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| | ==Crystal structure of PTPN3 (PTPH1) D811E, C842S mutant in complex with Eps15 pTyr849 peptide== | | ==Crystal structure of PTPN3 (PTPH1) D811E, C842S mutant in complex with Eps15 pTyr849 peptide== |
| - | <StructureSection load='4rhg' size='340' side='right' caption='[[4rhg]], [[Resolution|resolution]] 1.58Å' scene=''> | + | <StructureSection load='4rhg' size='340' side='right'caption='[[4rhg]], [[Resolution|resolution]] 1.58Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4rhg]] 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=4RHG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RHG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4rhg]] 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=4RHG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RHG FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2b49|2b49]], [[4rh5|4rh5]], [[4rh9|4rh9]], [[4ri4|4ri4]], [[4ri5|4ri5]]</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=4rhg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rhg OCA], [https://pdbe.org/4rhg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rhg RCSB], [https://www.ebi.ac.uk/pdbsum/4rhg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rhg ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPH1, PTPN3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rhg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rhg OCA], [http://pdbe.org/4rhg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rhg RCSB], [http://www.ebi.ac.uk/pdbsum/4rhg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rhg ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/EPS15_HUMAN EPS15_HUMAN]] Note=A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1;11)(p32;q23) with MLL/HRX. The result is a rogue activator protein. | + | [https://www.uniprot.org/uniprot/EPS15_HUMAN EPS15_HUMAN] Note=A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1;11)(p32;q23) with MLL/HRX. The result is a rogue activator protein. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PTN3_HUMAN PTN3_HUMAN]] May act at junctions between the membrane and the cytoskeleton. Possesses tyrosine phosphatase activity. [[http://www.uniprot.org/uniprot/EPS15_HUMAN EPS15_HUMAN]] Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2.<ref>PMID:18362181</ref> <ref>PMID:19458185</ref> <ref>PMID:22648170</ref> <ref>PMID:16903783</ref> | + | [https://www.uniprot.org/uniprot/EPS15_HUMAN EPS15_HUMAN] Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2.<ref>PMID:18362181</ref> <ref>PMID:19458185</ref> <ref>PMID:22648170</ref> <ref>PMID:16903783</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Tyrosine phosphatase|Tyrosine phosphatase]] | + | *[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Protein-tyrosine-phosphatase]] | + | [[Category: Large Structures]] |
| - | [[Category: Chen, K E]] | + | [[Category: Chen K-E]] |
| - | [[Category: Meng, T C]] | + | [[Category: Meng TC]] |
| - | [[Category: Wang, A H.J]] | + | [[Category: Wang AH-J]] |
| - | [[Category: Alpha beta]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase-protein binding complex]]
| + | |
| Structural highlights
Disease
EPS15_HUMAN Note=A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1;11)(p32;q23) with MLL/HRX. The result is a rogue activator protein.
Function
EPS15_HUMAN Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR seems to require association with DAB2.[1] [2] [3] [4]
Publication Abstract from PubMed
Epidermal growth factor receptor (EGFR) pathway substrate 15 (Eps15) is a newly identified substrate for protein tyrosine phosphatase N3 (PTPN3), which belongs to the FERM-containing PTP subfamily comprising five members including PTPN3, N4, N13, N14, and N21. We solved the crystal structures of the PTPN3-Eps15 phosphopeptide complex and found that His812 of PTPN3 and Pro850 of Eps15 are responsible for the specific interaction between them. We defined the critical role of the additional residue Tyr676 of PTPN3, which is replaced by Ile939 in PTPN14, in recognition of tyrosine phosphorylated Eps15. The WPD loop necessary for catalysis is present in all members but not PTPN21. We identified that Glu instead of Asp in the WPE loop contributes to the catalytic incapability of PTPN21 due to an extended distance beyond protonation targeting a phosphotyrosine substrate. Together with in vivo validations, our results provide novel insights into the substrate specificity and plasticity of FERM-containing PTPs.
Substrate Specificity and Plasticity of FERM-Containing Protein Tyrosine Phosphatases.,Chen KE, Li MY, Chou CC, Ho MR, Chen GC, Meng TC, Wang AH Structure. 2015 Feb 18. pii: S0969-2126(15)00041-6. doi:, 10.1016/j.str.2015.01.017. PMID:25728925[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Roxrud I, Raiborg C, Pedersen NM, Stang E, Stenmark H. An endosomally localized isoform of Eps15 interacts with Hrs to mediate degradation of epidermal growth factor receptor. J Cell Biol. 2008 Mar 24;180(6):1205-18. doi: 10.1083/jcb.200708115. PMID:18362181 doi:10.1083/jcb.200708115
- ↑ Mettlen M, Stoeber M, Loerke D, Antonescu CN, Danuser G, Schmid SL. Endocytic accessory proteins are functionally distinguished by their differential effects on the maturation of clathrin-coated pits. Mol Biol Cell. 2009 Jul;20(14):3251-60. doi: 10.1091/mbc.E09-03-0256. Epub 2009, May 20. PMID:19458185 doi:10.1091/mbc.E09-03-0256
- ↑ Teckchandani A, Mulkearns EE, Randolph TW, Toida N, Cooper JA. The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin beta1 endocytosis. Mol Biol Cell. 2012 Aug;23(15):2905-16. doi: 10.1091/mbc.E11-12-1007. Epub 2012, May 30. PMID:22648170 doi:10.1091/mbc.E11-12-1007
- ↑ Schmid EM, Ford MG, Burtey A, Praefcke GJ, Peak-Chew SY, Mills IG, Benmerah A, McMahon HT. Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly. PLoS Biol. 2006 Sep;4(9):e262. PMID:16903783 doi:http://dx.doi.org/10.1371/journal.pbio.0040262
- ↑ Chen KE, Li MY, Chou CC, Ho MR, Chen GC, Meng TC, Wang AH. Substrate Specificity and Plasticity of FERM-Containing Protein Tyrosine Phosphatases. Structure. 2015 Feb 18. pii: S0969-2126(15)00041-6. doi:, 10.1016/j.str.2015.01.017. PMID:25728925 doi:http://dx.doi.org/10.1016/j.str.2015.01.017
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