NEDD4

This gene is the founding member of the NEDD4 family of HECT ubiquitin ligases that function in the ubiquitin proteasome system of protein degradation. The encoded protein contains an N-terminal calcium and phospholipid binding C2 domain followed by multiple tryptophan-rich WW domains and, a C-terminal HECT ubiquitin ligase catalytic domain. It plays critical role in the regulation of a number of membrane receptors, endocytic machinery components and the tumor suppressor PTEN.

NEDD4

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 (PubMed:23644597).

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. Promotes ubiquitination of RAPGEF2. 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. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046).

(Microbial infection) Involved in the ubiquitination of Ebola virus protein VP40 which plays a role in viral budding.

Cellular response to UV Source: BHF-UCL
Formation of structure involved in a symbiotic process Source: UniProtKB
Glucocorticoid receptor signaling pathway Source: BHF-UCL
Lysosomal transport Source: UniProtKB
Negative regulation of sodium ion transmembrane transporter activity Source: BHF-UCL
Negative regulation of sodium ion transport Source: UniProtKB
Negative regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage Source: BHF-UCL
Negative regulation of vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
Neuromuscular junction development Source: GO_Central
Neuron projection development Source: BHF-UCL
Positive regulation of nucleocytoplasmic transport Source: BHF-UCL
Positive regulation of phosphatidylinositol 3-kinase signaling Source: BHF-UCL
Positive regulation of protein catabolic process Source: MGI
Progesterone receptor signaling pathway Source: BHF-UCL
Proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
Protein K63-linked ubiquitination Source: UniProtKB
Protein polyubiquitination Source: GO_Central
Protein targeting to lysosome Source: ARUK-UCL
Protein ubiquitination Source: UniProtKB
Receptor catabolic process Source: UniProtKB
Receptor internalization Source: UniProtKB
Regulation of dendrite morphogenesis Source: UniProtKB
Regulation of ion transmembrane transport Source: BHF-UCL
Regulation of macroautophagy Source: ParkinsonsUK-UCL
Regulation of membrane potential Source: BHF-UCL
Regulation of potassium ion transmembrane transporter activity Source: BHF-UCL
Regulation of synapse organization Source: GO_Central
Response to calcium ion Source: BHF-UCL
Ubiquitin-dependent protein catabolic process Source: BHF-UCL
Ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Source: BHF-UCL
Viral budding Source: BHF-UCL

Cytoplasm
Plasma membrane
Cell membrane
Note: 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 (By similarity). May be recruited to exosomes by NDFIP1.

Auto-ubiquitinated.