2pnb

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[[Image:2pnb.gif|left|200px]]<br /><applet load="2pnb" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2pnb" />
 
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'''STRUCTURE OF AN SH2 DOMAIN OF THE P85 ALPHA SUBUNIT OF PHOSPHATIDYLINOSITOL-3-OH KINASE'''<br />
 
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==Overview==
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==STRUCTURE OF AN SH2 DOMAIN OF THE P85 ALPHA SUBUNIT OF PHOSPHATIDYLINOSITOL-3-OH KINASE==
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Receptor protein-tyrosine kinases, through phosphorylation of specific tyrosine residues, generate high-affinity binding sites which direct assembly of multienzyme signalling complexes. Many of these signalling proteins, including phospholipase C gamma, GTPase-activating protein and phosphatidylinositol-3-OH kinase, contain src-homology 2 (SH2) domains, which bind with high affinity and specificity to tyrosine-phosphorylated sequences. The critical role played by SH2 domains in signalling has been highlighted by recent studies showing that mutation of specific phosphorylation sites on the platelet-derived growth factor receptor impair its association with phosphatidylinositol-3-OH kinase, preventing growth factor-induced mitogenesis. Here we report the solution structure of an isolated SH2 domain from the 85K regulatory subunit of phosphatidylinositol-3-OH kinase, determined using multidimensional nuclear magnetic resonance spectroscopy. The structure is characterized by a central region of beta-sheet flanked by two alpha-helices, with a highly flexible loop close to functionally important residues previously identified by site-directed mutagenesis.
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<StructureSection load='2pnb' size='340' side='right'caption='[[2pnb]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2pnb]] 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=2PNB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PNB FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2pnb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pnb OCA], [https://pdbe.org/2pnb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pnb RCSB], [https://www.ebi.ac.uk/pdbsum/2pnb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pnb ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pn/2pnb_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2pnb ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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2PNB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Active as [http://en.wikipedia.org/wiki/Phosphatidylinositol_3-kinase Phosphatidylinositol 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.137 2.7.1.137] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PNB OCA].
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*[[Phosphoinositide 3-kinase 3D structures|Phosphoinositide 3-kinase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Structure of an SH2 domain of the p85 alpha subunit of phosphatidylinositol-3-OH kinase., Booker GW, Breeze AL, Downing AK, Panayotou G, Gout I, Waterfield MD, Campbell ID, Nature. 1992 Aug 20;358(6388):684-7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=1323062 1323062]
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[[Category: Bos taurus]]
[[Category: Bos taurus]]
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[[Category: Phosphatidylinositol 3-kinase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Booker GW]]
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[[Category: Booker, G W.]]
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[[Category: Breeze AL]]
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[[Category: Breeze, A L.]]
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[[Category: Campbell ID]]
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[[Category: Campbell, I D.]]
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[[Category: Downing AK]]
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[[Category: Downing, A K.]]
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[[Category: Gout I]]
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[[Category: Gout, I.]]
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[[Category: Panayotou G]]
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[[Category: Panayotou, G.]]
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[[Category: Waterfield MD]]
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[[Category: Waterfield, M D.]]
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[[Category: signalling protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:31:13 2008''
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Current revision

STRUCTURE OF AN SH2 DOMAIN OF THE P85 ALPHA SUBUNIT OF PHOSPHATIDYLINOSITOL-3-OH KINASE

PDB ID 2pnb

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