Tight junction protein ZO-1 (IPR005418)

Short name: ZO-1

Overlapping homologous superfamilies


Family relationships


The zona occuldens proteins (ZO-1, ZO-2 and ZO-3) are a family of tight junction associated proteins that function as cross-linkers, anchoring the TJ strand proteins to the actin-based cytoskeleton [PMID: 9214391]. Each protein contains three PDZ (postsynaptic density, disc-large, ZO-1) domains, a single SH3 (Src Homology-3) domain and a catalytically inactive GK (guanylate kinase) domain, the presence of which identifies them as members of the membrane-associated guanylate kinase (MAGUK) protein family. The signature PDZ-SH3-GuK tandem of MAGUKs may form a structural supramodule with three domains interacting with each other to assemble into an integral structural unit [PMID: 21965684, PMID: 22030391].

They also share an acidic domain at the C-terminal region of the molecules not found in other MAGUK proteins. It has been demonstrated that the first PDZ domain is involved in binding the C-terminal -Y-V motif of claudins [PMID: 10601346]. By contrast, the occludin-binding domain of ZO-1 has been shown to lie in the GK and acidic domains [PMID: 9792688]. Although the precise location of the actin-binding motif has not been elucidated, it appears to be within the C-terminal half of the molecules, since transfection of this region into fibroblasts induces co-localisation of ZO-1 and ZO-2 with actin fibres.

This entry represents ZO-1, which was first identified as a 220kDa antigen for a monoclonal antibody raised to junction-enriched cell fractions [PMID: 3528172]. The protein shares ~65% overall similarity with ZO-2 and ZO-3 proteins, with highest levels of similarity in the MAGUK and acid domains. The structure of ZO-1 is distinct from the other ZO protein family members in that it contains a ZU5 domain at the C-terminal end of the molecule, although the function of this domain is unknown. Binding and tranfection studies indicate that ZO-1 is capable of associating with ZO-2 and ZO-3 through binding of the second PDZ domains [PMID: 9531559].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

No terms assigned in this category.

Cellular Component

GO:0005923 bicellular tight junction

Contributing signatures

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