1wr4

Structural highlights

Function

[NED4L_MOUSE] 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.^{[1] [2] [3] [4] [5]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Ubiquitin protein ligase

References

1. ↑ Kamynina E, Debonneville C, Bens M, Vandewalle A, Staub O. A novel mouse Nedd4 protein suppresses the activity of the epithelial Na+ channel. FASEB J. 2001 Jan;15(1):204-214. PMID:11149908 doi:http://dx.doi.org/10.1096/fj.00-0191com
2. ↑ Fotia AB, Dinudom A, Shearwin KE, Koch JP, Korbmacher C, Cook DI, Kumar S. The role of individual Nedd4-2 (KIAA0439) WW domains in binding and regulating epithelial sodium channels. FASEB J. 2003 Jan;17(1):70-2. Epub 2002 Nov 1. PMID:12424229 doi:http://dx.doi.org/10.1096/fj.02-0497fje
3. ↑ Debonneville C, Flores SY, Kamynina E, Plant PJ, Tauxe C, Thomas MA, Munster C, Chraibi A, Pratt JH, Horisberger JD, Pearce D, Loffing J, Staub O. Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression. EMBO J. 2001 Dec 17;20(24):7052-9. PMID:11742982 doi:http://dx.doi.org/10.1093/emboj/20.24.7052
4. ↑ Harvey KF, Dinudom A, Cook DI, Kumar S. The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial sodium channel. J Biol Chem. 2001 Mar 16;276(11):8597-601. Epub 2001 Jan 17. PMID:11244092 doi:http://dx.doi.org/10.1074/jbc.C000906200
5. ↑ Fotia AB, Ekberg J, Adams DJ, Cook DI, Poronnik P, Kumar S. Regulation of neuronal voltage-gated sodium channels by the ubiquitin-protein ligases Nedd4 and Nedd4-2. J Biol Chem. 2004 Jul 9;279(28):28930-5. Epub 2004 Apr 27. PMID:15123669 doi:http://dx.doi.org/10.1074/jbc.M402820200