAG-mediated activation of protein kinase C isoforms. Many other proteins shown to bind GNAQ and or GNA11 have been reported, many with regulatory functions, thus named GRK (G Protein regulatory kinases) or RGS (regulator of G protein signaling) proteins. |
| Homology | GNA11 is part of the G q family of alpha proteins. This family consists of GNAQ, GNA11, GNA14 and GNA15. On an aminoacid level GNA11 is 90% homologous to GNAQ, 82% homologous to GNA14 and 55% homologous to GNA15. |
| Reduced expression of GNA11 and silencing of MCT1 in human breast cancers. |
| Asada K, Miyamoto K, Fukutomi T, Tsuda H, Yagi Y, Wakazono K, Oishi S, Fukui H, Sugimura T, Ushijima T. |
| Oncology. 2003;64(4):380-8. |
| PMID 12759536 |
| |
| Functional importance of the amino terminus of Gq alpha. |
| Hepler JR, Biddlecome GH, Kleuss C, Camp LA, Hofmann SL, Ross EM, Gilman AG. |
| J Biol Chem. 1996 Jan 5;271(1):496-504. |
| PMID 8550609 |
| |
| Cell signalling diversity of the Gqalpha family of heterotrimeric G proteins. |
| Hubbard KB, Hepler JR. |
| Cell Signal. 2006 Feb;18(2):135-50. Epub 2005 Sep 22. (REVIEW) |
| PMID 16182515 |
| |
| Metastatic uveal melanoma. |
| Kivela T, Eskelin S, Kujala E. |
| Int Ophthalmol Clin. 2006 Winter;46(1):133-49. (REVIEW) |
| PMID 16365560 |
| |
| Activating mutations of the GNAQ gene: a frequent event in primary melanocytic neoplasms of the central nervous system. |
| Kusters-Vandevelde HV, Klaasen A, Kusters B, Groenen PJ, van Engen-van Grunsven IA, van Dijk MR, Reifenberger G, Wesseling P, Blokx WA. |
| Acta Neuropathol. 2009 Nov 22. [Epub ahead of print] |
| PMID 19936769 |
| |
| Mutational profile of GNAQQ209 in human tumors. |
| Lamba S, Felicioni L, Buttitta F, Bleeker FE, Malatesta S, Corbo V, Scarpa A, Rodolfo M, Knowles M, Frattini M, Marchetti A, Bardelli A. |
| PLoS One. 2009 Aug 31;4(8):e6833. |
| PMID 19718445 |
| |
| Structure of Galphaq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs. |
| Lutz S, Shankaranarayanan A, Coco C, Ridilla M, Nance MR, Vettel C, Baltus D, Evelyn CR, Neubig RR, Wieland T, Tesmer JJ. |
| Science. 2007 Dec 21;318(5858):1923-7. |
| PMID 18096806 |
| |
| Functions and regulatory mechanisms of Gq-signaling pathways. |
| Mizuno N, Itoh H. |
| Neurosignals. 2009;17(1):42-54. Epub 2009 Feb 12. (REVIEW) |
| PMID 19212139 |
| |
| Pasteurella multocida toxin activation of heterotrimeric G proteins by deamidation. |
| Orth JH, Preuss I, Fester I, Schlosser A, Wilson BA, Aktories K. |
| Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7179-84. Epub 2009 Apr 15. |
| PMID 19369209 |
| |
| Prognostic implications of monosomy 3 in uveal melanoma. |
| Prescher G, Bornfeld N, Hirche H, Horsthemke B, Jockel KH, Becher R. |
| Lancet. 1996 May 4;347(9010):1222-5. |
| PMID 8622452 |
| |
| Uveal melanoma: epidemiologic aspects. |
| Singh AD, Bergman L, Seregard S. |
| Ophthalmol Clin North Am. 2005 Mar;18(1):75-84, viii. (REVIEW) |
| PMID 15763193 |
| |
| A novel Galphaq/11-selective inhibitor. |
| Takasaki J, Saito T, Taniguchi M, Kawasaki T, Moritani Y, Hayashi K, Kobori M. |
| J Biol Chem. 2004 Nov 12;279(46):47438-45. Epub 2004 Aug 31. |
| PMID 15339913 |
| |
| Mutations in GNA11 in uveal melanoma. |
| Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T, Obenauf AC, Wackernagel W, Green G, Bouvier N, Sozen MM, Baimukanova G, Roy R, Heguy A, Dolgalev I, Khanin R, Busam K, Speicher MR, O'Brien J, Bastian BC. |
| N Engl J Med. 2010 Dec 2;363(23):2191-9. Epub 2010 Nov 17. |
| PMID 21083380 |
| |
| Kinetic scaffolding mediated by a phospholipase C-beta and Gq signaling complex. |
| Waldo GL, Ricks TK, Hicks SN, Cheever ML, Kawano T, Tsuboi K, Wang X, Montell C, Kozasa T, Sondek J, Harden TK. |
| Science. 2010 Nov 12;330(6006):974-80. Epub 2010 Oct 21. |
| PMID 20966218 |
| |
| Characterization of G-protein alpha subunits in the Gq class: expression in murine tissues and in stromal and hematopoietic cell lines. |
| Wilkie TM, Scherle PA, Strathmann MP, Slepak VZ, Simon MI. |
| Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10049-53. |
| PMID 1946421 |
| |
