Cytoskeleton-Associated Protein 4: Functions Beyond the Endoplasmic Reticulum in Physiology and Disease

Figure 1

CKAP4 structural domains. CKAP4 is a 63-kDa nonglycosylated type II transmembrane protein that is phosphorylated and palmitoylated. The C-terminus is 447 amino acids long and is located in either the lumen of the ER or extracellular space, depending on the localization of the protein. It contains an alpha helical region (503–602) and a leucine zipper (468–503), which are important for oligomerization and are characteristic of the bZIP DNA-binding motif [9, 19]. Additionally, the C-terminus also contains the sites for tyrosine sulfation and Akt phosphorylation. The N-terminus is 106 amino acids long and is located in the cytoplasm. It is comprised of two major domains the microtubule binding domain and the ER anchoring domain. The microtubule-binding domain contains the site of palmitoylation (Cys¹⁰⁰) which is important for the trafficking of the protein to the plasma membrane and a proline rich sequence (36–59), whereas the ER anchoring domain has three serine residues (3, 7, and 19) which are required for phosphorylation-dependent binding to microtubules and nuclear translocation in response to APF.