View source for 4yno


==Crystal structure of MAPK13 at INACTIVE FORM==
<StructureSection load='4yno' size='340' side='right'caption='[[4yno]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4yno]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4exu 4exu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YNO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YNO 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]] 1.7&#8491;</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=4yno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yno OCA], [https://pdbe.org/4yno PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yno RCSB], [https://www.ebi.ac.uk/pdbsum/4yno PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yno ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MK13_HUMAN MK13_HUMAN] Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells.<ref>PMID:9731215</ref> <ref>PMID:11500363</ref> <ref>PMID:11943212</ref> <ref>PMID:15632108</ref> <ref>PMID:17256148</ref> <ref>PMID:18006338</ref> <ref>PMID:18367666</ref> <ref>PMID:20478268</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Increased mucus production is a common cause of morbidity and mortality in inflammatory airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. However, the precise molecular mechanisms for pathogenic mucus production are largely undetermined. Accordingly, there are no specific and effective anti-mucus therapeutics. Here, we define a signaling pathway from chloride channel calcium-activated 1 (CLCA1) to MAPK13 that is responsible for IL-13-driven mucus production in human airway epithelial cells. The same pathway was also highly activated in the lungs of humans with excess mucus production due to COPD. We further validated the pathway by using structure-based drug design to develop a series of novel MAPK13 inhibitors with nanomolar potency that effectively reduced mucus production in human airway epithelial cells. These results uncover and validate a new pathway for regulating mucus production as well as a corresponding therapeutic approach to mucus overproduction in inflammatory airway diseases.

IL-13-induced airway mucus production is attenuated by MAPK13 inhibition.,Alevy YG, Patel AC, Romero AG, Patel DA, Tucker J, Roswit WT, Miller CA, Heier RF, Byers DE, Brett TJ, Holtzman MJ J Clin Invest. 2012 Dec 3;122(12):4555-68. doi: 10.1172/JCI64896. Epub 2012 Nov, 26. PMID:23187130<ref>PMID:23187130</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4yno" style="background-color:#fffaf0;"></div>

==See Also==
*[[Mitogen-activated protein kinase 3D structures|Mitogen-activated protein kinase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Brett TJ]]
[[Category: Miller CA]]