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| | ==NMR STRUCTURE OF THE N-SH2 DOMAIN OF THE P85 SUBUNIT OF PI3-KINASE== | | ==NMR STRUCTURE OF THE N-SH2 DOMAIN OF THE P85 SUBUNIT OF PI3-KINASE== |
| - | <StructureSection load='1fu6' size='340' side='right' caption='[[1fu6]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | + | <StructureSection load='1fu6' size='340' side='right'caption='[[1fu6]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1fu6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FU6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1FU6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1fu6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FU6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FU6 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fu5|1fu5]]</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=1fu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fu6 OCA], [http://pdbe.org/1fu6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1fu6 RCSB], [http://www.ebi.ac.uk/pdbsum/1fu6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1fu6 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=1fu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fu6 OCA], [https://pdbe.org/1fu6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fu6 RCSB], [https://www.ebi.ac.uk/pdbsum/1fu6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fu6 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/P85A_RAT P85A_RAT]] 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_RAT P85A_RAT] 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 1fu6" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1fu6" 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: Buffalo rat]] | + | [[Category: Large Structures]] |
| - | [[Category: Guenther, U L]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Liu, Y]] | + | [[Category: Guenther UL]] |
| - | [[Category: Schaffhausen, B]] | + | [[Category: Liu Y]] |
| - | [[Category: Weber, T]] | + | [[Category: Schaffhausen B]] |
| - | [[Category: Central beta-sheet with two flanking alpha-helice]]
| + | [[Category: Weber T]] |
| - | [[Category: Protein binding]]
| + | |
| Structural highlights
Function
P85A_RAT 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
The N-terminal src homology 2 (SH2) domain of the p85 subunit of phosphoinositide 3-kinase (PI3K) has a higher affinity for a peptide with two phosphotyrosines than for the same peptide with only one. This unexpected result was not observed for the C-terminal SH2 from the same protein. NMR structural analysis has been used to understand the behavior of the N-SH2. The structure of the free SH2 domain has been compared to that of the SH2 complexed with a doubly phosphorylated peptide derived from polyomavirus middle T antigen (MT). The structure of the free SH2 domain shows some differences from previous NMR and X-ray structures. In the N-SH2 complexed with a doubly phosphorylated peptide, a second site for phosphotyrosine interaction has been identified. Further, line shapes of NMR signals showed that the SH2 protein-ligand complex is subject to temperature-dependent conformational mobility. Conformational mobility is also supported by the spectra of the ligand peptide. A binding model which accounts for these results is developed.
NMR structure of the N-SH2 of the p85 subunit of phosphoinositide 3-kinase complexed to a doubly phosphorylated peptide reveals a second phosphotyrosine binding site.,Weber T, Schaffhausen B, Liu Y, Gunther UL Biochemistry. 2000 Dec 26;39(51):15860-9. PMID:11123912[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Weber T, Schaffhausen B, Liu Y, Gunther UL. NMR structure of the N-SH2 of the p85 subunit of phosphoinositide 3-kinase complexed to a doubly phosphorylated peptide reveals a second phosphotyrosine binding site. Biochemistry. 2000 Dec 26;39(51):15860-9. PMID:11123912
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