4dhz - Revision history

OCA at 08:19, 21 September 2022

OCA — Wed, 21 Sep 2022 08:19:08 GMT

←Older revision		Revision as of 08:19, 21 September 2022
Line 1:		Line 1:

	==The structure of h/ceOTUB1-ubiquitin aldehyde-UBC13~Ub==		==The structure of h/ceOTUB1-ubiquitin aldehyde-UBC13~Ub==
-	<StructureSection load='4dhz' size='340' side='right' caption='[[4dhz]], [[Resolution\|resolution]] 3.11Å' scene=''>	+	<StructureSection load='4dhz' size='340' side='right'caption='[[4dhz]], [[Resolution\|resolution]] 3.11Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4dhz]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Caeel Caeel~~] and [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DHZ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4DHZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4dhz]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DHZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DHZ FirstGlance]. <br>
-	</td></tr><tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLZ:AMINO-ACETALDEHYDE'>GLZ</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLZ:AMINO-ACETALDEHYDE'>GLZ</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4dhi\|4dhi]], [[4dhj\|4dhj]]</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=4dhz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dhz OCA], [https://pdbe.org/4dhz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dhz RCSB], [https://www.ebi.ac.uk/pdbsum/4dhz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dhz ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">OTUB1, OTB1, OTU1, HSPC263, C25D7.8, otub-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6239 CAEEL]), UBC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), UBE2N, BLU ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </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=4dhz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dhz OCA], [~~http~~://pdbe.org/4dhz PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4dhz RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4dhz PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4dhz ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[[http://www.uniprot.org/uniprot/UBE2N_HUMAN UBE2N_HUMAN]] The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly-ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes (By similarity).<ref>PMID:10089880</ref> <ref>PMID:14562038</ref> <ref>PMID:19269966</ref> <ref>PMID:20061386</ref> <ref>PMID:21512573</ref> [[http://www.uniprot.org/uniprot/OTUB1_HUMAN OTUB1_HUMAN]] Hydrolase that can specifically remove 'Lys-48'-linked conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation. Regulator of T-cell anergy, a phenomenon that occurs when T-cells are rendered unresponsive to antigen rechallenge and no longer respond to their cognate antigen. Acts via its interaction with RNF128/GRAIL, a crucial inductor of CD4 T-cell anergy. Isoform 1 destabilizes RNF128, leading to prevent anergy. In contrast, isoform 2 stabilizes RNF128 and promotes anergy. Surprisingly, it regulates RNF128-mediated ubiquitination, but does not deubiquitinate polyubiquitinated RNF128. Deubiquitinates estrogen receptor alpha (ESR1). Mediates deubiquitination of 'Lys-48'-linked polyubiquitin chains, but not 'Lys-63'-linked polyubiquitin chains. Not able to cleave di-ubiquitin. Also capable of removing NEDD8 from NEDD8 conjugates, but with a much lower preference compared to 'Lys-48'-linked ubiquitin.<ref>PMID:12704427</ref> <ref>PMID:14661020</ref> <ref>PMID:12401499</ref> <ref>PMID:19383985</ref> <ref>PMID:19211026</ref> <ref>PMID:20725033</ref> <ref>PMID:18954305</ref> Plays a key non-catalytic role in DNA repair regulation by inhibiting activity of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites. Inhibits RNF168 independently of ubiquitin thioesterase activity by binding and inhibiting UBE2N/UBC13, the E2 partner of RNF168, thereby limiting spreading of 'Lys-63'-linked histone H2A and H2AX marks. Inhibition occurs by binding to free ubiquitin: free ubiquitin acts as an allosteric regulator that increases affinity for UBE2N/UBC13 and disrupts interaction with UBE2V1. The OTUB1-UBE2N/UBC13-free ubiquitin complex adopts a configuration that mimics a cleaved 'Lys48'-linked di-ubiquitin chain.<ref>PMID:12704427</ref> <ref>PMID:14661020</ref> <ref>PMID:12401499</ref> <ref>PMID:19383985</ref> <ref>PMID:19211026</ref> <ref>PMID:20725033</ref> <ref>PMID:18954305</ref> [[~~http~~://www.uniprot.org/uniprot/~~UBC_HUMAN UBC_HUMAN~~]] ~~Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is~~ conjugated ~~to target~~ proteins ~~via~~ an ~~isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of~~ the ~~ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met~~ of ~~the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target~~ protein~~, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated~~ degradation~~) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification;~~ Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin ~~is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling~~.<ref>PMID:~~16543144</ref> <ref>PMID:19754430~~</ref>	+	[[https://www.uniprot.org/uniprot/OTUB1_HUMAN OTUB1_HUMAN]] Hydrolase that can specifically remove 'Lys-48'-linked conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation. Regulator of T-cell anergy, a phenomenon that occurs when T-cells are rendered unresponsive to antigen rechallenge and no longer respond to their cognate antigen. Acts via its interaction with RNF128/GRAIL, a crucial inductor of CD4 T-cell anergy. Isoform 1 destabilizes RNF128, leading to prevent anergy. In contrast, isoform 2 stabilizes RNF128 and promotes anergy. Surprisingly, it regulates RNF128-mediated ubiquitination, but does not deubiquitinate polyubiquitinated RNF128. Deubiquitinates estrogen receptor alpha (ESR1). Mediates deubiquitination of 'Lys-48'-linked polyubiquitin chains, but not 'Lys-63'-linked polyubiquitin chains. Not able to cleave di-ubiquitin. Also capable of removing NEDD8 from NEDD8 conjugates, but with a much lower preference compared to 'Lys-48'-linked ubiquitin.<ref>PMID:12704427</ref> <ref>PMID:14661020</ref> <ref>PMID:12401499</ref> <ref>PMID:19383985</ref> <ref>PMID:19211026</ref> <ref>PMID:20725033</ref> <ref>PMID:18954305</ref> Plays a key non-catalytic role in DNA repair regulation by inhibiting activity of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites. Inhibits RNF168 independently of ubiquitin thioesterase activity by binding and inhibiting UBE2N/UBC13, the E2 partner of RNF168, thereby limiting spreading of 'Lys-63'-linked histone H2A and H2AX marks. Inhibition occurs by binding to free ubiquitin: free ubiquitin acts as an allosteric regulator that increases affinity for UBE2N/UBC13 and disrupts interaction with UBE2V1. The OTUB1-UBE2N/UBC13-free ubiquitin complex adopts a configuration that mimics a cleaved 'Lys48'-linked di-ubiquitin chain.<ref>PMID:12704427</ref> <ref>PMID:14661020</ref> <ref>PMID:12401499</ref> <ref>PMID:19383985</ref> <ref>PMID:19211026</ref> <ref>PMID:20725033</ref> <ref>PMID:18954305</ref> [[https://www.uniprot.org/uniprot/OTUBL_CAEEL OTUBL_CAEEL]] Hydrolase that can remove conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation. Specifically cleaves 'Lys-48'-linked polyubiquitin.<ref>PMID:19211026</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4dhz" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4dhz" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Thioesterase 3D structures\|Thioesterase 3D structures]]
		+	*[[3D structures of ubiquitin\|3D structures of ubiquitin]]
		+	*[[3D structures of ubiquitin conjugating enzyme\|3D structures of ubiquitin conjugating enzyme]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Caeel~~]]	+	[[Category: Caenorhabditis elegans]]
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Ubiquitinyl hydrolase 1~~]]	+	[[Category: Large Structures]]
-	[[Category: Wang, T]]	+	[[Category: Wang T]]
-	[[Category: Wiener, R]]	+	[[Category: Wiener R]]
-	[[Category: Wolberger, C]]	+	[[Category: Wolberger C]]
-	[[Category: Zhang, X]]	+	[[Category: Zhang X]]
-	~~[[Category: Hydrolase-signaling protein-ligase complex]]~~	+
-	~~[[Category: Ubiquitination~~]]	+

