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Gene Review

GNB5  -  guanine nucleotide binding protein (G...

Homo sapiens

Synonyms: GB5, Gbeta5, Guanine nucleotide-binding protein subunit beta-5, Transducin beta chain 5
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Disease relevance of GNB5

  • Normal epithelial antigens recognized by GB3 and GB5 are diminished in intraductal and lost in infiltrating human breast carcinomas [1].
  • More strikingly, in the infiltrating carcinomas (n = 15), none of the tumor specimens were recognized by GB3 and only one out of fifteen biopsies was moderately reactive with GB5, indicating that the syntheses of the antigens of GB3 and GB5 were discontinued in the metastatic breast adenocarcinomas [1].

High impact information on GNB5

  • Here, we identify R7BP, a novel neuronally expressed protein that binds R7-Gbeta5 complexes and shuttles them between the plasma membrane and nucleus [2].
  • The expression of mRNA for RGS6 and Gbeta5 in human tissues overlaps [3].
  • Mutation of the highly conserved Phe-61 residue of Ggamma2 to tryptophan, the residue present in all GGL domains, increases the stability of the Gbeta5/Ggamma2 heterodimer, highlighting the importance of this residue to GGL/Gbeta5 association [3].
  • After expression in Sf9 cells, complexes of both RGS6 and RGS7 with the Gbeta5 subunit (but not Gbetas 1-4) are found in the cytosol [4].
  • The 39-kDa Gbeta5 protein displayed differential association with retinal and brain membranes [5].

Biological context of GNB5

  • This review summarizes the information about the assembly and function of G beta5-RGS dimers, as well as their posttranslational modifications and localization [6].
  • Molecular cloning and sequencing of polymerase chain reaction products revealed that the cDNA encoding the larger species of Gbeta5 (Gbeta5L) was identical to the shorter form with the addition of 126 base pairs of 5' DNA sequence potentially encoding an in-frame 42-amino acid extension [5].
  • To identify key modulation determinants within these two structural regions, we performed scanning mutagenesis in which individual residues of the Gbeta1 subunit were replaced by corresponding Gbeta5 residues [7].
  • Its gene is located on chromosome 3 with a genomic structure indistinguishable from that of the genes of Gbeta1 to Gbeta3, but entirely different from Gbeta5 [8].
  • In addition, we posit that the interaction between Gbeta5 isoforms and the GGL domains of RGS proteins represents a general mode of binding between beta-propeller proteins and their partners, extending beyond the realm of G-protein-linked signal transduction [9].

Anatomical context of GNB5

  • In transient COS-7 cell expression experiments, Gbeta5L formed functional Gbetagamma dimers and Galphabetagamma heterotrimers, and activated phosphoinositide-specific phospholipase Cbeta2 in a manner indistinguishable from the 39-kDa Gbeta5 protein [5].
  • GB3 and GB5 are mouse monoclonal antibodies raised against human amnion [1].
  • All (n = 8) of the normal mammary glandular basement membranes and epithelia reacted strongly with GB3 and GB5 [1].
  • GB3 detects the epidermal basement membrane, and GB5 reacts with the junctional substances between the epithelial cells [1].
  • In nonpregnant endometrium, GB5 labeled rare spiral arteries [10].

Physical interactions of GNB5

  • (ii) RGS9 forms a complex with a type of G-protein beta-subunit (Gbeta5) via its GGL domain, which facilitates the GAP function of RGS9 [11].
  • RGS6 splice variants with complete GGL domains interacted with G beta 5, irrespective of the type of N-terminal domain, while those lacking a complete GGL domain did not [12].
  • Gbeta5 could also interact with RGS11 and its N-terminal, but not its C-terminal domain [13].

Regulatory relationships of GNB5

  • RGS6 protein variants displayed subcellular distribution patterns ranging from an exclusive cytoplasmic to exclusive nuclear/nucleolar localization, and co-expression of G beta 5 promoted nuclear localization of RGS6 proteins [12].

Other interactions of GNB5

  • Enhancement of pheromone response by RGS9 and Gbeta5 in yeast [14].
  • The G-protein gamma-subunit-like (GGL) domain present within a subfamily of RGS proteins binds specifically to Gbeta5 [14].
  • GTPase activating protein (GAP) assays suggest that G beta5-RGS7 acts specifically on G alphao, however in cell-based assays it also inhibited G alphai- and G alphaq-mediated signaling [6].

