|
|
| Line 3: |
Line 3: |
| | <StructureSection load='2ikq' size='340' side='right'caption='[[2ikq]], [[Resolution|resolution]] 2.61Å' scene=''> | | <StructureSection load='2ikq' size='340' side='right'caption='[[2ikq]], [[Resolution|resolution]] 2.61Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ikq]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IKQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IKQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ikq]] 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=2IKQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IKQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.609Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2h0q|2h0q]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Sts-1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=2ikq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ikq OCA], [https://pdbe.org/2ikq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ikq RCSB], [https://www.ebi.ac.uk/pdbsum/2ikq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ikq 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=2ikq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ikq OCA], [https://pdbe.org/2ikq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ikq RCSB], [https://www.ebi.ac.uk/pdbsum/2ikq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ikq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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>
| + | [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 35: |
Line 34: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Chen, Y]] | + | [[Category: Chen Y]] |
| - | [[Category: Nassar, N]] | + | [[Category: Nassar N]] |
| - | [[Category: Acid phosphatase]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Pgm]]
| + | |
| - | [[Category: Phospho-histidine enzyme]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| 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.
Publication Abstract from PubMed
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.
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:17679096[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ 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
|
