Anti-NEDD4-2/NEDD4L Antibody Picoband® Fluoro647 Conjugated

Neural precursor cell expressed developmentally downregulated gene 4-like (NEDD4L) or NEDD4-2 (NEDD4-2) is an enzyme (ubiquitin ligase) of the NEDD4 family. This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation. The encoded protein mediates the ubiquitination of multiple target substrates and plays a critical role in epithelial sodium transport by regulating the cell surface expression of the epithelial sodium channel, ENaC. Single nucleotide polymorphisms in this gene may be associated with essential hypertension. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Ubiquitously expressed, with highest levels in prostate, pancreas and kidney (PubMed:14615060, PubMed:15496141, PubMed:19664597) . Expressed in melanocytes (PubMed:23999003) .

E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then ly 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, KCNH2, EAAT1 or CLC5 (PubMed:26363003) . Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046) . Plays a role in dendrite formation by melanocytes (PubMed:23999003) . Involved in the regulation of TOR signaling (PubMed:27694961) .

1. Broix, L., Jagline, H., Ivanova, E. L., Schmucker, S., Drouot, N., Clayton-Smith, J., Pagnamenta, A. T., Metcalfe, K. A., Isidor, B., Louvier, U. W., Poduri, A., Taylor, J. C., and 28 others.Mutations in the HECT domain of NEDD4L lead to AKT-mTOR pathway deregulation and cause periventricular nodular heterotopia. Nature Genet. 48: 1349-1358, 2016. 2. Dunn, D. M., Ishigami, T., Pankow, J., von Niederhausern, A., Alder, J., Hunt, S. C., Leppert, M. F., Lalouel, J.-M., Weiss, R. B. Common variant of human NEDD4L activates a cryptic splice site to form a frameshifted transcript. J. Hum. Genet. 47: 665-676, 2002.