1irs

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==IRS-1 PTB DOMAIN COMPLEXED WITH A IL-4 RECEPTOR PHOSPHOPEPTIDE, NMR, MINIMIZED AVERAGE STRUCTURE==
==IRS-1 PTB DOMAIN COMPLEXED WITH A IL-4 RECEPTOR PHOSPHOPEPTIDE, NMR, MINIMIZED AVERAGE STRUCTURE==
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<StructureSection load='1irs' size='340' side='right'caption='[[1irs]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''>
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<StructureSection load='1irs' size='340' side='right'caption='[[1irs]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[1irs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IRS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IRS FirstGlance]. <br>
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<table><tr><td colspan='2'>[[1irs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IRS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IRS FirstGlance]. <br>
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</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>
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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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTB DOMAIN OF IRS-1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1irs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1irs OCA], [https://pdbe.org/1irs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1irs RCSB], [https://www.ebi.ac.uk/pdbsum/1irs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1irs 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=1irs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1irs OCA], [https://pdbe.org/1irs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1irs RCSB], [https://www.ebi.ac.uk/pdbsum/1irs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1irs ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[https://www.uniprot.org/uniprot/IRS1_HUMAN IRS1_HUMAN]] Polymorphisms in IRS1 may be involved in the etiology of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[https://omim.org/entry/125853 125853]].<ref>PMID:14707024</ref> <ref>PMID:8723689</ref> <ref>PMID:10206679</ref> <ref>PMID:12843189</ref> <ref>PMID:15590636</ref>
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[https://www.uniprot.org/uniprot/IRS1_HUMAN IRS1_HUMAN] Polymorphisms in IRS1 may be involved in the etiology of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[https://omim.org/entry/125853 125853].<ref>PMID:14707024</ref> <ref>PMID:8723689</ref> <ref>PMID:10206679</ref> <ref>PMID:12843189</ref> <ref>PMID:15590636</ref>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/IRS1_HUMAN IRS1_HUMAN]] May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity).<ref>PMID:16878150</ref> <ref>PMID:14707024</ref> [[https://www.uniprot.org/uniprot/IL4RA_HUMAN IL4RA_HUMAN]] Receptor for both interleukin 4 and interleukin 13. Couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are involved in regulating IgE production and, chemokine and mucus production at sites of allergic inflammation. In certain cell types, can signal through activation of insulin receptor substrates, IRS1/IRS2.<ref>PMID:8124718</ref> Soluble IL4R (sIL4R) inhibits IL4-mediated cell proliferation and IL5 up-regulation by T-cells.<ref>PMID:8124718</ref>
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[https://www.uniprot.org/uniprot/IRS1_HUMAN IRS1_HUMAN] May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity).<ref>PMID:16878150</ref> <ref>PMID:14707024</ref>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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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=1irs ConSurf].
</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=1irs ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
 
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== Publication Abstract from PubMed ==
 
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We present the NMR structure of the PTB domain of insulin receptor substrate-1 (IRS-1) complexed to a tyrosine-phosphorylated peptide derived from the IL-4 receptor. Despite the lack of sequence homology and different binding specificity, the overall fold of the protein is similar to that of the Shc PTB domain and closely resembles that of PH domains. However, the PTB domain of IRS-1 is smaller than that of Shc (110 versus 170 residues) and binds to phosphopeptides in a distinct manner. We explain the phosphopeptide binding specificity based on the structure of the complex and results of site-directed mutagenesis experiments.
 
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Structural basis for IL-4 receptor phosphopeptide recognition by the IRS-1 PTB domain.,Zhou MM, Huang B, Olejniczak ET, Meadows RP, Shuker SB, Miyazaki M, Trub T, Shoelson SE, Fesik SW Nat Struct Biol. 1996 Apr;3(4):388-93. PMID:8599766<ref>PMID:8599766</ref>
 
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
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</div>
 
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<div class="pdbe-citations 1irs" style="background-color:#fffaf0;"></div>
 
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Feisk, S W]]
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[[Category: Feisk SW]]
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[[Category: Huang, B]]
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[[Category: Huang B]]
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[[Category: Meadows, R P]]
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[[Category: Meadows RP]]
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[[Category: Miyazaki, M]]
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[[Category: Miyazaki M]]
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[[Category: Olejniczak, E T]]
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[[Category: Olejniczak ET]]
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[[Category: Shoelson, S E]]
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[[Category: Shoelson SE]]
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[[Category: Shuker, S B]]
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[[Category: Shuker SB]]
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[[Category: Trub, T]]
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[[Category: Trub T]]
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[[Category: Zhou, M M]]
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[[Category: Zhou M-M]]
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[[Category: Complex]]
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[[Category: Signal transduction]]
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Revision as of 07:48, 3 April 2024

IRS-1 PTB DOMAIN COMPLEXED WITH A IL-4 RECEPTOR PHOSPHOPEPTIDE, NMR, MINIMIZED AVERAGE STRUCTURE

PDB ID 1irs

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