Gene Symbol: NEDD4L
Description: neural precursor cell expressed, developmentally down-regulated 4-like, E3 ubiquitin protein ligase
Alias: NEDD4-2, NEDD4.2, PVNH7, RSP5, hNEDD4-2, E3 ubiquitin-protein ligase NEDD4-like, HECT-type E3 ubiquitin transferase NED4L, ubiquitin-protein ligase Rsp5
Species: human
Products:     NEDD4L

Top Publications

  1. Kamynina E, Tauxe C, Staub O. Distinct characteristics of two human Nedd4 proteins with respect to epithelial Na(+) channel regulation. Am J Physiol Renal Physiol. 2001;281:F469-77 pubmed
    ..Taken together, our data demonstrate that hNedd4-2 inhibits ENaC, implying that this protein is a modulator of salt homeostasis, whereas hNedd4-1 is not primarily involved in ENaC regulation...
  2. Harvey K, Dinudom A, Cook D, Kumar S. The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial sodium channel. J Biol Chem. 2001;276:8597-601 pubmed
    ..We propose that KIAA0439 and Nedd4 proteins either play a redundant role in ENaC regulation or function in a tissue- and/or signal-specific manner to down-regulate ENaC. ..
  3. Dahlberg J, Nilsson L, von Wowern F, Melander O. Polymorphism in NEDD4L is associated with increased salt sensitivity, reduced levels of P-renin and increased levels of Nt-proANP. PLoS ONE. 2007;2:e432 pubmed
    Neuronal precursor cell expressed developmentally down-regulated 4-like (NEDD4L) is a regulator of the amiloride-sensitive epithelial sodium channel (ENaC), thus a candidate gene for salt sensitivity...
  4. Gao S, Alarcon C, Sapkota G, Rahman S, Chen P, Goerner N, et al. Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-beta signaling. Mol Cell. 2009;36:457-68 pubmed publisher
    ..Here, we identify Nedd4L as the ubiquitin ligase responsible for this step...
  5. Kamadurai H, Souphron J, Scott D, Duda D, Miller D, Stringer D, et al. Insights into ubiquitin transfer cascades from a structure of a UbcH5B approximately ubiquitin-HECT(NEDD4L) complex. Mol Cell. 2009;36:1095-102 pubmed publisher
    ..To gain insights into this process, we determined the crystal structure of a complex between the HECT domain of NEDD4L and the E2 UbcH5B bearing a covalently linked Ub at its active site (UbcH5B approximately Ub)...
  6. Itani O, Campbell J, Herrero J, Snyder P, Thomas C. Alternate promoters and variable splicing lead to hNedd4-2 isoforms with a C2 domain and varying number of WW domains. Am J Physiol Renal Physiol. 2003;285:F916-29 pubmed
    ..Understanding the function of variant proteins will increase our knowledge of the role of hNedd4-2 in the regulation of ENaC and define protein domains important for Nedd4-2 function. ..
  7. Lott J, Coddington Lawson S, Teesdale Spittle P, McDonald F. A single WW domain is the predominant mediator of the interaction between the human ubiquitin-protein ligase Nedd4 and the human epithelial sodium channel. Biochem J. 2002;361:481-8 pubmed
    ..Differential binding propensities between the various WW domains and Na(+) channel subunit peptides are explained on the basis of quantitative structural modelling of the complexes and their isolated components. ..
  8. Li N, Wang H, Yang J, Zhou L, Hong J, Guo Y, et al. Genetic variation of NEDD4L is associated with essential hypertension in female Kazakh general population: a case-control study. BMC Med Genet. 2009;10:130 pubmed publisher
    ..Genetic variation is thought to contribute to the etiology of hypertension. NEDD4L is a candidate gene for hypertension, both functionally and genetically...
  9. He S, Deng J, Li G, Wang B, Cao Y, Tu Y. Down-regulation of Nedd4L is associated with the aggressive progression and worse prognosis of malignant glioma. Jpn J Clin Oncol. 2012;42:196-201 pubmed publisher
    Human neural precursor cell-expressed developmentally down-regulated 4 like (Nedd4L), a ubiquitin protein ligase, is expressed by various cancer cells and might have an oncogenic property...

