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Gene Review

GNAZ  -  guanine nucleotide binding protein (G...

Homo sapiens

Synonyms: G(x) alpha chain, Guanine nucleotide-binding protein G(z) subunit alpha, Gz-alpha
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Disease relevance of GNAZ


Psychiatry related information on GNAZ


High impact information on GNAZ

  • Both adult and fetal human RPE cells contain mRNA for multiple G protein alpha subunits (G alpha) including Gs alpha, Gi-1 alpha, Gi-2 alpha, Gi-3 alpha, and Gz alpha (or Gx alpha), where Gs and Gi are proteins that stimulate or inhibit adenylyl cyclase, respectively, and Gz is a protein that may mediate pertussis toxin-insensitive events [7].
  • The deduced amino acid sequence of Gz alpha is 41-67% identical with those of other known G-protein alpha subunits [8].
  • In a further study of G-protein diversity and signal transduction in the retina, we have identified a G-protein alpha subunit, which we refer to as Gz alpha, by isolating a human retinal cDNA clone that cross-hybridizes at reduced stringency with bovine Tr alpha-subunit cDNA [8].
  • RNA encoding Gz alpha was also detected in individual human megakaryocytes by in situ hybridization [2].
  • The paucity of Gz alpha protein and RNA in the megakaryoblastic cell lines suggests that either there has been a selective loss of the ability to synthesize Gz alpha from these cells or that Gz alpha appears at a later stage in megakaryocyte development than does Gi alpha [2].

Biological context of GNAZ


Anatomical context of GNAZ

  • GNAZ in human fetal cochlea: expression, localization, and potential role in inner ear function [11].
  • To address the potential role of G proteins expressed in human fetal cochlea, degenerate oligonucleotide primers corresponding to the 3'-end of the conserved region of alpha-subunits were used for polymerase chain reaction amplification of reverse-transcribed total human fetal cochlear mRNAs; GNAZ and GNAQ were isolated [11].
  • Thus, based on immunoreactivity and nucleotide sequencing, platelets and megakaryocytes contain substantial quantities of a protein identical to brain and retinal Gz alpha [2].
  • Three different Gz alpha-selective antisera reacted with a 40-Kd protein in platelet membranes [2].
  • Reactivity was confined to perikaryon, dendrites, and a very short segment of proximal axons, except for the retinal ganglion cells, in which the axons in the nerve fiber layer showed intense Gz-alpha immunoreactivity proximal to the lamina cribrosa [3].

Associations of GNAZ with chemical compounds

  • A focus was placed on Ser25 and Ser27, the 2 serine residues within a sequence of Gz alpha used to obtain a phosphorylation-sensitive antibody [10].
  • Cloning of a complementary DNA (cDNA) for Gz alpha, a newly appreciated member of the family of guanine nucleotide-binding regulatory proteins (G proteins), has allowed preparation of specific antisera to identify the protein in tissues and to assay it during purification from bovine brain [12].
  • Gz alpha variants containing selected substitutions of alanine for serine residues were expressed in human kidney 293 cells, and the ability of each to be phosphorylated in response to phorbol 12-myristate 13-acetate was examined [10].
  • We have demonstrated previously by phosphoamino acid analysis and CNBr peptide mapping that phosphorylation occurs at a serine residue(s) within the NH2-terminal 53 residues of Gz alpha [10].
  • We have demonstrated previously that the G protein alpha subunit Gz alpha (or Gx alpha) in human platelets is subject to phosphorylation by agents that activate protein kinase C, including phorbol 12-myristate 13-acetate, thrombin, and the thromboxane A2 analog U46619 [13].

Regulatory relationships of GNAZ

  • GNAZ is expressed in high levels in neural tissue while GNAQ is ubiquitously expressed [11].

