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Gene Review

Gnai1  -  guanine nucleotide binding protein (G...

Mus musculus

Synonyms: AU046200, Adenylate cyclase-inhibiting G alpha protein, Gialpha1, Gnai-1, Guanine nucleotide-binding protein G(i) subunit alpha-1
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Disease relevance of Gnai1


High impact information on Gnai1

  • The C1b domain of the type V enzyme contributed to affinity for Gialpha, but the source of C2 had little effect [4].
  • Adenylyl cyclase activity reconstituted by mixture of the C1 and C2 domains of type V adenylyl cyclase was also inhibited by Gialpha [4].
  • These mutations suggest binding of Gialpha within the cleft formed by the alpha2 and alpha3 helices of C1, analogous to the Gsalpha binding site in C2 [4].
  • Mutagenesis of the membrane-bound enzyme identified residues whose alteration either increased or substantially decreased the IC50 for inhibition by Gialpha1 [4].
  • In AC II and AC IV transfectants, alpha2-AR activation initiated both positive (Gbetagamma) and negative signals (Gialpha) to the Gsalpha-stimulated enzyme, and both types of signals were blocked by cell pretreatment with pertussis toxin [5].

Biological context of Gnai1

  • Identification of a Gialpha binding site on type V adenylyl cyclase [4].
  • An RGS14 mutant (EN92/93AA), which does not block Gialpha-linked signaling, also inhibits serum response element activation [6].
  • Based on this, we propose that upregulation of the active conformation of the beta2ARs, Gsalpha protein and restoration of Gialpha as three possible mechanisms to explain this enhanced receptor activity [7].

Associations of Gnai1 with chemical compounds

  • Ectopic expression of Goalpha1 but not Gialpha1 increased the relative efficacy of clonidine and oxymetazoline such that the two ligands now behaved as close to full agonists in this assay system [8].
  • ICI-118,551 and propranolol treatment restored the elevated myocardial G-inhibitory protein (Gialpha) levels to that of wild type [7].

Other interactions of Gnai1

  • TNF-alpha modulatory effects on GPCR-induced ASM responsiveness were completely abrogated by pertussis toxin, an inhibitor of Gialpha proteins [9].


  1. Eotaxin modulates myelopoiesis and mast cell development from embryonic hematopoietic progenitors. Quackenbush, E.J., Wershil, B.K., Aguirre, V., Gutierrez-Ramos, J.C. Blood (1998) [Pubmed]
  2. Differentiation of F9 teratocarcinoma stem cells to primitive endoderm is regulated by the Gialpha2/Gsalpha axis via phospholipase C and not adenylylcyclase. Gao, P., Malbon, C.C. J. Biol. Chem. (1996) [Pubmed]
  3. Overexpressed cardiac Gsalpha in rabbits. Nishizawa, T., Vatner, S.F., Hong, C., Shen, Y.T., Hardt, S.E., Robbins, J., Ishikawa, Y., Sadoshima, J., Vatner, D.E. J. Mol. Cell. Cardiol. (2006) [Pubmed]
  4. Identification of a Gialpha binding site on type V adenylyl cyclase. Dessauer, C.W., Tesmer, J.J., Sprang, S.R., Gilman, A.G. J. Biol. Chem. (1998) [Pubmed]
  5. Factors determining the specificity of signal transduction by guanine nucleotide-binding protein-coupled receptors. Integration of stimulatory and inhibitory input to the effector adenylyl cyclase. Marjamaki, A., Sato, M., Bouet-Alard, R., Yang, Q., Limon-Boulez, I., Legrand, C., Lanier, S.M. J. Biol. Chem. (1997) [Pubmed]
  6. RGS14, a GTPase-activating protein for Gialpha, attenuates Gialpha- and G13alpha-mediated signaling pathways. Cho, H., Kozasa, T., Takekoshi, K., De Gunzburg, J., Kehrl, J.H. Mol. Pharmacol. (2000) [Pubmed]
  7. Treatment with inverse agonists enhances baseline atrial contractility in transgenic mice with chronic beta2-adrenoceptor activation. Nagaraja, S., Iyer, S., Liu, X., Eichberg, J., Bond, R.A. Br. J. Pharmacol. (1999) [Pubmed]
  8. Influence of G protein type on agonist efficacy. Yang, Q., Lanier, S.M. Mol. Pharmacol. (1999) [Pubmed]
  9. TNF-[alpha] modulates murine tracheal rings responsiveness to G-protein-coupled receptor agonists and KCl. Chen, H., Tliba, O., Van Besien, C.R., Panettieri, R.A., Amrani, Y. J. Appl. Physiol. (2003) [Pubmed]
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