2wx0

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{{STRUCTURE_2wx0| PDB=2wx0 | SCENE= }}
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==TAB2 NZF DOMAIN IN COMPLEX WITH LYS63-LINKED DI-UBIQUITIN, P21==
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===TAB2 NZF DOMAIN IN COMPLEX WITH LYS63-LINKED DI-UBIQUITIN, P21===
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<StructureSection load='2wx0' size='340' side='right' caption='[[2wx0]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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{{ABSTRACT_PUBMED_19935683}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2wx0]] is a 6 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=2WX0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WX0 FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2c7m|2c7m]], [[1yd8|1yd8]], [[1e0q|1e0q]], [[2c7n|2c7n]], [[2fif|2fif]], [[2d3g|2d3g]], [[1v80|1v80]], [[1p3q|1p3q]], [[1wr6|1wr6]], [[2fid|2fid]], [[1v81|1v81]], [[1aar|1aar]], [[1uzx|1uzx]], [[1wrd|1wrd]], [[2wx1|2wx1]], [[2wwz|2wwz]]</td></tr>
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<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=2wx0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wx0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wx0 RCSB], [http://www.ebi.ac.uk/pdbsum/2wx0 PDBsum]</span></td></tr>
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<table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/TAB2_HUMAN TAB2_HUMAN]] Defects in TAB2 are the cause of congenital heart disease non-syndromic type 2 (CHTD2) [MIM:[http://omim.org/entry/612863 612863]]. It is a disease characterized by congenital developmental abnormalities involving structures of the heart. Clinical features include left ventricular outflow tract obstruction, subaortic stenosis, residual aortic regurgitation, atrial fibrillation, bicuspid aortic valve and aortic dilation. Note=A chromosomal aberration involving TAB2 has been found in a family with congenital heart disease. Translocation t(2;6)(q21;q25).<ref>PMID:20493459</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/TAB2_HUMAN TAB2_HUMAN]] Adapter linking MAP3K7/TAK1 and TRAF6. Promotes MAP3K7 activation in the IL1 signaling pathway. The binding of 'Lys-63'-linked polyubiquitin chains to TAB2 promotes autophosphorylation of MAP3K7 at 'Thr-187'. Involved in heart development.<ref>PMID:10882101</ref> <ref>PMID:11460167</ref> <ref>PMID:20493459</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wx/2wx0_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The protein kinase TAK1 is activated by binding to Lys63 (K63)-linked ubiquitin chains through its subunit TAB2. Here we analyze crystal structures of the TAB2 NZF domain bound to Lys63-linked di- and triubiquitin, revealing that TAB2 binds adjacent ubiquitin moieties via two distinct binding sites. The conformational constraints imposed by TAB2 on a Lys63 dimer cannot be adopted by linear chains, explaining why TAK1 cannot be activated by linear ubiquitination events.
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==Disease==
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Two-sided ubiquitin binding explains specificity of the TAB2 NZF domain.,Kulathu Y, Akutsu M, Bremm A, Hofmann K, Komander D Nat Struct Mol Biol. 2009 Dec;16(12):1328-30. Epub 2009 Nov 22. PMID:19935683<ref>PMID:19935683</ref>
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[[http://www.uniprot.org/uniprot/TAB2_HUMAN TAB2_HUMAN]] Defects in TAB2 are the cause of congenital heart disease non-syndromic type 2 (CHTD2) [MIM:[http://omim.org/entry/612863 612863]]. It is a disease characterized by congenital developmental abnormalities involving structures of the heart. Clinical features include left ventricular outflow tract obstruction, subaortic stenosis, residual aortic regurgitation, atrial fibrillation, bicuspid aortic valve and aortic dilation. Note=A chromosomal aberration involving TAB2 has been found in a family with congenital heart disease. Translocation t(2;6)(q21;q25).<ref>PMID:20493459</ref>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/TAB2_HUMAN TAB2_HUMAN]] Adapter linking MAP3K7/TAK1 and TRAF6. Promotes MAP3K7 activation in the IL1 signaling pathway. The binding of 'Lys-63'-linked polyubiquitin chains to TAB2 promotes autophosphorylation of MAP3K7 at 'Thr-187'. Involved in heart development.<ref>PMID:10882101</ref><ref>PMID:11460167</ref><ref>PMID:20493459</ref>
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</div>
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==About this Structure==
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[[2wx0]] is a 6 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=2WX0 OCA].
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==See Also==
==See Also==
*[[Ubiquitin|Ubiquitin]]
*[[Ubiquitin|Ubiquitin]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:019935683</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Akutsu, M.]]
[[Category: Akutsu, M.]]

Revision as of 01:32, 1 October 2014

TAB2 NZF DOMAIN IN COMPLEX WITH LYS63-LINKED DI-UBIQUITIN, P21

2wx0, resolution 2.40Å

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