Conserved Site

Claudin, conserved site (IPR017974)

Short name: Claudin_CS


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 [PMID: 9647647]. 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 (IPR005417), which are transmembrane proteins that polymerise within plasma membranes to form fibrils [PMID: 11283726].

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 [PMID: 10370242]. Immunofluorescence studies have shown that claudins are targeted to and incorporated into tight junctions [PMID: 9647647]. 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 [PMID: 9786950].

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 [PMID: 9647647, PMID: 9892664]. 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 (IPR005418).

This entry represents a conserved region located in an extracellular loop between the first and second transmembrane regions.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns