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NEDD4 iso4
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. Involved in the pathway leading to the degradation of VEGFR- 2/KDFR, independently of its ubiquitin-ligase activity. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. According to PubMed:18562292 the direct link between NEDD4 and PTEN regulation through polyubiquitination described in PubMed:17218260 is questionable. Involved in ubiquitination of ERBB4 intracellular domain E4ICD. Involved in the budding of many viruses. 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. Interacts with UBE2D2. Binds SCNN1A, SCNN1B and SCNN1G. Binds, in vitro, through the WW2 and WW3 domains, to neural isoforms of ENAH that contain the PPSY motif. Interacts with BEAN1, LITAF, RNF11, WBP1, WBP2, TMEPAI and PRRG2. Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase and may induce its recruitment to exosomes. Interaction with PTEN is questionable according to PubMed:18562292. Interacts with viral proteins that contain a late- budding motif P-P-P-Y. This interaction is essential for viral particle budding of a lot of retroviruses, like HTLV-1 Gag and MLV Gag. Interacts (via C2 domain) with GRB10 (via SH2 domain). Interacts with ERBB4. Interacts with TNIK; the interaction is direct, allows the TNIK-dependent recruitment of RAP2A and its ubiquitination by NEDD4. Interacts (via WW3 domain) with TNK2; EGF promotes this interaction. Interacts (via WW3 domain) with FGFR1 (via C-terminus). Activated by NDFIP1- and NDFIP2-binding. 4 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
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| Protein type: EC 6.3.2.19; Nuclear receptor co-regulator; Ubiquitin ligase; Ubiquitin conjugating system; EC 6.3.2.-; Ligase |
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Cellular Component: Golgi apparatus; apicolateral plasma membrane; perinuclear region of cytoplasm; cytoplasm; plasma membrane; cell cortex; nucleus; chromatin; cytosol; ubiquitin ligase complex
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Molecular Function: sodium channel inhibitor activity; protein domain specific binding; protein binding; ubiquitin binding; phosphothreonine binding; beta-2 adrenergic receptor binding; ubiquitin-protein ligase activity; phosphoserine binding
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Biological Process: protein targeting to lysosome; lysosomal transport; progesterone receptor signaling pathway; negative regulation of vascular endothelial growth factor receptor signaling pathway; ubiquitin-dependent protein catabolic process via the multivesicular body pathway; transmission of virus; cytokine and chemokine mediated signaling pathway; regulation of dendrite morphogenesis; protein ubiquitination during ubiquitin-dependent protein catabolic process; positive regulation of nucleocytoplasmic transport; positive regulation of phosphoinositide 3-kinase cascade; regulation of membrane potential; glucocorticoid receptor signaling pathway; receptor catabolic process; virus-host interaction; receptor internalization; positive regulation of protein catabolic process; response to calcium ion; neurite development
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Reference #:
P46934-4 (UniProtKB)
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| Alt. Names/Synonyms: Cell proliferation-inducing gene 53 protein; E3 ubiquitin-protein ligase NEDD4; KIAA0093; MGC176705; NEDD-4; NEDD4; NEDD4-1; Neural precursor cell expressed developmentally down-regulated protein 4; neural precursor cell expressed, developmentally down-regulated 4; receptor-potentiating factor 1; RPF1 |
| Gene Symbols: NEDD4 |
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Molecular weight: 104,217 Da
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Basal Isoelectric point: 5.67
Predict pI for various phosphorylation states
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CST Pathways:
Notch Signaling
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Protein-Specific Antibodies or siRNAs from Cell Signaling Technology®
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