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| | <StructureSection load='1ygr' size='340' side='right'caption='[[1ygr]], [[Resolution|resolution]] 2.90Å' scene=''> | | <StructureSection load='1ygr' size='340' side='right'caption='[[1ygr]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1ygr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YGR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YGR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1ygr]] is a 4 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=1YGR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YGR FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</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]] 2.9Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</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=1ygr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ygr OCA], [https://pdbe.org/1ygr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ygr RCSB], [https://www.ebi.ac.uk/pdbsum/1ygr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ygr 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=1ygr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ygr OCA], [https://pdbe.org/1ygr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ygr RCSB], [https://www.ebi.ac.uk/pdbsum/1ygr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ygr ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/PTPRC_HUMAN PTPRC_HUMAN]] T-B+ severe combined immunodeficiency due to CD45 deficiency. The disease is caused by mutations affecting the gene represented in this entry. Disease susceptibility may be associated with variations affecting the gene represented in this entry. [[https://www.uniprot.org/uniprot/CD3Z_HUMAN CD3Z_HUMAN]] Defects in CD247 are the cause of immunodeficiency due to defect in CD3-zeta (CD3ZID) [MIM:[https://omim.org/entry/610163 610163]]. An immunological deficiency characterized by T-cells impaired immune response to alloantigens, tetanus toxoid and mitogens.<ref>PMID:16672702</ref>
| + | [https://www.uniprot.org/uniprot/PTPRC_HUMAN PTPRC_HUMAN] T-B+ severe combined immunodeficiency due to CD45 deficiency. The disease is caused by mutations affecting the gene represented in this entry. Disease susceptibility may be associated with variations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/PTPRC_HUMAN PTPRC_HUMAN]] Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor. Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. Upon T-cell activation, recruits and dephosphorylates SKAP1 and FYN. Dephosphorylates LYN, and thereby modulates LYN activity (By similarity). [[https://www.uniprot.org/uniprot/CD3Z_HUMAN CD3Z_HUMAN]] Probable role in assembly and expression of the TCR complex as well as signal transduction upon antigen triggering.
| + | [https://www.uniprot.org/uniprot/PTPRC_HUMAN PTPRC_HUMAN] Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor. Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. Upon T-cell activation, recruits and dephosphorylates SKAP1 and FYN. Dephosphorylates LYN, and thereby modulates LYN activity (By similarity). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Frederick, C A]] | + | [[Category: Frederick CA]] |
| - | [[Category: Nam, H J]] | + | [[Category: Nam HJ]] |
| - | [[Category: Poy, F]] | + | [[Category: Poy F]] |
| - | [[Category: Saito, H]] | + | [[Category: Saito H]] |
| - | [[Category: Cd3 zeta]]
| + | |
| - | [[Category: Cd45]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Itam]]
| + | |
| - | [[Category: Lca]]
| + | |
| - | [[Category: Lymphocyte activation]]
| + | |
| - | [[Category: Protein tyrosine phosphatase]]
| + | |
| - | [[Category: Rptp]]
| + | |
| Structural highlights
Disease
PTPRC_HUMAN T-B+ severe combined immunodeficiency due to CD45 deficiency. The disease is caused by mutations affecting the gene represented in this entry. Disease susceptibility may be associated with variations affecting the gene represented in this entry.
Function
PTPRC_HUMAN Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor. Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. Upon T-cell activation, recruits and dephosphorylates SKAP1 and FYN. Dephosphorylates LYN, and thereby modulates LYN activity (By similarity).
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
CD45 is the prototypic member of transmembrane receptor-like protein tyrosine phosphatases (RPTPs) and has essential roles in immune functions. The cytoplasmic region of CD45, like many other RPTPs, contains two homologous protein tyrosine phosphatase domains, active domain 1 (D1) and catalytically impaired domain 2 (D2). Here, we report crystal structure of the cytoplasmic D1D2 segment of human CD45 in native and phosphotyrosyl peptide-bound forms. The tertiary structures of D1 and D2 are very similar, but doubly phosphorylated CD3zeta immunoreceptor tyrosine-based activation motif peptide binds only the D1 active site. The D2 "active site" deviates from the other active sites significantly to the extent that excludes any possibility of catalytic activity. The relative orientation of D1 and D2 is very similar to that observed in leukocyte common antigen-related protein with both active sites in an open conformation and is restrained through an extensive network of hydrophobic interactions, hydrogen bonds, and salt bridges. This crystal structure is incompatible with the wedge model previously suggested for CD45 regulation.
Structural basis for the function and regulation of the receptor protein tyrosine phosphatase CD45.,Nam HJ, Poy F, Saito H, Frederick CA J Exp Med. 2005 Feb 7;201(3):441-52. Epub 2005 Jan 31. PMID:15684325[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nam HJ, Poy F, Saito H, Frederick CA. Structural basis for the function and regulation of the receptor protein tyrosine phosphatase CD45. J Exp Med. 2005 Feb 7;201(3):441-52. Epub 2005 Jan 31. PMID:15684325 doi:10.1084/jem.20041890
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