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| | <StructureSection load='1z3s' size='340' side='right'caption='[[1z3s]], [[Resolution|resolution]] 2.35Å' scene=''> | | <StructureSection load='1z3s' size='340' side='right'caption='[[1z3s]], [[Resolution|resolution]] 2.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1z3s]] is a 2 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=1Z3S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z3S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1z3s]] 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=1Z3S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z3S FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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]] 2.35Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1z3u|1z3u]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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=1z3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z3s OCA], [https://pdbe.org/1z3s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z3s RCSB], [https://www.ebi.ac.uk/pdbsum/1z3s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z3s 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=1z3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z3s OCA], [https://pdbe.org/1z3s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z3s RCSB], [https://www.ebi.ac.uk/pdbsum/1z3s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z3s ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ANGP2_HUMAN ANGP2_HUMAN]] Binds to TEK/TIE2, competing for the ANGPT1 binding site, and modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2 in the absence of ANGPT1. In the absence of angiogenic inducers, such as VEGF, ANGPT2-mediated loosening of cell-matrix contacts may induce endothelial cell apoptosis with consequent vascular regression. In concert with VEGF, it may facilitate endothelial cell migration and proliferation, thus serving as a permissive angiogenic signal.<ref>PMID:9204896</ref> <ref>PMID:15284220</ref> <ref>PMID:19116766</ref> <ref>PMID:19223473</ref>
| + | [https://www.uniprot.org/uniprot/ANGP2_HUMAN ANGP2_HUMAN] Binds to TEK/TIE2, competing for the ANGPT1 binding site, and modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2 in the absence of ANGPT1. In the absence of angiogenic inducers, such as VEGF, ANGPT2-mediated loosening of cell-matrix contacts may induce endothelial cell apoptosis with consequent vascular regression. In concert with VEGF, it may facilitate endothelial cell migration and proliferation, thus serving as a permissive angiogenic signal.<ref>PMID:9204896</ref> <ref>PMID:15284220</ref> <ref>PMID:19116766</ref> <ref>PMID:19223473</ref> |
| | == 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: Barton, W A]] | + | [[Category: Barton WA]] |
| - | [[Category: Nikolov, D B]] | + | [[Category: Nikolov DB]] |
| - | [[Category: Tzvetkova, D]] | + | [[Category: Tzvetkova D]] |
| - | [[Category: Angiogenesis]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Tie2 binding]]
| + | |
| Structural highlights
Function
ANGP2_HUMAN Binds to TEK/TIE2, competing for the ANGPT1 binding site, and modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2 in the absence of ANGPT1. In the absence of angiogenic inducers, such as VEGF, ANGPT2-mediated loosening of cell-matrix contacts may induce endothelial cell apoptosis with consequent vascular regression. In concert with VEGF, it may facilitate endothelial cell migration and proliferation, thus serving as a permissive angiogenic signal.[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
The angiopoietins comprise a small class of secreted glycoproteins that play crucial roles in the maturation and maintenance of the mammalian vascular and lymphatic systems. They exert their effects through a member of the tyrosine kinase receptor family, Tie2. Angiopoietin/Tie2 signaling is unique among tyrosine kinase receptor-ligand systems in that distinct angiopoietin ligands, although highly homologous, can function as agonists or antagonists in a context-dependent manner. In an effort to understand this molecular dichotomy, we have crystallized and determined the 2.4 A crystal structure of the Angiopoietin-2 (Ang2) receptor binding region. The structure reveals a fibrinogen fold with a unique C-terminal P domain. Conservation analysis and structure-based mutagenesis identify a groove on the Ang2 molecular surface that mediates receptor recognition.
Structure of the angiopoietin-2 receptor binding domain and identification of surfaces involved in Tie2 recognition.,Barton WA, Tzvetkova D, Nikolov DB Structure. 2005 May;13(5):825-32. PMID:15893672[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD. Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997 Jul 4;277(5322):55-60. PMID:9204896
- ↑ Lee HJ, Cho CH, Hwang SJ, Choi HH, Kim KT, Ahn SY, Kim JH, Oh JL, Lee GM, Koh GY. Biological characterization of angiopoietin-3 and angiopoietin-4. FASEB J. 2004 Aug;18(11):1200-8. PMID:15284220 doi:10.1096/fj.03-1466com
- ↑ Yacyshyn OK, Lai PF, Forse K, Teichert-Kuliszewska K, Jurasz P, Stewart DJ. Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human endothelial cells. Angiogenesis. 2009;12(1):25-33. doi: 10.1007/s10456-008-9126-0. Epub 2009 Jan 1. PMID:19116766 doi:10.1007/s10456-008-9126-0
- ↑ Yuan HT, Khankin EV, Karumanchi SA, Parikh SM. Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the endothelium. Mol Cell Biol. 2009 Apr;29(8):2011-22. doi: 10.1128/MCB.01472-08. Epub 2009 Feb, 17. PMID:19223473 doi:10.1128/MCB.01472-08
- ↑ Barton WA, Tzvetkova D, Nikolov DB. Structure of the angiopoietin-2 receptor binding domain and identification of surfaces involved in Tie2 recognition. Structure. 2005 May;13(5):825-32. PMID:15893672 doi:http://dx.doi.org/10.1016/j.str.2005.03.009
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