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[[Image:2iui.gif|left|200px]]


{{Structure
==Crystal structure of the PI3-kinase p85 N-terminal SH2 domain in complex with PDGFR phosphotyrosyl peptide==
|PDB= 2iui |SIZE=350|CAPTION= <scene name='initialview01'>2iui</scene>, resolution 2.40&Aring;
<StructureSection load='2iui' size='340' side='right'caption='[[2iui]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>
<table><tr><td colspan='2'>[[2iui]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IUI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IUI FirstGlance]. <br>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2iui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2iui OCA], [https://pdbe.org/2iui PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2iui RCSB], [https://www.ebi.ac.uk/pdbsum/2iui PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2iui ProSAT]</span></td></tr>
|RELATEDENTRY=
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2iui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2iui OCA], [http://www.ebi.ac.uk/pdbsum/2iui PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2iui RCSB]</span>
== Function ==
}}
[https://www.uniprot.org/uniprot/P85A_HUMAN P85A_HUMAN] 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.<ref>PMID:7518429</ref> <ref>PMID:17626883</ref> <ref>PMID:19805105</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/iu/2iui_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2iui ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Crystal structures of the amino-terminal SH2 domain of the p85alpha subunit of phosphatidylinositol (PI) 3-kinase, alone and in complex with phosphopeptides bearing pTyr-Met/Val-Xaa-Met motifs, show that phosphopeptides bind in the two-pronged manner seen in high-affinity Lck and Src SH2 complexes, with conserved interactions between the domain and the peptide segment from phosphotyrosine to Met+3. Peptide binding requires the rearrangement of a tyrosyl side chain in the BG loop to create the hydrophobic Met+3 binding pocket. The structures suggest a mechanism for the biological specificity exhibited by PI 3-kinase in its interactions with phosphoprotein partners.


'''CRYSTAL STRUCTURE OF THE PI3-KINASE P85 N-TERMINAL SH2 DOMAIN IN COMPLEX WITH PDGFR PHOSPHOTYROSYL PEPTIDE'''
Crystal structure of the PI 3-kinase p85 amino-terminal SH2 domain and its phosphopeptide complexes.,Nolte RT, Eck MJ, Schlessinger J, Shoelson SE, Harrison SC Nat Struct Biol. 1996 Apr;3(4):364-74. PMID:8599763<ref>PMID:8599763</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2iui" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
Crystal structures of the amino-terminal SH2 domain of the p85alpha subunit of phosphatidylinositol (PI) 3-kinase, alone and in complex with phosphopeptides bearing pTyr-Met/Val-Xaa-Met motifs, show that phosphopeptides bind in the two-pronged manner seen in high-affinity Lck and Src SH2 complexes, with conserved interactions between the domain and the peptide segment from phosphotyrosine to Met+3. Peptide binding requires the rearrangement of a tyrosyl side chain in the BG loop to create the hydrophobic Met+3 binding pocket. The structures suggest a mechanism for the biological specificity exhibited by PI 3-kinase in its interactions with phosphoprotein partners.
*[[Phosphoinositide 3-kinase 3D structures|Phosphoinositide 3-kinase 3D structures]]
 
== References ==
==About this Structure==
<references/>
2IUI is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IUI OCA].
__TOC__
 
</StructureSection>
==Reference==
Crystal structure of the PI 3-kinase p85 amino-terminal SH2 domain and its phosphopeptide complexes., Nolte RT, Eck MJ, Schlessinger J, Shoelson SE, Harrison SC, Nat Struct Biol. 1996 Apr;3(4):364-74. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8599763 8599763]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Eck, M J.]]
[[Category: Eck MJ]]
[[Category: Harrison, S C.]]
[[Category: Harrison SC]]
[[Category: Nolte, R T.]]
[[Category: Nolte RT]]
[[Category: Schlessinger, J.]]
[[Category: Schlessinger J]]
[[Category: Shoelson, S E.]]
[[Category: Shoelson SE]]
[[Category: disease mutation]]
[[Category: p85]]
[[Category: phosphorylation]]
[[Category: pi3-kinase]]
[[Category: pi3k]]
[[Category: polymorphism]]
[[Category: sh2]]
[[Category: sh2 domain]]
[[Category: sh3 domain]]
[[Category: transferase]]
[[Category: ubl conjugation]]
 
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