2dos - Revision history

OCA at 06:39, 1 May 2024

2024-05-01T06:39:41Z

← Older revision		Revision as of 06:39, 1 May 2024
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	==Structural basis for the recognition of Lys48-linked polyubiquitin chain by the Josephin domain of ataxin-3, a putative deubiquitinating enzyme==		==Structural basis for the recognition of Lys48-linked polyubiquitin chain by the Josephin domain of ataxin-3, a putative deubiquitinating enzyme==
	<StructureSection load='2dos' size='340' side='right'caption='[[2dos~~]], [[NMR_Ensembles_of_Models \| 10 NMR models~~]]' scene=''>		<StructureSection load='2dos' size='340' side='right'caption='[[2dos]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2dos]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DOS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DOS FirstGlance]. <br>		<table><tr><td colspan='2'>[[2dos]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DOS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DOS FirstGlance]. <br>
	</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=2dos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dos OCA], [https://pdbe.org/2dos PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dos RCSB], [https://www.ebi.ac.uk/pdbsum/2dos PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dos ProSAT]</span></td></tr>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2dos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dos OCA], [https://pdbe.org/2dos PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dos RCSB], [https://www.ebi.ac.uk/pdbsum/2dos PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dos ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/ATX3_HUMAN ATX3_HUMAN]] Defects in ATXN3 are the cause of spinocerebellar ataxia type 3 (SCA3) [MIM:[https://omim.org/entry/109150 109150]]; also known as Machado-Joseph disease (MJD). Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA3 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. The molecular defect in SCA3 is the a CAG repeat expansion in ATXN3 coding region. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:7874163</ref>		[https://www.uniprot.org/uniprot/ATX3_HUMAN ATX3_HUMAN] Defects in ATXN3 are the cause of spinocerebellar ataxia type 3 (SCA3) [MIM:[https://omim.org/entry/109150 109150]; also known as Machado-Joseph disease (MJD). Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA3 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. The molecular defect in SCA3 is the a CAG repeat expansion in ATXN3 coding region. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:7874163</ref>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/ATX3_HUMAN ATX3_HUMAN]] Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates. Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins. Involved in degradation of misfolded chaperone substrates via its interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP, and restricts the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. In response to misfolded substrate ubiquitination, mediates deubiquitination of monoubiquitinated STUB1/CHIP. Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription.<ref>PMID:12297501</ref> <ref>PMID:17696782</ref> <ref>PMID:16118278</ref>		[https://www.uniprot.org/uniprot/ATX3_HUMAN ATX3_HUMAN] Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates. Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins. Involved in degradation of misfolded chaperone substrates via its interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP, and restricts the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. In response to misfolded substrate ubiquitination, mediates deubiquitination of monoubiquitinated STUB1/CHIP. Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription.<ref>PMID:12297501</ref> <ref>PMID:17696782</ref> <ref>PMID:16118278</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 20:		Line 21:
	</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=2dos 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=2dos ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Ataxin-3, which is encoded by a gene that has been associated with Machado-Joseph disease, contains a catalytic N-terminal Josephin domain with deubiquitinase activity. Here, we show that the Josephin domain of ataxin 3 catalyzes endo-type cleavage of Lys48-linked polyubiquitin. Furthermore, NMR data obtained following site-specific paramagnetic spin labeling of Lys48-linked di-ubiquitin revealed that both ubiquitin units interact with the Josephin domain, with the C-terminal Gly76 of the proximal unit being situated in the vicinity of the catalytic triad of Josephin domain. Our results help to elucidate how the substrate is recognized by the Josephin domain and properly positioned for an endo-type deubiquitination reaction.

	Mode of substrate recognition by the Josephin domain of ataxin-3, which has an endo-type deubiquitinase activity.,Satoh T, Sumiyoshi A, Yagi-Utsumi M, Sakata E, Sasakawa H, Kurimoto E, Yamaguchi Y, Li W, Joazeiro CA, Hirokawa T, Kato K FEBS Lett. 2014 Nov 28;588(23):4422-30. doi: 10.1016/j.febslet.2014.10.013. Epub , 2014 Oct 19. PMID:25448680<ref>PMID:25448680</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 2dos" style="background-color:#fffaf0;"></div>~~
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Sumiyoshi, A]]		[[Category: Sumiyoshi A]]
	~~[[Category: Deubiquitinating enzyme]]~~
	~~[[Category: Hydrolase~~]]

