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| | <StructureSection load='2oni' size='340' side='right'caption='[[2oni]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='2oni' size='340' side='right'caption='[[2oni]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2oni]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ONI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ONI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2oni]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ONI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ONI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2nsq|2nsq]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NEDD4L, KIAA0439, NEDL3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2oni FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oni OCA], [https://pdbe.org/2oni PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oni RCSB], [https://www.ebi.ac.uk/pdbsum/2oni PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oni ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2oni FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oni OCA], [https://pdbe.org/2oni PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oni RCSB], [https://www.ebi.ac.uk/pdbsum/2oni PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oni ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/NED4L_HUMAN NED4L_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. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, Nav1.2, Nav1.3, Nav1.5, Nav1.7, Nav1.8, Kv1.3, EAAT1 or CLC5. Promotes ubiquitination and degradation of SGK1 and TNK2.<ref>PMID:12911626</ref> <ref>PMID:15217910</ref> <ref>PMID:15489223</ref> <ref>PMID:15040001</ref> <ref>PMID:15496141</ref> <ref>PMID:15576372</ref> <ref>PMID:19144635</ref>
| + | [https://www.uniprot.org/uniprot/NED4L_HUMAN NED4L_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. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, Nav1.2, Nav1.3, Nav1.5, Nav1.7, Nav1.8, Kv1.3, EAAT1 or CLC5. Promotes ubiquitination and degradation of SGK1 and TNK2.<ref>PMID:12911626</ref> <ref>PMID:15217910</ref> <ref>PMID:15489223</ref> <ref>PMID:15040001</ref> <ref>PMID:15496141</ref> <ref>PMID:15576372</ref> <ref>PMID:19144635</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Avvakumov, G V]] | + | [[Category: Avvakumov GV]] |
| - | [[Category: Bochkarev, A]] | + | [[Category: Bochkarev A]] |
| - | [[Category: Butler-Cole, C]] | + | [[Category: Butler-Cole C]] |
| - | [[Category: Dhe-Paganon, S]] | + | [[Category: Dhe-Paganon S]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Edwards AM]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Sundstrom M]] |
| - | [[Category: Sundstrom, M]] | + | [[Category: Walker JR]] |
| - | [[Category: Walker, J R]] | + | [[Category: Weigelt J]] |
| - | [[Category: Weigelt, J]] | + | [[Category: Xue S]] |
| - | [[Category: Xue, S]] | + | |
| - | [[Category: E3 ligase]]
| + | |
| - | [[Category: Hect domain]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Sgc]]
| + | |
| - | [[Category: Ubl-conjugation pathway]]
| + | |
| Structural highlights
Function
NED4L_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. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, Nav1.2, Nav1.3, Nav1.5, Nav1.7, Nav1.8, Kv1.3, EAAT1 or CLC5. Promotes ubiquitination and degradation of SGK1 and TNK2.[1] [2] [3] [4] [5] [6] [7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
See Also
References
- ↑ Boehmer C, Henke G, Schniepp R, Palmada M, Rothstein JD, Broer S, Lang F. 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 Sep;86(5):1181-8. PMID:12911626
- ↑ van Bemmelen MX, Rougier JS, Gavillet B, Apotheloz F, Daidie D, Tateyama M, Rivolta I, Thomas MA, Kass RS, Staub O, Abriel H. Cardiac voltage-gated sodium channel Nav1.5 is regulated by Nedd4-2 mediated ubiquitination. Circ Res. 2004 Aug 6;95(3):284-91. Epub 2004 Jun 24. PMID:15217910 doi:10.1161/01.RES.0000136816.05109.89
- ↑ Hryciw DH, Ekberg J, Lee A, Lensink IL, Kumar S, Guggino WB, Cook DI, Pollock CA, Poronnik P. Nedd4-2 functionally interacts with ClC-5: involvement in constitutive albumin endocytosis in proximal tubule cells. J Biol Chem. 2004 Dec 31;279(53):54996-5007. Epub 2004 Oct 15. PMID:15489223 doi:M411491200
- ↑ 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 May;199(2):194-9. PMID:15040001 doi:10.1002/jcp.10430
- ↑ Kuratomi G, Komuro A, Goto K, Shinozaki M, Miyazawa K, Miyazono K, Imamura T. 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 Mar 15;386(Pt 3):461-70. PMID:15496141 doi:BJ20040738
- ↑ Zhou R, Snyder PM. Nedd4-2 phosphorylation induces serum and glucocorticoid-regulated kinase (SGK) ubiquitination and degradation. J Biol Chem. 2005 Feb 11;280(6):4518-23. Epub 2004 Dec 2. PMID:15576372 doi:10.1074/jbc.M411053200
- ↑ Chan W, Tian R, Lee YF, Sit ST, Lim L, Manser E. Down-regulation of active ACK1 is mediated by association with the E3 ubiquitin ligase Nedd4-2. J Biol Chem. 2009 Mar 20;284(12):8185-94. doi: 10.1074/jbc.M806877200. Epub 2009 , Jan 14. PMID:19144635 doi:10.1074/jbc.M806877200
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