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| | ==Solution structure of first SH3 domain of adaptor Nck== | | ==Solution structure of first SH3 domain of adaptor Nck== |
| - | <StructureSection load='2js2' size='340' side='right'caption='[[2js2]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2js2' size='340' side='right'caption='[[2js2]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2js2]] is a 1 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=2JS2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JS2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2js2]] is a 1 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=2JS2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JS2 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2js0|2js0]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NCK1, NCK ([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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2js2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2js2 OCA], [https://pdbe.org/2js2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2js2 RCSB], [https://www.ebi.ac.uk/pdbsum/2js2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2js2 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=2js2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2js2 OCA], [https://pdbe.org/2js2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2js2 RCSB], [https://www.ebi.ac.uk/pdbsum/2js2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2js2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/NCK1_HUMAN NCK1_HUMAN]] Adapter protein which associates with tyrosine-phosphorylated growth factor receptors, such as KDR and PDGFRB, or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in the DNA damage response, not in the detection of the damage by ATM/ATR, but for efficient activation of downstream effectors, such as that of CHEK2. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling.<ref>PMID:10026169</ref> <ref>PMID:16835242</ref> <ref>PMID:17803907</ref>
| + | [https://www.uniprot.org/uniprot/NCK1_HUMAN NCK1_HUMAN] Adapter protein which associates with tyrosine-phosphorylated growth factor receptors, such as KDR and PDGFRB, or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in the DNA damage response, not in the detection of the damage by ATM/ATR, but for efficient activation of downstream effectors, such as that of CHEK2. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling.<ref>PMID:10026169</ref> <ref>PMID:16835242</ref> <ref>PMID:17803907</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Carlin, C R]] | + | [[Category: Carlin CR]] |
| - | [[Category: Choowongkomon, K]] | + | [[Category: Choowongkomon K]] |
| - | [[Category: Hake, M J]] | + | [[Category: Hake MJ]] |
| - | [[Category: Sonnichsen, F D]] | + | [[Category: Sonnichsen FD]] |
| - | [[Category: Adaptor]]
| + | |
| - | [[Category: Sh3 domain]]
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| - | [[Category: Signaling]]
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| - | [[Category: Signaling protein]]
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| Structural highlights
Function
NCK1_HUMAN Adapter protein which associates with tyrosine-phosphorylated growth factor receptors, such as KDR and PDGFRB, or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in the DNA damage response, not in the detection of the damage by ATM/ATR, but for efficient activation of downstream effectors, such as that of CHEK2. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Nck is a ubiquitously expressed adaptor protein containing Src homology 2 (SH2) and Src homology 3 (SH3) domains. It integrates downstream effector proteins with cell membrane receptors, such as the epidermal growth factor receptor (EGFR). EGFR plays a critical role in cellular proliferation and differentiation. The 45-residue juxtamembrane domain of EGFR (JM), located between the transmembrane and kinase domains, regulates receptor activation and trafficking to the basolateral membrane of polarized epithelia through a proline-rich motif that resembles a consensus SH3 domain binding site. We demonstrate here that the JM region can bind to Nck, showing a notable binding preference for the second SH3 domain. To elucidate the structural determinants for this interaction, we have determined the NMR solution structures of both the first and second Nck SH3 domains (Nck1-1 and Nck1-2). These domains adopt a canonical SH3 beta-barrel-like fold, containing five antiparallel strands separated by three loop regions and one 3 10-helical turn. Chemical shift perturbation studies have identified the residues that form the binding cleft of Nck1-2, which are primarily located in the RT and n-Src loops. JM binds to Nck1-2 with an affinity of approximately 80 microM through a positively charged sequence near the N-terminus, as opposed to the polyproline sequence. The two Nck SH3 domains exhibit both steric and electrostatic differences in their RT-Src and n-Src loops, and a model of the Nck1-2 domain complexed with the JM highlights the factors that define the putative binding mode for this ligand.
Specificity Determinants of a Novel Nck Interaction with the Juxtamembrane Domain of the Epidermal Growth Factor Receptor(,).,Hake MJ, Choowongkomon K, Kostenko O, Carlin CR, Sonnichsen FD Biochemistry. 2008 Feb 13;. PMID:18269246[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Braverman LE, Quilliam LA. Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck. J Biol Chem. 1999 Feb 26;274(9):5542-9. PMID:10026169
- ↑ Latreille M, Larose L. Nck in a complex containing the catalytic subunit of protein phosphatase 1 regulates eukaryotic initiation factor 2alpha signaling and cell survival to endoplasmic reticulum stress. J Biol Chem. 2006 Sep 8;281(36):26633-44. Epub 2006 Jul 11. PMID:16835242 doi:http://dx.doi.org/M513556200
- ↑ Kremer BE, Adang LA, Macara IG. Septins regulate actin organization and cell-cycle arrest through nuclear accumulation of NCK mediated by SOCS7. Cell. 2007 Sep 7;130(5):837-50. PMID:17803907 doi:http://dx.doi.org/10.1016/j.cell.2007.06.053
- ↑ Hake MJ, Choowongkomon K, Kostenko O, Carlin CR, Sonnichsen FD. Specificity Determinants of a Novel Nck Interaction with the Juxtamembrane Domain of the Epidermal Growth Factor Receptor(,). Biochemistry. 2008 Feb 13;. PMID:18269246 doi:http://dx.doi.org/10.1021/bi701549a
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