NEDD4L
Protein-coding gene in the species Homo sapiens / From Wikipedia, the free encyclopedia
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Neural precursor cell expressed developmentally downregulated gene 4-like (NEDD4L) or NEDD4-2 is an enzyme (ubiquitin ligase) of the NEDD4 family. In human the protein is encoded by the NEDD4L gene.[5][6][7][8] In mouse the protein is commonly known as NEDD4-2 and the gene Nedd4-2.
NEDD4-2 has been shown to ubiquitinate and therefore down regulate the epithelial sodium channel (ENaC) in the collecting ducts of the kidneys, therefore opposing the actions of aldosterone and increasing salt excretion. In Liddle's Syndrome NEDD4 is unable to bind to the ENaC and lead to salt retention and hypertension occur.[9]
NEDD4L belongs to the NEDD4 family of E3 HECT domain ubiquitin ligases.[10][11][12][13] It is the closest homologue of NEDD4, the prototypic member of the family and probably arose as a result of gene duplication.[12] While NEDD4 orthologues are present in all eukaryotes, NEDD4L proteins are limited to vertebrates. NEDD4L proteins are known to be involved in regulating many membrane proteins via ubiquitination and endocytosis.[10]
NEDD4L protein is expressed widely. The primary targets of NEDD4-2 include the epithelial sodium channel (ENaC), the Na+-Cl- co-transporter (NCC), and the voltage gated sodium channels (Navs), although additional targets are predicted from in vitro studies. NEDD4-2 gene in mice is essential for animal survival and the polymorphisms in NEDD4L are associated with human hypertension.[11][13]