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. Author manuscript; available in PMC: 2012 Feb 27.
Published in final edited form as: Sci Signal. 2010 Apr 27;3(119):ra33. doi: 10.1126/scisignal.2000800

Figure 6. Evolution of CASK.

Figure 6

A. Evolutionary changes in the nucleotide-binding pocket of CASK CaM-kinase domain. CASK CaM-kinase domain sequences from various animal species were aligned, and the residues corresponding to those mutated in CASK4M were identified and are shown. Corresponding human CaMKIIα residues are shown on the left for comparison.

B. Sequence conservation (identities) of CASK domains between human and placozoan CASK (from T. adhaerens). See Supplemental Figure S7 for a full sequence alignment.

C. Model comparing CASK and CaMKII catalytic cycles. Typically, CaM-kinases are held in an autoinhibited conformation by the autoregulatory domain (yellow) with an open, inactive nucleotide binding cleft. Upon binding of Ca2+ (purple)/CaM (green), this autoinhibition is released and the enzyme attains an active closed conformation amenable to Mg2+ (yellow)/ATP (blue) binding and substrate binding (lower panel). CASK CaM-kinase, on other hand, constitutively binds ATP, and is regulated by the recruitment of its substrates via the MAGUK scaffolding domains, especially the PDZ-domain.