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| | ==The fibrinogen-like domain of human Angptl4== | | ==The fibrinogen-like domain of human Angptl4== |
| - | <StructureSection load='6eub' size='340' side='right' caption='[[6eub]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='6eub' size='340' side='right'caption='[[6eub]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6eub]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EUB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EUB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6eub]] 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=6EUB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EUB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</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]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6eua|6eua]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene></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=6eub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eub OCA], [http://pdbe.org/6eub PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eub RCSB], [http://www.ebi.ac.uk/pdbsum/6eub PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eub 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=6eub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eub OCA], [https://pdbe.org/6eub PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6eub RCSB], [https://www.ebi.ac.uk/pdbsum/6eub PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6eub ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ANGL4_HUMAN ANGL4_HUMAN]] Protein with hypoxia-induced expression in endothelial cells. May act as a regulator of angiogenesis and modulate tumorigenesis. Inhibits proliferation, migration, and tubule formation of endothelial cells and reduces vascular leakage. May exert a protective function on endothelial cells through an endocrine action. It is directly involved in regulating glucose homeostasis, lipid metabolism, and insulin sensitivity. In response to hypoxia, the unprocessed form of the protein accumulates in the subendothelial extracellular matrix (ECM). The matrix-associated and immobilized unprocessed form limits the formation of actin stress fibers and focal contacts in the adhering endothelial cells and inhibits their adhesion. It also decreases motility of endothelial cells and inhibits the sprouting and tube formation (By similarity).<ref>PMID:12015030</ref> <ref>PMID:14583458</ref> | + | [https://www.uniprot.org/uniprot/ANGL4_HUMAN ANGL4_HUMAN] Protein with hypoxia-induced expression in endothelial cells. May act as a regulator of angiogenesis and modulate tumorigenesis. Inhibits proliferation, migration, and tubule formation of endothelial cells and reduces vascular leakage. May exert a protective function on endothelial cells through an endocrine action. It is directly involved in regulating glucose homeostasis, lipid metabolism, and insulin sensitivity. In response to hypoxia, the unprocessed form of the protein accumulates in the subendothelial extracellular matrix (ECM). The matrix-associated and immobilized unprocessed form limits the formation of actin stress fibers and focal contacts in the adhering endothelial cells and inhibits their adhesion. It also decreases motility of endothelial cells and inhibits the sprouting and tube formation (By similarity).<ref>PMID:12015030</ref> <ref>PMID:14583458</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Alanen, H I]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Biterova, E I]] | + | [[Category: Large Structures]] |
| - | [[Category: Esmaeeli, M]] | + | [[Category: Alanen HI]] |
| - | [[Category: Ruddock, L W]] | + | [[Category: Biterova EI]] |
| - | [[Category: Saaranen, M]] | + | [[Category: Esmaeeli M]] |
| - | [[Category: Angiopoietin-like]] | + | [[Category: Ruddock LW]] |
| - | [[Category: Coronary artery disease]] | + | [[Category: Saaranen M]] |
| - | [[Category: Lipid metabolism]]
| + | |
| - | [[Category: Plasma triglyceride]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
ANGL4_HUMAN Protein with hypoxia-induced expression in endothelial cells. May act as a regulator of angiogenesis and modulate tumorigenesis. Inhibits proliferation, migration, and tubule formation of endothelial cells and reduces vascular leakage. May exert a protective function on endothelial cells through an endocrine action. It is directly involved in regulating glucose homeostasis, lipid metabolism, and insulin sensitivity. In response to hypoxia, the unprocessed form of the protein accumulates in the subendothelial extracellular matrix (ECM). The matrix-associated and immobilized unprocessed form limits the formation of actin stress fibers and focal contacts in the adhering endothelial cells and inhibits their adhesion. It also decreases motility of endothelial cells and inhibits the sprouting and tube formation (By similarity).[1] [2]
Publication Abstract from PubMed
Coronary artery disease is the most common cause of death globally and is linked to a number of risk factors including serum low density lipoprotein, high density lipoprotein, triglycerides and lipoprotein(a). Recently two proteins, angiopoietin-like protein 3 and 4, have emerged from genetic studies as being factors that significantly modulate plasma triglyceride levels and coronary artery disease. The exact function and mechanism of action of both proteins remains to be elucidated, however, mutations in these proteins results in up to 34% reduction in coronary artery disease and inhibition of function results in reduced plasma triglyceride levels. Here we report the crystal structures of the fibrinogen-like domains of both proteins. These structures offer new insights into the reported loss of function mutations, the mechanisms of action of the proteins and open up the possibility for the rational design of low molecular weight inhibitors for intervention in coronary artery disease.
Structures of Angptl3 and Angptl4, modulators of triglyceride levels and coronary artery disease.,Biterova E, Esmaeeli M, Alanen HI, Saaranen M, Ruddock LW Sci Rep. 2018 Apr 30;8(1):6752. doi: 10.1038/s41598-018-25237-7. PMID:29713054[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhu H, Li J, Wan D, Yang Y, Qin W, Ge C, Yao M, Gu J. [Expression and function of hepatocellular carcinoma-related gene pp1158] Zhonghua Zhong Liu Za Zhi. 2002 Mar;24(2):123-5. PMID:12015030
- ↑ Ito Y, Oike Y, Yasunaga K, Hamada K, Miyata K, Matsumoto S, Sugano S, Tanihara H, Masuho Y, Suda T. Inhibition of angiogenesis and vascular leakiness by angiopoietin-related protein 4. Cancer Res. 2003 Oct 15;63(20):6651-7. PMID:14583458
- ↑ Biterova E, Esmaeeli M, Alanen HI, Saaranen M, Ruddock LW. Structures of Angptl3 and Angptl4, modulators of triglyceride levels and coronary artery disease. Sci Rep. 2018 Apr 30;8(1):6752. doi: 10.1038/s41598-018-25237-7. PMID:29713054 doi:http://dx.doi.org/10.1038/s41598-018-25237-7
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