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| | ==P395S mutant of the p85 regulatory subunit of the N-terminal src homology 2 domain of PI3-Kinase== | | ==P395S mutant of the p85 regulatory subunit of the N-terminal src homology 2 domain of PI3-Kinase== |
| - | <StructureSection load='1oo3' size='340' side='right' caption='[[1oo3]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | + | <StructureSection load='1oo3' size='340' side='right'caption='[[1oo3]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1oo3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OO3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OO3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1oo3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OO3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OO3 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1oo4|1oo4]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1oo3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oo3 OCA], [http://pdbe.org/1oo3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1oo3 RCSB], [http://www.ebi.ac.uk/pdbsum/1oo3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1oo3 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=1oo3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oo3 OCA], [https://pdbe.org/1oo3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1oo3 RCSB], [https://www.ebi.ac.uk/pdbsum/1oo3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1oo3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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). | + | [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). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 1oo3" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1oo3" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Phosphoinositide 3-kinase 3D structures|Phosphoinositide 3-kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bovin]] | + | [[Category: Bos taurus]] |
| - | [[Category: Guenther, U L]] | + | [[Category: Large Structures]] |
| - | [[Category: Schaffhausen, B]] | + | [[Category: Guenther UL]] |
| - | [[Category: Weyrauch, B]] | + | [[Category: Schaffhausen B]] |
| - | [[Category: Protein binding]] | + | [[Category: Weyrauch B]] |
| - | [[Category: Src homology 2 domain p85 regulatory subunit mutant]]
| + | |
| Structural highlights
Function
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).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Understanding the specificity of Src homology 2 (SH2) domains is important because of their critical role in cell signaling. Previous genetic analysis has characterized mutants of the N-terminal src homology 2 (SH2) domain of the p85 subunit of phosphoinositide 3-kinase (PI3K). The P395S mutant exhibits a specificity for phosphopeptide binding different from that of the wild-type SH2. The P395S mutant has an increased affinity for the platelet-derived growth factor receptor (PDGFr) compared to polyomavirus middle T antigen (MT). Solution structures of the P395S mutant of the p85 N-SH2 alone and complexed to a PDGFr phosphopeptide were determined to explain the change in specificity. Chemical shift perturbations caused by different peptides were compared for mutant and wild-type structures. The results show that the single P395S mutation has broad effects on the structure. Furthermore, they provide a rationale for the observed changes in binding preference.
Nuclear magnetic resonance structure of the P395S mutant of the N-SH2 domain of the p85 subunit of PI3 kinase: an SH2 domain with altered specificity.,Gunther UL, Weyrauch B, Zhang X, Schaffhausen B Biochemistry. 2003 Sep 30;42(38):11120-7. PMID:14503862[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gunther UL, Weyrauch B, Zhang X, Schaffhausen B. Nuclear magnetic resonance structure of the P395S mutant of the N-SH2 domain of the p85 subunit of PI3 kinase: an SH2 domain with altered specificity. Biochemistry. 2003 Sep 30;42(38):11120-7. PMID:14503862 doi:10.1021/bi034353x
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