Protein Domain : Claudin, conserved site IPR017974

Type	Conserved_site
Description	Zona occludens (ZO), or tight junctions (TJ), are specialised membrane domains found at the most apical region of polarised epithelial and endothelial cells. They create a primary barrier, preventing paracellular transport of solutes, and restricting the lateral diffusion of membrane lipids and proteins, thus maintaining cellular polarity [ ]. They also act as diffusion barriers within plasma membranes, creating and maintaining apical and basolateral membrane domains. Under freeze-fracture electron microscopy, TJs appear as a network of continuous anastomosing intramembranous strands. These strands consist mainly of claudins and occludin (), which are transmembrane proteins that polymerise within plasma membranes to form fibrils [].Recently, the molecular architecture of tight junctions has begun to be elucidated. One group of proteins thought to be major components of TJs is the claudin family []. Immunofluorescence studies have shown that claudins are targeted to and incorporated into tight junctions []. Furthermore, when claudins are introduced into cells that lack tight junctions, networks of strands and grooves form at cell-cell contact sites that closely resemble native TJs [].The claudin protein family is encoded by at least 17 human genes, with many homologues cloned from other species. Tissue distribution patterns for the claudin family members are distinct. Claudin-1 and -2, for example, are expressed at high levels in the liver and kidney, whereas claudin-3 mRNA is detected mainly in the lung and liver [ , ]. This suggests that multiple claudin family members may be involved in tight junction strand formation in a tissue-dependent manner. Hydropathy analysis suggests that all claudins share a common transmembrane (TM) topology. Each family member is predicted to possess four TM domains with intracellular N and C termini. Although their C-terminal cytoplasmic domain sequences vary, most claudin family members share a common motif of -Y-V in this region. This has been postulated as a possible binding motif for PDZ domains of other tight junction-associated membrane proteins, such as ZO-1 ( ). This entry represents a conserved region located in an extracellular loop between the first and second transmembrane regions.
Short Name	Claudin_CS