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{{STRUCTURE_2kxq|  PDB=2kxq  |  SCENE=  }}
===Solution Structure of Smurf2 WW2 and WW3 bound to Smad7 PY motif containing peptide===
{{ABSTRACT_PUBMED_20937913}}


==Function==
==Solution Structure of Smurf2 WW2 and WW3 bound to Smad7 PY motif containing peptide==
[[http://www.uniprot.org/uniprot/SMUF2_HUMAN SMUF2_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. Interacts with SMAD1 and SMAD7 in order to trigger their ubiquitination and proteasome-dependent degradation. In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with SCYE1. Forms a stable complex with the TGF-beta receptor-mediated phosphorylated SMAD2 and SMAD3. In this way, SMAD2 may recruit substrates, such as SNON, for ubiquitin-mediated degradation. Enhances the inhibitory activity of SMAD7 and reduces the transcriptional activity of SMAD2. Coexpression of SMURF2 with SMAD1 results in considerable decrease in steady-state level of SMAD1 protein and a smaller decrease of SMAD2 level.<ref>PMID:11389444</ref><ref>PMID:12717440</ref>  
<StructureSection load='2kxq' size='340' side='right'caption='[[2kxq]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2kxq]] 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=2KXQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KXQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2kxq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kxq OCA], [https://pdbe.org/2kxq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kxq RCSB], [https://www.ebi.ac.uk/pdbsum/2kxq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kxq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SMUF2_HUMAN SMUF2_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. Interacts with SMAD1 and SMAD7 in order to trigger their ubiquitination and proteasome-dependent degradation. In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with SCYE1. Forms a stable complex with the TGF-beta receptor-mediated phosphorylated SMAD2 and SMAD3. In this way, SMAD2 may recruit substrates, such as SNON, for ubiquitin-mediated degradation. Enhances the inhibitory activity of SMAD7 and reduces the transcriptional activity of SMAD2. Coexpression of SMURF2 with SMAD1 results in considerable decrease in steady-state level of SMAD1 protein and a smaller decrease of SMAD2 level.<ref>PMID:11389444</ref> <ref>PMID:12717440</ref>  


==About this Structure==
==See Also==
[[2kxq]] 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=2KXQ OCA].
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:020937913</ref><references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Chong, A.]]
[[Category: Large Structures]]
[[Category: Forman-Kay, J D.]]
[[Category: Chong A]]
[[Category: Lin, H.]]
[[Category: Forman-Kay JD]]
[[Category: Wrana, J.]]
[[Category: Lin H]]
[[Category: Modular binding]]
[[Category: Wrana J]]
[[Category: Protein binding]]
[[Category: Py motif]]
[[Category: Smurf2]]
[[Category: Tgf-beta]]
[[Category: Ww]]

Latest revision as of 09:50, 1 May 2024

Solution Structure of Smurf2 WW2 and WW3 bound to Smad7 PY motif containing peptideSolution Structure of Smurf2 WW2 and WW3 bound to Smad7 PY motif containing peptide

Structural highlights

2kxq is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SMUF2_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. Interacts with SMAD1 and SMAD7 in order to trigger their ubiquitination and proteasome-dependent degradation. In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with SCYE1. Forms a stable complex with the TGF-beta receptor-mediated phosphorylated SMAD2 and SMAD3. In this way, SMAD2 may recruit substrates, such as SNON, for ubiquitin-mediated degradation. Enhances the inhibitory activity of SMAD7 and reduces the transcriptional activity of SMAD2. Coexpression of SMURF2 with SMAD1 results in considerable decrease in steady-state level of SMAD1 protein and a smaller decrease of SMAD2 level.[1] [2]

See Also

References

  1. ↑ Bonni S, Wang HR, Causing CG, Kavsak P, Stroschein SL, Luo K, Wrana JL. TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation. Nat Cell Biol. 2001 Jun;3(6):587-95. PMID:11389444 doi:10.1038/35078562
  2. ↑ Di Guglielmo GM, Le Roy C, Goodfellow AF, Wrana JL. Distinct endocytic pathways regulate TGF-beta receptor signalling and turnover. Nat Cell Biol. 2003 May;5(5):410-21. PMID:12717440 doi:10.1038/ncb975
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