|
|
(9 intermediate revisions not shown.) |
Line 1: |
Line 1: |
- | [[Image:2h0q.jpg|left|200px]] | |
| | | |
- | <!--
| + | ==Crystal Structure of the PGM domain of the Suppressor of T-Cell receptor (Sts-1)== |
- | The line below this paragraph, containing "STRUCTURE_2h0q", creates the "Structure Box" on the page.
| + | <StructureSection load='2h0q' size='340' side='right'caption='[[2h0q]], [[Resolution|resolution]] 1.82Å' scene=''> |
- | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
- | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[2h0q]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H0Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H0Q FirstGlance]. <br> |
- | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.82Å</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=2h0q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h0q OCA], [https://pdbe.org/2h0q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h0q RCSB], [https://www.ebi.ac.uk/pdbsum/2h0q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h0q ProSAT]</span></td></tr> |
- | {{STRUCTURE_2h0q| PDB=2h0q | SCENE= }}
| + | </table> |
- | | + | == Function == |
- | '''Crystal Structure of the PGM domain of the Suppressor of T-Cell receptor (Sts-1)'''
| + | [https://www.uniprot.org/uniprot/UBS3B_MOUSE UBS3B_MOUSE] Interferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases. Promotes accumulation of activated target receptors, such as T-cell receptors and EGFR, on the cell surface. Exhibits tyrosine phosphatase activity toward several substrates including EGFR, FAK, SYK, and ZAP70. Down-regulates proteins that are dually modified by both protein tyrosine phosphorylation and ubiquitination.<ref>PMID:14738763</ref> <ref>PMID:19733910</ref> <ref>PMID:20585042</ref> <ref>PMID:17679096</ref> |
- | | + | == Evolutionary Conservation == |
- | | + | [[Image:Consurf_key_small.gif|200px|right]] |
- | ==Overview== | + | Check<jmol> |
- | Precise signaling by the T cell receptor (TCR) is crucial for a proper immune response. To ensure that T cells respond appropriately to antigenic stimuli, TCR signaling pathways are subject to multiple levels of regulation. Sts-1 negatively regulates signaling pathways downstream of the TCR by an unknown mechanism(s). Here, we demonstrate that Sts-1 is a phosphatase that can target the tyrosine kinase Zap-70 among other proteins. The X-ray structure of the Sts-1 C terminus reveals that it has homology to members of the phosphoglycerate mutase/acid phosphatase (PGM/AcP) family of enzymes, with residues known to be important for PGM/AcP catalytic activity conserved in nature and position in Sts-1. Point mutations that impair Sts-1 phosphatase activity in vitro also impair the ability of Sts-1 to regulate TCR signaling in T cells. These observations reveal a PGM/AcP-like enzyme activity involved in the control of antigen receptor signaling.
| + | <jmolCheckbox> |
- | | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h0/2h0q_consurf.spt"</scriptWhenChecked> |
- | ==About this Structure== | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
- | 2H0Q is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H0Q OCA].
| + | <text>to colour the structure by Evolutionary Conservation</text> |
- | | + | </jmolCheckbox> |
- | ==Reference== | + | </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=2h0q ConSurf]. |
- | A phosphatase activity of Sts-1 contributes to the suppression of TCR signaling., Mikhailik A, Ford B, Keller J, Chen Y, Nassar N, Carpino N, Mol Cell. 2007 Aug 3;27(3):486-97. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17679096 17679096]
| + | <div style="clear:both"></div> |
| + | == References == |
| + | <references/> |
| + | __TOC__ |
| + | </StructureSection> |
| + | [[Category: Large Structures]] |
| [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
- | [[Category: Single protein]]
| + | [[Category: Carpino N]] |
- | [[Category: Carpino, N.]] | + | [[Category: Ford B]] |
- | [[Category: Ford, B.]] | + | [[Category: Nassar N]] |
- | [[Category: Nassar, N.]] | + | |
- | [[Category: Pgm]]
| + | |
- | [[Category: Signaling protein]]
| + | |
- | [[Category: Sts-1]]
| + | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:43:53 2008''
| + | |
| Structural highlights
Function
UBS3B_MOUSE Interferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases. Promotes accumulation of activated target receptors, such as T-cell receptors and EGFR, on the cell surface. Exhibits tyrosine phosphatase activity toward several substrates including EGFR, FAK, SYK, and ZAP70. Down-regulates proteins that are dually modified by both protein tyrosine phosphorylation and ubiquitination.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Carpino N, Turner S, Mekala D, Takahashi Y, Zang H, Geiger TL, Doherty P, Ihle JN. Regulation of ZAP-70 activation and TCR signaling by two related proteins, Sts-1 and Sts-2. Immunity. 2004 Jan;20(1):37-46. PMID:14738763
- ↑ Carpino N, Chen Y, Nassar N, Oh HW. The Sts proteins target tyrosine phosphorylated, ubiquitinated proteins within TCR signaling pathways. Mol Immunol. 2009 Oct;46(16):3224-31. Epub 2009 Sep 5. PMID:19733910 doi:S0161-5890(09)00679-8
- ↑ Thomas DH, Getz TM, Newman TN, Dangelmaier CA, Carpino N, Kunapuli SP, Tsygankov AY, Daniel JL. A novel histidine tyrosine phosphatase, TULA-2, associates with Syk and negatively regulates GPVI signaling in platelets. Blood. 2010 Oct 7;116(14):2570-8. doi: 10.1182/blood-2010-02-268136. Epub 2010, Jun 28. PMID:20585042 doi:10.1182/blood-2010-02-268136
- ↑ Mikhailik A, Ford B, Keller J, Chen Y, Nassar N, Carpino N. A phosphatase activity of Sts-1 contributes to the suppression of TCR signaling. Mol Cell. 2007 Aug 3;27(3):486-97. PMID:17679096 doi:10.1016/j.molcel.2007.06.015
|