E3 ubiquitin-protein ligase NEDD4-like; NEDD4.2; Nedd4-2 (NEDD4L, KIAA0439, NEDL3)

Function

• E3 ubiquitin-protein ligase
  • ubiquitin conjugation, 3rd step
• inhibits TGF-beta signaling by triggering SMAD2 & TGFR1 ubiquitination & proteasome-dependent degradation
• ubiquitination & internalization of plasma membrane channels
  • ENaC, Nav1.2, Nav1.3, Nav1.5, Nav1.7, Nav1.8, Kv1.3, EAAT1, CLC5
• ubiquitination & degradation of SGK
• interacts with NDFIP2, UBE2E3, SCNN1A, SCNN1B, SCNN1G, SCN1A, CN2A, SCN3A, SCN5A, SCN8A, SCN9A, SCN10A, CLCN5,SMAD2, SMAD3, SMAD6, SMAD7, Epstein-Barr virus LMP2A, NDFIP1
• phosphorylated form interacts with 14-3-3 proteins
• phosphorylated by SGK or PKA
• phosphorylation impairs interaction with SCNN
• interaction with YWHAH inhibits dephosphorylation

Structure

• contains 1 C2 domain
• contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain
• contains 4 WW domains

Compartment

• cytoplasm
• may be recruited to exosomes by NDFIP1

Alternative splicing

named isoforms=8

Expression

• ubiquitously expressed
• highest levels in prostate, pancreas, kidney
• induction by androgens in prostate, albumin in kidney

More general terms

• E3 ubiquitin ligase
• phosphoprotein

Additional terms

• E3 ubiquitin-protein ligase NEDD4; cell proliferation-inducing gene 53 protein; neural cell expressed developmentally down-regulated protein 4; NEDD-4 (NEDD4, KIAA0093, NEDD4-1, PIG53)
• neural precursor cell expressed developmentally downregulated (NEDD) protein

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:23327
• OMIM: https://mirror.omim.org/entry/606384
• UniProt: http://www.uniprot.org/uniprot/Q96PU5.html