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| | ==Structure of CD3epsilon-Nck2 first SH3 domain complex== | | ==Structure of CD3epsilon-Nck2 first SH3 domain complex== |
| - | <StructureSection load='2jxb' size='340' side='right' caption='[[2jxb]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2jxb' size='340' side='right'caption='[[2jxb]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2jxb]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JXB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2JXB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2jxb]] 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=2JXB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JXB FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD3E, NCK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD3E, NCK2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=2jxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jxb OCA], [http://pdbe.org/2jxb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2jxb RCSB], [http://www.ebi.ac.uk/pdbsum/2jxb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2jxb 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=2jxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jxb OCA], [https://pdbe.org/2jxb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jxb RCSB], [https://www.ebi.ac.uk/pdbsum/2jxb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jxb ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NCK2_HUMAN NCK2_HUMAN]] Adapter protein which associates with tyrosine-phosphorylated growth factor receptors or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling.<ref>PMID:10026169</ref> <ref>PMID:16835242</ref> | + | [[https://www.uniprot.org/uniprot/NCK2_HUMAN NCK2_HUMAN]] Adapter protein which associates with tyrosine-phosphorylated growth factor receptors or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling.<ref>PMID:10026169</ref> <ref>PMID:16835242</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[CD3|CD3]] | + | *[[CD3 3D structures|CD3 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Ng, E]] | | [[Category: Ng, E]] |
| | [[Category: Park, S]] | | [[Category: Park, S]] |
| Structural highlights
Function
[NCK2_HUMAN] Adapter protein which associates with tyrosine-phosphorylated growth factor receptors or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling.[1] [2]
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
Recruitment of signaling molecules to the cytoplasmic domains of the CD3 subunits of the T-cell receptor (TCR) is crucial for early T-cell activation. These transient associations either do or do not require tyrosine phosphorylation of CD3 immune tyrosine activation motifs (ITAMs). Here we show that the non-ITAM-requiring adaptor protein Nck forms a complex with an atypical PxxDY motif of the CD3epsilon tail, which encompasses Tyr166 within the ITAM and a TCR endocytosis signal. As suggested by the structure of the complex, we find that Nck binding inhibits phosphorylation of the CD3epsilon ITAM by Fyn and Lck kinases in vitro. Moreover, the CD3epsilon-Nck interaction downregulates TCR surface expression upon physiological stimulation in mouse primary lymph node cells. This indicates that Nck performs an important regulatory function in T lymphocytes by inhibiting ITAM phosphorylation and/or removing cell surface TCR via CD3epsilon interaction.
Structural and functional evidence that Nck interaction with CD3epsilon regulates T-cell receptor activity.,Takeuchi K, Yang H, Ng E, Park SY, Sun ZY, Reinherz EL, Wagner G J Mol Biol. 2008 Jul 18;380(4):704-16. Epub 2008 May 22. PMID:18555270[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Takeuchi K, Yang H, Ng E, Park SY, Sun ZY, Reinherz EL, Wagner G. Structural and functional evidence that Nck interaction with CD3epsilon regulates T-cell receptor activity. J Mol Biol. 2008 Jul 18;380(4):704-16. Epub 2008 May 22. PMID:18555270 doi:10.1016/j.jmb.2008.05.037
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