- Peptide (C)KERDRYAYKIHLPE, corresponding to amino acid residues 277-290 of mouse CASK (Accession O70589). Intracellular.
- Rat and mouse brain lysates. Human brain neuroblastoma (SH-SY5Y) cell line lysates (1:200-1:2000).
- Western blot analysis of rat brain (lanes 1 and 4), mouse brain (lanes 2 and 5) and human neuroblastoma (SH-SY5Y) (lanes 3 and 6) cell line lysates:1,2. Anti-CASK Antibody (#AIP-018), (1:400).
3. Anti-CASK Antibody (1:200).
4,5,6. Anti-CASK Antibody, preincubated with CASK Blocking Peptide (#BLP-IP018).
- Rat brain sections (1:200).
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 CaV 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.