WWP2

NEDD4-like E3 ubiquitin-protein ligase WWP2 also known as atrophin-1-interacting protein 2 (AIP2) or WW domain-containing protein 2 (WWP2) is an is_associated_with::enzyme that in humans is encoded by the WWP2 is_associated_with::gene.

Function
This gene encodes a member of the NEDD4-like protein family. The family of proteins is known to possess ubiquitin-protein ligase activity. The encoded protein contains 4 tandem is_associated_with::WW domains. The WW domain is a protein motif consisting of 35 to 40 amino acids and is characterized by 4 conserved aromatic residues. The WW domain may mediate specific protein–protein interactions. Three alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Interactions
WWP2 has been shown to interact with is_associated_with::SCNN1B and is_associated_with::ATN1.

Clinical significance
Full-length WWP2 (WWP2-FL), together with N-terminal, (WWP2-N); C-terminal (WWP2-C) isoforms bind to SMAD proteins. WWP2-FL interacts with SMAD2, SMAD3 and SMAD7 in the TGF-β pathway. The WWP2-N isoform interacts with SMAD2 and SMAD3, whereas WWP2-C interacts only with SMAD7. Disruption of interactions between WWP2 and SMAD7 can stabilize SMAD7 protein levels and prevent TGF-β induced is_associated_with::Epithelial-mesenchymal transition. Hence inhibiting WWP2 may in turn lead to the disabling of an inhibitor that normally controls cell growth and is_associated_with::tumorogenesis. In tissue cultures lacking the inhibitor is_associated_with::SMAD7, cancer cells spread rapidly, so that silencing WWP2 prevented the spread.