More Information


  1. Hryciw D, Ekberg J, Lee A, Lensink I, Kumar S, Guggino W, et al. Nedd4-2 functionally interacts with ClC-5: involvement in constitutive albumin endocytosis in proximal tubule cells. J Biol Chem. 2004;279:54996-5007 pubmed
    ..These data demonstrate that normal constitutive uptake of albumin by the proximal tubule requires Nedd4-2, which may act via ubiquitination to shunt ClC-5 into the endocytic pathway. ..
  2. Jespersen T, Membrez M, Nicolas C, Pitard B, Staub O, Olesen S, et al. The KCNQ1 potassium channel is down-regulated by ubiquitylating enzymes of the Nedd4/Nedd4-like family. Cardiovasc Res. 2007;74:64-74 pubmed
    ..This mechanism may thereby be important in regulating the surface density of the KCNQ1 channels in cardiomyocytes and other cell types. ..
  3. Snyder P, Olson D, Thomas B. Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channel. J Biol Chem. 2002;277:5-8 pubmed
    ..These data suggest that SGK regulates epithelial Na+ absorption in part by modulating the function of hNedd4-2. ..
  4. Raikwar N, Vandewalle A, Thomas C. Nedd4-2 interacts with occludin to inhibit tight junction formation and enhance paracellular conductance in collecting duct epithelia. Am J Physiol Renal Physiol. 2010;299:F436-44 pubmed publisher
    ..In summary, we demonstrate that Nedd4-2 plays a role in tight junction assembly and the regulation of paracellular conductance in the collecting duct. ..
  5. Dussupt V, Sette P, Bello N, Javid M, Nagashima K, Bouamr F. Basic residues in the nucleocapsid domain of Gag are critical for late events of HIV-1 budding. J Virol. 2011;85:2304-15 pubmed publisher
    ..Together, these data support a model in which NC plays a critical role in HIV-1 budding. ..
  6. Wang H, Li N, Yao X, Hong J, Luo W, Chang J. [Association of the rs4149601 polymorphism of NEDD4L gene with obesity in Xinjiang Kazakh population]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2010;27:668-71 pubmed publisher
    ..of the rs4149601 polymorphisms of neural precursor cell expressed developmentally downregulated 4-like gene (NEDD4L) and obesity in Xinjiang Kazakh population...
  7. Ding Y, Zhang Y, Xu C, Tao Q, Chen Y. HECT domain-containing E3 ubiquitin ligase NEDD4L negatively regulates Wnt signaling by targeting dishevelled for proteasomal degradation. J Biol Chem. 2013;288:8289-98 pubmed publisher
    ..Dishevelled (Dvl) is a central mediator for both Wnt/β-catenin and Wnt/planar cell polarity pathways. NEDD4L, an E3 ubiquitin ligase, has been shown to regulate ion channel activity, cell signaling, and cell polarity...
  8. Russo C, Melista E, Cui J, Destefano A, Bakris G, Manolis A, et al. Association of NEDD4L ubiquitin ligase with essential hypertension. Hypertension. 2005;46:488-91 pubmed
    b>NEDD4L is a ubiquitin ligase that controls cell surface expression of kidney epithelial Na+ channels by ubiquitin-mediated endocytosis and lysosome targeting. Thus, it is a significant determinant of Na+ reabsorption in the distal nephron...
  9. Rauh R, Dinudom A, Fotia A, Paulides M, Kumar S, Korbmacher C, et al. Stimulation of the epithelial sodium channel (ENaC) by the serum- and glucocorticoid-inducible kinase (Sgk) involves the PY motifs of the channel but is independent of sodium feedback inhibition. Pflugers Arch. 2006;452:290-9 pubmed
    ..We conclude that the stimulatory effect of Sgk on ENaC requires the presence of the channel's PY motifs, but it is not due to the interruption of Na+ feedback regulation. ..
  10. Boehmer C, Henke G, Schniepp R, Palmada M, Rothstein J, Broer S, et al. Regulation of the glutamate transporter EAAT1 by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid-inducible kinase isoforms SGK1/3 and protein kinase B. J Neurochem. 2003;86:1181-8 pubmed
    ..The experiments reveal a powerful novel mechanism that regulates the activity of EAAT1. This mechanism might participate in the regulation of neuronal excitability and glutamate transport in other tissues. ..