Analytical, diagnostic and therapeutic context of GNB5

  • Western blot analysis showed that GB5 and GB12 transiently increased the expression of both anti-apoptotic protein (Bcl-2) and proapoptotic proteins (Bax and Bad) in HL-60 cells [15].


  1. Normal epithelial antigens recognized by GB3 and GB5 are diminished in intraductal and lost in infiltrating human breast carcinomas. Yeh, C.J., Hsi, B.L., Ettore, F. Breast Cancer Res. Treat. (1986) [Pubmed]
  2. Palmitoylation regulates plasma membrane-nuclear shuttling of R7BP, a novel membrane anchor for the RGS7 family. Drenan, R.M., Doupnik, C.A., Boyle, M.P., Muglia, L.J., Huettner, J.E., Linder, M.E., Blumer, K.J. J. Cell Biol. (2005) [Pubmed]
  3. Fidelity of G protein beta-subunit association by the G protein gamma-subunit-like domains of RGS6, RGS7, and RGS11. Snow, B.E., Betts, L., Mangion, J., Sondek, J., Siderovski, D.P. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  4. Regulators of G protein signaling 6 and 7. Purification of complexes with gbeta5 and assessment of their effects on g protein-mediated signaling pathways. Posner, B.A., Gilman, A.G., Harris, B.A. J. Biol. Chem. (1999) [Pubmed]
  5. A novel form of the G protein beta subunit Gbeta5 is specifically expressed in the vertebrate retina. Watson, A.J., Aragay, A.M., Slepak, V.Z., Simon, M.I. J. Biol. Chem. (1996) [Pubmed]
  6. A novel kind of G protein heterodimer: the G beta5-RGS complex. Witherow, D.S., Slepak, V.Z. Recept. Channels (2003) [Pubmed]
  7. Scanning mutagenesis reveals a role for serine 189 of the heterotrimeric G-protein beta 1 subunit in the inhibition of N-type calcium channels. Tedford, H.W., Kisilevsky, A.E., Peloquin, J.B., Zamponi, G.W. J. Neurophysiol. (2006) [Pubmed]
  8. The human G protein beta4 subunit: gene structure, expression, Ggamma and effector interaction. Rosskopf, D., Nikula, C., Manthey, I., Joisten, M., Frey, U., Kohnen, S., Siffert, W. FEBS Lett. (2003) [Pubmed]
  9. Ggamma-like (GGL) domains: new frontiers in G-protein signaling and beta-propeller scaffolding. Sondek, J., Siderovski, D.P. Biochem. Pharmacol. (2001) [Pubmed]
  10. Investigation of the expression of amnion antigens by spiral arteries in human utero-placental tissues. Bulmer, J.N., Wells, M., Lunny, D.P., Yeh, C.J., Hsi, B.L. American journal of reproductive immunology and microbiology : AJRIM. (1987) [Pubmed]
  11. Physiological actions of regulators of G-protein signaling (RGS) proteins. Ishii, M., Kurachi, Y. Life Sci. (2003) [Pubmed]
  12. Human RGS6 gene structure, complex alternative splicing, and role of N terminus and G protein gamma-subunit-like (GGL) domain in subcellular localization of RGS6 splice variants. Chatterjee, T.K., Liu, Z., Fisher, R.A. J. Biol. Chem. (2003) [Pubmed]
  13. Direct interactions between the heterotrimeric G protein subunit G beta 5 and the G protein gamma subunit-like domain-containing regulator of G protein signaling 11: gain of function of cyan fluorescent protein-tagged G gamma 3. Zhou, J.Y., Toth, P.T., Miller, R.J. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  14. Enhancement of pheromone response by RGS9 and Gbeta5 in yeast. Ajit, S.K., Young, K.H. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  15. Tumor-specific cytotoxicity of 3,5-dibenzoyl-1,4-dihydropyridines. Morshed, S.R., Hashimoto, K., Murotani, Y., Kawase, M., Shah, A., Satoh, K., Kikuchi, H., Nishikawa, H., Maki, J., Sakagami, H. Anticancer Res. (2005) [Pubmed]
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