2pie - Revision history

OCA at 11:02, 30 August 2023

2023-08-30T11:02:32Z

←Older revision		Revision as of 11:02, 30 August 2023
Line 3:		Line 3:
	<StructureSection load='2pie' size='340' side='right'caption='[[2pie]], [[Resolution\|resolution]] 1.35Å' scene=''>		<StructureSection load='2pie' size='340' side='right'caption='[[2pie]], [[Resolution\|resolution]] 1.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2pie]] 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=2PIE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PIE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2pie]] 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=2PIE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PIE FirstGlance]. <br>
-	</td></tr><tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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]] 1.35Å</td></tr>
-	~~<tr~~ id~~='related'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Related_structure~~\|~~Related:~~]]~~</b></td><td class="sblockDat"><div style='overflow: auto~~; ~~max-height: 3em;'>[[2csw\|2csw]]</div>~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~RNF8, KIAA0646 ([https~~:/~~/www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</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=2pie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pie OCA], [https://pdbe.org/2pie PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pie RCSB], [https://www.ebi.ac.uk/pdbsum/2pie PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pie 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=2pie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pie OCA], [https://pdbe.org/2pie PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pie RCSB], [https://www.ebi.ac.uk/pdbsum/2pie PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pie ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/RNF8_HUMAN RNF8_HUMAN]] E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Promotes the formation of 'Lys-63'-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains via interaction with the ubiquitin-conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward 'Lys-48'- versus 'Lys-63'-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases. For instance, interaction with phosphorylated HERC2 promotes the association between RNF8 and UBE2N/UBC13 and favors the specific formation of 'Lys-63'-linked ubiquitin chains. Promotes non-homologous end joining (NHEJ) by promoting the 'Lys-48'-linked ubiquitination and degradation the of KU80/XRCC5. Following DNA damage, mediates the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF168, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation. Involved in the activation of ATM by promoting histone H2B ubiquitination, which indirectly triggers histone H4 'Lys-16' acetylation (H4K16ac), establishing a chromatin environment that promotes efficient activation of ATM kinase. Required in the testis, where it plays a role in the replacement of histones during spermatogenesis. At uncapped telomeres, promotes the joining of deprotected chromosome ends by inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that it may enhance cancer development by aggraving telomere-induced genome instability in case of telomeric crisis. Promotes the assembly of RAD51 at DNA DSBs in the absence of BRCA1 and TP53BP1 Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. May be required for proper exit from mitosis after spindle checkpoint activation and may regulate cytokinesis. May play a role in the regulation of RXRA-mediated transcriptional activity. Not involved in RXRA ubiquitination by UBE2E2.<ref>PMID:11322894</ref> <ref>PMID:14981089</ref> <ref>PMID:18001824</ref> <ref>PMID:18077395</ref> <ref>PMID:18006705</ref> <ref>PMID:17724460</ref> <ref>PMID:18948756</ref> <ref>PMID:18337245</ref> <ref>PMID:19203578</ref> <ref>PMID:19203579</ref> <ref>PMID:19124460</ref> <ref>PMID:19015238</ref> <ref>PMID:19202061</ref> <ref>PMID:20550933</ref> <ref>PMID:21558560</ref> <ref>PMID:21857671</ref> <ref>PMID:22865450</ref> <ref>PMID:22373579</ref> <ref>PMID:22531782</ref> <ref>PMID:22705371</ref> <ref>PMID:22266820</ref> <ref>PMID:21911360</ref> <ref>PMID:18001825</ref> <ref>PMID:22980979</ref>	+	[https://www.uniprot.org/uniprot/RNF8_HUMAN RNF8_HUMAN] E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Promotes the formation of 'Lys-63'-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains via interaction with the ubiquitin-conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward 'Lys-48'- versus 'Lys-63'-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases. For instance, interaction with phosphorylated HERC2 promotes the association between RNF8 and UBE2N/UBC13 and favors the specific formation of 'Lys-63'-linked ubiquitin chains. Promotes non-homologous end joining (NHEJ) by promoting the 'Lys-48'-linked ubiquitination and degradation the of KU80/XRCC5. Following DNA damage, mediates the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF168, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation. Involved in the activation of ATM by promoting histone H2B ubiquitination, which indirectly triggers histone H4 'Lys-16' acetylation (H4K16ac), establishing a chromatin environment that promotes efficient activation of ATM kinase. Required in the testis, where it plays a role in the replacement of histones during spermatogenesis. At uncapped telomeres, promotes the joining of deprotected chromosome ends by inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that it may enhance cancer development by aggraving telomere-induced genome instability in case of telomeric crisis. Promotes the assembly of RAD51 at DNA DSBs in the absence of BRCA1 and TP53BP1 Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. May be required for proper exit from mitosis after spindle checkpoint activation and may regulate cytokinesis. May play a role in the regulation of RXRA-mediated transcriptional activity. Not involved in RXRA ubiquitination by UBE2E2.<ref>PMID:11322894</ref> <ref>PMID:14981089</ref> <ref>PMID:18001824</ref> <ref>PMID:18077395</ref> <ref>PMID:18006705</ref> <ref>PMID:17724460</ref> <ref>PMID:18948756</ref> <ref>PMID:18337245</ref> <ref>PMID:19203578</ref> <ref>PMID:19203579</ref> <ref>PMID:19124460</ref> <ref>PMID:19015238</ref> <ref>PMID:19202061</ref> <ref>PMID:20550933</ref> <ref>PMID:21558560</ref> <ref>PMID:21857671</ref> <ref>PMID:22865450</ref> <ref>PMID:22373579</ref> <ref>PMID:22531782</ref> <ref>PMID:22705371</ref> <ref>PMID:22266820</ref> <ref>PMID:21911360</ref> <ref>PMID:18001825</ref> <ref>PMID:22980979</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Grant~~, R A~~]]	+	[[Category: Grant RA]]
-	[[Category: Yaffe~~, M B]]~~	+	[[Category: Yaffe MB]]
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Fha domain]]~~	+
-	~~[[Category: Ligase]]~~	+
-	~~[[Category: Phosphopeptide]]~~	+
-	~~[[Category: Signaling protein~~]]	+

OCA at 15:24, 17 June 2021

2021-06-17T15:24:47Z

←Older revision		Revision as of 15:24, 17 June 2021
Line 1:		Line 1:

	==Crystal structure of the FHA domain of RNF8 in complex with its optimal phosphopeptide==		==Crystal structure of the FHA domain of RNF8 in complex with its optimal phosphopeptide==
-	<StructureSection load='2pie' size='340' side='right' caption='[[2pie]], [[Resolution\|resolution]] 1.35Å' scene=''>	+	<StructureSection load='2pie' size='340' side='right'caption='[[2pie]], [[Resolution\|resolution]] 1.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2pie]] 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=2PIE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2PIE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2pie]] 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=2PIE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PIE FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2csw\|2csw]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2csw\|2csw]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">RNF8, KIAA0646 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">RNF8, KIAA0646 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2pie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pie OCA], [~~http~~://pdbe.org/2pie PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2pie RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2pie PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2pie 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=2pie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pie OCA], [https://pdbe.org/2pie PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pie RCSB], [https://www.ebi.ac.uk/pdbsum/2pie PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pie ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/RNF8_HUMAN RNF8_HUMAN]] E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Promotes the formation of 'Lys-63'-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains via interaction with the ubiquitin-conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward 'Lys-48'- versus 'Lys-63'-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases. For instance, interaction with phosphorylated HERC2 promotes the association between RNF8 and UBE2N/UBC13 and favors the specific formation of 'Lys-63'-linked ubiquitin chains. Promotes non-homologous end joining (NHEJ) by promoting the 'Lys-48'-linked ubiquitination and degradation the of KU80/XRCC5. Following DNA damage, mediates the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF168, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation. Involved in the activation of ATM by promoting histone H2B ubiquitination, which indirectly triggers histone H4 'Lys-16' acetylation (H4K16ac), establishing a chromatin environment that promotes efficient activation of ATM kinase. Required in the testis, where it plays a role in the replacement of histones during spermatogenesis. At uncapped telomeres, promotes the joining of deprotected chromosome ends by inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that it may enhance cancer development by aggraving telomere-induced genome instability in case of telomeric crisis. Promotes the assembly of RAD51 at DNA DSBs in the absence of BRCA1 and TP53BP1 Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. May be required for proper exit from mitosis after spindle checkpoint activation and may regulate cytokinesis. May play a role in the regulation of RXRA-mediated transcriptional activity. Not involved in RXRA ubiquitination by UBE2E2.<ref>PMID:11322894</ref> <ref>PMID:14981089</ref> <ref>PMID:18001824</ref> <ref>PMID:18077395</ref> <ref>PMID:18006705</ref> <ref>PMID:17724460</ref> <ref>PMID:18948756</ref> <ref>PMID:18337245</ref> <ref>PMID:19203578</ref> <ref>PMID:19203579</ref> <ref>PMID:19124460</ref> <ref>PMID:19015238</ref> <ref>PMID:19202061</ref> <ref>PMID:20550933</ref> <ref>PMID:21558560</ref> <ref>PMID:21857671</ref> <ref>PMID:22865450</ref> <ref>PMID:22373579</ref> <ref>PMID:22531782</ref> <ref>PMID:22705371</ref> <ref>PMID:22266820</ref> <ref>PMID:21911360</ref> <ref>PMID:18001825</ref> <ref>PMID:22980979</ref>	+	[[https://www.uniprot.org/uniprot/RNF8_HUMAN RNF8_HUMAN]] E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Promotes the formation of 'Lys-63'-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains via interaction with the ubiquitin-conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward 'Lys-48'- versus 'Lys-63'-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases. For instance, interaction with phosphorylated HERC2 promotes the association between RNF8 and UBE2N/UBC13 and favors the specific formation of 'Lys-63'-linked ubiquitin chains. Promotes non-homologous end joining (NHEJ) by promoting the 'Lys-48'-linked ubiquitination and degradation the of KU80/XRCC5. Following DNA damage, mediates the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF168, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation. Involved in the activation of ATM by promoting histone H2B ubiquitination, which indirectly triggers histone H4 'Lys-16' acetylation (H4K16ac), establishing a chromatin environment that promotes efficient activation of ATM kinase. Required in the testis, where it plays a role in the replacement of histones during spermatogenesis. At uncapped telomeres, promotes the joining of deprotected chromosome ends by inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that it may enhance cancer development by aggraving telomere-induced genome instability in case of telomeric crisis. Promotes the assembly of RAD51 at DNA DSBs in the absence of BRCA1 and TP53BP1 Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. May be required for proper exit from mitosis after spindle checkpoint activation and may regulate cytokinesis. May play a role in the regulation of RXRA-mediated transcriptional activity. Not involved in RXRA ubiquitination by UBE2E2.<ref>PMID:11322894</ref> <ref>PMID:14981089</ref> <ref>PMID:18001824</ref> <ref>PMID:18077395</ref> <ref>PMID:18006705</ref> <ref>PMID:17724460</ref> <ref>PMID:18948756</ref> <ref>PMID:18337245</ref> <ref>PMID:19203578</ref> <ref>PMID:19203579</ref> <ref>PMID:19124460</ref> <ref>PMID:19015238</ref> <ref>PMID:19202061</ref> <ref>PMID:20550933</ref> <ref>PMID:21558560</ref> <ref>PMID:21857671</ref> <ref>PMID:22865450</ref> <ref>PMID:22373579</ref> <ref>PMID:22531782</ref> <ref>PMID:22705371</ref> <ref>PMID:22266820</ref> <ref>PMID:21911360</ref> <ref>PMID:18001825</ref> <ref>PMID:22980979</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pi/2pie_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pi/2pie_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 30:		Line 30:
	</div>		</div>
	<div class="pdbe-citations 2pie" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 2pie" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Ubiquitin protein ligase 3D structures\|Ubiquitin protein ligase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 35:		Line 38:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Grant, R A]]		[[Category: Grant, R A]]
	[[Category: Yaffe, M B]]		[[Category: Yaffe, M B]]

OCA at 09:26, 18 October 2017

2017-10-18T09:26:13Z

←Older revision		Revision as of 09:26, 18 October 2017
Line 1:		Line 1:
		+
	==Crystal structure of the FHA domain of RNF8 in complex with its optimal phosphopeptide==		==Crystal structure of the FHA domain of RNF8 in complex with its optimal phosphopeptide==
	<StructureSection load='2pie' size='340' side='right' caption='[[2pie]], [[Resolution\|resolution]] 1.35Å' scene=''>		<StructureSection load='2pie' size='340' side='right' caption='[[2pie]], [[Resolution\|resolution]] 1.35Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2csw\|2csw]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2csw\|2csw]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">RNF8, KIAA0646 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">RNF8, KIAA0646 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2pie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pie OCA], [http://pdbe.org/2pie PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2pie RCSB], [http://www.ebi.ac.uk/pdbsum/2pie PDBsum]</span></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=2pie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pie OCA], [http://pdbe.org/2pie PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2pie RCSB], [http://www.ebi.ac.uk/pdbsum/2pie PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2pie ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2pie ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 29:		Line 30:
	</div>		</div>
	<div class="pdbe-citations 2pie" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 2pie" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Ubiquitin protein ligase\|Ubiquitin protein ligase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 13:05, 11 September 2015

2015-09-11T13:05:39Z

←Older revision		Revision as of 13:05, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='2pie' size='340' side='right' caption='[[2pie]], [[Resolution\|resolution]] 1.35Å' scene=''>		<StructureSection load='2pie' size='340' side='right' caption='[[2pie]], [[Resolution\|resolution]] 1.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2pie]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PIE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PIE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2pie]] 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=2PIE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PIE FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2csw\|2csw]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2csw\|2csw]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">RNF8, KIAA0646 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">RNF8, KIAA0646 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2pie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pie OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2pie RCSB], [http://www.ebi.ac.uk/pdbsum/2pie PDBsum]</span></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=2pie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pie OCA], [http://pdbe.org/2pie PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2pie RCSB], [http://www.ebi.ac.uk/pdbsum/2pie PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 28:		Line 28:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 2pie" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 35:		Line 36:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Grant, R A]]		[[Category: Grant, R A]]
	[[Category: Yaffe, M B]]		[[Category: Yaffe, M B]]

OCA at 16:50, 25 December 2014

2014-12-25T16:50:36Z

←Older revision		Revision as of 16:50, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2pie]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PIE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PIE FirstGlance]. <br>		<table><tr><td colspan='2'>[[2pie]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PIE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PIE FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>	+	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2csw\|2csw]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2csw\|2csw]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">RNF8, KIAA0646 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">RNF8, KIAA0646 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pie OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2pie RCSB], [http://www.ebi.ac.uk/pdbsum/2pie PDBsum]</span></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=2pie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pie OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2pie RCSB], [http://www.ebi.ac.uk/pdbsum/2pie PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/RNF8_HUMAN RNF8_HUMAN]] E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Promotes the formation of 'Lys-63'-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains via interaction with the ubiquitin-conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward 'Lys-48'- versus 'Lys-63'-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases. For instance, interaction with phosphorylated HERC2 promotes the association between RNF8 and UBE2N/UBC13 and favors the specific formation of 'Lys-63'-linked ubiquitin chains. Promotes non-homologous end joining (NHEJ) by promoting the 'Lys-48'-linked ubiquitination and degradation the of KU80/XRCC5. Following DNA damage, mediates the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF168, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation. Involved in the activation of ATM by promoting histone H2B ubiquitination, which indirectly triggers histone H4 'Lys-16' acetylation (H4K16ac), establishing a chromatin environment that promotes efficient activation of ATM kinase. Required in the testis, where it plays a role in the replacement of histones during spermatogenesis. At uncapped telomeres, promotes the joining of deprotected chromosome ends by inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that it may enhance cancer development by aggraving telomere-induced genome instability in case of telomeric crisis. Promotes the assembly of RAD51 at DNA DSBs in the absence of BRCA1 and TP53BP1 Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. May be required for proper exit from mitosis after spindle checkpoint activation and may regulate cytokinesis. May play a role in the regulation of RXRA-mediated transcriptional activity. Not involved in RXRA ubiquitination by UBE2E2.<ref>PMID:11322894</ref> <ref>PMID:14981089</ref> <ref>PMID:18001824</ref> <ref>PMID:18077395</ref> <ref>PMID:18006705</ref> <ref>PMID:17724460</ref> <ref>PMID:18948756</ref> <ref>PMID:18337245</ref> <ref>PMID:19203578</ref> <ref>PMID:19203579</ref> <ref>PMID:19124460</ref> <ref>PMID:19015238</ref> <ref>PMID:19202061</ref> <ref>PMID:20550933</ref> <ref>PMID:21558560</ref> <ref>PMID:21857671</ref> <ref>PMID:22865450</ref> <ref>PMID:22373579</ref> <ref>PMID:22531782</ref> <ref>PMID:22705371</ref> <ref>PMID:22266820</ref> <ref>PMID:21911360</ref> <ref>PMID:18001825</ref> <ref>PMID:22980979</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 34:		Line 36:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Grant, R A.]]	+	[[Category: Grant, R A]]
-	[[Category: Yaffe, M B.]]	+	[[Category: Yaffe, M B]]
	[[Category: Complex]]		[[Category: Complex]]
	[[Category: Fha domain]]		[[Category: Fha domain]]

OCA at 20:09, 30 September 2014

2014-09-30T20:09:51Z

←Older revision		Revision as of 20:09, 30 September 2014
Line 1:		Line 1:
-	[[~~Image:~~2pie.~~png~~\|~~left~~\|200px]]	+	==Crystal structure of the FHA domain of RNF8 in complex with its optimal phosphopeptide==
		+	<StructureSection load='2pie' size='340' side='right' caption='[[2pie]], [[Resolution\|resolution]] 1.35Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2pie]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PIE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PIE FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2csw\|2csw]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">RNF8, KIAA0646 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2pie FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pie OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2pie RCSB], [http://www.ebi.ac.uk/pdbsum/2pie PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pi/2pie_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	DNA-damage signaling utilizes a multitude of posttranslational modifiers as molecular switches to regulate cell-cycle checkpoints, DNA repair, cellular senescence, and apoptosis. Here we show that RNF8, a FHA/RING domain-containing protein, plays a critical role in the early DNA-damage response. We have solved the X-ray crystal structure of the FHA domain structure at 1.35 A. We have shown that RNF8 facilitates the accumulation of checkpoint mediator proteins BRCA1 and 53BP1 to the damaged chromatin, on one hand through the phospho-dependent FHA domain-mediated binding of RNF8 to MDC1, on the other hand via its role in ubiquitylating H2AX and possibly other substrates at damage sites. Moreover, RNF8-depleted cells displayed a defective G2/M checkpoint and increased IR sensitivity. Together, our study implicates RNF8 as a novel DNA-damage-responsive protein that integrates protein phosphorylation and ubiquitylation signaling and plays a critical role in the cellular response to genotoxic stress.

-	~~{{STRUCTURE_2pie\| PDB=2pie \| SCENE= }}~~	+	RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly.,Huen MS, Grant R, Manke I, Minn K, Yu X, Yaffe MB, Chen J Cell. 2007 Nov 30;131(5):901-14. Epub 2007 Nov 20. PMID:18001825<ref>PMID:18001825</ref>

-	~~===Crystal structure~~ of the ~~FHA domain~~ of ~~RNF8 in complex with its optimal phosphopeptide===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-	~~{{ABSTRACT_PUBMED_18001825}}~~	+	==See Also==
-		+	*[[Ubiquitin protein ligase\|Ubiquitin protein ligase]]
-	==~~About this Structure~~==	+	== References ==
-	[[~~2pie~~]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PIE OCA].	+	<references/>
-		+	__TOC__
-	==~~Reference~~==	+	</StructureSection>
-	<~~ref group="xtra">PMID:018001825<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Grant, R A.]]		[[Category: Grant, R A.]]

OCA: Protected "2pie" [edit=sysop:move=sysop]

2013-01-07T12:31:23Z

Protected "2pie" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:31, 7 January 2013

OCA at 12:31, 7 January 2013

2013-01-07T12:31:20Z

←Older revision		Revision as of 12:31, 7 January 2013
Line 1:		Line 1:
-	{{Seed}}
	[[Image:2pie.png\|left\|200px]]		[[Image:2pie.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_2pie", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_2pie\| PDB=2pie \| SCENE= }}		{{STRUCTURE_2pie\| PDB=2pie \| SCENE= }}

	===Crystal structure of the FHA domain of RNF8 in complex with its optimal phosphopeptide===		===Crystal structure of the FHA domain of RNF8 in complex with its optimal phosphopeptide===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_18001825}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 18001825 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_18001825}}		{{ABSTRACT_PUBMED_18001825}}

	==About this Structure==		==About this Structure==
-	~~2PIE~~ is a 2 ~~chains~~ structure ~~of sequences~~ from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PIE OCA].	+	[[2pie]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PIE OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~18001825~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:018001825</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Grant, R A.]]		[[Category: Grant, R A.]]
Line 32:		Line 20:
	[[Category: Phosphopeptide]]		[[Category: Phosphopeptide]]
	[[Category: Signaling protein]]		[[Category: Signaling protein]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 22:13:58 2009''

OCA at 20:13, 17 February 2009

2009-02-17T20:13:59Z

←Older revision		Revision as of 20:13, 17 February 2009
Line 20:		Line 20:

	==About this Structure==		==About this Structure==
-	2PIE is a ~~[[Single protein]]~~ structure of ~~sequence~~ from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PIE OCA].	+	2PIE is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PIE OCA].

	==Reference==		==Reference==
-	RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly., Huen MS, Grant R, Manke I, Minn K, Yu X, Yaffe MB, Chen J, Cell. 2007 Nov 30;131(5):901-14. Epub 2007 Nov 20. PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/18001825 18001825]~~	+	<ref group="xtra">PMID:18001825</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Single protein]]
	[[Category: Grant, R A.]]		[[Category: Grant, R A.]]
	[[Category: Yaffe, M B.]]		[[Category: Yaffe, M B.]]
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	[[Category: Signaling protein]]		[[Category: Signaling protein]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue ~~Jul 29 06~~:30:~~33 2008~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 22:13:58 2009''

OCA at 03:30, 29 July 2008

2008-07-29T03:30:34Z

←Older revision		Revision as of 03:30, 29 July 2008
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-	[[Image:2pie.~~jpg~~\|left\|200px]]	+	{{Seed}}
		+	[[Image:2pie.png\|left\|200px]]

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	{{STRUCTURE_2pie\| PDB=2pie \| SCENE= }}		{{STRUCTURE_2pie\| PDB=2pie \| SCENE= }}

-	~~'''~~Crystal structure of the FHA domain of RNF8 in complex with its optimal phosphopeptide~~'''~~	+	===Crystal structure of the FHA domain of RNF8 in complex with its optimal phosphopeptide===


-	~~==Overview==~~	+	<!--
-	~~DNA~~-~~damage signaling utilizes a multitude of posttranslational modifiers as molecular switches to regulate cell~~-~~cycle checkpoints~~, ~~DNA repair~~, ~~cellular senescence, and apoptosis. Here we show that RNF8, a FHA/RING domain-containing protein, plays a critical role in~~ the ~~early DNA-damage response. We have solved~~ the ~~X-ray crystal structure of the FHA domain structure~~ at 1.~~35 A~~. ~~We have shown that RNF8 facilitates the accumulation of checkpoint mediator proteins BRCA1 and 53BP1 to the damaged chromatin~~, ~~on one hand through~~ the ~~phospho-dependent FHA domain-mediated binding of RNF8 to MDC1, on the other hand via its role in ubiquitylating H2AX and possibly other substrates at damage sites~~. ~~Moreover, RNF8~~-~~depleted cells displayed a defective G2/M checkpoint and increased IR sensitivity. Together, our study implicates RNF8 as a novel DNA~~-~~damage-responsive protein that integrates protein phosphorylation and ubiquitylation signaling and plays a critical role in the cellular response to genotoxic stress.~~	+	The line below this paragraph, {{ABSTRACT_PUBMED_18001825}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 18001825 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_18001825}}

	==About this Structure==		==About this Structure==
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	[[Category: Phosphopeptide]]		[[Category: Phosphopeptide]]
	[[Category: Signaling protein]]		[[Category: Signaling protein]]
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