Gene Symbol: Nedd4
Description: neural precursor cell expressed, developmentally down-regulated 4
Alias: AA959633, AL023035, AU019897, E430025J12Rik, EG639396, Gm7265, KIAA0093, Nedd4-1, Nedd4a, E3 ubiquitin-protein ligase NEDD4, HECT-type E3 ubiquitin transferase NEDD4, neural precursor cell expressed developmentally down-regulated protein 4, neural precursor cell expressed, developmentally down-regulated gene 4a
Species: mouse
Products:     Nedd4

Top Publications

  1. Lu P, Zhou X, Shen M, Lu K. Function of WW domains as phosphoserine- or phosphothreonine-binding modules. Science. 1999;283:1325-8 pubmed
    ..WW domains of the essential mitotic prolyl isomerase Pin1 and the ubiquitin ligase Nedd4 bound to phosphoproteins, including physiological substrates of enzymes, in a phosphorylation-dependent manner...
  2. Harvey K, Shearwin Whyatt L, Fotia A, Parton R, Kumar S. N4WBP5, a potential target for ubiquitination by the Nedd4 family of proteins, is a novel Golgi-associated protein. J Biol Chem. 2002;277:9307-17 pubmed
    b>Nedd4 belongs to a family of ubiquitin-protein ligases that is characterized by 2--4 WW domains, a carboxyl-terminal Hect (homologous to E6-AP Carboxyl terminus)domain and in most cases an amino-terminal C2 domain...
  3. Liu Y, Oppenheim R, Sugiura Y, Lin W. Abnormal development of the neuromuscular junction in Nedd4-deficient mice. Dev Biol. 2009;330:153-66 pubmed publisher
    b>Nedd4 (neural precursor cell expressed developmentally down-regulated gene 4) is an E3 ubiquitin ligase highly conserved from yeast to humans...
  4. Harvey K, Kumar S. Nedd4-like proteins: an emerging family of ubiquitin-protein ligases implicated in diverse cellular functions. Trends Cell Biol. 1999;9:166-9 pubmed
    The members of an emerging family of proteins similar to Nedd4 have a unique modular structure consisting of a Ca2+/lipid-binding domain, multiple protein-protein interaction modules and a ubiquitin-protein ligase domain...
  5. Rougier J, van Bemmelen M, Bruce M, Jespersen T, Gavillet B, Apothéloz F, et al. Molecular determinants of voltage-gated sodium channel regulation by the Nedd4/Nedd4-like proteins. Am J Physiol Cell Physiol. 2005;288:C692-701 pubmed
    ..COOH-terminal sequence, PPSYDSV, is a PY motif known to bind to WW domains of E3 protein-ubiquitin ligases of the Nedd4 family. We recently reported that cardiac Na(v)1.5 is regulated by Nedd4-2...
  6. Kumar S, Harvey K, Kinoshita M, Copeland N, Noda M, Jenkins N. cDNA cloning, expression analysis, and mapping of the mouse Nedd4 gene. Genomics. 1997;40:435-43 pubmed
    The Nedd4 gene was initially identified by a subtraction cloning approach as a highly expressed transcript in the mouse embryonic brain...
  7. Cao X, Lill N, Boase N, Shi P, Croucher D, Shan H, et al. Nedd4 controls animal growth by regulating IGF-1 signaling. Sci Signal. 2008;1:ra5 pubmed publisher
    The ubiquitin ligase Nedd4 has been proposed to regulate a number of signaling pathways, but its physiological role in mammals has not been characterized...
  8. Wang X, Trotman L, Koppie T, Alimonti A, Chen Z, Gao Z, et al. NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN. Cell. 2007;128:129-39 pubmed
    ..regulated by ubiquitin-mediated proteasomal degradation, and purified its ubiquitin ligase as HECT-domain protein NEDD4-1. In cells NEDD4-1 negatively regulates PTEN stability by catalyzing PTEN polyubiquitination...
  9. Kumar S, Tomooka Y, Noda M. Identification of a set of genes with developmentally down-regulated expression in the mouse brain. Biochem Biophys Res Commun. 1992;185:1155-61 pubmed
    ..Their patterns of expression indicate that these genes may play important roles during the embryonic development and differentiation of central nervous system. ..

More Information


  1. Conkright J, Apsley K, Martin E, Ridsdale R, Rice W, Na C, et al. Nedd4-2-mediated ubiquitination facilitates processing of surfactant protein-C. Am J Respir Cell Mol Biol. 2010;42:181-9 pubmed publisher
    ..Purified recombinant glutathione S-transferase-SP-C propeptide (residues 1-35) bound recombinant Nedd4-2 strongly, and Nedd4 weakly; the S(12)PPDYS(17)mutation abrogated binding of SP-C to Nedd4-2...
  2. Fouladkou F, Landry T, Kawabe H, Neeb A, Lu C, Brose N, et al. The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization. Proc Natl Acad Sci U S A. 2008;105:8585-90 pubmed publisher
    PTEN is a tumor suppressor frequently mutated in cancer. Recent reports implicated Nedd4-1 as the E3 ubiquitin ligase for PTEN that regulates its stability and nuclear localization...
  3. Fotia A, Cook D, Kumar S. The ubiquitin-protein ligases Nedd4 and Nedd4-2 show similar ubiquitin-conjugating enzyme specificities. Int J Biochem Cell Biol. 2006;38:472-9 pubmed
    b>Nedd4 and Nedd4-2 are closely related HECT-type ubiquitin-protein ligases (E3) implicated in the regulation of a number of proteins and pathways...
  4. Kamynina E, Debonneville C, Bens M, Vandewalle A, Staub O. A novel mouse Nedd4 protein suppresses the activity of the epithelial Na+ channel. FASEB J. 2001;15:204-214 pubmed
    ..mutations alter or delete PY motifs involved in protein-protein interactions with a ubiquitin-protein ligase, Nedd4. Here we show that Na+ transporting cells, derived from mouse cortical collecting duct, express two Nedd4 proteins ..
  5. Fouladkou F, Lu C, Jiang C, Zhou L, She Y, Walls J, et al. The ubiquitin ligase Nedd4-1 is required for heart development and is a suppressor of thrombospondin-1. J Biol Chem. 2010;285:6770-80 pubmed publisher
    b>Nedd4 (Nedd4-1) is a Hect domain E3 ubiquitin ligase that also contains a C2 domain and three WW domains. Despite numerous in vitro studies, its biological function in vivo is not well understood...
  6. Kawabe H, Neeb A, Dimova K, Young S, Takeda M, Katsurabayashi S, et al. Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development. Neuron. 2010;65:358-72 pubmed publisher
    b>Nedd4-1 is a "neuronal precursor cell expressed and developmentally downregulated protein" and among the most abundant E3 ubiquitin ligases in mammalian neurons...
  7. Bakkers J, Camacho Carvajal M, Nowak M, Kramer C, Danger B, Hammerschmidt M. Destabilization of DeltaNp63alpha by Nedd4-mediated ubiquitination and Ubc9-mediated sumoylation, and its implications on dorsoventral patterning of the zebrafish embryo. Cell Cycle. 2005;4:790-800 pubmed
    ..we isolated two DeltaNp63alpha-modifying enzymes, the SUMO-conjugating enzyme Ubc9 and the ubiquitin ligase Nedd4. The proteins bind to distinct sites in the C-terminal region of DeltaNp63alpha, which are absent in the shorter ..
  8. Heissmeyer V, Macian F, Im S, Varma R, Feske S, Venuprasad K, et al. Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins. Nat Immunol. 2004;5:255-65 pubmed
    ..Subsequent stimulation or homotypic cell adhesion promoted membrane translocation of Itch and the related protein Nedd4, resulting in degradation of two key signaling proteins, PKC-theta and PLC-gamma1...
  9. Huang Q, Szebenyi D. Structural basis for the interaction between the growth factor-binding protein GRB10 and the E3 ubiquitin ligase NEDD4. J Biol Chem. 2010;285:42130-9 pubmed publisher
    ..It has been shown that GRB10 can interact with the C2 domain of the E3 ubiquitin ligase NEDD4 through its Src homology 2 (SH2) domain...
  10. Dussart S, Douaisi M, Courcoul M, Bessou G, Vigne R, Decroly E. APOBEC3G ubiquitination by Nedd4-1 favors its packaging into HIV-1 particles. J Mol Biol. 2005;345:547-58 pubmed
    ..Here, we demonstrate that Nedd4-1, an HECT E3 ubiquitin ligase, interacts with APOBEC3G, through its WW2 and WW3 domains...
