1fu5

<StructureSection load='1fu5' size='340' side='right'caption='[[1fu5]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>

<table><tr><td colspan='2'>[[1fu5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FU5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FU5 FirstGlance]. <br>

</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1fu6|1fu6]]</div></td></tr>

[[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). [[https://www.uniprot.org/uniprot/MT_POVM3 MT_POVM3]] Plays a role in transformation by modulating the activities of cellular proteins involved in control of cell proliferation and by acting as a functional homolog of an activated tyrosine kinase-associated growth-factor receptor. Recruits upon association with host Ppp2/PP2A the Src tyrosine kinase components Src, Yes and Fyn, thereby activating their kinase activity. Activation of Shc1, Pclg1 and p85 mediate signal transduction pathways leading to cell cycle progression and cell division. MT plays also a role in regulation of early and late gene expression and in viral DNA replication.

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== 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<ref>PMID:11123912</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 1fu5" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Buffalo rat]]

[[Category: Guenther, U L]]

[[Category: Liu, Y]]

[[Category: Schaffhausen, B]]

[[Category: Weber, T]]

[[Category: Peptide binding protein]]

[[Category: Protein-peptide complex]]