CASK family
cask family
CASK is a unique MAGUK protein that contains an N-terminal CaM-kinase domain besides the typical MAGUK domains. The CASK CaM-kinase domain was presumed to be a catalytically inactive pseudokinase because it lacks the canonical DFG motif required for Mg2+ binding that was thought to be indispensable for kinase activity. However, it has been shown that CASK functions as an active protein kinase even without Mg2+ binding. High-resolution crystal structures revealed that the CASK CaM-kinase domain adopts a constitutively active conformation that binds ATP and catalyzes phosphotransfer without Mg2+. The CASK CaM-kinase domain phosphorylates itself and at least one physiological interactor, the synaptic protein neurexin1 (NRXN1), to which CASK is recruited via its PDZ domain.