  11. Lu C, Thoeni C, Connor A, Kawabe H, Gallinger S, Rotin D. Intestinal knockout of Nedd4 enhances growth of Apcmin tumors. Oncogene. 2016;35:5839-5849 pubmed publisher
    b>Nedd4 (Nedd4-1) is an E3 ubiquitin ligase that belongs to the HECT family and comprises a C2-WW(n)-HECT domain architecture...
  12. Bhalla V, Daidié D, Li H, Pao A, LaGrange L, Wang J, et al. Serum- and glucocorticoid-regulated kinase 1 regulates ubiquitin ligase neural precursor cell-expressed, developmentally down-regulated protein 4-2 by inducing interaction with 14-3-3. Mol Endocrinol. 2005;19:3073-84 pubmed
    ..Recent evidence has established that SGK1 phosphorylates and inhibits Nedd4-2 (neural precursor cell-expressed, developmentally down-regulated protein 4-2), a ubiquitin ligase that decreases ..
  13. Noyes N, Hampton B, Migliorini M, Strickland D. Regulation of Itch and Nedd4 E3 Ligase Activity and Degradation by LRAD3. Biochemistry. 2016;55:1204-13 pubmed publisher
    Itch and Nedd4 are members of the Nedd4 family of E3 ubiquitin ligases that are important in a number of biological processes. Precise regulation of their enzymatic activity is required for normal physiological function...
  14. Yang B, Gay D, Macleod M, Cao X, Hala T, Sweezer E, et al. Nedd4 augments the adaptive immune response by promoting ubiquitin-mediated degradation of Cbl-b in activated T cells. Nat Immunol. 2008;9:1356-63 pubmed publisher
    b>Nedd4 and Itch are E3 ubiquitin ligases that ubiquitinate similar targets in vitro and thus are thought to function similarly. T cells lacking Itch show spontaneous activation and T helper type 2 polarization...
  15. Zhao Z, Dammert M, Grummt I, Bierhoff H. lncRNA-Induced Nucleosome Repositioning Reinforces Transcriptional Repression of rRNA Genes upon Hypotonic Stress. Cell Rep. 2016;14:1876-82 pubmed publisher
    ..Here, we show that upregulation of PAPAS in response to hypoosmotic stress does not increase H4K20me3 because of Nedd4-dependent ubiquitinylation and proteasomal degradation of Suv4-20h2...
  16. Bachofner M, Speicher T, Bogorad R, Muzumdar S, Derrer C, Hürlimann F, et al. Large-Scale Quantitative Proteomics Identifies the Ubiquitin Ligase Nedd4-1 as an Essential Regulator of Liver Regeneration. Dev Cell. 2017;42:616-625.e8 pubmed publisher
    ..the ubiquitin-proteasome pathway were rapidly upregulated after two-third hepatectomy, with the ubiquitin ligase Nedd4-1 being a top hit...
  17. Camera D, Boase N, Kumar S, Pow D, Poronnik P. Subtle gait abnormalities in Nedd4 heterozygous mice. Behav Brain Res. 2014;260:15-24 pubmed publisher
    b>Nedd4 is a widely expressed ubiquitin ligase that is necessary for normal neuronal development and function...
  18. Vecchione A, Marchese A, Henry P, Rotin D, Morrione A. The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the insulin-like growth factor I receptor. Mol Cell Biol. 2003;23:3363-72 pubmed
    ..J. Biol. Chem. 272:26382-26387, 1997). With mGrb10alpha as bait in a yeast two-hybrid screen, mouse Nedd4 (mNedd4-1), a ubiquitin protein ligase, was previously isolated as an interacting protein of Grb10 (A...
  19. Scudder S, Goo M, Cartier A, Molteni A, Schwarz L, Wright R, et al. Synaptic strength is bidirectionally controlled by opposing activity-dependent regulation of Nedd4-1 and USP8. J Neurosci. 2014;34:16637-49 pubmed publisher
    ..Previous work has demonstrated that AMPARs undergo activity-dependent ubiquitination by the E3 ubiquitin ligase Nedd4-1, which promotes their internalization and degradation in lysosomes...
  20. Zhou Z, Kawabe H, Suzuki A, Shinmyozu K, Saga Y. NEDD4 controls spermatogonial stem cell homeostasis and stress response by regulating messenger ribonucleoprotein complexes. Nat Commun. 2017;8:15662 pubmed publisher
    ..However, the mechanisms underlying the dynamics of mRNP granules are poorly understood. Here, we report NEDD4, an E3 ubiquitin ligase, as a key regulator of mRNP dynamics that controls the size of the spermatogonial ..
