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| | ==Crystal structure of synthetic protein in complex with double pY peptide== | | ==Crystal structure of synthetic protein in complex with double pY peptide== |
| - | <StructureSection load='4jmh' size='340' side='right' caption='[[4jmh]], [[Resolution|resolution]] 2.41Å' scene=''> | + | <StructureSection load='4jmh' size='340' side='right'caption='[[4jmh]], [[Resolution|resolution]] 2.41Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4jmh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JMH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JMH FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4jmh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JMH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JMH 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> | + | </td></tr><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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jmg|4jmg]]</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=4jmh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jmh OCA], [https://pdbe.org/4jmh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jmh RCSB], [https://www.ebi.ac.uk/pdbsum/4jmh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jmh ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SHC, SHC1, SHCA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4jmh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jmh OCA], [http://pdbe.org/4jmh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jmh RCSB], [http://www.ebi.ac.uk/pdbsum/4jmh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jmh ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SHC1_HUMAN SHC1_HUMAN]] Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Isoform p46Shc and isoform p52Shc, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p46Shc and isoform p52Shc may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shc does not mediate Ras activation, but is involved in signal transduction pathways that regulate the cellular response to oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. The expression of isoform p66Shc has been correlated with life span (By similarity). Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis.<ref>PMID:14665640</ref> | + | [https://www.uniprot.org/uniprot/SHC1_HUMAN SHC1_HUMAN] Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Isoform p46Shc and isoform p52Shc, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p46Shc and isoform p52Shc may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shc does not mediate Ras activation, but is involved in signal transduction pathways that regulate the cellular response to oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. The expression of isoform p66Shc has been correlated with life span (By similarity). Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis.<ref>PMID:14665640</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Synthetic construct sequences]] | + | [[Category: Large Structures]] |
| - | [[Category: Koide, S]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Smith, L]] | + | [[Category: Koide S]] |
| - | [[Category: Yasui, N]] | + | [[Category: Smith L]] |
| - | [[Category: Binding to double py containing sequence]]
| + | [[Category: Yasui N]] |
| - | [[Category: De novo protein]]
| + | |
| - | [[Category: Synthetic protein]]
| + | |
| Structural highlights
Function
SHC1_HUMAN Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Isoform p46Shc and isoform p52Shc, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p46Shc and isoform p52Shc may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shc does not mediate Ras activation, but is involved in signal transduction pathways that regulate the cellular response to oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. The expression of isoform p66Shc has been correlated with life span (By similarity). Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis.[1]
Publication Abstract from PubMed
Cell signaling depends on dynamic protein-protein interaction (PPI) networks, often assembled through modular domains each interacting with multiple peptide motifs. This complexity raises a conceptual challenge, namely to define whether a particular cellular response requires assembly of the complete PPI network of interest or can be driven by a specific interaction. To address this issue, we designed variants of the Grb2 SH2 domain ("pY-clamps") whose specificity is highly biased toward a single phosphotyrosine (pY) motif among many potential pYXNX Grb2-binding sites. Surprisingly, directing Grb2 predominantly to a single pY site of the Ptpn11/Shp2 phosphatase, but not other sites tested, was sufficient for differentiation of the essential primitive endoderm lineage from embryonic stem cells. Our data suggest that discrete connections within complex PPI networks can underpin regulation of particular biological events. We propose that this directed wiring approach will be of general utility in functionally annotating specific PPIs.
Directed network wiring identifies a key protein interaction in embryonic stem cell differentiation.,Yasui N, Findlay GM, Gish GD, Hsiung MS, Huang J, Tucholska M, Taylor L, Smith L, Boldridge WC, Koide A, Pawson T, Koide S Mol Cell. 2014 Jun 19;54(6):1034-41. doi: 10.1016/j.molcel.2014.05.002. Epub 2014, Jun 5. PMID:24910098[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Audero E, Cascone I, Maniero F, Napione L, Arese M, Lanfrancone L, Bussolino F. Adaptor ShcA protein binds tyrosine kinase Tie2 receptor and regulates migration and sprouting but not survival of endothelial cells. J Biol Chem. 2004 Mar 26;279(13):13224-33. Epub 2003 Dec 9. PMID:14665640 doi:10.1074/jbc.M307456200
- ↑ Yasui N, Findlay GM, Gish GD, Hsiung MS, Huang J, Tucholska M, Taylor L, Smith L, Boldridge WC, Koide A, Pawson T, Koide S. Directed network wiring identifies a key protein interaction in embryonic stem cell differentiation. Mol Cell. 2014 Jun 19;54(6):1034-41. doi: 10.1016/j.molcel.2014.05.002. Epub 2014, Jun 5. PMID:24910098 doi:http://dx.doi.org/10.1016/j.molcel.2014.05.002
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