E3 ubiquitin-protein ligase NEDD4, also known as neural precursor cell expressed developmentally down-regulated protein 4 (whence "NEDD4") is an enzyme that is, in humans, encoded by the NEDD4 gene.[5][6]
NEDD4 is an E3 ubiquitin ligase enzyme, that targets proteins for ubiquitination.[7]NEDD4 is, in eukaryotes, a highly conserved gene, and the founding member of the NEDD4 family of E3 HECT ubiquitin ligases, which in humans consists of 9 members:
[8][9][10]
NEDD4 (the core topic of this article)
NEDD4-2 (or NEDD4L)
ITCH
SMURF1
SMURF2
WWP1
WWP2
NEDL1 (HECW1)
NEDDL2 (HECW2)].
NEDD4 regulates a large number of membrane proteins, such as ion channels and membrane receptors, via ubiquitination and endocytosis; its eponymous protein is widely expressed, and a large number of proteins have been predicted or demonstrated to bind in vitro.
In vivo, it is involved in the regulation of a diverse range of processes,[7]
including
insulin-like growth factor signalling,
neuronal architecture, and
viral budding.
NEDD4 also is an essential protein in animals, both for development and for survival.
[11]
^ abcGRCh38: Ensembl release 89: ENSG00000069869 – Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000032216 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Kumar S, Harvey KF, Kinoshita M, Copeland NG, Noda M, Jenkins NA (May 1997). "cDNA cloning, expression analysis, and mapping of the mouse Nedd4 gene". Genomics. 40 (3): 435–43. doi:10.1006/geno.1996.4582. PMID 9073511.
^Imhof MO, McDonnell DP (Jul 1996). "Yeast RSP5 and its human homolog hRPF1 potentiate hormone-dependent activation of transcription by human progesterone and glucocorticoid receptors". Mol Cell Biol. 16 (6): 2594–605. doi:10.1128/MCB.16.6.2594. PMC 231250. PMID 8649367.
^ abNovellasdemunt L, Kucharska A, Jamieson C, Prange-Barczynska M, Baulies A, Antas P, et al. (February 2020). "NEDD4 and NEDD4L regulate Wnt signalling and intestinal stem cell priming by degrading LGR5 receptor". The EMBO Journal. 39 (3): e102771. doi:10.15252/embj.2019102771. PMC 6996568. PMID 31867777.
^Rotin D, Kumar S (2009). "Physiological functions of the HECT family of ubiquitin ligases". Nat. Rev. Mol. Cell Biol. 10 (6): 398–409. doi:10.1038/nrm2690. PMID 19436320. S2CID 1894155.
^Scheffner M, Kumar S (2014). "Mammalian HECT ubiquitin-protein ligases: biological and pathophysiological aspects". Biochim. Biophys. Acta. 1843 (1): 61–74. doi:10.1016/j.bbamcr.2013.03.024. PMID 23545411.
^Yang B, Kumar S (2010). "Nedd4 and Nedd4-2: closely related ubiquitin-protein ligases with distinct physiological functions". Cell Death Differ. 17 (1): 68–77. doi:10.1038/cdd.2009.84. PMC 2818775. PMID 19557014.
^
Cao XR, Lill NL, Boase N, Shi PP, Croucher DR, Shan H, Qu J, Sweezer EM, Place T, Kirby PA, Daly RJ, Kumar S, Yang B (2008). "Nedd4 controls animal growth by regulating IGF-1 signaling". Sci Signal. 1 (38): ra5. doi:10.1126/scisignal.1160940. PMC 2833362. PMID 18812566.
ubiquitin-protein ligase NEDD4, also known as neural precursor cell expressed developmentally down-regulated protein 4 (whence "NEDD4") is an enzyme that is...
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...
Nedd4 family interacting protein 1 is a protein that in humans is encoded by the NDFIP1 gene. The protein encoded by this gene belongs to a small group...
NEDD4-like E3 ubiquitin-protein ligase WWP2 also known as atrophin-1-interacting protein 2 (AIP2) or WW domain-containing protein 2 (WWP2) is an enzyme...
the resulting polyphosphorylated Akt is ubiquitinated partly by E3 ligase NEDD4. Most of the ubiquitinated-phosphorylated-Akt1 is degraded by the proteasome...
NEDD4 family-interacting protein 2 is a protein that in humans is encoded by the NDFIP2 gene. NDFIP2 has been shown to interact with NEDD4. GRCh38: Ensembl...
NEDD4-like E3 ubiquitin-protein ligase WWP1 is an enzyme that in humans is encoded by the WWP1 gene. WW domain-containing proteins are found in all eukaryotes...
humans is encoded by the PMEPA1 gene. TMEPAI has been shown to interact with NEDD4. GRCh38: Ensembl release 89: ENSG00000124225 – Ensembl, May 2017 GRCm38:...
protein Putative microRNA host gene 1 protein MTRF1: NDFIP2: encoding protein NEDD4 family-interacting protein 2 NUPL1: encoding protein Nucleoporin p58/p45...
and verified through affinity capture-MS. C19orf18 protein interacts with Nedd4 family interacting protein 1 (NDFIP1) which promotes pancreatic beta cell...
Kumar S, Poronnik P, Hooper JD (August 2008). "The ubiquitin-protein ligase Nedd4-2 differentially interacts with and regulates members of the Tweety family...
Xiang, Y.; Aiyar, A.; Carter, C.; Leis, J. (2001). "Proteins related to the Nedd4 family of ubiquitin protein ligases interact with the L domain of Rous sarcoma...
variants has not been determined. UBE2D3 has been shown to interact with NEDD4. GRCh38: Ensembl release 89: ENSG00000109332 – Ensembl, May 2017 GRCm38:...
for proteasome-mediated destruction by an "E3 ubiquitin ligase" called NEDD4-2. This mechanism may be a distinct way to control the survival of a neuron...
serine-threonine kinases of the Hippo tumor suppressor pathway; Mus musculus (Mouse) NEDD4, involved in the embryonic development and differentiation of the central...
found for this gene. UBE2E1 has been shown to interact with Ataxin 1 and NEDD4. GRCh38: Ensembl release 89: ENSG00000170142 – Ensembl, May 2017 GRCm38:...
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