NEDD4L
NEDD4L (NEDD4-like E3 ubiquitin-protein ligase, also known as NEDD4-2, KIAA0439 and RSP5) is a HECT domain E3 ubiquitin ligase of the Nedd4 family. It polyubiquitinates substrate proteins to regulate signalling, membrane channel levels and epithelial sodium transport. Browse Assay Genie's current range of NEDD4L research reagents below, or read on for the biology behind the target.
NEDD4L is an E3 ubiquitin-protein ligase that mediates polyubiquitination of lysine and cysteine residues on target proteins. As a HECT domain ligase, it transfers ubiquitin from E2 ubiquitin-conjugating enzymes to substrates, targeting specific proteins for degradation. Through this activity it is implicated in the regulation of signalling pathways including autophagy, innate immunity and DNA repair, and in TOR signalling.
Its best-characterised role is in epithelial sodium transport, where it regulates cell surface expression of the epithelial sodium channel, ENaC. It also promotes ubiquitination and internalisation of other plasma membrane channels and transporters, including several voltage-gated sodium channels (SCN2A, SCN3A, SCN5A, SCN9A, SCN10A), KCNA3, KCNH2, EAAT1, KCNQ2, KCNQ3 and CLC5. NEDD4L promotes ubiquitination and degradation of SGK1 and TNK2, and ubiquitinates BRAT1, TTYH2 and TTYH3. Ubiquitination of BRAT1 is enhanced in the presence of NDFIP1.
NEDD4L also acts on growth and immune pathways. It inhibits TGF-beta signalling by triggering ubiquitination and proteasome-dependent degradation of SMAD2 and TGFBR1, and down-regulates autophagy and cell growth by reducing cellular ULK1 or ASCT2 levels. It ubiquitinates and regulates NTRK1 once activated by NGF, and contributes to dendrite formation by melanocytes. In antiviral innate immunity it catalyses 'Lys-29'-linked cysteine ubiquitination of TRAF3, enhancing its 'Lys-48' and 'Lys-63'-linked ubiquitination.
The NEDD4L gene belongs to the C2 domain containing group and the Nedd4 family of E3 ubiquitin protein ligases. The protein localises to the cytoplasm, Golgi apparatus and multivesicular body endosomes. Alternatively spliced transcript variants encoding multiple isoforms have been observed, and single nucleotide polymorphisms in the gene may be associated with essential hypertension. Its previous name was neural precursor cell expressed, developmentally down-regulated 4-like.
NEDD4L controls surface levels of ENaC and several sodium and potassium channels by ubiquitination and internalisation, making it central to channel turnover studies.
Single nucleotide polymorphisms in the NEDD4L gene may be associated with essential hypertension, linking the ligase to epithelial sodium transport research.
NEDD4L inhibits TGF-beta signalling by driving SMAD2 and TGFBR1 degradation, and restrains autophagy and growth through ULK1 and ASCT2.
NEDD4L catalyses Lys-29-linked ubiquitination of TRAF3 in antiviral innate immunity, offering a model for studying ubiquitin chain types.
NEDD4L is a HECT domain E3 ubiquitin ligase that polyubiquitinates target proteins, marking them for degradation or internalisation. It regulates cell surface ENaC and other ion channels, inhibits TGF-beta signalling, down-regulates autophagy via ULK1, and supports antiviral innate immunity through TRAF3 ubiquitination.
NEDD4L is also called NEDD4-2, KIAA0439 and RSP5. Its UniProt name is E3 ubiquitin-protein ligase NEDD4-like, and earlier names include neural precursor cell expressed, developmentally down-regulated 4-like. Alternative splicing produces multiple isoforms, so check the datasheet of any product for its validated reactivity.
NCBI Gene reports that single nucleotide polymorphisms in the NEDD4L gene may be associated with essential hypertension, consistent with its control of ENaC. A mouse ortholog, Nedd4l, exists; check the datasheet of any product for its validated reactivity.
Other NEDD-named proteins and Nedd4 family members that sit alongside NEDD4L in ubiquitin and signalling research.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q96PU5; product specifications from Assay Genie datasheets.