  11. Gao C, Pang L, Ren C, Ma T. Decreased expression of Nedd4L correlates with poor prognosis in gastric cancer patient. Med Oncol. 2012;29:1733-8 pubmed publisher
    The neural precursor cell expressed, developmentally down-regulated 4-like (Nedd4L) gene encodes an ubiquitin ligase that targets the epithelial sodium channel for degradation...
  12. Snyder P. Down-regulating destruction: phosphorylation regulates the E3 ubiquitin ligase Nedd4-2. Sci Signal. 2009;2:pe41 pubmed publisher
    ..Nedd4-2 phosphorylation is emerging as a central convergence point for the regulation of epithelial Na(+) transport. ..
  13. Chung H, Morita E, von Schwedler U, Muller B, Kräusslich H, Sundquist W. NEDD4L overexpression rescues the release and infectivity of human immunodeficiency virus type 1 constructs lacking PTAP and YPXL late domains. J Virol. 2008;82:4884-97 pubmed publisher
    ..We now report that overexpression of the HECT ubiquitin E3 ligase, NEDD4L/NEDD4-2, stimulated the release of HIV-1 constructs that lacked TSG101- and ALIX-binding late domains, increasing ..
  14. Araki N, Umemura M, Miyagi Y, Yabana M, Miki Y, Tamura K, et al. Expression, transcription, and possible antagonistic interaction of the human Nedd4L gene variant: implications for essential hypertension. Hypertension. 2008;51:773-7 pubmed publisher
    ..Among various modulating proteins, E3 ubiquitin ligase, Nedd4L, binds the PY motif of ENaC COOH terminals and catalyzes ubiquitination of the NH(2) terminus of the protein for ..
  15. Al Salihi M, Herhaus L, MacArtney T, Sapkota G. USP11 augments TGFβ signalling by deubiquitylating ALK5. Open Biol. 2012;2:120063 pubmed publisher
    ..Central to TGFβ pathway signalling in early embryogenesis and carcinogenesis is TGFβ-induced epithelial to mesenchymal transition. USP11 depletion results in inhibition of TGFβ-induced epithelial to mesenchymal transition. ..
  16. Wen H, Lin R, Jiao Y, Wang F, Wang S, Lu D, et al. Two polymorphisms in NEDD4L gene and essential hypertension in Chinese Hans - a population-based case-control study. Clin Exp Hypertens. 2008;30:87-94 pubmed publisher
    Neural precursor cell expressed developmentally down-regulated 4-like (NEDD4L) gene may play an important role in the development of hypertension by regulating the amiloride-sensitive epithelial sodium channel for sodium reabsorption...
  17. Usami Y, Popov S, Popova E, Gottlinger H. Efficient and specific rescue of human immunodeficiency virus type 1 budding defects by a Nedd4-like ubiquitin ligase. J Virol. 2008;82:4898-907 pubmed publisher
    ..These data suggest a novel mechanism by which HIV-1 Gag can connect to cellular budding machinery. ..
  18. He Y, Hryciw D, Carroll M, Myers S, Whitbread A, Kumar S, et al. The ubiquitin-protein ligase Nedd4-2 differentially interacts with and regulates members of the Tweety family of chloride ion channels. J Biol Chem. 2008;283:24000-10 pubmed publisher
    ..These data, indicating that Nedd4-2 differentially interacts with and regulates TTYH1-3, will be important for understanding mechanisms controlling Tweety proteins in physiology and disease. ..
  19. Kikonyogo A, Bouamr F, Vana M, Xiang Y, Aiyar A, Carter C, et al. Proteins related to the Nedd4 family of ubiquitin protein ligases interact with the L domain of Rous sarcoma virus and are required for gag budding from cells. Proc Natl Acad Sci U S A. 2001;98:11199-204 pubmed
    ..These findings mechanistically link the cellular ubiquitination pathway to retrovirus budding. ..
  20. Persaud A, Alberts P, Amsen E, Xiong X, Wasmuth J, Saadon Z, et al. Comparison of substrate specificity of the ubiquitin ligases Nedd4 and Nedd4-2 using proteome arrays. Mol Syst Biol. 2009;5:333 pubmed publisher
    ..The nine Nedd4 family proteins in mammals include two close relatives: Nedd4 (Nedd4-1) and Nedd4L (Nedd4-2), but their global substrate recognition or differences in substrate specificity are unknown...
  21. Qi H, Grenier J, Fournier A, Labrie C. Androgens differentially regulate the expression of NEDD4L transcripts in LNCaP human prostate cancer cells. Mol Cell Endocrinol. 2003;210:51-62 pubmed
    The NEDD4L gene encodes a ubiquitin ligase that targets the epithelial sodium channel for degradation...
  22. Dunn D, Ishigami T, Pankow J, von Niederhausern A, Alder J, Hunt S, et al. Common variant of human NEDD4L activates a cryptic splice site to form a frameshifted transcript. J Hum Genet. 2002;47:665-76 pubmed
    The ubiquitin ligase NEDD4L is a candidate gene for essential hypertension on both functional and genetic grounds...
  23. Yang B, Kumar S. Nedd4 and Nedd4-2: closely related ubiquitin-protein ligases with distinct physiological functions. Cell Death Differ. 2010;17:68-77 pubmed publisher, Nedd4 and its close relative, Nedd4-2, represent the ancestral ligases with strong similarity to the yeast, Rsp5. In Saccharomyces cerevisiae Rsp5 has a key role in regulating the trafficking, sorting, and degradation of a large ..
  24. Garrone N, Blazer Yost B, Weiss R, Lalouel J, Rohrwasser A. A human polymorphism affects NEDD4L subcellular targeting by leading to two isoforms that contain or lack a C2 domain. BMC Cell Biol. 2009;10:26 pubmed publisher
    ..b>NEDD4L is a member of the HECT class of E3 ubiquitin ligases...
  25. Chan W, Tian R, Lee Y, Sit S, Lim L, Manser E. Down-regulation of active ACK1 is mediated by association with the E3 ubiquitin ligase Nedd4-2. J Biol Chem. 2009;284:8185-94 pubmed publisher
    ..These processes are particularly pertinent given the report of genomic amplification of the ACK1 locus in metastatic tumors. ..
  26. Asher C, Sinha I, Garty H. Characterization of the interactions between Nedd4-2, ENaC, and sgk-1 using surface plasmon resonance. Biochim Biophys Acta. 2003;1612:59-64 pubmed
    ..The measurements demonstrate that WW3 and WW4 are the only Nedd4-2 domains interacting with both ENaC and sgk-1 and that their binding constants are in the 1-6 microM range. ..
  27. Henke G, Maier G, Wallisch S, Boehmer C, Lang F. Regulation of the voltage gated K+ channel Kv1.3 by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid inducible kinase SGK1. J Cell Physiol. 2004;199:194-9 pubmed
    ..3 in both, presence and absence of Nedd4-2. It is concluded that Kv1.3 is downregulated by Nedd4-2 and stimulates by SGK1, SGK2, and SGK3. The data thus disclose a novel mechanism of Kv1.3 channel regulation. ..
  28. Palmada M, Dieter M, Speil A, Bohmer C, Mack A, Wagner H, et al. Regulation of intestinal phosphate cotransporter NaPi IIb by ubiquitin ligase Nedd4-2 and by serum- and glucocorticoid-dependent kinase 1. Am J Physiol Gastrointest Liver Physiol. 2004;287:G143-50 pubmed
    ..Thus the present study reveals a novel signaling pathway in the regulation of intestinal phosphate transport, which may be important for regulation of phosphate balance. ..
  29. Kuratomi G, Komuro A, Goto K, Shinozaki M, Miyazawa K, Miyazono K, et al. NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) negatively regulates TGF-beta (transforming growth factor-beta) signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-beta type I receptor. Biochem J. 2005;386:461-70 pubmed
  30. Bruce M, Kanelis V, Fouladkou F, Debonneville A, Staub O, Rotin D. Regulation of Nedd4-2 self-ubiquitination and stability by a PY motif located within its HECT-domain. Biochem J. 2008;415:155-63 pubmed publisher
    ..These findings also point to a novel mechanism employed by a ubiquitin ligase to regulate itself differentially compared with substrate ubiquitination and stability. ..
  31. Debonneville C, Flores S, Kamynina E, Plant P, Tauxe C, Thomas M, et al. Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression. EMBO J. 2001;20:7052-9 pubmed
    ..Moreover, they suggest a novel and complete signaling cascade for aldosterone-dependent regulation of ENaC. ..
  32. Zhou R, Patel S, Snyder P. Nedd4-2 catalyzes ubiquitination and degradation of cell surface ENaC. J Biol Chem. 2007;282:20207-12 pubmed
    ..Together, the data suggest a model in which Nedd4-2 binds to and ubiquitinates ENaC at the cell surface, which targets surface ENaC for degradation, and thus, reduces epithelial Na(+) transport. ..
  33. Howitt J, Putz U, Lackovic J, Doan A, Dorstyn L, Cheng H, et al. Divalent metal transporter 1 (DMT1) regulation by Ndfip1 prevents metal toxicity in human neurons. Proc Natl Acad Sci U S A. 2009;106:15489-94 pubmed publisher
    ..Together, this evidence suggests a critical role for Ndfip1 in regulating metal transport in human neurons. ..
  34. Zhou R, Snyder P. Nedd4-2 phosphorylation induces serum and glucocorticoid-regulated kinase (SGK) ubiquitination and degradation. J Biol Chem. 2005;280:4518-23 pubmed
    ..Conversely, phosphorylation increases Nedd4-2-mediated degradation of SGK. Thus, by phosphorylating Nedd4-2, SGK induces its own degradation. This feedback inhibition may fine-tune the regulation of epithelial Na+ absorption. ..
  35. Luo F, Wang Y, Wang X, Sun K, Zhou X, Hui R. A functional variant of NEDD4L is associated with hypertension, antihypertensive response, and orthostatic hypotension. Hypertension. 2009;54:796-801 pubmed publisher
    b>NEDD4L is involved in the regulation of plasma volume and blood pressure by controlling cell surface expression of the kidney epithelial Na(+) channel...
  36. Chandran S, Li H, Dong W, Krasinska K, Adams C, Alexandrova L, et al. Neural precursor cell-expressed developmentally down-regulated protein 4-2 (Nedd4-2) regulation by 14-3-3 protein binding at canonical serum and glucocorticoid kinase 1 (SGK1) phosphorylation sites. J Biol Chem. 2011;286:37830-40 pubmed publisher
    ..We also propose that major site phosphorylation promotes cellular Nedd4-2 protein stability, which potentially represents a novel form of regulation for turnover of E3 ubiquitin ligases. ..
  37. Manunta P, Lavery G, Lanzani C, Braund P, Simonini M, Bodycote C, et al. Physiological interaction between alpha-adducin and WNK1-NEDD4L pathways on sodium-related blood pressure regulation. Hypertension. 2008;52:366-72 pubmed publisher
    ..In previous studies, variants in the genes for alpha-adducin (ADD1), WNK1, and NEDD4L, which all regulate renal sodium absorption, have been associated with increased BP...
  38. Snyder P, Olson D, Kabra R, Zhou R, Steines J. cAMP and serum and glucocorticoid-inducible kinase (SGK) regulate the epithelial Na(+) channel through convergent phosphorylation of Nedd4-2. J Biol Chem. 2004;279:45753-8 pubmed
    ..The data suggest that cAMP regulates ENaC in part by phosphorylation and inhibition of Nedd4-2. Moreover, Nedd4-2 is a central convergence point for kinase regulation of Na(+) transport. ..
  39. Maspero E, Valentini E, Mari S, Cecatiello V, Soffientini P, Pasqualato S, et al. Structure of a ubiquitin-loaded HECT ligase reveals the molecular basis for catalytic priming. Nat Struct Mol Biol. 2013;20:696-701 pubmed publisher
    ..We provide evidence that the Nedd4-family members are Lys63-specific enzymes whose catalysis is mediated by an essential C-terminal acidic residue...
  40. van Bemmelen M, Rougier J, Gavillet B, Apothéloz F, Daidié D, Tateyama M, et al. Cardiac voltage-gated sodium channel Nav1.5 is regulated by Nedd4-2 mediated ubiquitination. Circ Res. 2004;95:284-91 pubmed
    ..5. These results demonstrate that Na(v)1.5 can be ubiquitinated in heart tissues and that the ubiquitin-protein ligase Nedd4-2 acts on Na(v)1.5 by decreasing the channel density at the cell surface. ..
