ID:NED4L_HUMAN DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase NEDD4-like; EC=6.3.2.-; AltName: Full=NEDD4.2; AltName: Full=Nedd4-2; 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. 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, Nav1.2, Nav1.3, Nav1.5, Nav1.7, Nav1.8, Kv1.3, EAAT1 or CLC5. Promotes ubiquitination and degradation of SGK1 and TNK2. ENZYME REGULATION: Activated by NDFIP1- and NDFIP2-binding. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Interacts with UBE2E3 (By similarity). Interacts with NDFIP1 and NDFIP2 (By similarity); this interaction activates the E3 ubiquitin-protein ligase. Interacts via its WW domains with SCNN1A, SCNN1B, SCNN1G, SCN1A, SCN2A, SCN3A, SCN5A, SCN8A, SCN9A, SCN10A and CLCN5. Interacts with SMAD2, SMAD3, SMAD6 and SMAD7. The phosphorylated form interacts with 14-3-3 proteins. Interacts with Epstein-Barr virus LMP2A. Interacts with TNK2. Interacts with WNK1. Interacts with SGK1. Interacts (via C2 domain) with NPC2. SUBCELLULAR LOCATION: Cytoplasm. Note=May be recruited to exosomes by NDFIP1. TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in prostate, pancreas and kidney. INDUCTION: By androgens in prostate, and by albumin in kidney. PTM: Phosphorylated by SGK1 or PKA; which impairs interaction with SCNN. Interaction with YWHAH inhibits dephosphorylation. PTM: Auto-ubiquitinated. SIMILARITY: Contains 1 C2 domain. SIMILARITY: Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain. SIMILARITY: Contains 4 WW domains. SEQUENCE CAUTION: Sequence=BAA23711.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=BAA23711.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact;
ModBase Predicted Comparative 3D Structure on Q96PU5
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Other Names for This Gene
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