2m3o

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'''Unreleased structure'''
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{{STRUCTURE_2m3o| PDB=2m3o | SCENE= }}
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===Structure and dynamics of a human Nedd4 WW domain-ENaC complex===
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{{ABSTRACT_PUBMED_23665454}}
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The entry 2m3o is ON HOLD until Paper Publication
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==Disease==
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[[http://www.uniprot.org/uniprot/SCNNA_HUMAN SCNNA_HUMAN]] Idiopathic bronchiectasis;Generalized pseudohypoaldosteronism type 1. The disease is caused by mutations affecting the gene represented in this entry. The degree of channel function impairment differentially affects the renin-aldosterone system and urinary Na/K ratios, resulting in distinct genotype-phenotype relationships in PHA1 patients. Loss-of-function mutations are associated with a severe clinical course and age-dependent hyperactivation of the renin-aldosterone system. This feature is not observed in patients with missense mutations that reduce but do not eliminate channel function. Markedly reduced channel activity results in impaired linear growth and delayed puberty (PubMed:18634878). The disease is caused by mutations affecting the gene represented in this entry.
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Authors: Bobby, R., Medini, K., Neudecker, P., Lee, V., MacDonald, F.J., Brimble, M.A., Lott, J., Dingley, A.J.
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==Function==
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[[http://www.uniprot.org/uniprot/NEDD4_HUMAN NEDD4_HUMAN]] E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. According to PubMed:18562292 the direct link between NEDD4 and PTEN regulation through polyubiquitination described in PubMed:17218260 is questionable. Involved in ubiquitination of ERBB4 intracellular domain E4ICD. Involved in the budding of many viruses. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. Ubiquitinates TNK2 and regulates EGF-induced degradation of EGFR and TNF2.<ref>PMID:17218260</ref> <ref>PMID:18562292</ref> <ref>PMID:20086093</ref> <ref>PMID:21765395</ref> <ref>PMID:21399620</ref> [[http://www.uniprot.org/uniprot/SCNNA_HUMAN SCNNA_HUMAN]] Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception.
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Description: Structure and dynamics of a human Nedd4 WW domain-ENaC complex
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==About this Structure==
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[[2m3o]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M3O OCA].
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==Reference==
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<ref group="xtra">PMID:023665454</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
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[[Category: Bobby, R.]]
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[[Category: Brimble, M A.]]
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[[Category: Dingley, A J.]]
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[[Category: Lee, V.]]
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[[Category: Lott, J.]]
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[[Category: MacDonald, F J.]]
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[[Category: Medini, K.]]
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[[Category: Neudecker, P.]]
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[[Category: Enac]]
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[[Category: Peptide binding protein-protein binding complex]]
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[[Category: Ubiquitin e3 ligase]]
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[[Category: Ww domain]]

Revision as of 07:32, 28 August 2013

Template:STRUCTURE 2m3o

Contents

Structure and dynamics of a human Nedd4 WW domain-ENaC complex

Template:ABSTRACT PUBMED 23665454

Disease

[SCNNA_HUMAN] Idiopathic bronchiectasis;Generalized pseudohypoaldosteronism type 1. The disease is caused by mutations affecting the gene represented in this entry. The degree of channel function impairment differentially affects the renin-aldosterone system and urinary Na/K ratios, resulting in distinct genotype-phenotype relationships in PHA1 patients. Loss-of-function mutations are associated with a severe clinical course and age-dependent hyperactivation of the renin-aldosterone system. This feature is not observed in patients with missense mutations that reduce but do not eliminate channel function. Markedly reduced channel activity results in impaired linear growth and delayed puberty (PubMed:18634878). The disease is caused by mutations affecting the gene represented in this entry.

Function

[NEDD4_HUMAN] E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. According to PubMed:18562292 the direct link between NEDD4 and PTEN regulation through polyubiquitination described in PubMed:17218260 is questionable. Involved in ubiquitination of ERBB4 intracellular domain E4ICD. Involved in the budding of many viruses. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. Ubiquitinates TNK2 and regulates EGF-induced degradation of EGFR and TNF2.[1] [2] [3] [4] [5] [SCNNA_HUMAN] Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception.

About this Structure

2m3o is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

  • Bobby R, Medini K, Neudecker P, Lee TV, Brimble MA, McDonald FJ, Lott JS, Dingley AJ. Structure and dynamics of human Nedd4-1 WW3 in complex with the alphaENaC PY motif. Biochim Biophys Acta. 2013 Aug;1834(8):1632-41. doi:, 10.1016/j.bbapap.2013.04.031. Epub 2013 May 8. PMID:23665454 doi:10.1016/j.bbapap.2013.04.031
  1. ↑ Wang X, Trotman LC, Koppie T, Alimonti A, Chen Z, Gao Z, Wang J, Erdjument-Bromage H, Tempst P, Cordon-Cardo C, Pandolfi PP, Jiang X. NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN. Cell. 2007 Jan 12;128(1):129-39. PMID:17218260 doi:10.1016/j.cell.2006.11.039
  2. ↑ Fouladkou F, Landry T, Kawabe H, Neeb A, Lu C, Brose N, Stambolic V, Rotin D. The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization. Proc Natl Acad Sci U S A. 2008 Jun 24;105(25):8585-90. doi:, 10.1073/pnas.0803233105. Epub 2008 Jun 18. PMID:18562292 doi:10.1073/pnas.0803233105
  3. ↑ Lin Q, Wang J, Childress C, Sudol M, Carey DJ, 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 Mar;30(6):1541-54. doi: 10.1128/MCB.00013-10. Epub 2010 Jan, 19. PMID:20086093 doi:10.1128/MCB.00013-10
  4. ↑ Persaud A, Alberts P, Hayes M, Guettler S, Clarke I, Sicheri F, Dirks P, Ciruna B, Rotin D. Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and function. EMBO J. 2011 Jul 15;30(16):3259-73. doi: 10.1038/emboj.2011.234. PMID:21765395 doi:10.1038/emboj.2011.234
  5. ↑ Maspero E, Mari S, Valentini E, Musacchio A, Fish A, Pasqualato S, Polo S. Structure of the HECT:ubiquitin complex and its role in ubiquitin chain elongation. EMBO Rep. 2011 Mar 11. PMID:21399620 doi:10.1038/embor.2011.21

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