  21. Guo H, Qiao G, Ying H, Li Z, Zhao Y, Liang Y, et al. E3 ubiquitin ligase Cbl-b regulates Pten via Nedd4 in T cells independently of its ubiquitin ligase activity. Cell Rep. 2012;1:472-82 pubmed
    ..Suppression of Pten inactivation in T cells by Cbl-b is achieved by impeding the association of Pten with Nedd4, which targets Pten K13 for K63-linked polyubiquitination...
  22. Oberfeld B, Ruffieux Daidié D, Vitagliano J, Pos K, Verrey F, Staub O. Ubiquitin-specific protease 2-45 (Usp2-45) binds to epithelial Na+ channel (ENaC)-ubiquitylating enzyme Nedd4-2. Am J Physiol Renal Physiol. 2011;301:F189-96 pubmed publisher ubiquitylation is controlled by the activity of two counteracting enzymes, the E3 ubiquitin-protein ligase Nedd4-2 (mouse ortholog of human Nedd4L) and the ubiquitin-specific protease Usp2-45...
  23. Ermekova K, Zambrano N, Linn H, Minopoli G, Gertler F, Russo T, et al. The WW domain of neural protein FE65 interacts with proline-rich motifs in Mena, the mammalian homolog of Drosophila enabled. J Biol Chem. 1997;272:32869-77 pubmed
  24. Dussart S, Courcoul M, Bessou G, Douaisi M, Duverger Y, Vigne R, et al. The Vif protein of human immunodeficiency virus type 1 is posttranslationally modified by ubiquitin. Biochem Biophys Res Commun. 2004;315:66-72 pubmed
    ..Vif is mainly mono-ubiquitinated, a modification known to address the Gag precursor to the virus budding site. ..
  25. Jolliffe C, Harvey K, Haines B, Parasivam G, Kumar S. Identification of multiple proteins expressed in murine embryos as binding partners for the WW domains of the ubiquitin-protein ligase Nedd4. Biochem J. 2000;351 Pt 3:557-65 pubmed
    b>Nedd4 is a member of a growing family of ubiquitin-protein ligases which consist of a lipid-binding domain, two to four WW domains and a C-terminal ubiquitin-protein ligase domain...
  26. Boase N, Rychkov G, Townley S, Dinudom A, Candi E, Voss A, et al. Respiratory distress and perinatal lethality in Nedd4-2-deficient mice. Nat Commun. 2011;2:287 pubmed publisher
    ..In vitro studies show that the ubiquitin ligase Nedd4-2 ubiquitinates ENaC to regulate its cell surface expression...
  27. Hatakeyama S, Yada M, Matsumoto M, Ishida N, Nakayama K. U box proteins as a new family of ubiquitin-protein ligases. J Biol Chem. 2001;276:33111-20 pubmed
    ..These data suggest that U box proteins constitute a third family of E3 enzymes and that E4 activity may reflect a specialized type of E3 activity. ..
  28. Terabayashi T, Sakaguchi M, Shinmyozu K, Ohshima T, Johjima A, Ogura T, et al. Phosphorylation of Kif26b promotes its polyubiquitination and subsequent proteasomal degradation during kidney development. PLoS ONE. 2012;7:e39714 pubmed publisher
    ..interacts with an E3 ubiquitin ligase, neural precursor cell expressed developmentally down-regulated protein 4 (Nedd4) in developing kidney...
  29. Aitken J, Loomes K, Scott D, Reddy S, Phillips A, Prijic G, et al. Tetracycline treatment retards the onset and slows the progression of diabetes in human amylin/islet amyloid polypeptide transgenic mice. Diabetes. 2010;59:161-71 pubmed publisher
    ..Interventions capable of suppressing misfolding in soluble hA/hIAPP oligomers rather than mature fibrils may have potential for treating or preventing type 2 diabetes. ..
  30. Xu C, Fan C, Wang X. Regulation of Mdm2 protein stability and the p53 response by NEDD4-1 E3 ligase. Oncogene. 2015;34:281-9 pubmed publisher
    ..Here we report biochemical identification of NEDD4-1 as an E3 ligase for Mdm2 that contributes to the regulation of Mdm2 protein stability in cells...
