2lty

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{{STRUCTURE_2lty| PDB=2lty | SCENE= }}
 
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===NEDD4L WW2 domain in complex with a Smad7 derived peptide===
 
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{{ABSTRACT_PUBMED_22921829}}
 
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==Disease==
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==NEDD4L WW2 domain in complex with a Smad7 derived peptide==
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[[http://www.uniprot.org/uniprot/SMAD7_HUMAN SMAD7_HUMAN]] Genetic variations in SMAD7 influence susceptibility to colorectal cancer type 3 (CRCS3) [MIM:[http://omim.org/entry/612229 612229]]. Colorectal cancer consists of tumors or cancer of either the colon or rectum or both. Cancers of the large intestine are the second most common form of cancer found in males and females. Symptoms include rectal bleeding, occult blood in stools, bowel obstruction and weight loss. Treatment is based largely on the extent of cancer penetration into the intestinal wall. Surgical cures are possible if the malignancy is confined to the intestine. Risk can be reduced when following a diet which is low in fat and high in fiber.<ref>PMID:17934461</ref>
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<StructureSection load='2lty' size='340' side='right'caption='[[2lty]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2lty]] 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=2LTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LTY 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=2lty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lty OCA], [https://pdbe.org/2lty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lty RCSB], [https://www.ebi.ac.uk/pdbsum/2lty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lty 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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==Function==
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==See Also==
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[[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> [[http://www.uniprot.org/uniprot/SMAD7_HUMAN SMAD7_HUMAN]] Antagonist of signaling by TGF-beta (transforming growth factor) type 1 receptor superfamily members; has been shown to inhibit TGF-beta (Transforming growth factor) and activin signaling by associating with their receptors thus preventing SMAD2 access. Functions as an adapter to recruit SMURF2 to the TGF-beta receptor complex. Also acts by recruiting the PPP1R15A-PP1 complex to TGFBR1, which promotes its dephosphorylation. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator (By similarity).<ref>PMID:9892009</ref><ref>PMID:11163210</ref><ref>PMID:12023024</ref><ref>PMID:14718519</ref><ref>PMID:17327236</ref>
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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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[[2lty]] 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=2LTY OCA].
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__TOC__
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</StructureSection>
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==Reference==
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<references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Aragon, E.]]
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[[Category: Large Structures]]
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[[Category: Gao, S.]]
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[[Category: Aragon E]]
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[[Category: Goerner, N.]]
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[[Category: Gao S]]
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[[Category: Lopes, T.]]
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[[Category: Goerner N]]
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[[Category: Macias, M J.]]
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[[Category: Lopes T]]
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[[Category: Massague, J.]]
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[[Category: Macias MJ]]
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[[Category: Xi, Q.]]
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[[Category: Massague J]]
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[[Category: Nedd4l]]
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[[Category: Xi Q]]
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[[Category: Protein binding-peptide complex]]
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[[Category: Smad7]]
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[[Category: Ww]]
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Current revision

NEDD4L WW2 domain in complex with a Smad7 derived peptide

PDB ID 2lty

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