View source for 6ewx


==Structure of Pragmin pseudo-kinase reveals a dimerization mechanism to regulate protein tyrosine phosphorylation and nuclear transcription==
<StructureSection load='6ewx' size='340' side='right'caption='[[6ewx]], [[Resolution|resolution]] 2.77&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ewx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EWX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EWX 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]] 2.771&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=6ewx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ewx OCA], [https://pdbe.org/6ewx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ewx RCSB], [https://www.ebi.ac.uk/pdbsum/6ewx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ewx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PRAG1_RAT PRAG1_RAT] Catalytically inactive protein kinase that acts as a scaffold protein (PubMed:29503074). Functions as an effector of the small GTPase RND2, which stimulates RhoA activity and inhibits NGF-induced neurite outgrowth (PubMed:16481321). Promotes Src family kinase (SFK) signallig by regulating the subcellular localization of CSK, a negative regulator of these kinases, leading to the regulation of cell morphology and motility by a CSK-dependent mechanism (PubMed:27116701, PubMed:21873224). Acts as a critical coactivator of Notch signaling (By similarity).[UniProtKB:Q571I4]<ref>PMID:16481321</ref> <ref>PMID:21873224</ref> <ref>PMID:27116701</ref> <ref>PMID:29503074</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The pseudo-kinase and signaling protein Pragmin has been linked to cancer by regulating protein tyrosine phosphorylation via unknown mechanisms. Here we present the crystal structure of the Pragmin 906-1,368 amino acid C terminus, which encompasses its kinase domain. We show that Pragmin contains a classical protein-kinase fold devoid of catalytic activity, despite a conserved catalytic lysine (K997). By proteomics, we discovered that this pseudo-kinase uses the tyrosine kinase CSK to induce protein tyrosine phosphorylation in human cells. Interestingly, the protein-kinase domain is flanked by N- and C-terminal extensions forming an original dimerization domain that regulates Pragmin self-association and stimulates CSK activity. A1329E mutation in the C-terminal extension destabilizes Pragmin dimerization and reduces CSK activation. These results reveal a dimerization mechanism by which a pseudo-kinase can induce protein tyrosine phosphorylation. Further sequence-structure analysis identified an additional member (C19orf35) of the superfamily of dimeric Pragmin/SgK269/PEAK1 pseudo-kinases.

Dimerization of the Pragmin Pseudo-Kinase Regulates Protein Tyrosine Phosphorylation.,Lecointre C, Simon V, Kerneur C, Allemand F, Fournet A, Montarras I, Pons JL, Gelin M, Brignatz C, Urbach S, Labesse G, Roche S Structure. 2018 Apr 3;26(4):545-554.e4. doi: 10.1016/j.str.2018.01.017. Epub 2018, Mar 1. PMID:29503074<ref>PMID:29503074</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ewx" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Allemand F]]
[[Category: Fournet A]]
[[Category: Gelin M]]
[[Category: Labesse G]]