  31. Simonin A, Fuster D. Nedd4-1 and beta-arrestin-1 are key regulators of Na+/H+ exchanger 1 ubiquitylation, endocytosis, and function. J Biol Chem. 2010;285:38293-303 pubmed publisher
    ..This process requires the adapter protein ?-arrestin-1 that interacts with both the E3 ubiquitin ligase Nedd4-1 and the NHE1 C terminus...
  32. Staub O, Dho S, Henry P, Correa J, Ishikawa T, McGlade J, et al. WW domains of Nedd4 bind to the proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle's syndrome. EMBO J. 1996;15:2371-80 pubmed
    ..Using a yeast two-hybrid screen, we have now identified the rat homologue of Nedd4 (rNedd4) as the binding partner for the P2 regions of beta and gammarENaC...
  33. Fombonne J, Bissey P, Guix C, Sadoul R, Thibert C, Mehlen P. Patched dependence receptor triggers apoptosis through ubiquitination of caspase-9. Proc Natl Acad Sci U S A. 2012;109:10510-5 pubmed publisher
    ..We show here that this caspase-activating complex also includes the E3 ubiquitin ligase NEDD4. We demonstrate that Ptc-mediated apoptosis and Ptc-induced caspase-9 activation require NEDD4...
  34. Goh C, Low L, Putz U, Gunnersen J, Hammond V, Howitt J, et al. Ndfip1 expression in developing neurons indicates a role for protein ubiquitination by Nedd4 E3 ligases during cortical development. Neurosci Lett. 2013;555:225-30 pubmed publisher
    ..The E3 ubiquitin ligases, including Nedd4 family proteins, are a major group of enzymes responsible for adding ubiquitin chains to protein substrates prior ..
  35. Gavva N, Gavva R, Ermekova K, Sudol M, Shen C. Interaction of WW domains with hematopoietic transcription factor p45/NF-E2 and RNA polymerase II. J Biol Chem. 1997;272:24105-8 pubmed
    ..We discuss the data in terms of possible new pathways through which the processes of transcriptional regulation by NF-E2 could be regulated in erythroid and megakaryote cells. ..
  36. Weston A, Underhill T. Analysis of Nedd4 expression during skeletal development in the mouse limb. Mech Dev. 2000;94:247-50 pubmed
    b>Nedd4, a ubiquitin-protein ligase, was originally identified as being down-regulated during development of the mouse brain (Nedd denotes neural precursor cell expressed developmentally down-regulated) (Kumar, S., Tomooka, Y., Noda, M...
  37. Monami G, Emiliozzi V, Morrione A. Grb10/Nedd4-mediated multiubiquitination of the insulin-like growth factor receptor regulates receptor internalization. J Cell Physiol. 2008;216:426-37 pubmed publisher
    ..We have shown that Grb10 binds the E3 ubiquitin ligase Nedd4 and promotes IGF-I-stimulated ubiquitination, internalization, and degradation of the IGF-IR, thereby giving rise ..
  38. Rougier J, Albesa M, Abriel H, Viard P. Neuronal precursor cell-expressed developmentally down-regulated 4-1 (NEDD4-1) controls the sorting of newly synthesized Ca(V)1.2 calcium channels. J Biol Chem. 2011;286:8829-38 pubmed publisher
    Neuronal precursor cell-expressed developmentally down-regulated 4 (Nedd4) proteins are ubiquitin ligases, which attach ubiquitin moieties to their target proteins, a post-translational modification that is most commonly associated with ..
  39. Flasza M, Gorman P, Roylance R, Canfield A, Baron M. Alternative splicing determines the domain structure of WWP1, a Nedd4 family protein. Biochem Biophys Res Commun. 2002;290:431-7 pubmed
    ..Here we show that a human Nedd4 family gene, WWP1, is localized on 8q21 and generates at least six isoforms through alternative splicing...
  40. Loebel D, O Rourke M, Steiner K, Banyer J, Tam P. Isolation of differentially expressed genes from wild-type and Twist mutant mouse limb buds. Genesis. 2002;33:103-13 pubmed
  41. Sun J, Keim C, Wang J, Kazadi D, Oliver P, Rabadan R, et al. E3-ubiquitin ligase Nedd4 determines the fate of AID-associated RNA polymerase II in B cells. Genes Dev. 2013;27:1821-33 pubmed publisher
    ..Here we report that E3-ubiquitin ligase Nedd4 destabilizes AID-associated RNA polII by a ubiquitination event, leading to generation of 3' end free RNA exosome ..
