NEDD4 Recombinant Rabbit Monoclonal Antibody [JE35-58]

Function

In vitro, NEDD4 has been shown to bind and ubiquitinate a number of ion channels and membrane transporters resulting in their subsequent endocytosis and degradation by the proteasome, including the epithelial sodium channel (ENaC), voltage-gated calcium and voltage-gated sodium channels. NEDD4 mediates ubiquitination and subsequent down-regulation of components of the epidermal growth factor (EGF) signalling pathway, such as HER3 and HER4 EGF receptors, and ACK. The fibroblast growth factor receptor 1 (FGFR1) undergoes NEDD4 mediated ubiquitination and down-regulation, and contains a novel site (VL***PSR) that binds the C2 and WW3 domain of NEDD4. There is a role for NEDD4 in viral budding via ubiquitination of viral matrix proteins for a number of viruses, and NEDD4 also interacts with components of the endocytic machinery required for budding. NEDD4 can also function independently of its ubiquitin ligase activity. NEDD4 interacts with VEGFR2, leading to the degradation of VEGFR2 irrespective of whether the HECT domain is catalytically active. NEDD4 can bind and ubiquitinate the epithelial sodium channel (ENaC), leading to down-regulation of sodium channel activity. However, in vivo studies have implicated the NEDD4 family member NEDD4-2 as the main ligase responsible for ENaC regulation.

Background References

1. Yang Y et al. Nedd4 ubiquitylates VDAC2/3 to suppress erastin-induced ferroptosis in melanoma. Nat Commun. 2020 Jan

2. Wang ZW et al. NEDD4 E3 ligase: Functions and mechanism in human cancer. Semin Cancer Biol. 2020 Dec

Subcellular Location

Cytoplasm, Cell membrane.

UNIPROT

SwissProt: P46934 Human

SwissProt: P46935 Mouse

SwissProt: Q62940 Rat

Synonyms