This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

6ewx

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Structure of Pragmin pseudo-kinase reveals a dimerization mechanism to regulate protein tyrosine phosphorylation and nuclear transcription

Structural highlights

6ewx is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.771Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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]^[1] ^[2] ^[3] ^[4]

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^[5]

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

References

↑ Tanaka H, Katoh H, Negishi M. Pragmin, a novel effector of Rnd2 GTPase, stimulates RhoA activity. J Biol Chem. 2006 Apr 14;281(15):10355-64. PMID:16481321 doi:10.1074/jbc.M511314200
↑ Safari F, Murata-Kamiya N, Saito Y, Hatakeyama M. Mammalian Pragmin regulates Src family kinases via the Glu-Pro-Ile-Tyr-Ala (EPIYA) motif that is exploited by bacterial effectors. Proc Natl Acad Sci U S A. 2011 Sep 6;108(36):14938-43. PMID:21873224 doi:10.1073/pnas.1107740108
↑ Senda Y, Murata-Kamiya N, Hatakeyama M. C-terminal Src kinase-mediated EPIYA phosphorylation of Pragmin creates a feed-forward C-terminal Src kinase activation loop that promotes cell motility. Cancer Sci. 2016 Jul;107(7):972-80. PMID:27116701 doi:10.1111/cas.12962
↑ Lecointre C, Simon V, Kerneur C, Allemand F, Fournet A, Montarras I, Pons JL, Gelin M, Brignatz C, Urbach S, Labesse G, Roche S. Dimerization of the Pragmin Pseudo-Kinase Regulates Protein Tyrosine Phosphorylation. Structure. 2018 Apr 3;26(4):545-554.e4. doi: 10.1016/j.str.2018.01.017. Epub 2018, Mar 1. PMID:29503074 doi:http://dx.doi.org/10.1016/j.str.2018.01.017
↑ Lecointre C, Simon V, Kerneur C, Allemand F, Fournet A, Montarras I, Pons JL, Gelin M, Brignatz C, Urbach S, Labesse G, Roche S. Dimerization of the Pragmin Pseudo-Kinase Regulates Protein Tyrosine Phosphorylation. Structure. 2018 Apr 3;26(4):545-554.e4. doi: 10.1016/j.str.2018.01.017. Epub 2018, Mar 1. PMID:29503074 doi:http://dx.doi.org/10.1016/j.str.2018.01.017

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6ewx"

@@ Line 1: / Line 1: @@
 ==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=''>
+<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 [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EWX FirstGlance]. <br>
+<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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 2.771&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Prag1, Pragmin, RGD1311793_predicted, rCG_43329 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ewx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ewx OCA], [http://pdbe.org/6ewx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ewx RCSB], [http://www.ebi.ac.uk/pdbsum/6ewx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ewx ProSAT]</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=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 ==
@@ Line 21: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Buffalo rat]]
+[[Category: Large Structures]]
-[[Category: Allemand, F]]
+[[Category: Rattus norvegicus]]
-[[Category: Fournet, A]]
+[[Category: Allemand F]]
-[[Category: Gelin, M]]
+[[Category: Fournet A]]
-[[Category: Labesse, G]]
+[[Category: Gelin M]]
-[[Category: Cancer]]
+[[Category: Labesse G]]
-[[Category: Cell invasion]]
-[[Category: Pseudokinase]]
-[[Category: Scaffolding protein]]

6ewx

From Proteopedia

Current revision

Structure of Pragmin pseudo-kinase reveals a dimerization mechanism to regulate protein tyrosine phosphorylation and nuclear transcription

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox