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Gene Review

GNA12  -  guanine nucleotide binding protein (G...

Homo sapiens

Synonyms: G alpha-12, G-protein subunit alpha-12, Guanine nucleotide-binding protein subunit alpha-12, NNX3, RMP, ...
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Disease relevance of GNA12

  • To determine whether the pertussis toxin-insensitive G12 protein is involved in the thrombin-stimulated DNA synthesis, an inhibitory antibody against the C-terminal sequence of G alpha 12 subunit was microinjected into 1321N1 cells [1].

High impact information on GNA12


Chemical compound and disease context of GNA12


Biological context of GNA12

  • As an addition to genetic information reported earlier, we provide here 20 novel single nucleotide polymorphisms (SNPs) in the region corresponding to a gene encoding alpha subunits of G(12) protein, GNA12, in the Japanese population: 16 in introns, two in the coding region, and two in the 3' flanking region [5].
  • Recent analyses have indicated that G alpha 12 and G alpha 13 regulate cytoplasmic as well as nuclear signaling events such as activation of the Jun N-terminal kinase signaling module, Na+/H+ exchangers, focal adhesion assemblies, and transcriptional activation of specific primary response genes [6].
  • The data indicate a protective effect of the RMP synchronous administration (by enzyme induction mechanisms) in the preservation of fibrinogen blood levels [7].
  • Transfection with antagonist minigenes coding for small peptide antagonists to G alpha 12 and G alpha13 subunits of heterotrimeric G proteins prevented PTH-stimulated activation of PLD, whereas an antagonist minigene to G alphas failed to produce this effect [8].
  • In addition to stimulating Gi-Ras-mediated cell proliferation, LPA and S1P induce rapid G alpha 12/13-RhoA-mediated cytoskeletal changes underlying such diverse responses as neurite retraction, cell rounding, and enhanced tumor cell invasiveness [9].

Anatomical context of GNA12


Associations of GNA12 with chemical compounds

  • For isolation of functionally active G alpha 12, it was mandatory to use sucrose monolaurate as a detergent [10].
  • Purified G alpha 12 bound guanosine 5'-[gamma-thio]triphosphate slowly and substoichiometrically [10].
  • Fatty acid analysis after labeling with [3H]palmitic acid showed that palmitate represents the predominant fatty acid linked to G alpha 12 and G alpha 13 [13].
  • Nineteen randomized patients, treated with isoniazid (INH, CAS 54-85-3) for tuberculosis chemoprophylaxis or isoniazid plus rifampicin (RMP, CAS 13292-46-1) combination for tuberculosis therapy, were studied in order to explore the effects of these drugs on fibrinogen and antithrombin III blood levels [7].

Regulatory relationships of GNA12

  • G alpha 12 required a higher Mg2+ concentration for AlF4- -induced dissociation from immobilized G beta gamma than did G alpha 13 [10].

Other interactions of GNA12

  • This regularly deleted region is bordered by markers GNA12 (3p21.1-p21.3) and VHL (3p25) that were maintained in a fraction of tumors [14].
  • Furthermore, the exchange of a few carboxyl-terminal residues of G alpha q by those of G alpha 12 or G alpha o allows the resulting chimeric G alpha subunits (G alpha ql and G alpha qol respectively) to couple Gi-coupled receptors to PLC [15].
  • Using specific antisera against subtypes of Gi proteins, we found that ADP stimulated labelling of the G alpha 12 immunoprecipitate, but not of the G alpha 13 precipitate [16].
  • Distinct biochemical properties of the native members of the G12 G-protein subfamily. Characterization of G alpha 12 purified from rat brain [10].


