Description
Product Characteristics: NEDD4 (neural precursor expressed, developmentally down-regulated protein 4, aliases: KIAA0093, MGC176705, NEDD4-1) is a gene that is highly expressed in early embryonic central nervous system. A family of NEDD4-like proteins has more recently been defined. NEDD4 and NEDD4-like proteins contain multiple functional domains including a calcium-dependent phospholipid and membrane binding domain (C2 domain), two to four protein binding domains (WW domains), and an E3 ubiquitin-protein ligase domain (HECT domain). NEDD4 and NEDD4-2 have been shown to down-regulate both neuronal voltage-gated Na+ channels (NaVs) and epithelial Na+ channels (ENaCs) in response to increased intracellular Na+ concentrations. The WW domains of NEDD4 bind to PY motifs (amino acid sequence PPXY) found in multiple NaV and ENaC proteins, and ubiquitination of these proteins, mediated by the HECT domain of NEDD4, results in their internalization and removal from the plasma membrane. Mutation of the PY motifs in ENaC proteins is associated with Liddle's Syndrome, an autosomal-dominant form of hypertension. In addition to targeting sodium channels, NEDD4-2 has also been shown to negatively regulate TGF-β signaling by targeting Smad2 for degradation. Mouse and human NEDD4 are cleaved by caspase proteins during apoptosis, although the significance of this cleavage is not clear.
Synonyms: E3 ubiquitin protein ligase Nedd4 antibody, KIAA0093 antibody, NEDD 4 antibody, Neural precursor cell expressed developmentally down regulated 4 antibody
Target Information: 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. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. Involved in ubiquitination of ERBB4 intracellular domain E4ICD1 (PubMed:19193720). Predominantly involved in ubiquitination of membrane bound forms of ERBB4 rather than processed precursors and intermediate membrane-anchored 80 kDa fragments (m80HER4), with a lesser role in ubiquitination of ERBB4 intracellular domain E4ICD1 (PubMed:19047365). Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. Ubiquitinates TNK2 and regulates EGF-induced degradation of EGFR and TNF2 (By similarity)