ZO2: a scaffolding protein of the MAGUK (membrane-associated guanylate kinase) family associated with epithelial tight junctions (TJ). May mediate dynamic changes in the composition of TJs. Plays a role in tight junctions and adherens junctions. Forms homodimers, and heterodimer with ZO-1 and ZO-3. The ZOs shuttle between the TJ and the nucleus, where they may regulate gene expression. Interacts with occluding, UBN1 and scribble. Interacts with SAFB in the nucleus. 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 are involved in the epithelial-mesenchymal transitions (EMT) in tumors. Five isoforms of the human protein are produced by alternative promoters. Isoform A1 is abundant in the heart and brain. Detected in brain and skeletal muscle. It is present almost exclusively in normal tissues. Isoform C1 is expressed at high level in the kidney, pancreas, heart and placenta. Not detected in brain and skeletal muscle. Found in normal as well as in most neoplastic tissues..
Protein type: Motility/polarity/chemotaxis; Adaptor/scaffold
Chromosomal Location of Human Ortholog: 9q13-q21
Cellular Component: nucleoplasm; tight junction; adherens junction; cytoplasm; plasma membrane; cell junction; cytosol
Molecular Function: protein binding, bridging; protein C-terminus binding; protein domain specific binding; guanylate kinase activity; protein binding
Biological Process: response to organic substance; apoptosis; cell structure disassembly during apoptosis; nucleotide phosphorylation; intestinal absorption
Disease: Hypercholanemia, Familial; Cholestasis, Progressive Familial Intrahepatic, 4
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