2nsq

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[[Image:2nsq.gif|left|200px]]
 
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==Crystal structure of the C2 domain of the human E3 ubiquitin-protein ligase NEDD4-like protein==
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The line below this paragraph, containing "STRUCTURE_2nsq", creates the "Structure Box" on the page.
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<StructureSection load='2nsq' size='340' side='right'caption='[[2nsq]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<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>
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or leave the SCENE parameter empty for the default display.
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</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>
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<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>
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{{STRUCTURE_2nsq| PDB=2nsq | SCENE= }}
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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=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>
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</table>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ns/2nsq_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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'''Crystal structure of the C2 domain of the human E3 ubiquitin-protein ligase NEDD4-like protein'''
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==See Also==
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*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
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== References ==
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==Overview==
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<references/>
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The validation of full-length cDNA represents a crucial step in gene identification and subsequent functional analysis. In searching for candidate genes for bipolar disorder on chromosome 18q21, a novel gene homologous to NEDD4 (Neural precursor cells expressed developmentally down-regulated) was identified using exon trapping and cDNA cloning. This novel gene is termed NEDD4L (Human Gene Nomenclature Committee symbol). Typical NEDD4 orthologues that contain a C2 (Ca(2+)/lipid-binding) and a HECT (Homologous to the E6-AP Carboxyl Terminus) ubiquitin-protein ligase domain, and multiple WW domains have been shown to regulate the epithelial sodium channel (ENaC). In mice, Nedd4 has two distinct isoforms termed Nedd4-1 that belongs to the typical NEDD4 class, and Nedd4-2 that is homologous to Nedd4-1 but lacks the C2 domain. NEDD4L contains the WW and HECT domains seen in the NEDD4 gene family, but lacks the C2 domain in the N-terminus. BLAST database search showed that the deduced polypeptide of NEDD4L has 97 and 62% sequence identity to mouse Nedd4-2 and human NEDD4, respectively. Multiple forms of transcripts of NEDD4L have been isolated, which differ in transcription start and termination sites together with the presence or absence of an alternative spliced exon. Northern blot analysis showed a 3.4 kb mRNA species was specifically expressed in heart and skeletal muscle, while a 3.2 kb band and/or an additional 3.6 kb band is seen in other tissues tested. Striking homology of NEDD4L to mouse Nedd4-2 suggests it is the human homologue of mouse Nedd4-2. Its position in a region of linkage for autosomal dominant orthostatic hypotensive disorder and its potential role in regulating ENaC make NEDD4L a candidate gene for this disorder.
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__TOC__
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</StructureSection>
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==About this Structure==
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2NSQ is a [[Single protein]] structure of 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].
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==Reference==
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NEDD4L on human chromosome 18q21 has multiple forms of transcripts and is a homologue of the mouse Nedd4-2 gene., Chen H, Ross CA, Wang N, Huo Y, MacKinnon DF, Potash JB, Simpson SG, McMahon FJ, DePaulo Jr JR, McInnis MG, Eur J Hum Genet. 2001 Dec;9(12):922-30. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11840194 11840194]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Arrowsmith, C H.]]
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[[Category: Arrowsmith CH]]
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[[Category: Avvakumov, G V.]]
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[[Category: Avvakumov GV]]
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[[Category: Bochkarev, A.]]
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[[Category: Bochkarev A]]
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[[Category: Butler-Cole, C.]]
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[[Category: Butler-Cole C]]
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[[Category: Dhe-Paganon, S.]]
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[[Category: Dhe-Paganon S]]
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[[Category: Edwards, A M.]]
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[[Category: Edwards AM]]
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[[Category: Jr., P J.Finerty.]]
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[[Category: Finerty Jr PJ]]
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[[Category: SGC, Structural Genomics Consortium.]]
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[[Category: Sundstrom M]]
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[[Category: Sundstrom, M.]]
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[[Category: Walker JR]]
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[[Category: Walker, J R.]]
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[[Category: Weigelt J]]
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[[Category: Weigelt, J.]]
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[[Category: Xue S]]
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[[Category: Xue, S.]]
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[[Category: C2 domain]]
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[[Category: Ligase]]
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[[Category: Sgc]]
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[[Category: Structural genomics consortium]]
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[[Category: Ubl-conjugation pathway]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 09:52:00 2008''
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Current revision

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

PDB ID 2nsq

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