View source for 3ka0


==MK2 complex with inhibitor 6-(5-(2-aminopyrimidin-4-ylamino)-2-hydroxyphenyl)-N-methylbenzo[b]thiophene-2-carboxamide==
<StructureSection load='3ka0' size='340' side='right'caption='[[3ka0]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3ka0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KA0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KA0 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MK3:6-{5-[(2-AMINOPYRIMIDIN-4-YL)AMINO]-2-HYDROXYPHENYL}-N-METHYLIDENE-1-BENZOTHIOPHENE-2-CARBOXAMIDE'>MK3</scene></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=3ka0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ka0 OCA], [https://pdbe.org/3ka0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ka0 RCSB], [https://www.ebi.ac.uk/pdbsum/3ka0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ka0 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MAPK2_HUMAN MAPK2_HUMAN] Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, ELAVL1, HNRNPA0, HSF1, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilize GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3.<ref>PMID:8280084</ref> <ref>PMID:8093612</ref> <ref>PMID:8774846</ref> <ref>PMID:10383393</ref> <ref>PMID:12456657</ref> <ref>PMID:11844797</ref> <ref>PMID:12565831</ref> <ref>PMID:14499342</ref> <ref>PMID:14517288</ref> <ref>PMID:15014438</ref> <ref>PMID:15629715</ref> <ref>PMID:16456544</ref> <ref>PMID:16278218</ref> <ref>PMID:17481585</ref> <ref>PMID:18021073</ref> <ref>PMID:20932473</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ka/3ka0_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/main_output.php?pdb_ID=3ka0 ConSurf].
<div style="clear:both"></div>

==See Also==
*[[Mitogen-activated protein kinase 3D structures|Mitogen-activated protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Argiriadi MA]]
[[Category: Borhani DW]]
[[Category: Talanian RV]]