OCA at 10:33, 8 December 2021

2021-12-08T10:33:22Z

← Older revision		Revision as of 10:33, 8 December 2021
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	<StructureSection load='2dos' size='340' side='right'caption='[[2dos]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>		<StructureSection load='2dos' size='340' side='right'caption='[[2dos]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2dos]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DOS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2DOS FirstGlance]. <br>		<table><tr><td colspan='2'>[[2dos]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DOS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DOS FirstGlance]. <br>
	</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=2dos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dos OCA], [~~http~~://pdbe.org/2dos PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2dos RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2dos PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2dos ProSAT]</span></td></tr>		</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=2dos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dos OCA], [https://pdbe.org/2dos PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dos RCSB], [https://www.ebi.ac.uk/pdbsum/2dos PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dos ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[~~http~~://www.uniprot.org/uniprot/ATX3_HUMAN ATX3_HUMAN]] Defects in ATXN3 are the cause of spinocerebellar ataxia type 3 (SCA3) [MIM:[~~http~~://omim.org/entry/109150 109150]]; also known as Machado-Joseph disease (MJD). Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA3 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. The molecular defect in SCA3 is the a CAG repeat expansion in ATXN3 coding region. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:7874163</ref>		[[https://www.uniprot.org/uniprot/ATX3_HUMAN ATX3_HUMAN]] Defects in ATXN3 are the cause of spinocerebellar ataxia type 3 (SCA3) [MIM:[https://omim.org/entry/109150 109150]]; also known as Machado-Joseph disease (MJD). Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA3 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. The molecular defect in SCA3 is the a CAG repeat expansion in ATXN3 coding region. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:7874163</ref>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/ATX3_HUMAN ATX3_HUMAN]] Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates. Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins. Involved in degradation of misfolded chaperone substrates via its interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP, and restricts the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. In response to misfolded substrate ubiquitination, mediates deubiquitination of monoubiquitinated STUB1/CHIP. Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription.<ref>PMID:12297501</ref> <ref>PMID:17696782</ref> <ref>PMID:16118278</ref>		[[https://www.uniprot.org/uniprot/ATX3_HUMAN ATX3_HUMAN]] Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates. Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins. Involved in degradation of misfolded chaperone substrates via its interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP, and restricts the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. In response to misfolded substrate ubiquitination, mediates deubiquitination of monoubiquitinated STUB1/CHIP. Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription.<ref>PMID:12297501</ref> <ref>PMID:17696782</ref> <ref>PMID:16118278</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 07:45, 4 March 2020

2020-03-04T07:45:48Z

← Older revision		Revision as of 07:45, 4 March 2020
Line 1:		Line 1:

	==Structural basis for the recognition of Lys48-linked polyubiquitin chain by the Josephin domain of ataxin-3, a putative deubiquitinating enzyme==		==Structural basis for the recognition of Lys48-linked polyubiquitin chain by the Josephin domain of ataxin-3, a putative deubiquitinating enzyme==
	<StructureSection load='2dos' size='340' side='right' caption='[[2dos]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>		<StructureSection load='2dos' size='340' side='right'caption='[[2dos]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2dos]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DOS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DOS FirstGlance]. <br>		<table><tr><td colspan='2'>[[2dos]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DOS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DOS FirstGlance]. <br>
Line 34:		Line 34:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Sumiyoshi, A]]		[[Category: Sumiyoshi, A]]
	[[Category: Deubiquitinating enzyme]]		[[Category: Deubiquitinating enzyme]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 06:31, 30 May 2018

2018-05-30T06:31:41Z

← Older revision		Revision as of 06:31, 30 May 2018
Line 1:		Line 1:

	==Structural basis for the recognition of Lys48-linked polyubiquitin chain by the Josephin domain of ataxin-3, a putative deubiquitinating enzyme==		==Structural basis for the recognition of Lys48-linked polyubiquitin chain by the Josephin domain of ataxin-3, a putative deubiquitinating enzyme==
	<StructureSection load='2dos' size='340' side='right' caption='[[2dos]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>		<StructureSection load='2dos' size='340' side='right' caption='[[2dos]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2dos]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DOS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DOS FirstGlance]. <br>		<table><tr><td colspan='2'>[[2dos]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DOS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DOS FirstGlance]. <br>
	</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=2dos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dos OCA], [http://pdbe.org/2dos PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2dos RCSB], [http://www.ebi.ac.uk/pdbsum/2dos PDBsum]</span></td></tr>		</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=2dos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dos OCA], [http://pdbe.org/2dos PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2dos RCSB], [http://www.ebi.ac.uk/pdbsum/2dos PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2dos ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 13:		Line 14:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/do/2dos_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/do/2dos_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>

OCA at 20:57, 7 February 2016

2016-02-07T20:57:33Z

← Older revision		Revision as of 20:57, 7 February 2016
Line 17:		Line 17:
	<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=2dos ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 04:55, 10 September 2015

