Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Isoform 1, isoform 2 and isoform 3 phosphorylate CAMK1 and CAMK4. Isoform 3 phosphorylates CAMK1D. Isoform 4, isoform 5 and isoform 6 lacking part of the calmodulin-binding domain are inactive. Efficiently phosphorylates 5'-AMP-activated protein kinase (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1. This phosphorylation is stimulated in response to Ca(2+) signals (By similarity). Seems to be involved in hippocampal activation of CREB1 (By similarity). May play a role in neurite growth. Isoform 3 may promote neurite elongation, while isoform 1 may promoter neurite branching. ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Activated by Ca(2+)/calmodulin. Binding of calmodulin may relieve intrasteric autoinhibition. Autophosphorylation does not alter activity or regulation by Ca(2+)/calmodulin. In part, activity is independent on Ca(2+)/calmodulin (By similarity). Interacts with calmodulin. Predominantly nuclear in unstimulated cells, relocalizes into cytoplasm and neurites after forskolin induction. Ubiquitously expressed with higher levels in the brain. Intermediate levels are detected in spleen, prostate, thyroid and leukocytes. The lowest level is in lung. Up-regulated by PKA pathway. The autoinhibitory domain overlaps with the calmodulin binding region and may be involved in intrasteric autoinhibition. The RP domain (arginine/proline-rich) is involved in the recognition of CAMKI and CAMK4 as substrates. Autophosphorylated and phosphorylated by PKA. Each isoform may show a different pattern of phosphorylation. Major isoform. Major isoform. Inactive. Does not activate CAMK1 and CAMK4. Inactive. Does not activate CAMK1 and CAMK4. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Truncated N-terminus. Extended N-terminus. Intron retention.