Protein: E3 ubiquitin-protein ligase NEDD4 (EC 2.3.2.26) (HECT-type E3 ubiquitin transferase NEDD4) (Neural precursor cell expressed developmentally down-regulated protein 4) (NEDD-4) (P46935)
Organism: Mus musculus (Mouse)
Function: 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. Specifically ubiquitinates 'Lys-63' in target proteins (By similarity). 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. 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. Promotes ubiquitination of RAPGEF2. 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). Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (By similarity). Ubiquitinates DAZAP2, leading to its proteasomal degradation (By similarity). Ubiquitinates POLR2A (By similarity).
Subcellular location: Cytoplasm {ECO:0000269|PubMed:9182527}. Nucleus {ECO:0000250|UniProtKB:P46934}. Cell membrane {ECO:0000269|PubMed:18286479}; Peripheral membrane protein {ECO:0000269|PubMed:18286479}. Note=Predominantly cytoplasmic but also located in the nucleus (By similarity). Recruited to the plasma membrane by GRB10. Once complexed with GRB10 and IGF1R, follows IGF1R internalization, remaining associated with early endosomes. Uncouples from IGF1R-containing endosomes before the sorting of the receptor to the lysosomal compartment (PubMed:18286479). May be recruited to exosomes by NDFIP1 (By similarity). {ECO:0000250|UniProtKB:P46934, ECO:0000269|PubMed:18286479}.
Interaction partners:
- Epithelial sodium channel subunit beta
- NEDD4 family-interacting protein 1
- Growth factor receptor-bound protein 10
- NEDD4 family-interacting protein 2
- Epithelial sodium channel subunit alpha
- Arrestin domain-containing protein 3
- Disks large homolog 3
- Protein TMEPAI
- Ubiquitin-like protein ISG15
- E3 ubiquitin-protein ligase NEDD4-like
Sequence:
MSSDMAADESEAPVLSEDEVWEFCLDKTEDGGGSPGSDVTDTCEPPCGCWELNPNSLEEEHVLFTADPYLELHNDDTRVVRVKVIAGIGLAKKDILGASDPYVRVTLYDPMSGILTSVQTKTIKKSLNPKWNEEILFRVLPQRHRILFEVFDENRLTRDDFLGQVDVPLYPLPTENPRMERPYTFKDFVLHPRSHKSRVKGYLRLKMTYLPKNGSEDENADQAEELEPGWVVLDQPDAATHLPHPPEPSPLPPGWEERQDVLGRTYYVNHESRRTQWKRPSPDDDLTDEDNDDMQLQAQRAFTTRRQISEDVDGPDNRESPENWEIVREDENTEYSGQAVQSPPSGHIDVQTHLAEEFNTRLAVCGNPATSQPVTSSNHSSRGGSLQTCIFEEQPTLPVLLPTSSGLPPGWEEKQDDRGRSYYVDHNSKTTTWSKPTMQDDPRSKIPAHLRGKTDSNDLGPLPPGWEERTHTDGRVFFINHNIKKTQWEDPRLQNVAITGPAVPYSRDYKRKYEFFRRKLKKQTDIPNKFEMKLRRANILEDSYRRIMGVKRADLLKARLWIEFDGEKGLDYGGVAREWFFLISKEMFNPYYGLFEYSATDNYTLQINPNSGLCNEDHLSYFKFIGRVAGMAVYHGKLLDGFFIRPFYKMMLQKLITLHDMESVDSEYYSSLRWILENDPTELDLRFIIDEELFGQTHQHELKTGGSEIVVTNKNKKEYIYLVIQWRFVNRIQKQMAAFKEGFFELIPQDLIKIFDENELELLMCGLGDVDVNDWREHTKYKNGYSMNHQVIHWFWKAVWMMDSEKRIRLLQFVTGTSRVPMNGFAELYGSNGPQSFTVEQWGTPDKLPRAHTCFNRLDLPPYESFDELWDKLQMAIENTQGFDGVD