2015-09-10T04:55:50Z

← Older revision		Revision as of 04:55, 10 September 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2dos]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DOS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DOS FirstGlance]. <br>		<table><tr><td colspan='2'>[[2dos]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DOS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DOS FirstGlance]. <br>
	</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=2dos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dos OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2dos RCSB], [http://www.ebi.ac.uk/pdbsum/2dos PDBsum]</span></td></tr>		</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=2dos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dos OCA], [http://pdbe.org/2dos PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2dos RCSB], [http://www.ebi.ac.uk/pdbsum/2dos PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 27:		Line 27:
	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 2dos" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 09:38, 31 December 2014

2014-12-31T09:38:17Z

← Older revision		Revision as of 09:38, 31 December 2014
Line 19:		Line 19:
	</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/chain_selection.php?pdb_ID=2ata ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Ataxin-3, which is encoded by a gene that has been associated with Machado-Joseph disease, contains a catalytic N-terminal Josephin domain with deubiquitinase activity. Here, we show that the Josephin domain of ataxin 3 catalyzes endo-type cleavage of Lys48-linked polyubiquitin. Furthermore, NMR data obtained following site-specific paramagnetic spin labeling of Lys48-linked di-ubiquitin revealed that both ubiquitin units interact with the Josephin domain, with the C-terminal Gly76 of the proximal unit being situated in the vicinity of the catalytic triad of Josephin domain. Our results help to elucidate how the substrate is recognized by the Josephin domain and properly positioned for an endo-type deubiquitination reaction.

			Mode of substrate recognition by the Josephin domain of ataxin-3, which has an endo-type deubiquitinase activity.,Satoh T, Sumiyoshi A, Yagi-Utsumi M, Sakata E, Sasakawa H, Kurimoto E, Yamaguchi Y, Li W, Joazeiro CA, Hirokawa T, Kato K FEBS Lett. 2014 Nov 28;588(23):4422-30. doi: 10.1016/j.febslet.2014.10.013. Epub , 2014 Oct 19. PMID:25448680<ref>PMID:25448680</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:54, 3 December 2014

2014-12-03T07:54:25Z

← Older revision		Revision as of 07:54, 3 December 2014
Line 2:		Line 2:
	<StructureSection load='2dos' size='340' side='right' caption='[[2dos]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>		<StructureSection load='2dos' size='340' side='right' caption='[[2dos]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2dos]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DOS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DOS FirstGlance]. <br>		<table><tr><td colspan='2'>[[2dos]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DOS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DOS FirstGlance]. <br>
	</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=2dos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dos OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2dos RCSB], [http://www.ebi.ac.uk/pdbsum/2dos PDBsum]</span></td></tr>		</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=2dos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dos OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2dos RCSB], [http://www.ebi.ac.uk/pdbsum/2dos PDBsum]</span></td></tr>
	<table>		</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/ATX3_HUMAN ATX3_HUMAN]] Defects in ATXN3 are the cause of spinocerebellar ataxia type 3 (SCA3) [MIM:[http://omim.org/entry/109150 109150]]; also known as Machado-Joseph disease (MJD). Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA3 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. The molecular defect in SCA3 is the a CAG repeat expansion in ATXN3 coding region. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:7874163</ref>		[[http://www.uniprot.org/uniprot/ATX3_HUMAN ATX3_HUMAN]] Defects in ATXN3 are the cause of spinocerebellar ataxia type 3 (SCA3) [MIM:[http://omim.org/entry/109150 109150]]; also known as Machado-Joseph disease (MJD). Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA3 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. The molecular defect in SCA3 is the a CAG repeat expansion in ATXN3 coding region. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:7874163</ref>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Sumiyoshi, A.]]		[[Category: Sumiyoshi, A]]
	[[Category: Deubiquitinating enzyme]]		[[Category: Deubiquitinating enzyme]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 01:05, 30 September 2014