  42. Tuckow A, Kazi A, Kimball S, Jefferson L. Identification of ubiquitin-modified lysine residues and novel phosphorylation sites on eukaryotic initiation factor 2B epsilon. Biochem Biophys Res Commun. 2013;436:41-6 pubmed publisher
    ..Moreover, peptides corresponding to the amino acid sequence of the E3 ligase NEDD4 were also detected in the LC-MS/MS analysis, and an interaction between endogenous eIF2B? with NEDD4 was confirmed ..
  43. Sanchez Perez A, Kumar S, Cook D. GRK2 interacts with and phosphorylates Nedd4 and Nedd4-2. Biochem Biophys Res Commun. 2007;359:611-5 pubmed
    ..They are inhibited by ubiquitin protein ligases, such as Nedd4 and Nedd4-2, which bind to proline-rich motifs (PY motifs) present in the C-termini of ENaC subunits...
  44. Kwak Y, Wang B, Pan W, Xu H, Jiang X, Liao F. Functional interaction of phosphatase and tensin homologue (PTEN) with the E3 ligase NEDD4-1 during neuronal response to zinc. J Biol Chem. 2010;285:9847-57 pubmed publisher
    ..b>NEDD4-1-mediated PTEN ubiquitination and subsequent degradation via the ubiquitin proteosomal system have recently been ..
  45. Ando K, PARSONS M, Shah R, Charendoff C, Paris S, Liu P, et al. NPM1 directs PIDDosome-dependent caspase-2 activation in the nucleolus. J Cell Biol. 2017;216:1795-1810 pubmed publisher
    ..Thus we have identified the nucleolus as a novel site for caspase-2 activation and function. ..
  46. Gunn T, Silvius D, Bagher P, Sun K, Walker K. MGRN1-dependent pigment-type switching requires its ubiquitination activity but not its interaction with TSG101 or NEDD4. Pigment Cell Melanoma Res. 2013;26:263-8 pubmed publisher
    ..Here, we show that MGRN1 also interacts with but does not ubiquitinate NEDD4, a HECT-domain ubiquitin ligase involved in endosomal trafficking...
  47. Sarkar A, Zohn I. Hectd1 regulates intracellular localization and secretion of Hsp90 to control cellular behavior of the cranial mesenchyme. J Cell Biol. 2012;196:789-800 pubmed publisher
  48. Hsia H, Kumar R, Lucà R, Takeda M, Courchet J, Nakashima J, et al. Ubiquitin E3 ligase Nedd4-1 acts as a downstream target of PI3K/PTEN-mTORC1 signaling to promote neurite growth. Proc Natl Acad Sci U S A. 2014;111:13205-10 pubmed publisher
    ..Previous studies have indicated that the Nedd4-family E3 ubiquitin ligases Nedd4-1 and Nedd4-2 may ubiquitinate phosphatase and tensin homolog (PTEN) and thereby ..
  49. Fang N, Chan G, Zhu M, Comyn S, Persaud A, Deshaies R, et al. Rsp5/Nedd4 is the main ubiquitin ligase that targets cytosolic misfolded proteins following heat stress. Nat Cell Biol. 2014;16:1227-37 pubmed publisher
    ..We found that Rsp5 and its mammalian homologue Nedd4 are important E3 ligases responsible for the increased ubiquitylation induced by heat stress...
  50. Van Campenhout C, Eitelhuber A, Gloeckner C, Giallonardo P, Gegg M, Oller H, et al. Dlg3 trafficking and apical tight junction formation is regulated by nedd4 and nedd4-2 e3 ubiquitin ligases. Dev Cell. 2011;21:479-91 pubmed publisher
    ..Remarkably, of the four Dlg family members, Dlg3 exerts a distinct function by recruiting the ubiquitin ligases Nedd4 and Nedd4-2 through its PPxY motifs...
  51. Lackovic J, Howitt J, Callaway J, Silke J, Bartlett P, Tan S. Differential regulation of Nedd4 ubiquitin ligases and their adaptor protein Ndfip1 in a rat model of ischemic stroke. Exp Neurol. 2012;235:326-35 pubmed publisher
    ..Here, we demonstrate endogenous induction of HECT-type E3 ligases of the Nedd4 family and their adaptor Nedd4-family interacting protein 1 (Ndfip1) following transient focal cerebral ischemia ..
