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Gene Review

CAMK2G  -  calcium/calmodulin-dependent protein...

Homo sapiens

Synonyms: CAMK, CAMK-II, CAMKG, CaM kinase II subunit gamma, CaMK-II subunit gamma, ...
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Disease relevance of CAMK2G


Psychiatry related information on CAMK2G


High impact information on CAMK2G


Chemical compound and disease context of CAMK2G


Biological context of CAMK2G


Anatomical context of CAMK2G

  • To characterize the CaM kinase present in these tissues we have cloned an isoform of this kinase from human T lymphocytes [2].
  • In addition, we have observed a specific increase in the concentration of CaM kinase II in dendrites of neurons receiving tetanic stimulation [17].
  • In RBL-2H3 m1 cells, inhibition of CaM kinase II decreased Thr-1940 phosphorylation, and inhibited release of the secretory granule marker hexosaminidase in response to carbachol but not to antigen [18].
  • Similarly, co-transfected Ala --> Thr-1940 human NMHC-IIA was phosphorylated by activated CaM kinase II in HeLa cells, while wild type was not [18].
  • In this study we provide the first conclusive evidence for the expression of CaM kinase II in human islets of Langerhans and show that multiple isoforms are expressed [19].

Associations of CAMK2G with chemical compounds

  • A single CaM kinase II site was also identified at serine 744 within sub-kinase domain III, and autokinase activity was significantly affected by mutation of this serine to an aspartic acid making this site appear constitutively phosphorylated [15].
  • These data indicate a role for CaM kinase stimulation and resultant threonine phosphorylation of NMHC-IIA in RBL-2H3 m1 cell activation [18].
  • When transfected into Jurkat T cells, the gamma B cDNA encoded a functional kinase which cosedimented on sucrose gradients with endogenous T cell CaM kinase activity and formed a large multimeric enzyme [2].
  • Calcium/calmodulin-dependent protein kinase II (CaM kinase II) has been proposed to play a key role in glucose stimulated insulin secretion [20].
  • Autophosphorylation was inhibited by the CaMKII(281-302) peptide, which corresponds to the CaMKII autoinhibitory domain, and by 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4- phenylpiperazine (KN-62), a specific CaM kinase antagonist [21].

Enzymatic interactions of CAMK2G

  • A GST fusion protein comprising residues 1126-1255 of HER-2 was phosphorylated by purified Cam kinase II, in contrast to a GST protein comprising residues 1005-1125 [22].
  • The IP3 receptor is stoichiometrically phosphorylated by protein kinase C (PKC) and Ca2+ calmodulin-dependent protein kinase II (CaM kinase II) as well as by PKA [23].
  • When activated, CaM kinase II phosphorylates synapsin I, which reduces its binding to vesicles and/or cytoskeletal structures, enabling more vesicles to be released during a presynaptic depolarization [24].
  • Calmodulin kinase II (CAMKII) is phosphorylated in response to PDGF-BB in the NF1 MPNST cell lines, whereas no phosphorylation of CAMKII was observed in nhSCs [25].

Regulatory relationships of CAMK2G

  • In contrast, CaM kinase II was unable to activate either ATF1 or CREB [26].
  • Inhibition of PKC, MAP kinase, or CaM kinase II does not affect mitotic extract-induced dissociation of LAP2beta from HA95 [27].
  • The effects of a calcium chelator, calcium channel blockers, calmodulin antagonists, and an inhibitor of calcium/calmodulin-dependent protein kinase II (CaM kinase II) indicate that depolarization-induced glucagon gene transcription depends on calcium influx and CaM kinase II [28].
  • In serum-deprived MDA-MB-231 cells, the combination of insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) stimulated cell proliferation and activated CaM kinase III to activities observed in the presence of 10% serum [29].
  • CaM-kinase IV that was expressed in cancerous hepatocytes was phosphorylated mainly by CaM-kinase kinase that also was expressed in tumor cells [30].

Other interactions of CAMK2G

  • Smad2 is a target substrate for Cam kinase II in vitro at serine-110, -240, and -260 [31].
  • Here we report that Smad-TGF-beta-dependent transcriptional responses are prevented by expression of a constitutively activated Ca(2+)-calmodulin-dependent protein kinase II (Cam kinase II) [31].
  • We have addressed the mechanism by which CaM kinase II phosphorylation of the EGFR might regulate receptor autokinase activity and show that this modification can hinder association of the cytoplasmic tail with the kinase domain to prevent an enzyme-substrate interaction [15].
  • To obtain structural information and the sequences of the exon-intron boundaries, the published genomic structures of the rat and mouse genes allowed the putative exon-intron boundaries of human CAMK2G to be amplified by vectorette polymerase chain reaction and sequenced [1].
  • We mapped the human SRP72 gene to chromosome 18 and, as the CaM kinase II gamma gene was previously mapped to human chromosome 10q22, we suggest this novel cDNA may have resulted from trans-splicing [20].

