5c56: Difference between revisions

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==Crystal structure of USP7/HAUSP in complex with ICP0==
==Crystal structure of USP7/HAUSP in complex with ICP0==
<StructureSection load='5c56' size='340' side='right' caption='[[5c56]], [[Resolution|resolution]] 2.69&Aring;' scene=''>
<StructureSection load='5c56' size='340' side='right'caption='[[5c56]], [[Resolution|resolution]] 2.69&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5c56]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C56 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5C56 FirstGlance]. <br>
<table><tr><td colspan='2'>[[5c56]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_alphaherpesvirus_1 Human alphaherpesvirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C56 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5C56 FirstGlance]. <br>
</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </span></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.685&#8491;</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=5c56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c56 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5c56 RCSB], [http://www.ebi.ac.uk/pdbsum/5c56 PDBsum]</span></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=5c56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c56 OCA], [https://pdbe.org/5c56 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5c56 RCSB], [https://www.ebi.ac.uk/pdbsum/5c56 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5c56 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/UBP7_HUMAN UBP7_HUMAN]] Hydrolase that deubiquitinates target proteins such as FOXO4, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN and DAXX. Together with DAXX, prevents MDM2 self-ubiquitination and enhances the E3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53 ubiquitination and proteasomal degradation. Deubiquitinates p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even in the presence of excess MDM2, and also induces p53/TP53-dependent cell growth repression and apoptosis. Deubiquitination of FOXO4 in presence of hydrogen peroxide is not dependent on p53/TP53 and inhibits FOXO4-induced transcriptional activity. In association with DAXX, is involved in the deubiquitination and translocation of PTEN from the nucleus to the cytoplasm, both processes that are counteracted by PML. Involved in cell proliferation during early embryonic development. Involved in transcription-coupled nucleotide excision repair (TC-NER) in response to UV damage: recruited to DNA damage sites following interaction with KIAA1530/UVSSA and promotes deubiquitination of ERCC6, preventing UV-induced degradation of ERCC6. Contributes to the overall stabilization and trans-activation capability of the herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110 during HSV-1 infection. Involved in maintenance of DNA methylation via its interaction with UHRF1 and DNMT1: acts by mediating deubiquitination of UHRF1 and DNMT1, preventing their degradation and promoting DNA methylation by DNMT1. Exhibits a preference towards 'Lys-48'-linked Ubiquitin chains.<ref>PMID:11923872</ref> <ref>PMID:14506283</ref> <ref>PMID:15053880</ref> <ref>PMID:16160161</ref> <ref>PMID:16964248</ref> <ref>PMID:18716620</ref> <ref>PMID:18590780</ref> <ref>PMID:20153724</ref> <ref>PMID:21745816</ref> <ref>PMID:22411829</ref> <ref>PMID:22689415</ref> <ref>PMID:22466611</ref> <ref>PMID:22466612</ref> 
[https://www.uniprot.org/uniprot/ICP0_HHV11 ICP0_HHV11] SUMO-targeted ubiquitin ligase that plays an essential role in nuclear antiviral defense evasion triggered by dsDNA viruses (PubMed:32001251). Acts during the initial stages of lytic infection and the reactivation of latent viral genome. Prevents the antiviral effect of nuclear bodies by degrading host PML, SP100 and MORC3 (PubMed:27440897, PubMed:34759314). Prevents antiviral response to viral DNA induced by IFI16 by degrading it. Additionally, inhibits host IRF3 nuclear signaling to prevent interferon production by the infected cells. Interestingly, the E3 ubiquitin ligase activity associated with the RING finger domain does not seem to be directly required to inhibit the activation of IRF3 but instead plays a critical role in modulating the cellular localization of ICP0. Upon reactivation of latent genome, suppresses the silencing of viral DNA by dissociating either HDAC1 or HDAC2 from the HDAC-RCOR1-REST-KDM1A complex localized at the ND10 structures and causes their dispersal. Two cellular histone ubiquitin ligases RNF8 and RNF168 are also targeted by ICP0 for degradation, leading to a loss of ubiquitinated forms of H2A, a relief of transcriptional repression, and the activation of latent viral genomes. Enhances the localization of host CCND3 to ND10 bodies that serve as precursors of replication compartments to enable efficient viral replication. Like many RING-finger E3 ubiquitin ligases, ICP0 can induce its own ubiquitination, an activity that promotes its instability due to its targeting to the 26S proteasome for degradation. ICP0 restricts this process by recruiting the cellular ubiquitin-specific protease USP7 that cleaves the anchored ubiquitin chains from ICP0, thereby promoting its stabilization.<ref>PMID:15897453</ref> <ref>PMID:16160161</ref> <ref>PMID:20075863</ref> <ref>PMID:20106921</ref> <ref>PMID:20454685</ref> <ref>PMID:22405594</ref> <ref>PMID:23027953</ref> <ref>PMID:27440897</ref> <ref>PMID:34759314</ref>  
 
==See Also==
*[[Thioesterase 3D structures|Thioesterase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Ubiquitinyl hydrolase 1]]
[[Category: Homo sapiens]]
[[Category: Cheng, J]]
[[Category: Human alphaherpesvirus 1]]
[[Category: Fang, J]]
[[Category: Large Structures]]
[[Category: Gong, R]]
[[Category: Cheng J]]
[[Category: Li, Z]]
[[Category: Fang J]]
[[Category: Sun, C]]
[[Category: Gong R]]
[[Category: Xu, Y]]
[[Category: Li Z]]
[[Category: Yang, H]]
[[Category: Sun C]]
[[Category: Yang, Y]]
[[Category: Xu Y]]
[[Category: Deubiquitination]]
[[Category: Yang H]]
[[Category: Usp7]]
[[Category: Yang Y]]
[[Category: Virus protein icp0]]

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