NEDD4 (neural precursor cell expressed developmentally downregulated 4) was first identified in a screen for genes that are downregulated during development of the mouse brain (Kumar et al. 1992). Further characterization showed that mouse NEDD4 is a HECT type of ubiquitin ligase, comprising three WW domains (involved in protein-protein interactions) and a C2 calcium/phospholipid binding domain (Staub et al. 1996; Kumar et al. 1997). Discovery of the HECT domain gave the initial clues as to the function of NEDD4, as this domain was first identified in the papilloma virus oncoprotein E6-associated protein (E6-AP) and shown to be involved in the ubiquitination of p53 (Boase and Kumar 2015). The HECT family of ubiquitin ligases is found in all eukaryotic organisms, with NEDD4 the founding member of the NEDD4 family of HECT ligases, which contains nine human proteins (Scheffner...
- Li JJ, Ferry Jr RJ, Diao S, Xue B, Bahouth SW, Liao FF. Nedd4 haploinsufficient mice display moderate insulin resistance, enhanced lipolysis, and protection against high-fat diet-induced obesity. Endocrinology. 2015;156:1283–91. https://doi.org/10.1210/en.2014-1909.CrossRefPubMedPubMedCentralGoogle Scholar