Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in 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 (PubMed:15312654). Regulates dendritic spine development. Also regulates the migration of developing neurons. Phosphorylates the transcription factor FOXO3 to activate its transcriptional activity (By similarity). Acts as a negative regulator of 2-arachidonoylglycerol (2-AG)-mediated synaptic signaling via modulation of DAGLA activity (By similarity). 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 results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-286 which turns the kinase in a constitutively active form and confers to the kinase a Ca(2+)-independent activity. There are 4 genes encoding calcium/calmodulin-dependent protein kinase type II chains: CAMK2A, CAMK2B, CAMK2G and CAMK2D. The corresponding proteins assemble into homo- or heteromultimeric holoenzymes composed of 12 subunits with two hexameric rings stacked one on top of the other (By similarity). Interacts with BAALC (PubMed:15659234). Interacts with MPDZ (PubMed:15312654). Interacts with SYN1 (PubMed:1328883). Interacts with CAMK2N2 (PubMed:9724800). Interacts with SYNGAP1 (PubMed:15312654). Interacts with SYNPO2 (PubMed:17923693). Interacts with SHANK3. Interacts with GRIN2B. Interacts with CACNB2. Interacts with LRRC7. Interacts with GRM5 (By similarity). Interacts with DAGLA (via C-terminal); this interaction is enhanced by autophosphorylation of CAMK2A at Thr-286 (By similarity). Interacts with CAMK2N1; this interaction requires CAMK2A activation by Ca(2+) (PubMed:11182241). Postsynaptic lipid rafts. Autophosphorylation of Thr-286 following activation by Ca(2+)/calmodulin. Phosphorylation of Thr-286 locks the kinase into an activated state. Palmitoylated (PubMed:23687301). Probably palmitoylated by ZDHHC3 and ZDHHC7 (PubMed:23687301). Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.