3k2l

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{{STRUCTURE_3k2l| PDB=3k2l | SCENE= }}
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==Crystal Structure of dual-specificity tyrosine phosphorylation regulated kinase 2 (DYRK2)==
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===Crystal Structure of dual-specificity tyrosine phosphorylation regulated kinase 2 (DYRK2)===
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<StructureSection load='3k2l' size='340' side='right' caption='[[3k2l]], [[Resolution|resolution]] 2.36&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23665168}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3k2l]] is a 1 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=3K2L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3K2L FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DYRK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.1 2.7.12.1] </span></td></tr>
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<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=3k2l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k2l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3k2l RCSB], [http://www.ebi.ac.uk/pdbsum/3k2l PDBsum]</span></td></tr>
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</table>
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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/k2/3k2l_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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Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinases (DYRKs) play key roles in brain development, regulation of splicing, and apoptosis, and are potential drug targets for neurodegenerative diseases and cancer. We present crystal structures of one representative member of each DYRK subfamily: DYRK1A with an ATP-mimetic inhibitor and consensus peptide, and DYRK2 including NAPA and DH (DYRK homology) box regions. The current activation model suggests that DYRKs are Ser/Thr kinases that only autophosphorylate the second tyrosine of the activation loop YxY motif during protein translation. The structures explain the roles of this tyrosine and of the DH box in DYRK activation and provide a structural model for DYRK substrate recognition. Phosphorylation of a library of naturally occurring peptides identified substrate motifs that lack proline in the P+1 position, suggesting that DYRK1A is not a strictly proline-directed kinase. Our data also show that DYRK1A wild-type and Y321F mutant retain tyrosine autophosphorylation activity.
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==Function==
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Structures of Down Syndrome Kinases, DYRKs, Reveal Mechanisms of Kinase Activation and Substrate Recognition.,Soundararajan M, Roos AK, Savitsky P, Filippakopoulos P, Kettenbach AN, Olsen JV, Gerber SA, Eswaran J, Knapp S, Elkins JM Structure. 2013 Jun 4;21(6):986-96. doi: 10.1016/j.str.2013.03.012. Epub 2013 May, 9. PMID:23665168<ref>PMID:23665168</ref>
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[[http://www.uniprot.org/uniprot/DYRK2_HUMAN DYRK2_HUMAN]] Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro).<ref>PMID:9748265</ref> <ref>PMID:11311121</ref> <ref>PMID:12588975</ref> <ref>PMID:14593110</ref> <ref>PMID:15910284</ref> <ref>PMID:16611631</ref> <ref>PMID:16511445</ref> <ref>PMID:17349958</ref> <ref>PMID:18599021</ref> <ref>PMID:18455992</ref> <ref>PMID:19287380</ref> <ref>PMID:22307329</ref> <ref>PMID:22878263</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3k2l]] is a 1 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=3K2L OCA].
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</div>
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:023665168</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Dual-specificity kinase]]
[[Category: Dual-specificity kinase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Arrowsmith, C H.]]
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[[Category: Arrowsmith, C H]]
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[[Category: Berridge, G.]]
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[[Category: Berridge, G]]
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[[Category: Bountra, C.]]
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[[Category: Bountra, C]]
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[[Category: Delft, F von.]]
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[[Category: Delft, F von]]
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[[Category: Edwards, A.]]
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[[Category: Edwards, A]]
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[[Category: Fedorov, O.]]
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[[Category: Fedorov, O]]
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[[Category: Filippakopoulos, P.]]
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[[Category: Filippakopoulos, P]]
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[[Category: Hapka, E.]]
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[[Category: Hapka, E]]
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[[Category: Knapp, S.]]
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[[Category: Knapp, S]]
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[[Category: Krojer, T.]]
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[[Category: Krojer, T]]
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[[Category: Mikros, E.]]
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[[Category: Mikros, E]]
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[[Category: Myrianthopoulos, V.]]
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[[Category: Myrianthopoulos, V]]
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[[Category: Pike, A C.W.]]
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[[Category: Pike, A C.W]]
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[[Category: SGC, Structural Genomics Consortium.]]
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[[Category: Structural genomic]]
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[[Category: Shrestha, L.]]
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[[Category: Shrestha, L]]
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[[Category: Soundararajan, M.]]
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[[Category: Soundararajan, M]]
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[[Category: Ugochukwu, E.]]
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[[Category: Ugochukwu, E]]
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[[Category: Wang, J.]]
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[[Category: Wang, J]]
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[[Category: Weigelt, J.]]
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[[Category: Weigelt, J]]
[[Category: Apoptosis]]
[[Category: Apoptosis]]
[[Category: Atp-binding]]
[[Category: Atp-binding]]
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[[Category: Serine/threonine-protein kinase]]
[[Category: Serine/threonine-protein kinase]]
[[Category: Sgc]]
[[Category: Sgc]]
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[[Category: Structural genomics consortium]]
 
[[Category: Transferase]]
[[Category: Transferase]]
[[Category: Tyrosine-protein kinase]]
[[Category: Tyrosine-protein kinase]]

Revision as of 15:51, 18 December 2014

Crystal Structure of dual-specificity tyrosine phosphorylation regulated kinase 2 (DYRK2)

3k2l, resolution 2.36Å

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