  52. Wiszniak S, Kabbara S, Lumb R, Scherer M, Secker G, Harvey N, et al. The ubiquitin ligase Nedd4 regulates craniofacial development by promoting cranial neural crest cell survival and stem-cell like properties. Dev Biol. 2013;383:186-200 pubmed publisher
    ..Here we report an essential role for the ubiquitin ligase Nedd4 in cranial NC cell development...
  53. Fang D, He K, Wang N, Sang Z, Qiu X, Xu G, et al. NEDD4 ubiquitinates TRAF3 to promote CD40-mediated AKT activation. Nat Commun. 2014;5:4513 pubmed publisher
    ..Here we report that the neural precursor cell expressed developmentally downregulated protein 4 (NEDD4), homologous to E6-AP Carboxyl Terminus family E3 ubiquitin ligase, is a novel component of the CD40 signalling ..
  54. Fukushima T, Yoshihara H, Furuta H, Kamei H, Hakuno F, Luan J, et al. Nedd4-induced monoubiquitination of IRS-2 enhances IGF signalling and mitogenic activity. Nat Commun. 2015;6:6780 pubmed publisher
    ..Here we identify Nedd4 as an IRS-2 ubiquitin ligase...
  55. Morrione A, Plant P, Valentinis B, Staub O, Kumar S, Rotin D, et al. mGrb10 interacts with Nedd4. J Biol Chem. 1999;274:24094-9 pubmed
    ..We have isolated a mouse cDNA clone containing the C2 domain of mouse Nedd4, a ubiquitin protein ligase (E3) that also contains a hect (homologous to the E6-AP carboxyl-terminus) domain and ..
  56. Fotia A, Ekberg J, Adams D, Cook D, Poronnik P, Kumar S. Regulation of neuronal voltage-gated sodium channels by the ubiquitin-protein ligases Nedd4 and Nedd4-2. J Biol Chem. 2004;279:28930-5 pubmed
    b>Nedd4 and Nedd4-2 are ubiquitin-protein ligases known to regulate a number of membrane proteins including receptors and ion transporters...
  57. Li S, Mi L, Yu L, Yu Q, Liu T, Wang G, et al. Zbtb7b engages the long noncoding RNA Blnc1 to drive brown and beige fat development and thermogenesis. Proc Natl Acad Sci U S A. 2017;114:E7111-E7120 pubmed publisher
    ..These findings illustrate the emerging concept of a protein-lncRNA regulatory network in the control of adipose tissue biology and energy metabolism. ..
  58. D Cruz R, Plant P, Pablo L, Lin S, Chackowicz J, Correa J, et al. PDLIM7 is a novel target of the ubiquitin ligase Nedd4-1 in skeletal muscle. Biochem J. 2016;473:267-76 pubmed publisher
    ..system (UPS) is the predominant proteolytic machinery responsible for atrophy of skeletal muscle, and Nedd4-1 (neural precursor cell-expressed developmentally down-regulated 4-1) is one of a series of E3 ubiquitin ligases ..
  59. Kwak Y, Wang B, Li J, Wang R, Deng Q, Diao S, et al. Upregulation of the E3 ligase NEDD4-1 by oxidative stress degrades IGF-1 receptor protein in neurodegeneration. J Neurosci. 2012;32:10971-81 pubmed
    The importance of ubiquitin E3 ligases in neurodegeneration is being increasingly recognized. The crucial role of NEDD4-1 in neural development is well appreciated; however, its role in neurodegeneration remains unexplored...
  60. Yunokuchi I, Fan H, Iwamoto Y, Araki C, Yuda M, Umemura H, et al. Prolyl isomerase Pin1 shares functional similarity with phosphorylated CTD interacting factor PCIF1 in vertebrate cells. Genes Cells. 2009;14:1105-18 pubmed publisher
    ..These results suggest that Pin1 may have overlapping cellular function with PCIF1 in vertebrate cells. ..
  61. Edinger R, Lebowitz J, Li H, Alzamora R, Wang H, Johnson J, et al. Functional regulation of the epithelial Na+ channel by IkappaB kinase-beta occurs via phosphorylation of the ubiquitin ligase Nedd4-2. J Biol Chem. 2009;284:150-7 pubmed publisher
    ..stimulation of ENaC activity occurs through enhanced channel surface expression and the ubiquitin-protein ligase Nedd4-2 has emerged as a central locus for ENaC regulation at the plasma membrane, we tested the role of Nedd4-2 in this ..
