1u5r

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[[Image:1u5r.gif|left|200px]]
 
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{{Structure
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==Crystal Structure of the TAO2 Kinase Domain: Activation and Specifity of a Ste20p MAP3K==
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|PDB= 1u5r |SIZE=350|CAPTION= <scene name='initialview01'>1u5r</scene>, resolution 2.1&Aring;
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<StructureSection load='1u5r' size='340' side='right'caption='[[1u5r]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=ATP:ADENOSINE-5&#39;-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>
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<table><tr><td colspan='2'>[[1u5r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U5R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1U5R FirstGlance]. <br>
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|ACTIVITY=
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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|GENE= serine/threonine protein kinase TAO2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
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|DOMAIN=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1u5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u5r OCA], [https://pdbe.org/1u5r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1u5r RCSB], [https://www.ebi.ac.uk/pdbsum/1u5r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1u5r ProSAT]</span></td></tr>
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|RELATEDENTRY=[[1u5q|1U5Q]]
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1u5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u5r OCA], [http://www.ebi.ac.uk/pdbsum/1u5r PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1u5r RCSB]</span>
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== Function ==
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}}
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[https://www.uniprot.org/uniprot/TAOK2_RAT TAOK2_RAT] Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade. Phosphorylates itself, MBP, activated MAPK8, MAP2K3, MAP2K6 and tubulins. Activates the MAPK14/p38 MAPK signaling pathway through the specific activation and phosphorylation of the upstream MAP2K3 and MAP2K6 kinases. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. May affect microtubule organization and stability. May play a role in the osmotic stress-MAPK8 pathway. Prevents MAP3K7-mediated activation of CHUK, and thus NF-kappa-B activation. Isoform 2, but not isoform 1, is required for PCDH8 endocytosis. Following homophilic interactions between PCDH8 extracellular domains, isoform 2 phosphorylates and activates MAPK14/p38 MAPK which in turn phosphorylates isoform 2. This process leads to PCDH8 endocytosis and CDH2 cointernalization. Both isoforms are involved in MAPK14/p38 MAPK activation.<ref>PMID:10497253</ref> <ref>PMID:17988630</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/u5/1u5r_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=1u5r 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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TAO2 is a mitogen-activated protein kinase kinase kinase (MAP3K) that doubly phosphorylates and activates the MAP kinase kinases (MAP2Ks) MEK3 and MEK6. The structure of the kinase domain of TAO2 (1-320) has been solved in its phosphorylated active conformation. The structure, together with structure-based mutagenic analysis, reveals that positively charged residues in the substrate binding groove mediate the first step in the dual phosphorylation of MEK6, on the threonine residue in the motif DS*VAKT*I (*denotes phosphorylation site) of MEK6. TAO2 is a Ste20p homolog, and the structure of active TAO2, in comparison with that of low-activity p21-activated protein kinase (PAK1), a Ste20p-related MAP4K, reveals how this group of kinases is activated by phosphorylation. Finally, active TAO2 displays unusual interactions with ATP, involving, in part, a subgroup-specific C-terminal extension of TAO2. The observed interactions may be useful in making specific inhibitors of TAO kinases.
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'''Crystal Structure of the TAO2 Kinase Domain: Activation and Specifity of a Ste20p MAP3K'''
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Crystal structure of the TAO2 kinase domain: activation and specificity of a Ste20p MAP3K.,Zhou T, Raman M, Gao Y, Earnest S, Chen Z, Machius M, Cobb MH, Goldsmith EJ Structure. 2004 Oct;12(10):1891-900. PMID:15458637<ref>PMID:15458637</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1u5r" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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TAO2 is a mitogen-activated protein kinase kinase kinase (MAP3K) that doubly phosphorylates and activates the MAP kinase kinases (MAP2Ks) MEK3 and MEK6. The structure of the kinase domain of TAO2 (1-320) has been solved in its phosphorylated active conformation. The structure, together with structure-based mutagenic analysis, reveals that positively charged residues in the substrate binding groove mediate the first step in the dual phosphorylation of MEK6, on the threonine residue in the motif DS*VAKT*I (*denotes phosphorylation site) of MEK6. TAO2 is a Ste20p homolog, and the structure of active TAO2, in comparison with that of low-activity p21-activated protein kinase (PAK1), a Ste20p-related MAP4K, reveals how this group of kinases is activated by phosphorylation. Finally, active TAO2 displays unusual interactions with ATP, involving, in part, a subgroup-specific C-terminal extension of TAO2. The observed interactions may be useful in making specific inhibitors of TAO kinases.
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*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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1U5R is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U5R OCA].
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__TOC__
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</StructureSection>
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==Reference==
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[[Category: Large Structures]]
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Crystal structure of the TAO2 kinase domain: activation and specificity of a Ste20p MAP3K., Zhou T, Raman M, Gao Y, Earnest S, Chen Z, Machius M, Cobb MH, Goldsmith EJ, Structure. 2004 Oct;12(10):1891-900. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15458637 15458637]
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[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
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[[Category: Single protein]]
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[[Category: Chen Z]]
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[[Category: Chen, Z.]]
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[[Category: Cobb MH]]
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[[Category: Cobb, M H.]]
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[[Category: Earnest S]]
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[[Category: Earnest, S.]]
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[[Category: Gao Y]]
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[[Category: Gao, Y.]]
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[[Category: Goldsmith EJ]]
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[[Category: Goldsmith, E J.]]
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[[Category: Machius M]]
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[[Category: Machius, M.]]
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[[Category: Raman M]]
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[[Category: Raman, M.]]
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[[Category: Zhou T]]
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[[Category: Zhou, T.]]
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[[Category: serine/threonine protein kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:05:47 2008''
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Crystal Structure of the TAO2 Kinase Domain: Activation and Specifity of a Ste20p MAP3K

PDB ID 1u5r

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