E3 ubiquitin-protein ligase NEDD4 (NEDD4)

E3 ubiquitin-protein ligase NEDD4 is an enzyme encoded by the human *NEDD4* gene. It is a founding member of the HECT domain-containing family of E3 ubiquitin ligases. The primary function is to catalyze the transfer of ubiquitin from an E2 conjugating enzyme to specific substrate proteins—most notably various ion channels and membrane receptors—marking them for endocytosis and proteasomal degradation. Through these actions, it regulates key cellular processes including signal transduction pathways (such as insulin-like growth factor signaling), neuronal architecture during brain development, receptor downregulation (including EGFR family members), bone formation/remodeling, viral budding mechanisms for several viruses via matrix protein modification, among others. Dysregulation has been implicated in cancer progression—where it can promote tumorigenesis by degrading tumor suppressor substrates—as well as developmental disorders affecting neural tissues and mineralized tissues like bone and teeth.

Other names

Neural precursor cell expressed developmentally down-regulated protein 4NEDD4 ubiquitin-protein ligaseNedd4 (gene/protein symbol)

Drugs or molecules targeting NEDD4 typically act by inhibiting its E3 ligase activity, thereby preventing the ubiquitination and subsequent degradation or endocytosis of its substrate proteins. This can modulate pathways involved in cell proliferation, survival, or receptor signaling.