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{{STRUCTURE_2nsq|  PDB=2nsq  |  SCENE=  }}
===Crystal structure of the C2 domain of the human E3 ubiquitin-protein ligase NEDD4-like protein===
{{ABSTRACT_PUBMED_11840194}}


==Function==
==Crystal structure of the C2 domain of the human E3 ubiquitin-protein ligase NEDD4-like protein==
[[http://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>
<StructureSection load='2nsq' size='340' side='right'caption='[[2nsq]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2nsq]] 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=2NSQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NSQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=2nsq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nsq OCA], [https://pdbe.org/2nsq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nsq RCSB], [https://www.ebi.ac.uk/pdbsum/2nsq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nsq ProSAT]</span></td></tr>
</table>
== 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>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ns/2nsq_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2nsq ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
[[2nsq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NSQ OCA].
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:011840194</ref><references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Arrowsmith, C H.]]
[[Category: Large Structures]]
[[Category: Avvakumov, G V.]]
[[Category: Arrowsmith CH]]
[[Category: Bochkarev, A.]]
[[Category: Avvakumov GV]]
[[Category: Butler-Cole, C.]]
[[Category: Bochkarev A]]
[[Category: Dhe-Paganon, S.]]
[[Category: Butler-Cole C]]
[[Category: Edwards, A M.]]
[[Category: Dhe-Paganon S]]
[[Category: Finerty, P J.]]
[[Category: Edwards AM]]
[[Category: SGC, Structural Genomics Consortium.]]
[[Category: Finerty Jr PJ]]
[[Category: Sundstrom, M.]]
[[Category: Sundstrom M]]
[[Category: Walker, J R.]]
[[Category: Walker JR]]
[[Category: Weigelt, J.]]
[[Category: Weigelt J]]
[[Category: Xue, S.]]
[[Category: Xue S]]
[[Category: C2 domain]]
[[Category: Ligase]]
[[Category: Sgc]]
[[Category: Structural genomics consortium]]
[[Category: Ubl-conjugation pathway]]

Latest revision as of 10:19, 30 August 2023

Crystal structure of the C2 domain of the human E3 ubiquitin-protein ligase NEDD4-like protein

2nsq, resolution 1.85Å

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