  1. G12 requirement for thrombin-stimulated gene expression and DNA synthesis in 1321N1 astrocytoma cells. Aragay, A.M., Collins, L.R., Post, G.R., Watson, A.J., Feramisco, J.R., Brown, J.H., Simon, M.I. J. Biol. Chem. (1995) [Pubmed]
  2. Expression cDNA cloning of a transforming gene encoding the wild-type G alpha 12 gene product. Chan, A.M., Fleming, T.P., McGovern, E.S., Chedid, M., Miki, T., Aaronson, S.A. Mol. Cell. Biol. (1993) [Pubmed]
  3. Coupling of the thrombin receptor to G12 may account for selective effects of thrombin on gene expression and DNA synthesis in 1321N1 astrocytoma cells. Post, G.R., Collins, L.R., Kennedy, E.D., Moskowitz, S.A., Aragay, A.M., Goldstein, D., Brown, J.H. Mol. Biol. Cell (1996) [Pubmed]
  4. Heterotrimeric G proteins as fluoride targets in bone (review). Susa, M. Int. J. Mol. Med. (1999) [Pubmed]
  5. Identification of 20 novel SNPs in the guanine nucleotide binding protein alpha 12 gene locus. Iida, A., Saito, S., Sekine, A., Tabei, W., Kataoka, Y., Nakamura, Y. J. Hum. Genet. (2004) [Pubmed]
  6. Signaling by the G12 class of G proteins. Dhanasekaran, N., Dermott, J.M. Cell. Signal. (1996) [Pubmed]
  7. Fibrinogen and antithrombin III blood levels fluctuations during isoniazid or isoniazid plus rifampicin administration. Farmakis, M., Travlou, O., Aroni, S., Fertakis, A. Arzneimittel-Forschung. (1992) [Pubmed]
  8. G alpha12/G alpha13 subunits of heterotrimeric G proteins mediate parathyroid hormone activation of phospholipase D in UMR-106 osteoblastic cells. Singh, A.T., Gilchrist, A., Voyno-Yasenetskaya, T., Radeff-Huang, J.M., Stern, P.H. Endocrinology (2005) [Pubmed]
  9. Development of our current understanding of bioactive lysophospholipids. Moolenaar, W.H. Ann. N. Y. Acad. Sci. (2000) [Pubmed]
  10. Distinct biochemical properties of the native members of the G12 G-protein subfamily. Characterization of G alpha 12 purified from rat brain. Harhammer, R., Nürnberg, B., Harteneck, C., Leopoldt, D., Exner, T., Schultz, G. Biochem. J. (1996) [Pubmed]
  11. Identification of isoforms of G proteins and PKC that colocalize with tight junctions. Dodane, V., Kachar, B. J. Membr. Biol. (1996) [Pubmed]
  12. Expression of the heterotrimeric G protein Gi and ATP release are impaired in erythrocytes of humans with diabetes mellitus. Sprague, R., Stephenson, A., Bowles, E., Stumpf, M., Ricketts, G., Lonigro, A. Adv. Exp. Med. Biol. (2006) [Pubmed]
  13. The alpha-subunits of G-proteins G12 and G13 are palmitoylated, but not amidically myristoylated. Veit, M., Nürnberg, B., Spicher, K., Harteneck, C., Ponimaskin, E., Schultz, G., Schmidt, M.F. FEBS Lett. (1994) [Pubmed]
  14. Nonrandom loss of human chromosome 3 fragments from mouse-human microcell hybrids following progressive growth in SCID mice. Imreh, S., Kholodnyuk, I., Allikmetts, R., Stanbridge, E.J., Zabarovsky, E.R., Klein, G. Genes Chromosomes Cancer (1994) [Pubmed]
  15. Coupling of metabotropic glutamate receptors 2 and 4 to G alpha 15, G alpha 16, and chimeric G alpha q/i proteins: characterization of new antagonists. Gomeza, J., Mary, S., Brabet, I., Parmentier, M.L., Restituito, S., Bockaert, J., Pin, J.P. Mol. Pharmacol. (1996) [Pubmed]
  16. The human platelet ADP receptor activates Gi2 proteins. Ohlmann, P., Laugwitz, K.L., Nürnberg, B., Spicher, K., Schultz, G., Cazenave, J.P., Gachet, C. Biochem. J. (1995) [Pubmed]
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