2m3o

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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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==Disease==
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==Structure and dynamics of a human Nedd4 WW domain-ENaC complex==
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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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<StructureSection load='2m3o' size='340' side='right'caption='[[2m3o]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2m3o]] is a 2 chain structure with sequence from [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M3O FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2m3o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m3o OCA], [https://pdbe.org/2m3o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m3o RCSB], [https://www.ebi.ac.uk/pdbsum/2m3o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m3o ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://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>
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==Function==
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==See Also==
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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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*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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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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__TOC__
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</StructureSection>
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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]]
[[Category: Homo sapiens]]
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[[Category: Bobby, R.]]
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[[Category: Large Structures]]
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[[Category: Brimble, M A.]]
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[[Category: Bobby R]]
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[[Category: Dingley, A J.]]
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[[Category: Brimble MA]]
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[[Category: Lee, V.]]
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[[Category: Dingley AJ]]
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[[Category: Lott, J.]]
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[[Category: Lee V]]
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[[Category: MacDonald, F J.]]
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[[Category: Lott J]]
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[[Category: Medini, K.]]
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[[Category: MacDonald FJ]]
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[[Category: Neudecker, P.]]
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[[Category: Medini K]]
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[[Category: Enac]]
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[[Category: Neudecker P]]
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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]]
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Current revision

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

PDB ID 2m3o

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