OCA at 07:53, 15 November 2017

OCA — Wed, 15 Nov 2017 07:53:02 GMT

←Older revision		Revision as of 07:53, 15 November 2017
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 4dhz" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4dhz" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Thioesterase\|Thioesterase]]
-	*[[Ubiquitin\|Ubiquitin]]
-	*[[Ubiquitin conjugating enzyme\|Ubiquitin conjugating enzyme]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 20:00, 5 August 2016

OCA — Fri, 05 Aug 2016 20:00:46 GMT

←Older revision		Revision as of 20:00, 5 August 2016
Line 1:		Line 1:
		+
	==The structure of h/ceOTUB1-ubiquitin aldehyde-UBC13~Ub==		==The structure of h/ceOTUB1-ubiquitin aldehyde-UBC13~Ub==
	<StructureSection load='4dhz' size='340' side='right' caption='[[4dhz]], [[Resolution\|resolution]] 3.11Å' scene=''>		<StructureSection load='4dhz' size='340' side='right' caption='[[4dhz]], [[Resolution\|resolution]] 3.11Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4dhz]] is a 4 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=4DHZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DHZ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4dhz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Caeel Caeel] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DHZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DHZ FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLZ:AMINO-ACETALDEHYDE'>GLZ</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=GLZ:AMINO-ACETALDEHYDE'>GLZ</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4dhi\|4dhi]], [[4dhj\|4dhj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4dhi\|4dhi]], [[4dhj\|4dhj]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">OTUB1, OTB1, OTU1, HSPC263, C25D7.8, otub-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=~~9606 Homo sapiens~~]), UBC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~]), UBE2N, BLU ([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">OTUB1, OTB1, OTU1, HSPC263, C25D7.8, otub-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6239 CAEEL]), UBC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), UBE2N, BLU ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </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=4dhz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dhz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dhz RCSB], [http://www.ebi.ac.uk/pdbsum/4dhz 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=4dhz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dhz OCA], [http://pdbe.org/4dhz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dhz RCSB], [http://www.ebi.ac.uk/pdbsum/4dhz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dhz ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	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 4dhz" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 28:		Line 30:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Caeel]]
		+	[[Category: Human]]
	[[Category: Ubiquitinyl hydrolase 1]]		[[Category: Ubiquitinyl hydrolase 1]]
	[[Category: Wang, T]]		[[Category: Wang, T]]

OCA at 05:25, 25 December 2014

OCA — Thu, 25 Dec 2014 05:25:48 GMT

←Older revision		Revision as of 05:25, 25 December 2014
Line 9:		Line 9:
	<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=4dhz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dhz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dhz RCSB], [http://www.ebi.ac.uk/pdbsum/4dhz 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=4dhz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dhz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dhz RCSB], [http://www.ebi.ac.uk/pdbsum/4dhz PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/UBE2N_HUMAN UBE2N_HUMAN]] The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly-ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes (By similarity).<ref>PMID:10089880</ref> <ref>PMID:14562038</ref> <ref>PMID:19269966</ref> <ref>PMID:20061386</ref> <ref>PMID:21512573</ref> [[http://www.uniprot.org/uniprot/OTUB1_HUMAN OTUB1_HUMAN]] Hydrolase that can specifically remove 'Lys-48'-linked conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation. Regulator of T-cell anergy, a phenomenon that occurs when T-cells are rendered unresponsive to antigen rechallenge and no longer respond to their cognate antigen. Acts via its interaction with RNF128/GRAIL, a crucial inductor of CD4 T-cell anergy. Isoform 1 destabilizes RNF128, leading to prevent anergy. In contrast, isoform 2 stabilizes RNF128 and promotes anergy. Surprisingly, it regulates RNF128-mediated ubiquitination, but does not deubiquitinate polyubiquitinated RNF128. Deubiquitinates estrogen receptor alpha (ESR1). Mediates deubiquitination of 'Lys-48'-linked polyubiquitin chains, but not 'Lys-63'-linked polyubiquitin chains. Not able to cleave di-ubiquitin. Also capable of removing NEDD8 from NEDD8 conjugates, but with a much lower preference compared to 'Lys-48'-linked ubiquitin.<ref>PMID:12704427</ref> <ref>PMID:14661020</ref> <ref>PMID:12401499</ref> <ref>PMID:19383985</ref> <ref>PMID:19211026</ref> <ref>PMID:20725033</ref> <ref>PMID:18954305</ref> Plays a key non-catalytic role in DNA repair regulation by inhibiting activity of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites. Inhibits RNF168 independently of ubiquitin thioesterase activity by binding and inhibiting UBE2N/UBC13, the E2 partner of RNF168, thereby limiting spreading of 'Lys-63'-linked histone H2A and H2AX marks. Inhibition occurs by binding to free ubiquitin: free ubiquitin acts as an allosteric regulator that increases affinity for UBE2N/UBC13 and disrupts interaction with UBE2V1. The OTUB1-UBE2N/UBC13-free ubiquitin complex adopts a configuration that mimics a cleaved 'Lys48'-linked di-ubiquitin chain.<ref>PMID:12704427</ref> <ref>PMID:14661020</ref> <ref>PMID:12401499</ref> <ref>PMID:19383985</ref> <ref>PMID:19211026</ref> <ref>PMID:20725033</ref> <ref>PMID:18954305</ref> [[http://www.uniprot.org/uniprot/UBC_HUMAN UBC_HUMAN]] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.<ref>PMID:16543144</ref> <ref>PMID:19754430</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 16:50, 9 December 2014

OCA — Tue, 09 Dec 2014 16:50:04 GMT

←Older revision		Revision as of 16:50, 9 December 2014
Line 1:		Line 1:
-	[[~~Image:~~4dhz.~~png~~\|~~left~~\|~~200px~~]]	+	==The structure of h/ceOTUB1-ubiquitin aldehyde-UBC13~Ub==
		+	<StructureSection load='4dhz' size='340' side='right' caption='[[4dhz]], [[Resolution\|resolution]] 3.11Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4dhz]] is a 4 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=4DHZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DHZ FirstGlance]. <br>
		+	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLZ:AMINO-ACETALDEHYDE'>GLZ</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4dhi\|4dhi]], [[4dhj\|4dhj]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">OTUB1, OTB1, OTU1, HSPC263, C25D7.8, otub-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), UBC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), UBE2N, BLU ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </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=4dhz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dhz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dhz RCSB], [http://www.ebi.ac.uk/pdbsum/4dhz PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Histones are ubiquitinated in response to DNA double-strand breaks (DSB), promoting recruitment of repair proteins to chromatin. UBC13 (also known as UBE2N) is a ubiquitin-conjugating enzyme (E2) that heterodimerizes with UEV1A (also known as UBE2V1) and synthesizes K63-linked polyubiquitin (K63Ub) chains at DSB sites in concert with the ubiquitin ligase (E3), RNF168 (ref. 3). K63Ub synthesis is regulated in a non-canonical manner by the deubiquitinating enzyme, OTUB1 (OTU domain-containing ubiquitin aldehyde-binding protein 1), which binds preferentially to the UBC13 approximately Ub thiolester. Residues amino-terminal to the OTU domain, which had been implicated in ubiquitin binding, are required for binding to UBC13 approximately Ub and inhibition of K63Ub synthesis. Here we describe structural and biochemical studies elucidating how OTUB1 inhibits UBC13 and other E2 enzymes. We unexpectedly find that OTUB1 binding to UBC13 approximately Ub is allosterically regulated by free ubiquitin, which binds to a second site in OTUB1 and increases its affinity for UBC13 approximately Ub, while at the same time disrupting interactions with UEV1A in a manner that depends on the OTUB1 N terminus. Crystal structures of an OTUB1-UBC13 complex and of OTUB1 bound to ubiquitin aldehyde and a chemical UBC13 approximately Ub conjugate show that binding of free ubiquitin to OTUB1 triggers conformational changes in the OTU domain and formation of a ubiquitin-binding helix in the N terminus, thus promoting binding of the conjugated donor ubiquitin in UBC13 approximately Ub to OTUB1. The donor ubiquitin thus cannot interact with the E2 enzyme, which has been shown to be important for ubiquitin transfer. The N-terminal helix of OTUB1 is positioned to interfere with UEV1A binding to UBC13, as well as with attack on the thiolester by an acceptor ubiquitin, thereby inhibiting K63Ub synthesis. OTUB1 binding also occludes the RING E3 binding site on UBC13, thus providing a further component of inhibition. The general features of the inhibition mechanism explain how OTUB1 inhibits other E2 enzymes in a non-catalytic manner.

-	~~{{STRUCTURE_4dhz\| PDB=4dhz \| SCENE= }}~~	+	The mechanism of OTUB1-mediated inhibition of ubiquitination.,Wiener R, Zhang X, Wang T, Wolberger C Nature. 2012 Feb 22. doi: 10.1038/nature10911. PMID:22367539<ref>PMID:22367539</ref>

-	~~===The structure of h~~/~~ceOTUB1-ubiquitin aldehyde-UBC13~Ub===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_22367539}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[4dhz]] is~~ a ~~4 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=4DHZ OCA].~~	+

	==See Also==		==See Also==
	*[[Thioesterase\|Thioesterase]]		*[[Thioesterase\|Thioesterase]]
-		+	*[[Ubiquitin\|Ubiquitin]]
-	==~~Reference~~==	+	*[[Ubiquitin conjugating enzyme\|Ubiquitin conjugating enzyme]]
-	<~~ref group="xtra">PMID:022367539<~~/~~ref~~><~~references group="xtra"~~/>	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Ubiquitinyl hydrolase 1]]		[[Category: Ubiquitinyl hydrolase 1]]
-	[[Category: Wang, T.]]	+	[[Category: Wang, T]]
-	[[Category: Wiener, R.]]	+	[[Category: Wiener, R]]
-	[[Category: Wolberger, C.]]	+	[[Category: Wolberger, C]]
-	[[Category: Zhang, X.]]	+	[[Category: Zhang, X]]
	[[Category: Hydrolase-signaling protein-ligase complex]]		[[Category: Hydrolase-signaling protein-ligase complex]]
	[[Category: Ubiquitination]]		[[Category: Ubiquitination]]

OCA at 13:08, 20 October 2012

OCA — Sat, 20 Oct 2012 13:08:36 GMT

←Older revision		Revision as of 13:08, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[4dhz]] is a 4 chain structure ~~of [[Thioesterase]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens~~] and [http://en.wikipedia.org/wiki/Homo_sapiens,_caenorhabditis_elegans Homo sapiens, caenorhabditis elegans~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DHZ OCA].	+	[[4dhz]] is a 4 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=4DHZ OCA].

	==See Also==		==See Also==
Line 16:		Line 16:
	<ref group="xtra">PMID:022367539</ref><references group="xtra"/>		<ref group="xtra">PMID:022367539</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Homo sapiens, caenorhabditis elegans]]
	[[Category: Ubiquitinyl hydrolase 1]]		[[Category: Ubiquitinyl hydrolase 1]]
	[[Category: Wang, T.]]		[[Category: Wang, T.]]

OCA at 11:01, 26 July 2012

OCA — Thu, 26 Jul 2012 11:01:55 GMT

←Older revision		Revision as of 11:01, 26 July 2012
Line 1:		Line 1:
	[[Image:4dhz.png\|left\|200px]]		[[Image:4dhz.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_4dhz", 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_4dhz\| PDB=4dhz \| SCENE= }}		{{STRUCTURE_4dhz\| PDB=4dhz \| SCENE= }}

	===The structure of h/ceOTUB1-ubiquitin aldehyde-UBC13~Ub===		===The structure of h/ceOTUB1-ubiquitin aldehyde-UBC13~Ub===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_22367539}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 22367539 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_22367539}}		{{ABSTRACT_PUBMED_22367539}}

	==About this Structure==		==About this Structure==
-	[[4dhz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Homo_sapiens,_caenorhabditis_elegans Homo sapiens, caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DHZ OCA].	+	[[4dhz]] is a 4 chain structure of [[Thioesterase]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Homo_sapiens,_caenorhabditis_elegans Homo sapiens, caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DHZ OCA].
		+
		+	==See Also==
		+	*[[Thioesterase\|Thioesterase]]

	==Reference==		==Reference==

OCA at 05:51, 14 March 2012

OCA — Wed, 14 Mar 2012 05:51:08 GMT

←Older revision		Revision as of 05:51, 14 March 2012
Line 11:		Line 11:
	===The structure of h/ceOTUB1-ubiquitin aldehyde-UBC13~Ub===		===The structure of h/ceOTUB1-ubiquitin aldehyde-UBC13~Ub===

		+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22367539}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22367539 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22367539}}

	==About this Structure==		==About this Structure==
	[[4dhz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Homo_sapiens,_caenorhabditis_elegans Homo sapiens, caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DHZ OCA].		[[4dhz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Homo_sapiens,_caenorhabditis_elegans Homo sapiens, caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DHZ OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022367539</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Homo sapiens, caenorhabditis elegans]]		[[Category: Homo sapiens, caenorhabditis elegans]]

OCA at 07:54, 29 February 2012

OCA — Wed, 29 Feb 2012 07:54:50 GMT

←Older revision		Revision as of 07:54, 29 February 2012
Line 1:		Line 1:
-	[[Image:4dhz.~~jpg~~\|left\|200px]]	+	[[Image:4dhz.png\|left\|200px]]

	<!--		<!--

OCA at 08:03, 22 February 2012

OCA — Wed, 22 Feb 2012 08:03:34 GMT

←Older revision		Revision as of 08:03, 22 February 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4dhz.jpg\|left\|200px]]

-	The ~~entry 4dhz~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_4dhz", 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_4dhz\| PDB=4dhz \| SCENE= }}

-	~~Authors: Wiener, R., Zhang, X., Wang, T., Wolberger, C.~~	+	===The structure of h/ceOTUB1-ubiquitin aldehyde-UBC13~Ub===

-	~~Description: The~~ structure ~~of h~~/~~ceOTUB1~~-~~ubiquitin aldehyde~~-~~UBC13~Ub~~	+
		+	==About this Structure==
		+	[[4dhz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Homo_sapiens,_caenorhabditis_elegans Homo sapiens, caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DHZ OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Homo sapiens, caenorhabditis elegans]]
		+	[[Category: Ubiquitinyl hydrolase 1]]
		+	[[Category: Wang, T.]]
		+	[[Category: Wiener, R.]]
		+	[[Category: Wolberger, C.]]
		+	[[Category: Zhang, X.]]
		+	[[Category: Hydrolase-signaling protein-ligase complex]]
		+	[[Category: Ubiquitination]]