Calcium/calmodulin-dependent protein kinase type II subunit alpha

Definition:

Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in various processes, such as synaptic plasticity, neurotransmitter release and long-term potentiation. Member of the NMDAR signaling complex in excitatory synapses, it regulates NMDAR-dependent potentiation of the AMPAR and therefore excitatory synaptic transmission (By similarity). Regulates dendritic spine development. Also regulates the migration of developing neurons. Phosphorylates the transcription factor FOXO3 to activate its transcriptional activity. Phosphorylates the transcription factor ETS1 in response to calcium signaling, thereby decreasing ETS1 affinity for DNA (By similarity). In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway. In response to interferon-beta (IFN-beta) stimulation, stimulates the JAK-STAT signaling pathway. Acts as a negative regulator of 2-arachidonoylglycerol (2-AG)-mediated synaptic signaling via modulation of DAGLA activity (By similarity).

References:

[1]. Sébastien Küry, et al. De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability. Am J Hum Genet. 2017 Nov 2;101(5):768-788. [Content Brief]

[2]. Li Tao, et al. CAMKII and calcineurin regulate the lifespan of Caenorhabditis elegans through the FOXO transcription factor DAF-16. Elife. 2013 Jun 25;2:e00518. [Content Brief]

[3]. Jayasree S Nair, et al. Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in response to IFN-gamma. Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5971-6. [Content Brief]

[4]. Noémie Alphonse, et al. A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling. Cell. 2022 Jun 23;185(13):2354-2369.e17. [Content Brief]

[5]. Jason R Stephenson, et al. A Novel Human CAMK2A Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and Causes ASD-Related Behaviors. J Neurosci. 2017 Feb 22;37(8):2216-2233. [Content Brief]

[6]. Tara R Gaertner, et al. Comparative analyses of the three-dimensional structures and enzymatic properties of alpha, beta, gamma and delta isoforms of Ca2+-calmodulin-dependent protein kinase II. J Biol Chem. 2004 Mar 26;279(13):12484-94. [Content Brief]

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