2n8t

Structural highlights

Function

[NEDD4_RAT] 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. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Is involved in ubiquitination of ERBB4 intracellular domain E4ICD. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. Ubiquitinates TNK2 and regulates EGF-induced degradation of EGFR and TNF2 (By similarity).^[1] [CXA1_RAT] Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. Negative regulator of bladder functional capacity: acts by enhancing intercellular electrical and chemical transmission, thus sensitizing bladder muscles to cholinergic neural stimuli and causing them to contract (By similarity).

References

1. ↑ Kawabe H, Neeb A, Dimova K, Young SM Jr, Takeda M, Katsurabayashi S, Mitkovski M, Malakhova OA, Zhang DE, Umikawa M, Kariya K, Goebbels S, Nave KA, Rosenmund C, Jahn O, Rhee J, Brose N. Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development. Neuron. 2010 Feb 11;65(3):358-72. doi: 10.1016/j.neuron.2010.01.007. PMID:20159449 doi:10.1016/j.neuron.2010.01.007
2. ↑ Spagnol G, Kieken F, Kopanic JL, Li H, Zach S, Stauch KL, Grosely R, Sorgen PL. Structural Studies of the Nedd4 WW Domains and their Selectivity for the Cx43 Carboxyl-terminus. J Biol Chem. 2016 Feb 3. pii: jbc.M115.701417. PMID:26841867 doi:http://dx.doi.org/10.1074/jbc.M115.701417