3v6b

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Current revision (02:32, 21 November 2024) (edit) (undo)
 
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3v6b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v6b OCA], [https://pdbe.org/3v6b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v6b RCSB], [https://www.ebi.ac.uk/pdbsum/3v6b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v6b 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=3v6b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v6b OCA], [https://pdbe.org/3v6b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v6b RCSB], [https://www.ebi.ac.uk/pdbsum/3v6b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v6b ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
 
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[https://www.uniprot.org/uniprot/VGFR2_HUMAN VGFR2_HUMAN] Defects in KDR are associated with susceptibility to hemangioma capillary infantile (HCI) [MIM:[https://omim.org/entry/602089 602089]. HCI are benign, highly proliferative lesions involving aberrant localized growth of capillary endothelium. They are the most common tumor of infancy, occurring in up to 10% of all births. Hemangiomas tend to appear shortly after birth and show rapid neonatal growth for up to 12 months characterized by endothelial hypercellularity and increased numbers of mast cells. This phase is followed by slow involution at a rate of about 10% per year and replacement by fibrofatty stroma.<ref>PMID:11807987</ref> <ref>PMID:18931684</ref> Note=Plays a major role in tumor angiogenesis. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.
 
== Function ==
== Function ==
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[https://www.uniprot.org/uniprot/VGFR2_HUMAN VGFR2_HUMAN] Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC.<ref>PMID:19668192</ref> <ref>PMID:1417831</ref> <ref>PMID:7929439</ref> <ref>PMID:9160888</ref> <ref>PMID:9837777</ref> <ref>PMID:9804796</ref> <ref>PMID:10600473</ref> <ref>PMID:10102632</ref> <ref>PMID:11387210</ref> <ref>PMID:12649282</ref> <ref>PMID:15026417</ref> <ref>PMID:15215251</ref> <ref>PMID:15962004</ref> <ref>PMID:16966330</ref> <ref>PMID:17303569</ref> <ref>PMID:19834490</ref> <ref>PMID:20179233</ref> <ref>PMID:20224550</ref> <ref>PMID:20705758</ref> <ref>PMID:10368301</ref> <ref>PMID:18529047</ref> <ref>PMID:20080685</ref>
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[https://www.uniprot.org/uniprot/VEGFH_ORFN2 VEGFH_ORFN2] Induces endothelial proliferation.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Vascular Endothelial Growth Factors (VEGFs) activate three receptor tyrosine kinases, VEGFR-1-3, promoting angiogenic and lymphangiogenic signaling. The extracellular receptor domain (ECD) consists of seven immunoglobulin-homology domains; domains 2 and 3 (D23) represent the ligand binding domain, while the function of D4-7 is unclear. Ligand binding promotes receptor dimerization and instigates transmembrane signaling and receptor kinase activation. Isothermal titration calorimetry showed that the Gibbs free energy of VEGF-A, -C or -E binding to D23 or the full length ECD is dominated by favorable entropic contribution with enthalpic penalty. The free energy of VEGF binding to the ECD is 1.0-1.7 kcal/mol less favorable than for binding to D23. A model of the VEGF-E/VEGFR-2 ECD complex derived from small angle scattering data provided evidence for homotypic interactions in D4-7. We also solved the crystal structures of complexes between VEGF-A or -E with D23 which revealed comparable binding surfaces and similar interactions between the ligands and the receptor, but showed variation in D23 twist angles. The energetically unfavorable homotypic interactions in D4-7 may be required for re-orientation of receptor monomers. This mechanism might prevent ligand-independent activation of VEGFR-2 to evade the deleterious consequences for blood and lymph vessel homeostasis arising from inappropriate receptor activation.
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Thermodynamic and structural description of allosterically regulated VEGF receptor 2 dimerization.,Brozzo MS, Bjelic S, Kisko K, Schleier T, Leppanen VM, Alitalo K, Winkler FK, Ballmer-Hofer K Blood. 2011 Dec 29. PMID:22207738<ref>PMID:22207738</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3v6b" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==

Current revision

VEGFR-2/VEGF-E complex structure

PDB ID 3v6b

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

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