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| | <StructureSection load='7cng' size='340' side='right'caption='[[7cng]], [[Resolution|resolution]] 3.49Å' scene=''> | | <StructureSection load='7cng' size='340' side='right'caption='[[7cng]], [[Resolution|resolution]] 3.49Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7cng]] 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=7CNG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CNG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7cng]] 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=7CNG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CNG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 3.49Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDK5R1, CDK5R, NCK5A ([https://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=SO4:SULFATE+ION'>SO4</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=7cng FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cng OCA], [https://pdbe.org/7cng PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cng RCSB], [https://www.ebi.ac.uk/pdbsum/7cng PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cng 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=7cng FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cng OCA], [https://pdbe.org/7cng PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cng RCSB], [https://www.ebi.ac.uk/pdbsum/7cng PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cng ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/FEM1B_HUMAN FEM1B_HUMAN]] Component of an E3 ubiquitin-protein ligase complex, in which it may act as a substrate recognition subunit. Involved in apoptosis by acting as a death receptor-associated protein that mediates apoptosis. Also involved in glucose homeostasis in pancreatic islet. Functions as an adapter/mediator in replication stress-induced signaling that leads to the activation of CHEK1.<ref>PMID:10542291</ref> <ref>PMID:19330022</ref> | + | [https://www.uniprot.org/uniprot/CD5R1_HUMAN CD5R1_HUMAN] p35 is a neuron specific activator of CDK5. The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Activator of TPKII.[https://www.uniprot.org/uniprot/FEM1B_HUMAN FEM1B_HUMAN] Component of an E3 ubiquitin-protein ligase complex, in which it may act as a substrate recognition subunit. Involved in apoptosis by acting as a death receptor-associated protein that mediates apoptosis. Also involved in glucose homeostasis in pancreatic islet. Functions as an adapter/mediator in replication stress-induced signaling that leads to the activation of CHEK1.<ref>PMID:10542291</ref> <ref>PMID:19330022</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: Chen, X]] | + | [[Category: Chen X]] |
| - | [[Category: Liao, S]] | + | [[Category: Liao S]] |
| - | [[Category: Xu, C]] | + | [[Category: Xu C]] |
| - | [[Category: Degron]]
| + | |
| - | [[Category: E3 ligase]]
| + | |
| - | [[Category: Peptide binding protein]]
| + | |
| - | [[Category: Ubiquitination]]
| + | |
| Structural highlights
Function
CD5R1_HUMAN p35 is a neuron specific activator of CDK5. The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Activator of TPKII.FEM1B_HUMAN Component of an E3 ubiquitin-protein ligase complex, in which it may act as a substrate recognition subunit. Involved in apoptosis by acting as a death receptor-associated protein that mediates apoptosis. Also involved in glucose homeostasis in pancreatic islet. Functions as an adapter/mediator in replication stress-induced signaling that leads to the activation of CHEK1.[1] [2]
Publication Abstract from PubMed
Degrons are elements within protein substrates that mediate the interaction with specific degradation machineries to control proteolysis. Recently, a few classes of C-terminal degrons (C-degrons) that are recognized by dedicated cullin-RING ligases (CRLs) have been identified. Specifically, CRL2 using the related substrate adapters FEM1A/B/C was found to recognize C degrons ending with arginine (Arg/C-degron). Here, we uncover the molecular mechanism of Arg/C-degron recognition by solving a subset of structures of FEM1 proteins in complex with Arg/C-degron-bearing substrates. Our structural research, complemented by binding assays and global protein stability (GPS) analyses, demonstrates that FEM1A/C and FEM1B selectively target distinct classes of Arg/C-degrons. Overall, our study not only sheds light on the molecular mechanism underlying Arg/C-degron recognition for precise control of substrate turnover, but also provides valuable information for development of chemical probes for selectively regulating proteostasis.
Molecular basis for arginine C-terminal degron recognition by Cul2(FEM1) E3 ligase.,Chen X, Liao S, Makaros Y, Guo Q, Zhu Z, Krizelman R, Dahan K, Tu X, Yao X, Koren I, Xu C Nat Chem Biol. 2021 Jan 4. pii: 10.1038/s41589-020-00704-3. doi:, 10.1038/s41589-020-00704-3. PMID:33398168[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chan SL, Tan KO, Zhang L, Yee KS, Ronca F, Chan MY, Yu VC. F1Aalpha, a death receptor-binding protein homologous to the Caenorhabditis elegans sex-determining protein, FEM-1, is a caspase substrate that mediates apoptosis. J Biol Chem. 1999 Nov 5;274(45):32461-8. PMID:10542291
- ↑ Sun TP, Shieh SY. Human FEM1B is required for Rad9 recruitment and CHK1 activation in response to replication stress. Oncogene. 2009 May 7;28(18):1971-81. doi: 10.1038/onc.2009.58. Epub 2009 Mar 30. PMID:19330022 doi:http://dx.doi.org/10.1038/onc.2009.58
- ↑ Chen X, Liao S, Makaros Y, Guo Q, Zhu Z, Krizelman R, Dahan K, Tu X, Yao X, Koren I, Xu C. Molecular basis for arginine C-terminal degron recognition by Cul2(FEM1) E3 ligase. Nat Chem Biol. 2021 Jan 4. pii: 10.1038/s41589-020-00704-3. doi:, 10.1038/s41589-020-00704-3. PMID:33398168 doi:http://dx.doi.org/10.1038/s41589-020-00704-3
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