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E3 ubiquitin-protein ligase NEDD4-like; NEDD4.2; Nedd4-2 (NEDD4L, KIAA0439, NEDL3)
Function:
1) E3 ubiquitin-protein ligase
- ubiquitin conjugation, 3rd step
2) inhibits TGF-beta signaling by triggering SMAD2 & TGFR1 ubiquitination & proteasome-dependent degradation
3) ubiquitination & internalization of plasma membrane channels
- ENaC, Nav1.2, Nav1.3, Nav1.5, Nav1.7, Nav1.8, Kv1.3, EAAT1, CLC5
4) ubiquitination & degradation of SGK
5) interacts with NDFIP2, UBE2E3, SCNN1A, SCNN1B, SCNN1G, SCN1A, CN2A, SCN3A, SCN5A, SCN8A, SCN9A, SCN10A, CLCN5,SMAD2, SMAD3, SMAD6, SMAD7, Epstein-Barr virus LMP2A, NDFIP1
6) phosphorylated form interacts with 14-3-3 proteins
7) phosphorylated by SGK or PKA
8) phosphorylation impairs interaction with SCNN
9) 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
Related
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
General
phosphoprotein
E3 ubiquitin ligase; ubiquitin-ligating enzyme E3; N end-recognizing protein
Properties
SIZE: entity length = 975 aa
MW = 112 kD
COMPARTMENT: cytoplasm
MOTIF: acetylation site
SITE: N-TERMINUS
EFFECTOR-BOUND: acetyl
C2 domain {7-109}
MOTIF: binding site
FOR-BINDING-OF: phospholipid
Ca+2-binding site
WW domain (W/rsp5/WWP domain) {193-226}
Thr phosphorylation site {T302}
Ser phosphorylation site {S303}
Thr phosphorylation site {T318}
Ser phosphorylation site {S342}
Thr phosphorylation site {T367}
WW domain (W/rsp5/WWP domain) {385-418}
Ser phosphorylation site {S446}
Ser phosphorylation site {S448}
Ser phosphorylation site {S449}
Ser phosphorylation site {S464}
Ser phosphorylation site {S479}
Ser phosphorylation site {S483}
Ser phosphorylation site {S487}
WW domain (W/rsp5/WWP domain) {497-530}
WW domain (W/rsp5/WWP domain) {548-581}
HECT domain {640-974}
MOTIF: cysteine residue {C942}
Database Correlations
OMIM 606384
UniProt Q96PU5
PFAM correlations
Kegg hsa:23327
References
UniProt :accession Q96PU5