Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Capable of regulating both type I apoptotic and type II autophagic cell death signals. The former involves caspase activation, chromatin and mitochondrial condensation while the latter involves caspase-independent cell death in conjunction with accumulation of mature autophagic vesicles, plasma membrane blebs, and nuclear condensation without DNA degradation. Mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation (By similarity). Regulates granulocytes motility by controlling cell spreading and polarization (PubMed:24163421). 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. Regulated by a double locking mechanism, involving autophosphorylation at Ser-318, calmodulin binding, and dimerization. In the inactive state, Ser-318 is phosphorylated, and the kinase is dimeric. Activation involves: dephosphorylation at Ser-318, release-of-autoinhibition mechanism where calmodulin binding induces a conformational change that relieves the steric block of the active site by the autoinhibitory domain, and generation of the monomeric active form of the kinase. Homodimer in its autoinhibited state. Active as monomer. Interacts with 14-3-3 proteins YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ and SFN; the interaction requires DAPK2 phosphorylation at Thr-369 and suppresses DAPK2 kinase activity and DAPK2-induced apoptosis. Expressed in peritubular interstitial cells of the renal cortex (PubMed:24906443). Isoform 1 is found in the adult brain while isoform 2 is expressed in brains of embryos and young mice (at protein level) (PubMed:21408167). The autoinhibitory domain sterically blocks the substrate peptide-binding site by making both hydrophobic and electrostatic contacts with the kinase core. Autophosphorylation at Ser-318 inhibits its catalytic activity. Dephosphorylated at Ser-318 in response to activated Fas and TNF-alpha receptors. No visible phenotype. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily.