|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==human RNF4 RING domain== | | ==human RNF4 RING domain== |
| - | <StructureSection load='4ppe' size='340' side='right' caption='[[4ppe]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4ppe' size='340' side='right'caption='[[4ppe]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ppe]] 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=4PPE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PPE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ppe]] 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=4PPE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PPE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RES4-26, RNF4, SNURF ([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=ZN:ZINC+ION'>ZN</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=4ppe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppe OCA], [http://pdbe.org/4ppe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ppe RCSB], [http://www.ebi.ac.uk/pdbsum/4ppe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ppe 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=4ppe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppe OCA], [https://pdbe.org/4ppe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ppe RCSB], [https://www.ebi.ac.uk/pdbsum/4ppe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ppe ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RNF4_HUMAN RNF4_HUMAN]] E3 ubiquitin-protein ligase which binds polysumoylated chains covalently attached to proteins and mediates 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination of those substrates and their subsequent targeting to the proteasome for degradation. Regulates the degradation of several proteins including PML and the transcriptional activator PEA3. Involved in chromosome alignment and spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK complex by targeting polysumoylated CENPI to proteasomal degradation. Regulates the cellular responses to hypoxia and heat shock through degradation of respectively EPAS1 and PARP1. Alternatively, it may also bind DNA/nucleosomes and have a more direct role in the regulation of transcription for instance enhancing basal transcription and steroid receptor-mediated transcriptional activation.<ref>PMID:12885770</ref> <ref>PMID:18408734</ref> <ref>PMID:19307308</ref> <ref>PMID:20212317</ref> <ref>PMID:20943951</ref> <ref>PMID:20026589</ref> | + | [https://www.uniprot.org/uniprot/RNF4_HUMAN RNF4_HUMAN] E3 ubiquitin-protein ligase which binds polysumoylated chains covalently attached to proteins and mediates 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination of those substrates and their subsequent targeting to the proteasome for degradation. Regulates the degradation of several proteins including PML and the transcriptional activator PEA3. Involved in chromosome alignment and spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK complex by targeting polysumoylated CENPI to proteasomal degradation. Regulates the cellular responses to hypoxia and heat shock through degradation of respectively EPAS1 and PARP1. Alternatively, it may also bind DNA/nucleosomes and have a more direct role in the regulation of transcription for instance enhancing basal transcription and steroid receptor-mediated transcriptional activation.<ref>PMID:12885770</ref> <ref>PMID:18408734</ref> <ref>PMID:19307308</ref> <ref>PMID:20212317</ref> <ref>PMID:20943951</ref> <ref>PMID:20026589</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The post-translational modification of DNA repair and checkpoint proteins by ubiquitin and small ubiquitin-like modifier (SUMO) critically orchestrates the DNA damage response (DDR). The ubiquitin ligase RNF4 integrates signaling by SUMO and ubiquitin, through its selective recognition and ubiquitination of SUMO-modified proteins. Here, we define a key new determinant for target discrimination by RNF4, in addition to interaction with SUMO. We identify a nucleosome-targeting motif within the RNF4 RING domain that can bind DNA and thereby enables RNF4 to selectively ubiquitinate nucleosomal histones. Furthermore, RNF4 nucleosome-targeting is crucially required for the repair of TRF2-depleted dysfunctional telomeres by 53BP1-mediated non-homologous end joining.
| + | |
| - | | + | |
| - | RNF4 interacts with both SUMO and nucleosomes to promote the DNA damage response.,Groocock LM, Nie M, Prudden J, Moiani D, Wang T, Cheltsov A, Rambo RP, Arvai AS, Hitomi C, Tainer JA, Luger K, Perry JJ, Lazzerini-Denchi E, Boddy MN EMBO Rep. 2014 May;15(5):601-8. doi: 10.1002/embr.201338369. Epub 2014 Apr 8. PMID:24714598<ref>PMID:24714598</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4ppe" style="background-color:#fffaf0;"></div>
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Ubiquitin protein ligase|Ubiquitin protein ligase]] | + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Arvai, A S]] | + | [[Category: Large Structures]] |
| - | [[Category: Hitomi, C]] | + | [[Category: Arvai AS]] |
| - | [[Category: Perry, J J]] | + | [[Category: Hitomi C]] |
| - | [[Category: Tainer, J A]] | + | [[Category: Perry JJ]] |
| - | [[Category: Ligase]] | + | [[Category: Tainer JA]] |
| - | [[Category: Ring domain]]
| + | |
| - | [[Category: Ubiquitin ligase]]
| + | |
| Structural highlights
Function
RNF4_HUMAN E3 ubiquitin-protein ligase which binds polysumoylated chains covalently attached to proteins and mediates 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination of those substrates and their subsequent targeting to the proteasome for degradation. Regulates the degradation of several proteins including PML and the transcriptional activator PEA3. Involved in chromosome alignment and spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK complex by targeting polysumoylated CENPI to proteasomal degradation. Regulates the cellular responses to hypoxia and heat shock through degradation of respectively EPAS1 and PARP1. Alternatively, it may also bind DNA/nucleosomes and have a more direct role in the regulation of transcription for instance enhancing basal transcription and steroid receptor-mediated transcriptional activation.[1] [2] [3] [4] [5] [6]
See Also
References
- ↑ Kaiser FJ, Moroy T, Chang GT, Horsthemke B, Ludecke HJ. The RING finger protein RNF4, a co-regulator of transcription, interacts with the TRPS1 transcription factor. J Biol Chem. 2003 Oct 3;278(40):38780-5. Epub 2003 Jul 28. PMID:12885770 doi:http://dx.doi.org/10.1074/jbc.M306259200
- ↑ Tatham MH, Geoffroy MC, Shen L, Plechanovova A, Hattersley N, Jaffray EG, Palvimo JJ, Hay RT. RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation. Nat Cell Biol. 2008 May;10(5):538-46. doi: 10.1038/ncb1716. Epub 2008 Apr 13. PMID:18408734 doi:10.1038/ncb1716
- ↑ Guo B, Sharrocks AD. Extracellular signal-regulated kinase mitogen-activated protein kinase signaling initiates a dynamic interplay between sumoylation and ubiquitination to regulate the activity of the transcriptional activator PEA3. Mol Cell Biol. 2009 Jun;29(11):3204-18. doi: 10.1128/MCB.01128-08. Epub 2009 Mar , 23. PMID:19307308 doi:http://dx.doi.org/10.1128/MCB.01128-08
- ↑ Mukhopadhyay D, Arnaoutov A, Dasso M. The SUMO protease SENP6 is essential for inner kinetochore assembly. J Cell Biol. 2010 Mar 8;188(5):681-92. doi: 10.1083/jcb.200909008. PMID:20212317 doi:http://dx.doi.org/10.1083/jcb.200909008
- ↑ Geoffroy MC, Jaffray EG, Walker KJ, Hay RT. Arsenic-induced SUMO-dependent recruitment of RNF4 into PML nuclear bodies. Mol Biol Cell. 2010 Dec;21(23):4227-39. doi: 10.1091/mbc.E10-05-0449. Epub 2010, Oct 13. PMID:20943951 doi:10.1091/mbc.E10-05-0449
- ↑ van Hagen M, Overmeer RM, Abolvardi SS, Vertegaal AC. RNF4 and VHL regulate the proteasomal degradation of SUMO-conjugated Hypoxia-Inducible Factor-2alpha. Nucleic Acids Res. 2010 Apr;38(6):1922-31. doi: 10.1093/nar/gkp1157. Epub 2009, Dec 21. PMID:20026589 doi:http://dx.doi.org/10.1093/nar/gkp1157
|
