Claudin-12 (IPR013287)

Short name: Claudin12

Overlapping homologous superfamilies


Family relationships



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).

Orthologues of the claudin 12 subtype have been identifed in humans and zebrafish. Whilst these proteins clearly belong to the tetraspanin superfamily, they represent the most divergent claudin subtype in terms of primary structure [PMID: 11517306]. Claudin 12 mRNA has been detected in the brain, prostate, colon and uterus [PMID: 11247307].

Contributing signatures

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