Regulated protein degradation involves conjugation of ubiquitin to proteins for degradation by the 26S proteasome. Protein ubiquitination is the end product of a multienzyme cascade that involves sequential thiol-ester bond interactions between ubiquitin and enzymes termed E1-E3. Neuronal precursor cell-expressed developmentally down-regulated 4 (Nedd4) is a multimodular ubiquitin protein ligase E3 that contains a Ca 2+-lipid binding domain (CaLB), 3 WW domains, and a C-terminal ubiquitin protein ligase hect domain. The CaLB is characteristic of C2 domain-containing proteins, such as PKC, phospholipase C, phospholipase A2, and synaptogamin. Nedd4 is expressed differentially in the fetal and adult brain and its highest expression is in lung and kidney. Although it localizes in the cytoplasm, increased intracellular Ca 2+ induces plasma membrane association of Nedd4. In addition, increases in intracellular Na+ leads to Nedd4 binding to epithelial Na+ channels via its WW domains, which results in targeting of Na+ channels for degradation. Thus, the subcellular localization and protein interactions of Nedd4 are regulated in a Ca2+- and Na+-dependent manner.
This antibody is routinely tested by western blot analysis. Other applications were tested at BD Biosciences Pharmingen during antibody development only or reported in the literature.