View source for 3fme


==Crystal Structure of Human Mitogen-Activated Protein Kinase Kinase 6 (MEK6) Activated Mutant (S207D, T211D)==
<StructureSection load='3fme' size='340' side='right' caption='[[3fme]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3fme]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FME OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FME FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=STU:STAUROSPORINE'>STU</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MAP2K6, MEK6, MKK6, PRKMK6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase Mitogen-activated protein kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.2 2.7.12.2] </span></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=3fme FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fme OCA], [http://pdbe.org/3fme PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fme RCSB], [http://www.ebi.ac.uk/pdbsum/3fme PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fme ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/MP2K6_HUMAN MP2K6_HUMAN]] Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK11 activator in response to TNF. MAP2K6/MKK6 also phosphorylates and activates PAK6. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Nuclear targets of p38 MAP kinase include the transcription factors ATF2 and ELK1. Within the p38 MAPK signal transduction pathway, MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14 activation, and is therefore required for STAT4 activation and STAT4-regulated gene expression in response to IL-12 stimulation. The pathway is also crucial for IL-6-induced SOCS3 expression and down-regulation of IL-6-mediated gene induction; and for IFNG-dependent gene transcription. Has a role in osteoclast differentiation through NF-kappa-B transactivation by TNFSF11, and in endochondral ossification and since SOX9 is another likely downstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediates apoptotic cell death in thymocytes. Acts also as a regulator for melanocytes dendricity, through the modulation of Rho family GTPases.<ref>PMID:8622669</ref> <ref>PMID:8626699</ref> <ref>PMID:8663074</ref> <ref>PMID:9218798</ref> <ref>PMID:10961885</ref> <ref>PMID:11727828</ref> <ref>PMID:15550393</ref> <ref>PMID:20869211</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/fm/3fme_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=3fme ConSurf].
<div style="clear:both"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Mitogen-activated protein kinase kinase]]
[[Category: Arrowsmith, C H]]
[[Category: Barr, A]]
[[Category: Berridge, G]]
[[Category: Bountra, C]]
[[Category: Delft, F von]]
[[Category: Edwards, A M]]
[[Category: Elkins, J]]
[[Category: Fedorov, O]]
[[Category: Filippakopoulos, P]]
[[Category: Keates, T]]
[[Category: Knapp, S]]
[[Category: Pike, A C.W]]
[[Category: Structural genomic]]
[[Category: Savitsky, P]]
[[Category: Soundararajan, M]]
[[Category: Weigelt, J]]
[[Category: Active mutant]]
[[Category: Atp-binding]]
[[Category: Kinase]]
[[Category: Nucleotide-binding]]
[[Category: Phosphoprotein]]
[[Category: Scg]]
[[Category: Serine/threonine-protein kinase]]
[[Category: Sgc]]
[[Category: Transferase]]
[[Category: Tyrosine-protein kinase]]