  41. Weiss E, Popova E, Yamanaka H, Kim H, Huibregtse J, Gottlinger H. Rescue of HIV-1 release by targeting widely divergent NEDD4-type ubiquitin ligases and isolated catalytic HECT domains to Gag. PLoS Pathog. 2010;6:e1001107 pubmed publisher transfer the ability to stimulate HIV-1 budding to other NEDD4 family members, including the yeast homologue Rsp5, and even to isolated catalytic HECT domains...
  42. Itani O, Stokes J, Thomas C. Nedd4-2 isoforms differentially associate with ENaC and regulate its activity. Am J Physiol Renal Physiol. 2005;289:F334-46 pubmed
    ..Our data illustrate that naturally occurring hNedd4-2 isoforms differentially associate with ENaC to regulate its activity. ..
  43. Fava C, von Wowern F, Berglund G, Carlson J, Hedblad B, Rosberg L, et al. 24-h ambulatory blood pressure is linked to chromosome 18q21-22 and genetic variation of NEDD4L associates with cross-sectional and longitudinal blood pressure in Swedes. Kidney Int. 2006;70:562-9 pubmed
    ..This locus harbors the neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) gene, which is instrumental for the regulation of the amiloride-sensitive epithelial sodium channel (ENaC)...
  44. Wiesner S, Ogunjimi A, Wang H, Rotin D, Sicheri F, Wrana J, et al. Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain. Cell. 2007;130:651-62 pubmed
    ..Thus, interactions between C2 and HECT domains autoinhibit a subset of HECT-type E3s to protect them and their substrates from futile degradation in cells. ..
  45. Takeuchi T, Adachi Y, Nagayama T, Furihata M. Nedd4L modulates the transcription of metalloproteinase-1 and -13 genes to increase the invasive activity of gallbladder cancer. Int J Exp Pathol. 2011;92:79-86 pubmed publisher
    The aim of this study was to examine whether Nedd4L (neural precursor cell expressed, developmentally down-regulated 4-like) participated in gallbladder carcinogenesis...
  46. Wang Y, Qin T, Hu W, Chen B, Dai M, Xu G. Genome-Wide Methylation Patterns in Androgen-Independent Prostate Cancer Cells: A Comprehensive Analysis Combining MeDIP-Bisulfite, RNA, and microRNA Sequencing Data. Genes (Basel). 2018;9: pubmed publisher
    ..Based on the time-course analysis of genes in the networks, NEDD4L and PBX3 were targeted by SOX5, while GNAQ, ANLN, and KIF11 were targeted ..
  47. Utrilla R, Nieto Marín P, Alfayate S, Tinaquero D, Matamoros M, Pérez Hernández M, et al. Kir2.1-Nav1.5 Channel Complexes Are Differently Regulated than Kir2.1 and Nav1.5 Channels Alone. Front Physiol. 2017;8:903 pubmed publisher
    ..These results suggested that Kir2.1 and Nav1.5 channels closely interact with each other leading to the formation of a pool of complexed channels whose biology is similar to that of the Nav1.5 channels. ..
  48. Bossmann M, Ackermann B, Thome U, Laube M. Signaling Cascade Involved in Rapid Stimulation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) by Dexamethasone. Int J Mol Sci. 2017;18: pubmed publisher
    ..We further demonstrated a reduced neural precursor cell expressed, developmentally downregulated 4-like (NEDD4L) ubiquitin E3 ligase activity induced by dexa, possibly responsible for the elevated CFTR activity...
  49. Wang T, Hogan Cann A, Kang Y, Cui Z, Guo J, Yang T, et al. Muscarinic receptor activation increases hERG channel expression through phosphorylation of ubiquitin ligase Nedd4-2. Mol Pharmacol. 2014;85:877-86 pubmed publisher
    ..Blockade of the protein kinase C (PKC) pathway abolished the carbachol-induced enhancement of hERG channels. Our data suggest that muscarinic activation increases hERG channel expression by phosphorylating Nedd4-2 via the PKC pathway. ..
  50. Lin Q, Wang J, Childress C, Sudol M, Carey D, Yang W. HECT E3 ubiquitin ligase Nedd4-1 ubiquitinates ACK and regulates epidermal growth factor (EGF)-induced degradation of EGF receptor and ACK. Mol Cell Biol. 2010;30:1541-54 pubmed publisher
    ..The WW3 domain in Nedd4-1 is critical for binding to ACK. Although ACK binds to both Nedd4-1 and Nedd4-2 (also Nedd4L), Nedd4-1 is the E3 ubiquitin ligase for ubiquitination of ACK in cells...
