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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. [provided by RefSeq, Jul 2016]
Protein class

Enzymes, Metabolic proteins, Transporters

Predicted location

Intracellular

Single cell type specificity

Cell type enhanced (Alveolar cells type 2, Alveolar cells type 1, Respiratory ciliated cells, granulocytes, Oligodendrocyte precursor cells)

Immune cell specificity

Not detected in immune cells

Cell line specificity

Low cell line specificity

Interaction

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, PMEPAI and PRRG2 (By similarity). Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase and may induce its recruitment to exosomes (By similarity). Interaction with PTEN is questionable according to PubMed:18562292. Interacts (via C2 domain) with GRB10 (via SH2 domain). Interacts with ERBB4 (By similarity). 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). Interacts with OTUD7B. Interacts with ISG15. Interacts (via WW domain) with RAPGEF2; this interaction leads to ubiquitination and degradation via the proteasome pathway. Interacts (via WW domains) with ARRDC3 (via PPXY motifs) (PubMed:20559325, PubMed:24379409). Interacts with LAPTM4B; may play a role in the lysosomal sorting of LAPTM4B (PubMed:22096579). Interacts (via WW domains) with ARRDC1, ARRDC2 and ARRDC3 (PubMed:21191027). Interacts with ZBTB7B (By similarity). Interacts with PRRG4 (via cytoplasmic domain) (PubMed:23873930). Interacts directly with LDLRAD3; this interaction promotes NEDD4 auto-ubiquitination. Interacts with ADRB2 (PubMed:23166351). (Microbial infection) Interacts with viral proteins that contain a late-budding motif P-P-P-Y. This interaction is essential for viral particle budding of many retroviruses, like HTLV-1 Gag and MLV Gag. Interacts with Herpes simplex virus 2 (HHV-2) protein UL56; this interaction induces NEDD4 degradation (PubMed:18353951). Interacts with Ebola virus protein VP40 (PubMed:12559917).

Molecular function

Transferase

More Types Infomation

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