NEDD4 Antibody

Background

NEDD4 (neural precursor expressed, developmentally down-regulated protein 4, aliases: KIAA0093, MGC176705, NEDD4-1) is a gene that is highly expressed in early embryonic central nervous system. A family of NEDD4-like proteins has more recently been defined. NEDD4 and NEDD4-like proteins contain multiple functional domains including a calcium-dependent phospholipid and membrane binding domain (C2 domain), two to four protein binding domains (WW domains), and an E3 ubiquitin-protein ligase domain (HECT domain). NEDD4 and NEDD4-2 have been shown to down-regulate both neuronal voltage-gated Na+ channels (NaVs) and epithelial Na+ channels (ENaCs) in response to increased intracellular Na+ concentrations. The WW domains of NEDD4 bind to PY motifs (amino acid sequence PPXY) found in multiple NaV and ENaC proteins, and ubiquitination of these proteins, mediated by the HECT domain of NEDD4, results in their internalization and removal from the plasma membrane. Mutation of the PY motifs in ENaC proteins is associated with Liddle's Syndrome, an autosomal-dominant form of hypertension. In addition to targeting sodium channels, NEDD4-2 has also been shown to negatively regulate TGF-β signaling by targeting Smad2 for degradation. Mouse and human NEDD4 are cleaved by caspase proteins during apoptosis, although the significance of this cleavage is not clear.