ZO-1, ZO-2 and ZO-3 are tight junction (TJ)-associated proteins that belong to the MAGUK family. In addition to the presence of the characteristic MAGUK modules (PDZ, SH3 and GK), ZOs have a distinctive carboxyl terminal with splicing domains, acidic- and proline-rich regions. The modular organization of these proteins allows them to function as scaffolds, which associate to transmembrane TJ proteins, the cytoskeleton and signal transduction molecules. ZOs shuttle between the TJ and the nucleus, where they may regulate gene expression.
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