a scaffolding protein of the MAGUK (membrane-associated guanylate kinase) family associated with tight junctions (TJ). May mediate dynamic changes in the composition of TJs. The N-terminal may be involved in transducing a signal required for tight junction assembly, while the C-terminal may have specific properties of tight junctions. The alpha domain might be involved in stabilizing junctions. Plays a role in the regulation of cell migration by targeting the protein kinase MRCKb to the leading edge of migrating cells. Interacts with BVES (via the C-terminus cytoplasmic tail). Interacts with HSPA4 and KIRREL1. Forms homodimers and heterodimers with ZO-2 or ZO-3. Interacts with occludin, CALM, claudins, CGN, CXADR, GJA12, GJD3 and UBN1. Interacts (via ZU5 domain) with MRCKb and MYZAP. Interacts (via PDZ domain) with Cx43. ZO-2 and ZO-3 shuttle between the TJ and the nucleus, where they may regulate gene expression. TJ, or zonula occludens, are the closely associated areas of two cells whose membranes are tightly joined together. They are composed of a branching network of strands, the efficiency of which increases exponentially with the number of strands. The strands associate with transmembrane proteins that bind to similar proteins on adjacent cells, and with submembranous proteins that are anchored to the actin component of the cytoskeleton. Thus, TJs join together the cytoskeletons of adjacent cells. They endow tissues with substantial form, shape and location, enforce cellular polarity, and form barriers to molecules and pathogens. Molecules forming the membranous part of TJs include occludin, claudins, tricellulin and junctional adhesion molecules. These molecules interact with the proteins ZO-1, ZO-2 and ZO-3. Tight junction proteins can be up- or downregulated in cancer and are involved in the epithelial-mesenchymal transitions (EMT) in tumors. Alternative splicing produces two isoforms. The long isoform is found in most epithelial cell junctions. The short isoform is found both in endothelial cells and the highly specialized epithelial junctions of renal glomeruli and Sertoli cells of the seminiferous tubules. Note: This description may include information from UniProtKB.
Protein type: Adaptor/scaffold; Motility/polarity/chemotaxis