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 TGFR1 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 SGK. ,induction:By androgens in prostate , and by albumin in kidney. ,pathway:Protein modification; protein ubiquitination. ,PTM:Phosphorylated by SGK or PKA; which impairs interaction with SCNN. Interaction with YWHAH inhibits dephosphorylation. ,similarity:Contains 1 C2 domain. ,similarity:Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain. ,similarity:Contains 4 WW domains. ,subunit:Interacts with NDFIP2 and UBE2E3 (By similarity) . 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 NDFIP1 in vitro. ,tissue specificity:Ubiquitously expressed , with highest levels in prostate , pancreas and kidney. ,
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