Tchem NEDD4 E3 ubiquitin-protein ligase NEDD4

Protein Summary

Description

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. 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. [provided by RefSeq, Jul 2016]

Uniprot Accession IDs

• P46934
• A1KY35
• A6ND72
• A7MD29
• B4E2R7
• B7ZM59
• B7ZM60
• B9EGN5
• D6RF89

Gene Name

• NEDD4

Ensembl ID

• ENST00000338963
• ENSP00000345530
• ENSG00000069869
• ENST00000435532
• ENSP00000410613
• ENST00000506154
• ENSP00000422705
• ENST00000508342
• ENSP00000424827

Symbol

• KIAA0093
• NEDD4-1
• RPF1
• NEDD4-1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
hub protein	1
interacting protein	0.98
molecular function	0.98
transcription factor perturbation	0.91

Protein Classes

PANTHER Classes

Protein / Ligase / Ubiquitin-protein Ligase / E3 Ubiquitin-protein Ligase Nedd4

DTO Classes

Protein / Enzyme / Ligase / Ubiquitin-protein Ligase / E3 Ubiquitin-protein Ligase Nedd4

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 403.58   (req: < 5)

Gene RIFs: 163   (req: <= 3)

Antibodies: 232   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 403.58   (req: >= 5)

Gene RIFs: 163   (req: > 3)

Antibodies: 232   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 47

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 2

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0