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5tj7

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Revision as of 12:12, 23 September 2020

Structure of WWP2 WW2-2,3-linker-HECT aa 334-398 linked to 485-865

Structural highlights

5tj7 is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	5tj8, 5tjq
Activity:	Transferase, with EC number 2.3.2.26
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[WWP2_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. Polyubiquitinates POU5F1 by 'Lys-63'-linked conjugation and promotes it to proteasomal degradation; in embryonic stem cells (ESCs) the ubiquitination is proposed to regulate POU5F1 protein level. Ubiquitinates EGR2 and promotes it to proteasomal degradation; in T-cells the ubiquitination inhibits activation-induced cell death. Ubiquitinates SLC11A2; the ubiquitination is enhanced by presence of NDFIP1 and NDFIP2. Ubiquitinates RPB1 and promotes it to proteasomal degradation.^[1] ^[2]

Publication Abstract from PubMed

The HECT E3 ligases ubiquitinate numerous transcription factors and signaling molecules, and their activity must be tightly controlled to prevent cancer, immune disorders, and other diseases. In this study, we have found unexpectedly that peptide linkers tethering WW domains in several HECT family members are key regulatory elements of their catalytic activities. Biochemical, structural, and cellular analyses have revealed that the linkers can lock the HECT domain in an inactive conformation and block the proposed allosteric ubiquitin binding site. Such linker-mediated autoinhibition of the HECT domain can be relieved by linker post-translational modifications, but complete removal of the brake can induce hyperactive autoubiquitination and E3 self destruction. These results clarify the mechanisms of several HECT protein cancer associated mutations and provide a new framework for understanding how HECT ubiquitin ligases must be finely tuned to ensure normal cellular behavior.

A Tunable Brake for HECT Ubiquitin Ligases.,Chen Z, Jiang H, Xu W, Li X, Dempsey DR, Zhang X, Devreotes P, Wolberger C, Amzel LM, Gabelli SB, Cole PA Mol Cell. 2017 May 4;66(3):345-357.e6. doi: 10.1016/j.molcel.2017.03.020. PMID:28475870^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Xu H, Wang W, Li C, Yu H, Yang A, Wang B, Jin Y. WWP2 promotes degradation of transcription factor OCT4 in human embryonic stem cells. Cell Res. 2009 May;19(5):561-73. doi: 10.1038/cr.2009.31. PMID:19274063 doi:http://dx.doi.org/10.1038/cr.2009.31
↑ Chen A, Gao B, Zhang J, McEwen T, Ye SQ, Zhang D, Fang D. The HECT-type E3 ubiquitin ligase AIP2 inhibits activation-induced T-cell death by catalyzing EGR2 ubiquitination. Mol Cell Biol. 2009 Oct;29(19):5348-56. doi: 10.1128/MCB.00407-09. Epub 2009 Aug , 3. PMID:19651900 doi:http://dx.doi.org/10.1128/MCB.00407-09
↑ Chen Z, Jiang H, Xu W, Li X, Dempsey DR, Zhang X, Devreotes P, Wolberger C, Amzel LM, Gabelli SB, Cole PA. A Tunable Brake for HECT Ubiquitin Ligases. Mol Cell. 2017 May 4;66(3):345-357.e6. doi: 10.1016/j.molcel.2017.03.020. PMID:28475870 doi:http://dx.doi.org/10.1016/j.molcel.2017.03.020

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5tj7"

@@ Line 1: / Line 1: @@
 ==Structure of WWP2 WW2-2,3-linker-HECT aa 334-398 linked to 485-865==
-<StructureSection load='5tj7' size='340' side='right' caption='[[5tj7]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
+<StructureSection load='5tj7' size='340' side='right'caption='[[5tj7]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5tj7]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TJ7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TJ7 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5tj7]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TJ7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5TJ7 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tj8|5tj8]], [[5tjq|5tjq]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.26 2.3.2.26] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5tj7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tj7 OCA], [http://pdbe.org/5tj7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tj7 RCSB], [http://www.ebi.ac.uk/pdbsum/5tj7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tj7 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5tj7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tj7 OCA], [http://pdbe.org/5tj7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tj7 RCSB], [http://www.ebi.ac.uk/pdbsum/5tj7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tj7 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 5tj7" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
+*[[WWP2|WWP2]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Transferase]]
 [[Category: Chen, Z]]

5tj7

From Proteopedia

Revision as of 12:12, 23 September 2020

Structure of WWP2 WW2-2,3-linker-HECT aa 334-398 linked to 485-865

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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