title: NEDD4-2 (NEDD4L): the ubiquitin ligase for multiple membrane proteins.
abstract: NEDD4-2 (also known as NEDD4L, neural precursor cell expressed developmentally down-regulated 4-like) is a ubiquitin protein ligase of the Nedd4 family which is known to bind and regulate a number of membrane proteins to aid in their internalization and turnover. Several of the NEDD4-2 substrates include ion channels, such as the epithelial and voltage-gated sodium channels. Given the critical function of NEDD4-2 in regulating membrane proteins, this ligase is essential for the maintenance of cellular homeostasis. In this article we review the biology and function of this important ubiquitin-protein ligase and discuss its pathophysiological significance.
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, SA 5001, Australia; Department of Medicine, The University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Pranay
authors.initials: P
authors.lastname: Goel
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, SA 5001, Australia.
authors.forename: Jantina A
authors.initials: JA
authors.lastname: Manning
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, SA 5001, Australia; Department of Medicine, The University of Adelaide, Adelaide, SA 5005, Australia. Electronic address: sharad.kumar@unisa.edu.au.
authors.forename: Sharad
authors.initials: S
authors.lastname: Kumar
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D051656:KCNQ Potassium Channels / Q000378:metabolism*; D051379:Mice; D000075702:Nedd4 Ubiquitin Protein Ligases; D009369:Neoplasms / Q000473:pathology; D011485:Protein Binding; D021381:Protein Transport; D037721:Pulmonary Surfactant-Associated Protein C / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D053503:Epithelial Sodium Channels; D051656:KCNQ Potassium Channels; D037721:Pulmonary Surfactant-Associated Protein C; D018125:Receptors, Transforming Growth Factor beta; D061566:Voltage-Gated Sodium Channels; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; C000618485:Nedd4L protein, human; C000618461:Nedd4l protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: Epithelial sodium channel (ENaC); Hypertension; NEDD4 family; Ubiquitin; Ubiquitin protein ligases; Voltage-gated sodium channels (Na(v)s)