Anti-CASK Antibody

The CASK protein belongs to the membrane-associated guanylate kinase family of proteins (MAGUK). MAGUK proteins generally target neuronal synapses and regulate trafficking, targeting, and signaling of ion channels (like Ca_V channels).

CASK consists of the following modular domains- the PDZ, Src homolog 3 (SH3), and guanylate kinase (GK) domains that are the characteristic protein domains shared by all MAGUK proteins. In addition, CASK contains two L27 domains preceding the single PDZ domain and has a unique CaMK-like domain at its N-terminal region.

The PDZ domain, consisting of approximately 90 amino acid residues, is specialized for binding to short peptide motifs at the extreme C-terminal tail of its binding partners, although other modes of interaction also occur. The Src homolog 3 (SH3) domain typically interacts with a proline-rich sequence. In addition to interaction with the proline-rich motif, the CASK SH3 domain mediates interaction with the GK domain. This interaction can occur intra- or intermolecularly. CASK protein can therefore form a homodimer via the inter-molecular SH3-GK interaction. Because the CASK SH3 domain also recognizes the GK domain of other MAGUK proteins, such as p55, CASK also forms heterodimers with other MAGUK proteins via an intermolecular SH3-GK interaction. The CASK CaMK-like domain functions as a protein-protein interacting domain, which binds to several cellular proteins, such as Mint1/X11, Caskin 1, CIP98, and Carom.

CASK is mostly expressed in (but not restricted to) neurons; expression levels of CASK are 3-5-fold higher in the brain than in other organs. In addition to playing an important role in the nervous system, CASK has also been suggested as having a role in establishing epithelial cell polarity in mammals¹.