InterPro domain: IPR013543

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity [ 1 ]:

• Serine/threonine-protein kinases
• Tyrosine-protein kinases
• Dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)

Protein kinase function is evolutionarily conserved from Escherichia coli to human [ 2 ]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation [ 3 ]. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [ 4 ], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [ 5 ].

This domain is found at the C terminus of the Calcium/calmodulin dependent protein kinases II (CaMKII). These proteins also have a Ser/Thr protein kinase domain ( IPR000719 ) at their N terminus [ 6 ]. The function of the CaMKII association domain is the assembly of the single proteins into large (8 to 14 subunits) multimers [ 7 ] and is a prominent kinase in the central nervous system that may function in long-term potentiation and neurotransmitter release.

1. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241, 42-52
2. The protein kinase complement of the human genome. Science 298, 1912-34
3. Evolution of protein kinase signaling from yeast to man. Trends Biochem. Sci. 27, 514-20
4. High-throughput structural biology in drug discovery: protein kinases. Curr. Pharm. Des. 10, 1069-82
5. Creating chemical diversity to target protein kinases. Comb. Chem. High Throughput Screen. 7, 453-72
6. Differential functional properties of calmodulin-dependent protein kinase IIgamma variants isolated from smooth muscle. Biochem. J. 372, 347-57
7. CaMKII, an enzyme on the move: regulation of temporospatial localization. Mol. Interv. 3, 386-403