  62. Camera D, Coleman H, Parkington H, Jenkins T, Pow D, Boase N, et al. Learning, memory and long-term potentiation are altered in Nedd4 heterozygous mice. Behav Brain Res. 2016;303:176-81 pubmed publisher
    ..AMPA receptor trafficking is a key determinant of LTP and recently ubiquitination by Nedd4 has been shown to play an important role via direct action on the GluA1 subunit, although the physiological ..
  63. Bellet M, Piobbico D, Bartoli D, Castelli M, Pieroni S, Brunacci C, et al. NEDD4 controls the expression of GUCD1, a protein upregulated in proliferating liver cells. Cell Cycle. 2014;13:1902-11 pubmed publisher
    ..assay, aimed at identifying any relevant interaction partners of GUCD1, revealed direct interactions with NEDD4-1 (E3 ubiquitin protein ligase neural precursor cell expressed, developmentally downregulated gene 4), resulting ..
  64. Gormley K, Dong Y, Sagnella G. Regulation of the epithelial sodium channel by accessory proteins. Biochem J. 2003;371:1-14 pubmed
    ..Several proteins acting in concert are an intrinsic part of this process but Nedd4 (neural precursor cell expressed developmentally down-regulated 4) is of central importance...
  65. Nagpal P, Plant P, Correa J, Bain A, Takeda M, Kawabe H, et al. The ubiquitin ligase Nedd4-1 participates in denervation-induced skeletal muscle atrophy in mice. PLoS ONE. 2012;7:e46427 pubmed publisher
    ..Our previous work suggested that the ubiquitin-protein ligase Nedd4-1 is a potential mediator of skeletal muscle atrophy associated with inactivity (denervation, unloading and ..
  66. Liang X, Butterworth M, Peters K, Walker W, Frizzell R. An obligatory heterodimer of 14-3-3beta and 14-3-3epsilon is required for aldosterone regulation of the epithelial sodium channel. J Biol Chem. 2008;283:27418-25 pubmed publisher
    Increased distal nephron sodium absorption in response to aldosterone involves Nedd4-2 phosphorylation, which blocks its ability to ubiquitylate ENaC and increases apical membrane channel density by reducing its endocytosis...
  67. Bustos F, de la Vega E, Cabezas F, Thompson J, Cornelison D, Olwin B, et al. NEDD4 Regulates PAX7 Levels Promoting Activation of the Differentiation Program in Skeletal Muscle Precursors. Stem Cells. 2015;33:3138-51 pubmed publisher
    ..Here we show that Pax7 levels are directly regulated by the ubiquitin-ligase Nedd4. Our results indicate that Nedd4 is expressed in quiescent and activated satellite cells, that Nedd4 and Pax7 ..
  68. Yuan L, Lv Y, Li H, Gao H, Song S, Zhang Y, et al. Deubiquitylase OTUD3 regulates PTEN stability and suppresses tumorigenesis. Nat Cell Biol. 2015;17:1169-81 pubmed publisher
    ..These findings demonstrate that OTUD3 is an essential regulator of PTEN and that the OTUD3-PTEN signalling axis plays a critical role in tumour suppression. ..
  69. Murdaca J, Treins C, Monthouël Kartmann M, Pontier Bres R, Kumar S, Van Obberghen E, et al. Grb10 prevents Nedd4-mediated vascular endothelial growth factor receptor-2 degradation. J Biol Chem. 2004;279:26754-61 pubmed
    ..In the present manuscript, we demonstrate that Grb10 stimulates VEGF-R2 expression by inhibiting the Nedd4-mediated VEGF-R2 degradation...
  70. Gautam V, Trinidad J, Rimerman R, Costa B, Burlingame A, Monaghan D. Nedd4 is a specific E3 ubiquitin ligase for the NMDA receptor subunit GluN2D. Neuropharmacology. 2013;74:96-107 pubmed publisher
    ..fragments used as bait, only the construct containing amino acids 983-1097 associated with an E3 ubiquitin ligase, Nedd4. A direct interaction between GluN2D and Nedd4 was confirmed both in vivo and in vitro...