Analytical, diagnostic and therapeutic context of CAMK2G


  1. Human calcium/calmodulin-dependent protein kinase II gamma gene (CAMK2G): cloning, genomic structure and detection of variants in subjects with type II diabetes. Gloyn, A.L., Desai, M., Clark, A., Levy, J.C., Holman, R.R., Frayling, T.M., Hattersley, A.T., Ashcroft, S.J. Diabetologia (2002) [Pubmed]
  2. Cloning and analysis of two new isoforms of multifunctional Ca2+/calmodulin-dependent protein kinase. Expression in multiple human tissues. Nghiem, P., Saati, S.M., Martens, C.L., Gardner, P., Schulman, H. J. Biol. Chem. (1993) [Pubmed]
  3. CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte hypertrophy. Backs, J., Song, K., Bezprozvannaya, S., Chang, S., Olson, E.N. J. Clin. Invest. (2006) [Pubmed]
  4. Ca2+/calmodulin-dependent protein kinase II: localization in the interphase nucleus and the mitotic apparatus of mammalian cells. Ohta, Y., Ohba, T., Miyamoto, E. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  5. Global forebrain ischemia induces a posttranslational modification of multifunctional calcium- and calmodulin-dependent kinase II. Churn, S.B., Taft, W.C., Billingsley, M.S., Sankaran, B., DeLorenzo, R.J. J. Neurochem. (1992) [Pubmed]
  6. Calcium/calmodulin-dependent protein kinase II immunostaining is preserved in Alzheimer's disease hippocampal neurons. Simonian, N.A., Elvhage, T., Czernik, A.J., Greengard, P., Hyman, B.T. Brain Res. (1994) [Pubmed]
  7. Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy. Robitaille, J., MacDonald, M.L., Kaykas, A., Sheldahl, L.C., Zeisler, J., Dubé, M.P., Zhang, L.H., Singaraja, R.R., Guernsey, D.L., Zheng, B., Siebert, L.F., Hoskin-Mott, A., Trese, M.T., Pimstone, S.N., Shastry, B.S., Moon, R.T., Hayden, M.R., Goldberg, Y.P., Samuels, M.E. Nat. Genet. (2002) [Pubmed]
  8. Mechanisms of organophosphorus ester-induced delayed neurotoxicity: type I and type II. Abou-Donia, M.B., Lapadula, D.M. Annu. Rev. Pharmacol. Toxicol. (1990) [Pubmed]
  9. The CaM kinase II hypothesis for the storage of synaptic memory. Lisman, J. Trends Neurosci. (1994) [Pubmed]
  10. Anti-immunoglobulin M activates nuclear calcium/calmodulin-dependent protein kinase II in human B lymphocytes. Valentine, M.A., Czernik, A.J., Rachie, N., Hidaka, H., Fisher, C.L., Cambier, J.C., Bomsztyk, K. J. Exp. Med. (1995) [Pubmed]
  11. Activation of Ca2+/calmodulin-dependent protein kinase II by stimulation with bradykinin in neuroblastoma x glioma hybrid NG108-15 cells. Yamakawa, T., Fukunaga, K., Higashida, H., Miyamoto, E. Brain Res. (1992) [Pubmed]
  12. Lithium-induced activation of Akt and CaM kinase II contributes to its neuroprotective action in a rat microsphere embolism model. Sasaki, T., Han, F., Shioda, N., Moriguchi, S., Kasahara, J., Ishiguro, K., Fukunaga, K. Brain Res. (2006) [Pubmed]
  13. Role of calcium in inactivation of calcium/calmodulin dependent protein kinase II after cerebral ischemia. Hiestand, D.M., Haley, B.E., Kindy, M.S. J. Neurol. Sci. (1992) [Pubmed]
  14. FK506 attenuates the post-ischemic perturbation of protein kinases and tyrosine phosphorylation in the gerbil hippocampal CA1 sectors. Katsura, K.I., Kurihara, J., Watanabe, M., Takahashi, K., Katayama, Y. Acta Neurochir. Suppl. (2003) [Pubmed]
  15. Ca2+/calmodulin-dependent kinase II phosphorylates the epidermal growth factor receptor on multiple sites in the cytoplasmic tail and serine 744 within the kinase domain to regulate signal generation. Feinmesser, R.L., Wicks, S.J., Taverner, C.J., Chantry, A. J. Biol. Chem. (1999) [Pubmed]
  16. Regulation of intrasteric inhibition of the multifunctional calcium/calmodulin-dependent protein kinase. Cruzalegui, F.H., Kapiloff, M.S., Morfin, J.P., Kemp, B.E., Rosenfeld, M.G., Means, A.R. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  17. Signal transduction molecules at the glutamatergic postsynaptic membrane. Kennedy, M.B. Brain Res. Brain Res. Rev. (1998) [Pubmed]
