Tbio NEDD4L E3 ubiquitin-protein ligase NEDD4-like

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. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8, KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC5 (PubMed:26363003, PubMed:27445338). Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Plays a role in dendrite formation by melanocytes (PubMed:23999003). Involved in the regulation of TOR signaling (PubMed:27694961). Ubiquitinates and regulates protein levels of NTRK1 once this one is activated by NGF (PubMed:27445338). This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation. The encoded protein mediates the ubiquitination of multiple target substrates and plays a critical role in epithelial sodium transport by regulating the cell surface expression of the epithelial sodium channel, ENaC. Single nucleotide polymorphisms in this gene may be associated with essential hypertension. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

Uniprot Accession IDs

• Q96PU5
• O43165
• Q3LSM7
• Q7Z5F1
• Q7Z5F2
• Q7Z5N3
• Q8N5A7
• Q8WUU9
• Q9BW58
• Q9H2W4
• Q9NT88

Gene Name

• NEDD4L

Ensembl ID

• ENST00000256830
• ENSP00000256830
• ENSG00000049759
• ENST00000356462
• ENSP00000348847
• ENST00000357895
• ENSP00000350569
• ENST00000382850
• ENSP00000372301
• ENST00000400345
• ENSP00000383199
• ENST00000431212
• ENSP00000389406
• ENST00000435432
• ENSP00000393395
• ENST00000456173
• ENSP00000405440
• ENST00000456986
• ENSP00000411947
• ENST00000586263
• ENSP00000468546

Symbol

• KIAA0439
• NEDL3
• RSP5
• PVNH7
• NEDD4-2
• NEDD4.2
• hNEDD4-2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
transcription factor perturbation	0.98
transcription factor binding site profile	0.92
virus perturbation	0.92
transcription factor	0.91

Protein Classes

PANTHER Classes

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

DTO Classes

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

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: 514.39   (req: < 5)

Gene RIFs: 143   (req: <= 3)

Antibodies: 216   (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: 514.39   (req: >= 5)

Gene RIFs: 143   (req: > 3)

Antibodies: 216   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 39

Tchem

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

Active Ligand: 0

Tclin

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

Active Drug: 0