NEDD4L

NEDD4L
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2LAJ, 2LB2, 2LTY, 2MPT, 2NSQ, 2ONI, 3JVZ, 3JW0, 5HPK
Identifiers
Aliases	NEDD4L, NEDD4-2, NEDD4.2, RSP5, hNEDD4-2, neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase, PVNH7, NEDD4 like E3 ubiquitin protein ligase
External IDs	OMIM: 606384; MGI: 1933754; HomoloGene: 86986; GeneCards: NEDD4L; OMA:NEDD4L - orthologs
Gene location (Human)
Chr.	Chromosome 18 (human)
End	58,401,540 bp
Gene location (Mouse)
Chr.	Chromosome 18 (mouse)
End	65,217,828 bp
RNA expression pattern
	Top expressed in
	ventricular zone; ; ganglionic eminence; ; olfactory zone of nasal mucosa; ; right lung; ; secondary oocyte; ; body of pancreas; ; upper lobe of left lung; ; rectum; ; epithelium of colon; ; human kidney;
	Top expressed in
	Rostral migratory stream; ; olfactory tubercle; ; zygote; ; mammillary body; ; nucleus accumbens; ; secondary oocyte; ; habenula; ; anterior amygdaloid area; ; lateral septal nucleus; ; left lung lobe;
	More reference expression data
	n/a
Gene ontology
Molecular function	potassium channel inhibitor activity; sodium channel regulator activity; transmembrane transporter binding; sodium channel inhibitor activity; potassium channel regulator activity; protein binding; transferase activity; ubiquitin-protein transferase activity; ubiquitin protein ligase activity;
Cellular component	cytosol; plasma membrane; intracellular anatomical structure; nucleoplasm; extracellular exosome; endosome; multivesicular body; Golgi apparatus; cytoplasm;
Biological process	negative regulation of sodium ion transmembrane transport; cell differentiation; positive regulation of caveolin-mediated endocytosis; excretion; positive regulation of protein catabolic process; viral life cycle; sodium ion transport; cellular sodium ion homeostasis; negative regulation of sodium ion transmembrane transporter activity; regulation of membrane potential; regulation of ion transmembrane transport; ventricular cardiac muscle cell action potential; response to metal ion; negative regulation of transcription by RNA polymerase II; protein monoubiquitination; water homeostasis; regulation of membrane depolarization; protein K48-linked ubiquitination; positive regulation of endocytosis; negative regulation of protein localization to cell surface; ion transmembrane transport; negative regulation of potassium ion transmembrane transporter activity; protein ubiquitination; regulation of potassium ion transmembrane transporter activity; regulation of protein catabolic process; negative regulation of potassium ion transmembrane transport; regulation of membrane repolarization; positive regulation of dendrite extension; proteasome-mediated ubiquitin-dependent protein catabolic process; protein polyubiquitination; viral process; ubiquitin-dependent protein catabolic process; regulation of protein stability; regulation of dendrite morphogenesis;
	Sources:Amigo / QuickGO
Orthologs
	23327
	83814
	ENSG00000049759
	ENSMUSG00000024589
	Q96PU5
	Q8CFI0
NM_001144964; NM_001144965; NM_001144966; NM_001144967; NM_001144968;
	NM_001144969; NM_001144970; NM_001144971; NM_001243960; NM_015277
	NM_001114386; NM_031881
NP_001138436; NP_001138437; NP_001138438; NP_001138439; NP_001138440;
	NP_001138441; NP_001138442; NP_001138443; NP_001230889; NP_056092
NP_001107858; NP_114087; NP_001390936; NP_001390937; NP_001390938;
	NP_001390942
	Wikidata
View/Edit Human	View/Edit Mouse

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. 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.

NEDD4L belongs to the NEDD4 family of E3 HECT domain ubiquitin ligases. It is the closest homologue of NEDD4, the prototypic member of the family and probably arose as a result of gene duplication. 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.

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 (Na_vs), 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.