Other interactions of GNAZ

  • Recent studies have shown that human retina and rat brain contain mRNA encoding a novel 40-Kd G protein alpha subunit referred to as Gz alpha [2].
  • Recombinant Gi alpha 1, Gi alpha 2, Gi alpha 3, Go alpha (A), Gs alpha, and Gz alpha all failed to stimulate any of the isoforms of PLC [14].

Analytical, diagnostic and therapeutic context of GNAZ


  1. Isolation of genes from the rhabdoid tumor deletion region in chromosome band 22q11.2. Zhou, J., Fogelgren, B., Wang, Z., Roe, B.A., Biegel, J.A. Gene (2000) [Pubmed]
  2. Identification of Gz alpha as a pertussis toxin-insensitive G protein in human platelets and megakaryocytes. Gagnon, A.W., Manning, D.R., Catani, L., Gewirtz, A., Poncz, M., Brass, L.F. Blood (1991) [Pubmed]
  3. Novel localization of a G protein, Gz-alpha, in neurons of brain and retina. Hinton, D.R., Blanks, J.C., Fong, H.K., Casey, P.J., Hildebrandt, E., Simons, M.I. J. Neurosci. (1990) [Pubmed]
  4. Alterations in the expression of G-proteins and regulation of adenylate cyclase in human neuroblastoma SH-SY5Y cells chronically exposed to low-efficacy mu-opioids. Ammer, H., Schulz, R. Biochem. J. (1993) [Pubmed]
  5. G protein abnormalities in pituitary adenomas. Spada, A., Lania, A., Ballarè, E. Mol. Cell. Endocrinol. (1998) [Pubmed]
  6. Analysis of GNAZ gene polymorphism in bipolar affective disorder. Saito, T., Papolos, D.F., Chernak, D., Rapaport, M.H., Kelsoe, J.R., Lachman, H.M. Am. J. Med. Genet. (1999) [Pubmed]
  7. Guanine nucleotide-binding regulatory proteins in retinal pigment epithelial cells. Jiang, M., Pandey, S., Tran, V.T., Fong, H.K. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  8. Identification of a GTP-binding protein alpha subunit that lacks an apparent ADP-ribosylation site for pertussis toxin. Fong, H.K., Yoshimoto, K.K., Eversole-Cire, P., Simon, M.I. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  9. Novel conserved synteny between human chromosome 22 and cattle chromosome 22 established by linkage mapping of transducin alpha-1 subunit (GNAZ). Aleyasin, A., Barendse, W. Mamm. Genome (1997) [Pubmed]
  10. Analysis of Gz alpha by site-directed mutagenesis. Sites and specificity of protein kinase C-dependent phosphorylation. Lounsbury, K.M., Schlegel, B., Poncz, M., Brass, L.F., Manning, D.R. J. Biol. Chem. (1993) [Pubmed]
  11. GNAZ in human fetal cochlea: expression, localization, and potential role in inner ear function. Magovcevic, I., Khetarpal, U., Bieber, F.R., Morton, C.C. Hear. Res. (1995) [Pubmed]
  12. Gz, a guanine nucleotide-binding protein with unique biochemical properties. Casey, P.J., Fong, H.K., Simon, M.I., Gilman, A.G. J. Biol. Chem. (1990) [Pubmed]
  13. Phosphorylation of Gz in human platelets. Selectivity and site of modification. Lounsbury, K.M., Casey, P.J., Brass, L.F., Manning, D.R. J. Biol. Chem. (1991) [Pubmed]
  14. Purification from Sf9 cells and characterization of recombinant Gq alpha and G11 alpha. Activation of purified phospholipase C isozymes by G alpha subunits. Hepler, J.R., Kozasa, T., Smrcka, A.V., Simon, M.I., Rhee, S.G., Sternweis, P.C., Gilman, A.G. J. Biol. Chem. (1993) [Pubmed]
  15. Multiple coupling of human D5 dopamine receptors to guanine nucleotide binding proteins Gs and Gz. Sidhu, A., Kimura, K., Uh, M., White, B.H., Patel, S. J. Neurochem. (1998) [Pubmed]
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