Nedd4 and Nedd4-2: closely related ubiquitin-protein ligases with distinct physiological functions.
The Nedd4 (neural precursor cell-expressed developmentally downregulated gene 4) family of ubiquitin ligases (E3s) is characterized by a distinct modular domain architecture, with each member consisting of a C2 domain, 2-4 WW domains, and a HECT-type ligase domain. Of the nine mammalian members of this family, Nedd4 and its close relative, Nedd4-2, represent the ancestral ligases with strong similarity to the yeast, Rsp5. In Saccharomyces cerevisiae Rsp5 has a key role in regulating the trafficking, sorting, and degradation of a large number of proteins in multiple cellular compartments. However, in mammals the Nedd4 family members, including Nedd4 and Nedd4-2, appear to have distinct functions, thereby suggesting that these E3s target specific proteins for ubiquitylation. In this article we focus on the biology and emerging functions of Nedd4 and Nedd4-2, and review recent in vivo studies on these E3s.
Yang
B
B
Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. baoli-yang@uiowa.edu
Kumar
S
S
D048948:14-3-3 Proteins / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000145:classification / Q000378:metabolism / Q000502:physiology*; D053503:Epithelial Sodium Channels / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000378:metabolism; D000075702:Nedd4 Ubiquitin Protein Ligases; D009469:Neuromuscular Junction / Q000502:physiology; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology; D015222:Sodium Channels / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000145:classification / Q000378:metabolism / Q000502:physiology*; D054875:Ubiquitination; D000099184:Serum-Glucocorticoid Regulated Kinases
D048948:14-3-3 Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D000075702:Nedd4 Ubiquitin Protein Ligases; D051059:PTEN Phosphohydrolase; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; D015222:Sodium Channels; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D000099184:Serum-Glucocorticoid Regulated Kinases; C469287:RSP5 protein, S cerevisiae