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| | <StructureSection load='6uzt' size='340' side='right'caption='[[6uzt]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='6uzt' size='340' side='right'caption='[[6uzt]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6uzt]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UZT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UZT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6uzt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UZT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UZT FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPRA, PTPA, PTPRL2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 1.8Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </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=6uzt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uzt OCA], [https://pdbe.org/6uzt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uzt RCSB], [https://www.ebi.ac.uk/pdbsum/6uzt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uzt ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6uzt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uzt OCA], [http://pdbe.org/6uzt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uzt RCSB], [http://www.ebi.ac.uk/pdbsum/6uzt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uzt ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PTPRA_HUMAN PTPRA_HUMAN]] Tyrosine protein phosphatase which is involved in integrin-mediated focal adhesion formation (By similarity). Following integrin engagement, specifically recruits BCAR3, BCAR1 and CRK to focal adhesions thereby promoting SRC-mediated phosphorylation of BRAC1 and the subsequent activation of PAK and small GTPase RAC1 and CDC42 (By similarity).[UniProtKB:P18052] | + | [https://www.uniprot.org/uniprot/PTPRA_HUMAN PTPRA_HUMAN] Tyrosine protein phosphatase which is involved in integrin-mediated focal adhesion formation (By similarity). Following integrin engagement, specifically recruits BCAR3, BCAR1 and CRK to focal adhesions thereby promoting SRC-mediated phosphorylation of BRAC1 and the subsequent activation of PAK and small GTPase RAC1 and CDC42 (By similarity).[UniProtKB:P18052] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6uzt" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6uzt" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Protein-tyrosine-phosphatase]]
| + | [[Category: Bottini N]] |
| - | [[Category: Bottini, N]] | + | [[Category: Santelli E]] |
| - | [[Category: Santelli, E]] | + | [[Category: Stanford SM]] |
| - | [[Category: Stanford, S M]] | + | [[Category: Svensson MND]] |
| - | [[Category: Svensson, M N.D]] | + | [[Category: Wen Y]] |
| - | [[Category: Wen, Y]] | + | [[Category: Yang S]] |
| - | [[Category: Yang, S]] | + | |
| - | [[Category: Alpha/beta protein]]
| + | |
| - | [[Category: Enzyme]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Protein tyrosine phosphatase]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
PTPRA_HUMAN Tyrosine protein phosphatase which is involved in integrin-mediated focal adhesion formation (By similarity). Following integrin engagement, specifically recruits BCAR3, BCAR1 and CRK to focal adhesions thereby promoting SRC-mediated phosphorylation of BRAC1 and the subsequent activation of PAK and small GTPase RAC1 and CDC42 (By similarity).[UniProtKB:P18052]
Publication Abstract from PubMed
Receptor-type protein tyrosine phosphatase alpha (RPTPalpha) is an important positive regulator of SRC kinase activation and a known promoter of cancer growth, fibrosis, and arthritis. The domain structure of RPTPs comprises an extracellular region, a transmembrane helix, and two tandem intracellular catalytic domains referred as D1 and D2. The D2 domain of RPTPs is believed to mostly play a regulatory function; however, no regulatory model has been established for RPTPalpha-D2 or other RPTP-D2 domains. Here, we solved the 1.8 A resolution crystal structure of the cytoplasmic region of RPTPalpha, encompassing D1 and D2, trapped in a conformation that revealed a possible mechanism through which D2 can allosterically inhibit D1 activity. Using a D2-truncation RPTPalpha variant and mutational analysis of the D1/D2 interfaces, we show that D2 inhibits RPTPalpha phosphatase activity and identified a P405FTP408 motif in D1 that mediates the inhibitory effect of D2. Expression of the gain-of-function F406A/T407A RPTPalpha variant in HEK293T cells enhanced SRC activation, supporting the relevance of our proposed D2-mediated regulation mechanism in cell signaling. There is emerging interest in the development of allosteric inhibitors of RPTPs, but a scarcity of validated allosteric sites for RPTPs. The results of our study not only shed light on the regulatory role of RPTP-D2 domains, but also provide a potentially useful tool for the discovery of chemical probes targeting RPTPalpha and other RPTPs.
RPTPalpha phosphatase activity is allosterically regulated by the membrane-distal catalytic domain.,Wen Y, Yang S, Wakabayashi K, Svensson MND, Stanford SM, Santelli E, Bottini N J Biol Chem. 2020 Mar 5. pii: RA119.011808. doi: 10.1074/jbc.RA119.011808. PMID:32139509[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wen Y, Yang S, Wakabayashi K, Svensson MND, Stanford SM, Santelli E, Bottini N. RPTPalpha phosphatase activity is allosterically regulated by the membrane-distal catalytic domain. J Biol Chem. 2020 Mar 5. pii: RA119.011808. doi: 10.1074/jbc.RA119.011808. PMID:32139509 doi:http://dx.doi.org/10.1074/jbc.RA119.011808
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