  51. Lu M, Zhang L, Sartippour M, Norris A, Brooks M. EG-1 interacts with c-Src and activates its signaling pathway. Int J Oncol. 2006;29:1013-8 pubmed
    ..Furthermore, EG-1 shows interaction with multiple other SH3- and WW-containing molecules involved in various signaling pathways. These observations suggest that EG-1 may be involved in signaling pathways including c-Src activation. ..
  52. Hsu S, Delgado E, Otero P, Teng K, Kutay H, Meehan K, et al. MicroRNA-122 regulates polyploidization in the murine liver. Hepatology. 2016;64:599-615 pubmed publisher
    ..Finally, we identified direct targets of miR-122 (Cux1, Rhoa, Iqgap1, Mapre1, Nedd4l, and Slc25a34) that regulate cytokinesis...
  53. Wang H, Li N, Hong J, Yao X, Luo W, Chang J. [Association between rs4149601 polymorphism and essential hypertension in Kazakh]. Zhonghua Xin Xue Guan Bing Za Zhi. 2010;38:918-22 pubmed
    ..a functional rs4149601 polymorphism of neural precursor cell expressed developmentally downregulated 4-like gene (NEDD4L) and essential hypertension in Kazakh...
  54. Yan J, Du F, Li S, Yuan Y, Jiang J, Li S, et al. AUF1 modulates TGF-? signal in renal tubular epithelial cells via post-transcriptional regulation of Nedd4L expression. Biochim Biophys Acta Mol Cell Res. 2018;1865:48-56 pubmed publisher
    ..Mechanically, AUF1 downregulation decreased phosphorylated Smad2/3 via increasing their E3 ligase Nedd4L at the posttranscriptional level...
  55. Sette P, Nagashima K, Piper R, Bouamr F. Ubiquitin conjugation to Gag is essential for ESCRT-mediated HIV-1 budding. Retrovirology. 2013;10:79 pubmed publisher
    ..These studies demonstrate a necessary and natural role for ubiquitin in ESCRT-dependent viral release and indicate a critical role for ubiquitination of Gag rather than ubiquitination of ESCRTs themselves. ..
  56. Yu L, Cai H, Yue Q, Alli A, Wang D, Al Khalili O, et al. WNK4 inhibition of ENaC is independent of Nedd4-2-mediated ENaC ubiquitination. Am J Physiol Renal Physiol. 2013;305:F31-41 pubmed publisher
    ..WNK4 associates with wild-type as well as Liddle's mutated ENaC, and WNK4 reduces both wild-type and mutated ENaC expressed in HEK293 cells. ..
  57. Andersen M, Krzystanek K, Petersen F, Bomholtz S, Olesen S, Abriel H, et al. A phosphoinositide 3-kinase (PI3K)-serum- and glucocorticoid-inducible kinase 1 (SGK1) pathway promotes Kv7.1 channel surface expression by inhibiting Nedd4-2 protein. J Biol Chem. 2013;288:36841-54 pubmed publisher
    ..1 surface expression by inhibiting Nedd4-2-dependent endocytosis and thereby demonstrates that Nedd4-2 is a key regulator of Kv7.1 localization and turnover in epithelial cells. ..
  58. Soundararajan R, Melters D, Shih I, Wang J, Pearce D. Epithelial sodium channel regulated by differential composition of a signaling complex. Proc Natl Acad Sci U S A. 2009;106:7804-9 pubmed publisher
  59. Zhou R, Kabra R, Olson D, Piper R, Snyder P. Hrs controls sorting of the epithelial Na+ channel between endosomal degradation and recycling pathways. J Biol Chem. 2010;285:30523-30 pubmed publisher
    ..In contrast, Hrs-?UIM had no effect on degradation of uncleaved inactive channels. The data support a model in which Nedd4-2 induces binding of ENaC to Hrs, which mediates the sorting decision between ENaC degradation and recycling. ..
  60. Zheng X, Morrison A, Feingold E, Turner S, Ferrell R. Association between NEDD4L gene and sodium lithium countertransport. Am J Hypertens. 2011;24:145-8 pubmed publisher
    ..linkage analysis, and in the light of its potential biochemical function, E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) was identified as being both a positional and a functional candidate gene for SLC...