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Immunohistochemistry (Paraffin) Analysis: A 1:250 dilution from a representative detected NEDD44 in rat cerebral cortex, rat cerebellum, and human colon cancer tissue sections.
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E3 ubiquitin-protein ligase NEDD4 (UniProt: P46934; also known as EC: 2.3.2.26, Cell proliferation-inducing gene 53 protein, HECT-type E3 ubiquitin transferase Nedd4, Neural precursor cell expressed developmentally down-regulated protein 4, NEDD-4) is encoded by the Nedd4 (also known as KIAA0093, Nedd4-1) gene (Gene ID: 4734) in human. NEDD4 is a peripheral membrane protein that is recruited to the plasma membrane by GRB10. Once complexed with GRB10 and IGF1R, it follows IGF1R internalization and remains associated with early endosomes. Nedd4 can accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. It is shown to specifically ubiquitinate Lysine 63 in target proteins. It also monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. NEDD4 is reported to polyubiquitinate the epithelial sodium channel and any mutations that disrupt association between Nedd4 and sodium channel can lead to Liddle s syndrome, a hyperaldosteronism-like hypertension disease. NEDD4 can interact with viral proteins that contain a late-budding motif P-P-P-Y and this interaction is believed to be essential for viral particle budding of many retroviruses, like HTLV-1 Gag, and MLV Gag. It contains four WW domains (WW 1-4; aa 610-643; 767-800; 840-873; and 892-925) and one HECT domain (aa 984-1318). The WW domains mediate its interaction with PPxY motif-containing proteins.
Biochem/physiol Actions
NEDD4 is an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. NEDD4 is involved in the budding of many viruses.
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