View source for 6d85


==Structure of the Bovine p85a BH domain E217K mutant==
<StructureSection load='6d85' size='340' side='right'caption='[[6d85]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6d85]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D85 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D85 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]] 2.203&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6d85 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d85 OCA], [https://pdbe.org/6d85 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d85 RCSB], [https://www.ebi.ac.uk/pdbsum/6d85 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d85 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/P85A_BOVIN P85A_BOVIN] Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (By similarity).
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== Publication Abstract from PubMed ==
The p85alpha protein regulates flux through the PI3K/PTEN signaling pathway, and also controls receptor trafficking via regulation of Rab-family GTPases. In this report, we determined the impact of several cancer patient-derived p85alpha mutations located within the N-terminal domains of p85alpha previously shown to bind PTEN and Rab5, and regulate their respective functions. One p85alpha mutation, L30F, significantly reduced the steady state binding to PTEN, yet enhanced the stimulation of PTEN lipid phosphatase activity. Three other p85alpha mutations (E137K, K288Q, E297K) also altered the regulation of PTEN catalytic activity. In contrast, many p85alpha mutations reduced the binding to Rab5 (L30F, I69L, I82F, I177N, E217K), and several impacted the GAP activity of p85alpha towards Rab5 (E137K, I177N, E217K, E297K). We determined the crystal structure of several of these p85alpha BH domain mutants (E137K, E217K, R262T E297K) for bovine p85alpha BH and found that the mutations did not alter the overall domain structure. Thus, several p85alpha mutations found in human cancers may deregulate PTEN and/or Rab5 regulated pathways to contribute to oncogenesis. We also engineered several experimental mutations within the p85alpha BH domain and identified L191 and V263 as important for both binding and regulation of Rab5 activity.

Patient-derived mutations within the N-terminal domains of p85alpha impact PTEN or Rab5 binding and regulation.,Mellor P, Marshall JDS, Ruan X, Whitecross DE, Ross RL, Knowles MA, Moore SA, Anderson DH Sci Rep. 2018 May 8;8(1):7108. doi: 10.1038/s41598-018-25487-5. PMID:29740032<ref>PMID:29740032</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6d85" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Bos taurus]]
[[Category: Large Structures]]
[[Category: Anderson DH]]
[[Category: Marshall JD]]
[[Category: Moore SA]]