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| | <StructureSection load='5lc2' size='340' side='right'caption='[[5lc2]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='5lc2' size='340' side='right'caption='[[5lc2]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5lc2]] is a 2 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=5LC2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LC2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5lc2]] 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=5LC2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LC2 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FAM3C, ILEI, GS3786 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 1.8Å</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=5lc2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lc2 OCA], [http://pdbe.org/5lc2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lc2 RCSB], [http://www.ebi.ac.uk/pdbsum/5lc2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lc2 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=5lc2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lc2 OCA], [https://pdbe.org/5lc2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lc2 RCSB], [https://www.ebi.ac.uk/pdbsum/5lc2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lc2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FAM3C_HUMAN FAM3C_HUMAN]] May be involved in retinal laminar formation. Promotes epithelial to mesenchymal transition. | + | [https://www.uniprot.org/uniprot/FAM3C_HUMAN FAM3C_HUMAN] May be involved in retinal laminar formation. Promotes epithelial to mesenchymal transition. |
| | <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: Jansson, A]] | + | [[Category: Jansson A]] |
| - | [[Category: Johansson, P]] | + | [[Category: Johansson P]] |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
FAM3C_HUMAN May be involved in retinal laminar formation. Promotes epithelial to mesenchymal transition.
Publication Abstract from PubMed
Production and secretion of pro-metastatic proteins is a feature of many tumor cells. The FAM3C Interleukin-like epithelial-to-mesenchymal-transition (EMT) inducer, ILEI has been shown to be strongly up-regulated in several cancers and to be essential for tumor formation and metastasis in epithelial cells, correlating with a significant decrease in overall survival in colon and breast cancer patients. ILEI has been seen to interact with the gamma-secretase presenilin 1 subunit (PS1). However, not much is known about the mechanism-of-action or the detailed ILEI structure. We here present the crystal structures of FAM3C ILEI and show that it exists as monomers but also as covalent dimers. The observed ILEI beta-beta-alpha fold confirmed previous indications that the FAM3C proteins do not form classical four-helix-bundle structures as was initially predicted. This provides the first experimental evidence that the Interleukin-like EMT-inducers are not evolutionarily related to the interleukins. However, more surprisingly the ILEI dimer structure was found to feature a trans-linked domain swap, converting an intramolecular disulfide to intermolecular. Interestingly, dimeric but not monomeric ILEI was subsequently found to cause a dose-dependent increase in EpRas cell invasiveness comparable to TGF-beta, indicating that the dimer might be the active ILEI species. This is in line with a parallel study showing that covalent oligomerization of ILEI is essential for EMT and tumor progression in vivo. The structures and the activity data gives some first insight into the relationship between dimerization and ILEI function as well as indicate an intriguing link between ILEI, the PS1-protease, TGF-beta and the TGF-beta receptor 1.
The interleukin-like epithelial-mesenchymal transition inducer ILEI exhibits a non-interleukin-like fold and is active as a domain-swapped dimer.,Jansson AM, Csiszar A, Maier J, Nystrom AC, Ax E, Johansson P, Holmberg Schiavone L J Biol Chem. 2017 Jul 27. pii: jbc.M117.782904. doi: 10.1074/jbc.M117.782904. PMID:28751379[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jansson AM, Csiszar A, Maier J, Nystrom AC, Ax E, Johansson P, Holmberg Schiavone L. The interleukin-like epithelial-mesenchymal transition inducer ILEI exhibits a non-interleukin-like fold and is active as a domain-swapped dimer. J Biol Chem. 2017 Jul 27. pii: jbc.M117.782904. doi: 10.1074/jbc.M117.782904. PMID:28751379 doi:http://dx.doi.org/10.1074/jbc.M117.782904
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