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| | <StructureSection load='5mvx' size='340' side='right'caption='[[5mvx]], [[Resolution|resolution]] 2.17Å' scene=''> | | <StructureSection load='5mvx' size='340' side='right'caption='[[5mvx]], [[Resolution|resolution]] 2.17Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5mvx]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MVX OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MVX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5mvx]] 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=5MVX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MVX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</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]] 2.17Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DLL4, UNQ1895/PRO4341 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mvx OCA], [http://pdbe.org/5mvx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mvx RCSB], [http://www.ebi.ac.uk/pdbsum/5mvx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mvx 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=5mvx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mvx OCA], [https://pdbe.org/5mvx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mvx RCSB], [https://www.ebi.ac.uk/pdbsum/5mvx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mvx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/DLL4_HUMAN DLL4_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/DLL4_HUMAN DLL4_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DLL4_HUMAN DLL4_HUMAN]] Involved in the Notch signaling pathway as Notch ligand (PubMed:11134954). Activates NOTCH1 and NOTCH4. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting (PubMed:20616313). Essential for retinal progenitor proliferation. Required for suppressing rod fates in late retinal progenitors as well as for proper generation of other retinal cell types (By similarity). During spinal cord neurogenesis, inhibits V2a interneuron fate (PubMed:17728344).[UniProtKB:Q9JI71]<ref>PMID:11134954</ref> <ref>PMID:17728344</ref> <ref>PMID:20616313</ref> | + | [https://www.uniprot.org/uniprot/DLL4_HUMAN DLL4_HUMAN] Involved in the Notch signaling pathway as Notch ligand (PubMed:11134954). Activates NOTCH1 and NOTCH4. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting (PubMed:20616313). Essential for retinal progenitor proliferation. Required for suppressing rod fates in late retinal progenitors as well as for proper generation of other retinal cell types (By similarity). During spinal cord neurogenesis, inhibits V2a interneuron fate (PubMed:17728344).[UniProtKB:Q9JI71]<ref>PMID:11134954</ref> <ref>PMID:17728344</ref> <ref>PMID:20616313</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: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Handford, P A]] | + | [[Category: Handford PA]] |
| - | [[Category: Lea, S M]] | + | [[Category: Lea SM]] |
| - | [[Category: Suckling, R J]] | + | [[Category: Suckling RJ]] |
| - | [[Category: C2]]
| + | |
| - | [[Category: Egf]]
| + | |
| - | [[Category: Notch]]
| + | |
| - | [[Category: Signaling]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Disease
DLL4_HUMAN The disease is caused by mutations affecting the gene represented in this entry.
Function
DLL4_HUMAN Involved in the Notch signaling pathway as Notch ligand (PubMed:11134954). Activates NOTCH1 and NOTCH4. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting (PubMed:20616313). Essential for retinal progenitor proliferation. Required for suppressing rod fates in late retinal progenitors as well as for proper generation of other retinal cell types (By similarity). During spinal cord neurogenesis, inhibits V2a interneuron fate (PubMed:17728344).[UniProtKB:Q9JI71][1] [2] [3]
Publication Abstract from PubMed
Recent data have expanded our understanding of Notch signalling by identifying a C2 domain at the N-terminus of Notch ligands, which has both lipid- and receptor-binding properties. We present novel structures of human ligands Jagged2 and Delta-like4 and human Notch2, together with functional assays, which suggest that ligand-mediated coupling of membrane recognition and Notch binding is likely to be critical in establishing the optimal context for Notch signalling. Comparisons between the Jagged and Delta family show a huge diversity in the structures of the loops at the apex of the C2 domain implicated in membrane recognition and Jagged1 missense mutations, which affect these loops and are associated with extrahepatic biliary atresia, lead to a loss of membrane recognition, but do not alter Notch binding. Taken together, these data suggest that C2 domain binding to membranes is an important element in tuning ligand-dependent Notch signalling in different physiological contexts.
Structural and functional dissection of the interplay between lipid and Notch binding by human Notch ligands.,Suckling RJ, Korona B, Whiteman P, Chillakuri C, Holt L, Handford PA, Lea SM EMBO J. 2017 Aug 1;36(15):2204-2215. doi: 10.15252/embj.201796632. Epub 2017 Jun , 1. PMID:28572448[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yoneya T, Tahara T, Nagao K, Yamada Y, Yamamoto T, Osawa M, Miyatani S, Nishikawa M. Molecular cloning of delta-4, a new mouse and human Notch ligand. J Biochem. 2001 Jan;129(1):27-34. PMID:11134954
- ↑ Del Barrio MG, Taveira-Marques R, Muroyama Y, Yuk DI, Li S, Wines-Samuelson M, Shen J, Smith HK, Xiang M, Rowitch D, Richardson WD. A regulatory network involving Foxn4, Mash1 and delta-like 4/Notch1 generates V2a and V2b spinal interneurons from a common progenitor pool. Development. 2007 Oct;134(19):3427-36. Epub 2007 Aug 29. PMID:17728344 doi:http://dx.doi.org/10.1242/dev.005868
- ↑ Brutsch R, Liebler SS, Wustehube J, Bartol A, Herberich SE, Adam MG, Telzerow A, Augustin HG, Fischer A. Integrin cytoplasmic domain-associated protein-1 attenuates sprouting angiogenesis. Circ Res. 2010 Sep 3;107(5):592-601. doi: 10.1161/CIRCRESAHA.110.217257. Epub, 2010 Jul 8. PMID:20616313 doi:http://dx.doi.org/10.1161/CIRCRESAHA.110.217257
- ↑ Suckling RJ, Korona B, Whiteman P, Chillakuri C, Holt L, Handford PA, Lea SM. Structural and functional dissection of the interplay between lipid and Notch binding by human Notch ligands. EMBO J. 2017 Aug 1;36(15):2204-2215. doi: 10.15252/embj.201796632. Epub 2017 Jun , 1. PMID:28572448 doi:http://dx.doi.org/10.15252/embj.201796632
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