View source for 7klz


==Structure of SPOP MATH domain in complex with a Geminin peptide==
<StructureSection load='7klz' size='340' side='right'caption='[[7klz]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7klz]] is a 4 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=7KLZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KLZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=7klz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7klz OCA], [https://pdbe.org/7klz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7klz RCSB], [https://www.ebi.ac.uk/pdbsum/7klz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7klz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SPOP_HUMAN SPOP_HUMAN] Inhibits IPF1/PDX1 transactivation of established target promoters, such as insulin, may be by recruiting a repressor complex (By similarity). In complex with CUL3, involved in ubiquitination of BMI1, H2AFY and DAXX, and probably also in ubiquitination and proteasomal degradation of Gli2 or Gli3.<ref>PMID:14528312</ref> <ref>PMID:15897469</ref> <ref>PMID:16524876</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Geminin and its binding partner Cdt1 are essential for the regulation of DNA replication. Here we show that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP binds Geminin at endogenous level and regulates DNA replication. SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127. This poly-ubiquitination of Geminin prevents DNA replication over-firing by indirectly blocking the association of Cdt1 with the MCM protein complex, an interaction required for DNA unwinding and replication. SPOP is frequently mutated in certain human cancer types and implicated in tumorigenesis. We show that cancer-associated SPOP mutations impair Geminin K27-linked poly-ubiquitination and induce replication origin over-firing and re-replication. The replication stress caused by SPOP mutations triggers replication catastrophe and cell death upon ATR inhibition. Our results reveal a tumor suppressor role of SPOP in preventing DNA replication over-firing and genome instability and suggest that SPOP-mutated tumors may be susceptible to ATR inhibitor therapy.

SPOP mutation induces replication over-firing by impairing Geminin ubiquitination and triggers replication catastrophe upon ATR inhibition.,Ma J, Shi Q, Cui G, Sheng H, Botuyan MV, Zhou Y, Yan Y, He Y, Wang L, Wang Y, Mer G, Ye D, Wang C, Huang H Nat Commun. 2021 Oct 1;12(1):5779. doi: 10.1038/s41467-021-26049-6. PMID:34599168<ref>PMID:34599168</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7klz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Speckle-type POZ protein 3D structures|Speckle-type POZ protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Botuyan MV]]
[[Category: Cui G]]
[[Category: Mer G]]