2014-09-30T01:05:08Z

← Older revision		Revision as of 01:05, 30 September 2014
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	~~{{STRUCTURE_2dos\| PDB=2dos \| SCENE= }}~~		==Structural basis for the recognition of Lys48-linked polyubiquitin chain by the Josephin domain of ataxin-3, a putative deubiquitinating enzyme==
	===Structural basis for the recognition of Lys48-linked polyubiquitin chain by the Josephin domain of ataxin-3, a putative deubiquitinating enzyme===		<StructureSection load='2dos' size='340' side='right' caption='[[2dos]], [[NMR_Ensembles_of_Models \| 10 NMR models]]' scene=''>
			== Structural highlights ==
	==Disease==		<table><tr><td colspan='2'>[[2dos]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DOS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2DOS FirstGlance]. <br>
	[[http://www.uniprot.org/uniprot/ATX3_HUMAN ATX3_HUMAN]] Defects in ATXN3 are the cause of spinocerebellar ataxia type 3 (SCA3) [MIM:[http://omim.org/entry/109150 109150]]; also known as Machado-Joseph disease (MJD). Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA3 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. The molecular defect in SCA3 is the a CAG repeat expansion in ATXN3 coding region. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:7874163</ref>		</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=2dos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dos OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2dos RCSB], [http://www.ebi.ac.uk/pdbsum/2dos PDBsum]</span></td></tr>
			<table>
	==Function==		== Disease ==
	[[http://www.uniprot.org/uniprot/ATX3_HUMAN ATX3_HUMAN]] Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates. Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins. Involved in degradation of misfolded chaperone substrates via its interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP, and restricts the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. In response to misfolded substrate ubiquitination, mediates deubiquitination of monoubiquitinated STUB1/CHIP. Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription.<ref>PMID:12297501</ref><ref>PMID:17696782</ref><ref>PMID:16118278</ref>		[[http://www.uniprot.org/uniprot/ATX3_HUMAN ATX3_HUMAN]] Defects in ATXN3 are the cause of spinocerebellar ataxia type 3 (SCA3) [MIM:[http://omim.org/entry/109150 109150]]; also known as Machado-Joseph disease (MJD). Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA3 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. The molecular defect in SCA3 is the a CAG repeat expansion in ATXN3 coding region. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:7874163</ref>
			== Function ==
	==~~About this Structure~~==		[[http://www.uniprot.org/uniprot/ATX3_HUMAN ATX3_HUMAN]] Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates. Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins. Involved in degradation of misfolded chaperone substrates via its interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP, and restricts the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. In response to misfolded substrate ubiquitination, mediates deubiquitination of monoubiquitinated STUB1/CHIP. Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription.<ref>PMID:12297501</ref> <ref>PMID:17696782</ref> <ref>PMID:16118278</ref>
	[[~~2dos~~]] ~~is a 1 chain~~ structure ~~with sequence from~~ [http://en.~~wikipedia~~.~~org/wiki~~/~~Homo_sapiens Homo sapiens~~]. ~~Full experimental information is~~ available from [http://~~oca~~.~~weizmann~~.ac.il/~~oca-bin~~/~~ocashort~~?id=~~2DOS OCA~~].		== Evolutionary Conservation ==
			[[Image:Consurf_key_small.gif\|200px\|right]]
	==~~Reference~~==		Check<jmol>
	<references ~~group="xtra"~~/><~~references~~/>		<jmolCheckbox>
			<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/do/2dos_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>
			== References ==
			<references/>
			__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Sumiyoshi, A.]]		[[Category: Sumiyoshi, A.]]
	[[Category: Deubiquitinating enzyme]]		[[Category: Deubiquitinating enzyme]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 00:21, 25 March 2013

2013-03-25T00:21:13Z

← Older revision		Revision as of 00:21, 25 March 2013
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	~~[[Image:2dos.png\|left\|200px]]~~

	{{STRUCTURE_2dos\| PDB=2dos \| SCENE= }}		{{STRUCTURE_2dos\| PDB=2dos \| SCENE= }}
			===Structural basis for the recognition of Lys48-linked polyubiquitin chain by the Josephin domain of ataxin-3, a putative deubiquitinating enzyme===

	===~~Structural basis for~~ the ~~recognition~~ of ~~Lys48~~-~~linked polyubiquitin chain by~~ the ~~Josephin domain~~ of ~~ataxin-3~~, a ~~putative deubiquitinating enzyme===~~		==Disease==
			[[http://www.uniprot.org/uniprot/ATX3_HUMAN ATX3_HUMAN]] Defects in ATXN3 are the cause of spinocerebellar ataxia type 3 (SCA3) [MIM:[http://omim.org/entry/109150 109150]]; also known as Machado-Joseph disease (MJD). Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA3 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. The molecular defect in SCA3 is the a CAG repeat expansion in ATXN3 coding region. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:7874163</ref>

			==Function==
			[[http://www.uniprot.org/uniprot/ATX3_HUMAN ATX3_HUMAN]] Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates. Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins. Involved in degradation of misfolded chaperone substrates via its interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP, and restricts the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. In response to misfolded substrate ubiquitination, mediates deubiquitination of monoubiquitinated STUB1/CHIP. Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription.<ref>PMID:12297501</ref><ref>PMID:17696782</ref><ref>PMID:16118278</ref>

	==About this Structure==		==About this Structure==
	[[2dos]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DOS OCA].		[[2dos]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DOS OCA].

			==Reference==
			<references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Sumiyoshi, A.]]		[[Category: Sumiyoshi, A.]]
	[[Category: Deubiquitinating enzyme]]		[[Category: Deubiquitinating enzyme]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]