  18. Calcium-dependent threonine phosphorylation of nonmuscle myosin in stimulated RBL-2H3 mast cells. Buxton, D.B., Adelstein, R.S. J. Biol. Chem. (2000) [Pubmed]
  19. Human islets of Langerhans express multiple isoforms of calcium/calmodulin-dependent protein kinase II. Breen, M.A., Ashcroft, S.J. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  20. A truncated isoform of Ca2+/calmodulin-dependent protein kinase II expressed in human islets of Langerhans may result from trans-splicing. Breen, M.A., Ashcroft, S.J. FEBS Lett. (1997) [Pubmed]
  21. Expression of Ca2+/calmodulin-dependent protein kinase types II and IV, and reduced DNA synthesis due to the Ca2+/calmodulin-dependent protein kinase inhibitor KN-62 (1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenyl piperazine) in small cell lung carcinoma. Williams, C.L., Phelps, S.H., Porter, R.A. Biochem. Pharmacol. (1996) [Pubmed]
  22. HER-2/c-erbB2 is phosphorylated by calmodulin-dependent protein kinase II on a single site in the cytoplasmic tail at threonine-1172. Feinmesser, R.L., Gray, K., Means, A.R., Chantry, A. Oncogene (1996) [Pubmed]
  23. Inositol trisphosphate receptor: phosphorylation by protein kinase C and calcium calmodulin-dependent protein kinases in reconstituted lipid vesicles. Ferris, C.D., Huganir, R.L., Bredt, D.S., Cameron, A.M., Snyder, S.H. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  24. Regulation by synapsin I and Ca(2+)-calmodulin-dependent protein kinase II of the transmitter release in squid giant synapse. Llinás, R., Gruner, J.A., Sugimori, M., McGuinness, T.L., Greengard, P. J. Physiol. (Lond.) (1991) [Pubmed]
  25. Schwann cell lines derived from malignant peripheral nerve sheath tumors respond abnormally to platelet-derived growth factor-BB. Dang, I., DeVries, G.H. J. Neurosci. Res. (2005) [Pubmed]
  26. Regulation of activating transcription factor-1 and the cAMP response element-binding protein by Ca2+/calmodulin-dependent protein kinases type I, II, and IV. Sun, P., Lou, L., Maurer, R.A. J. Biol. Chem. (1996) [Pubmed]
  27. In vitro modulation of the interaction between HA95 and LAP2beta by cAMP signaling. Martins, S.B., Marstad, A., Collas, P. Biochemistry (2003) [Pubmed]
  28. Membrane depolarization and calcium influx induce glucagon gene transcription in pancreatic islet cells through the cyclic AMP-responsive element. Schwaninger, M., Lux, G., Blume, R., Oetjen, E., Hidaka, H., Knepel, W. J. Biol. Chem. (1993) [Pubmed]
  29. Activity and regulation by growth factors of calmodulin-dependent protein kinase III (elongation factor 2-kinase) in human breast cancer. Parmer, T.G., Ward, M.D., Yurkow, E.J., Vyas, V.H., Kearney, T.J., Hait, W.N. Br. J. Cancer (1999) [Pubmed]
  30. Enhanced expression and activation of Ca(2+)/calmodulin-dependent protein kinase IV in hepatocellular carcinoma. Tamura, N., Tai, Y., Sugimoto, K., Kobayashi, R., Konishi, R., Nishioka, M., Masaki, T., Nagahata, S., Tokuda, M. Cancer (2000) [Pubmed]
  31. Inactivation of smad-transforming growth factor beta signaling by Ca(2+)-calmodulin-dependent protein kinase II. Wicks, S.J., Lui, S., Abdel-Wahab, N., Mason, R.M., Chantry, A. Mol. Cell. Biol. (2000) [Pubmed]
  32. Localization of the CAMKG gene encoding gamma isoforms of multifunctional calcium/calmodulin-dependent protein kinase (CaM kinase) to human chromosome 10 band q22 and mouse chromosome 14. Li, X., Nghiem, P., Schulman, H., Francke, U. Cytogenet. Cell Genet. (1994) [Pubmed]
  33. Carbachol stimulates binding of a photoreactive calmodulin derivative to calmodulin-binding proteins in intact SK-N-SH human neuroblastoma cells. Mangels, L.A., Gnegy, M.E. J. Biol. Chem. (1992) [Pubmed]
  34. Novel Ca2+/calmodulin-dependent protein kinase II gamma-subunit variants expressed in vascular smooth muscle, brain, and cardiomyocytes. Singer, H.A., Benscoter, H.A., Schworer, C.M. J. Biol. Chem. (1997) [Pubmed]
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