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| | <StructureSection load='7xc0' size='340' side='right'caption='[[7xc0]], [[Resolution|resolution]] 1.56Å' scene=''> | | <StructureSection load='7xc0' size='340' side='right'caption='[[7xc0]], [[Resolution|resolution]] 1.56Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7xc0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7XC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XC0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7xc0]] is a 1 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=7XC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XC0 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]] 1.56Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7xc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xc0 OCA], [https://pdbe.org/7xc0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xc0 RCSB], [https://www.ebi.ac.uk/pdbsum/7xc0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xc0 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=7xc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xc0 OCA], [https://pdbe.org/7xc0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xc0 RCSB], [https://www.ebi.ac.uk/pdbsum/7xc0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xc0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/PTPRH_HUMAN PTPRH_HUMAN]] Protein phosphatase that may contribute to contact inhibition of cell growth and motility by mediating the dephosphorylation of focal adhesion-associated substrates and thus negatively regulating integrin-promoted signaling processes. Induces apoptotic cell death by at least two distinct mechanisms: inhibition of cell survival signaling mediated by PI 3-kinase, Akt, and ILK and activation of a caspase-dependent proapoptotic pathway. Inhibits the basal activity of LCK and its activation in response to TCR stimulation and TCR-induced activation of MAP kinase and surface expression of CD69. Inhibits TCR-induced tyrosine phosphorylation of LAT and ZAP70. Inhibits both basal activity of DOK1 and its CD2-induced tyrosine phosphorylation. Induces dephosphorylation of BCAR1, focal adhesion kinase and SRC. Reduces migratory activity of activity of Jurkat cells. Reduces tyrosine phosphorylation of CEACAM20 and thereby contributes to suppress the intestinal immune response CEACAM20 (By similarity).[UniProtKB:E9Q0N2]<ref>PMID:11278335</ref> <ref>PMID:12101188</ref> <ref>PMID:12837766</ref> <ref>PMID:15850787</ref>
| + | [https://www.uniprot.org/uniprot/PTPRH_HUMAN PTPRH_HUMAN] Protein phosphatase that may contribute to contact inhibition of cell growth and motility by mediating the dephosphorylation of focal adhesion-associated substrates and thus negatively regulating integrin-promoted signaling processes. Induces apoptotic cell death by at least two distinct mechanisms: inhibition of cell survival signaling mediated by PI 3-kinase, Akt, and ILK and activation of a caspase-dependent proapoptotic pathway. Inhibits the basal activity of LCK and its activation in response to TCR stimulation and TCR-induced activation of MAP kinase and surface expression of CD69. Inhibits TCR-induced tyrosine phosphorylation of LAT and ZAP70. Inhibits both basal activity of DOK1 and its CD2-induced tyrosine phosphorylation. Induces dephosphorylation of BCAR1, focal adhesion kinase and SRC. Reduces migratory activity of activity of Jurkat cells. Reduces tyrosine phosphorylation of CEACAM20 and thereby contributes to suppress the intestinal immune response CEACAM20 (By similarity).[UniProtKB:E9Q0N2]<ref>PMID:11278335</ref> <ref>PMID:12101188</ref> <ref>PMID:12837766</ref> <ref>PMID:15850787</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Receptor-type protein tyrosine phosphatases (RPTPs) receive extracellular stimuli and transfer them into cells. They regulate cell growth, differentiation and death via specific signals. They have also been implicated in cancer, diabetes and neurological diseases. RPTPH, a member of the type 3 RPTP (R3-PTP) family, is an important regulator of colorectal cancer and hepatic carcinoma. Despite its importance in drug development, the structure of RPTPH has not yet been resolved. Here, the crystal structure of the catalytic domain of RPTPH was determined at 1.56 A resolution. Despite similarities to other R3-PTPs in its overall structure, RPTPH exhibited differences in its loop regions and side-chain conformations. Compared with other R3-PTPs, RPTPH has unique side chains near its active site that may confer specificity for inhibitor binding. Therefore, detailed information on the structure of RPTPH provides clues for the development of specific inhibitors.
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| - | | + | |
| - | Crystal structure of the catalytic domain of human RPTPH.,Kim M, Ryu SE Acta Crystallogr F Struct Biol Commun. 2022 Jul 1;78(Pt 7):265-269. doi:, 10.1107/S2053230X22006173. Epub 2022 Jun 15. PMID:35787553<ref>PMID:35787553</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 7xc0" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Protein-tyrosine-phosphatase]]
| + | [[Category: Kim M]] |
| - | [[Category: Kim, M]] | + | [[Category: Ryu SE]] |
| - | [[Category: Ryu, S E]] | + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Phosphatase]]
| + | |
| Structural highlights
Function
PTPRH_HUMAN Protein phosphatase that may contribute to contact inhibition of cell growth and motility by mediating the dephosphorylation of focal adhesion-associated substrates and thus negatively regulating integrin-promoted signaling processes. Induces apoptotic cell death by at least two distinct mechanisms: inhibition of cell survival signaling mediated by PI 3-kinase, Akt, and ILK and activation of a caspase-dependent proapoptotic pathway. Inhibits the basal activity of LCK and its activation in response to TCR stimulation and TCR-induced activation of MAP kinase and surface expression of CD69. Inhibits TCR-induced tyrosine phosphorylation of LAT and ZAP70. Inhibits both basal activity of DOK1 and its CD2-induced tyrosine phosphorylation. Induces dephosphorylation of BCAR1, focal adhesion kinase and SRC. Reduces migratory activity of activity of Jurkat cells. Reduces tyrosine phosphorylation of CEACAM20 and thereby contributes to suppress the intestinal immune response CEACAM20 (By similarity).[UniProtKB:E9Q0N2][1] [2] [3] [4]
References
- ↑ Noguchi T, Tsuda M, Takeda H, Takada T, Inagaki K, Yamao T, Fukunaga K, Matozaki T, Kasuga M. Inhibition of cell growth and spreading by stomach cancer-associated protein-tyrosine phosphatase-1 (SAP-1) through dephosphorylation of p130cas. J Biol Chem. 2001 May 4;276(18):15216-24. Epub 2001 Feb 14. PMID:11278335 doi:http://dx.doi.org/10.1074/jbc.M007208200
- ↑ Takada T, Noguchi T, Inagaki K, Hosooka T, Fukunaga K, Yamao T, Ogawa W, Matozaki T, Kasuga M. Induction of apoptosis by stomach cancer-associated protein-tyrosine phosphatase-1. J Biol Chem. 2002 Sep 13;277(37):34359-66. doi: 10.1074/jbc.M206541200. Epub 2002, Jul 5. PMID:12101188 doi:http://dx.doi.org/10.1074/jbc.M206541200
- ↑ Ito T, Okazawa H, Maruyama K, Tomizawa K, Motegi S, Ohnishi H, Kuwano H, Kosugi A, Matozaki T. Interaction of SAP-1, a transmembrane-type protein-tyrosine phosphatase, with the tyrosine kinase Lck. Roles in regulation of T cell function. J Biol Chem. 2003 Sep 12;278(37):34854-63. Epub 2003 Jul 1. PMID:12837766 doi:http://dx.doi.org/10.1074/jbc.M300648200
- ↑ Walchli S, Espanel X, Hooft van Huijsduijnen R. Sap-1/PTPRH activity is regulated by reversible dimerization. Biochem Biophys Res Commun. 2005 Jun 3;331(2):497-502. PMID:15850787 doi:http://dx.doi.org/S0006-291X(05)00574-7
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