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==STRUCTURAL INSIGHTS INTO THE RECOGNITION OF SUBSTRATES AND ACTIVATORS BY THE OSR1 KINASE==
 
<StructureSection load='2v3s' size='340' side='right' caption='[[2v3s]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
==Structural insights into the recognition of substrates and activators by the OSR1 kinase==
<StructureSection load='2v3s' size='340' side='right'caption='[[2v3s]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2v3s]] is a 4 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=2V3S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2V3S FirstGlance]. <br>
<table><tr><td colspan='2'>[[2v3s]] is a 4 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=2V3S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V3S FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr>
</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></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=2v3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v3s OCA], [http://pdbe.org/2v3s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2v3s RCSB], [http://www.ebi.ac.uk/pdbsum/2v3s PDBsum]</span></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=2v3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v3s OCA], [https://pdbe.org/2v3s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v3s RCSB], [https://www.ebi.ac.uk/pdbsum/2v3s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v3s ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/WNK4_HUMAN WNK4_HUMAN]] Defects in WNK4 are a cause of pseudohypoaldosteronism type 2B (PHA2B) [MIM:[http://omim.org/entry/614491 614491]]. PHAII is an autosomal dominant disease characterized by severe hypertension, hyperkalemia, and sensitivity to thiazide diuretics which may result from a chloride shunt in the renal distal nephron.<ref>PMID:11498583</ref> 
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/WNK4_HUMAN WNK4_HUMAN]] Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D, SGK1, TRPV5 and TRPV6. Regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation which appears to prevent membrane trafficking of SLC12A3. Also inhibits the renal K(+) channel, KCNJ1, via a kinase-independent mechanism by which it induces clearance of the protein from the cell surface by clathrin-dependent endocytosis. WNK4 appears to act as a molecular switch that can vary the balance between NaCl reabsorption and K(+) secretion to maintain integrated homeostasis. Phosphorylates NEDD4L.<ref>PMID:20525693</ref>
[https://www.uniprot.org/uniprot/OXSR1_HUMAN OXSR1_HUMAN] Regulates downstream kinases in response to environmental stress. May also have a function in regulating the actin cytoskeleton.<ref>PMID:14707132</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v3/2v3s_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v3/2v3s_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
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==See Also==
==See Also==
*[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Large Structures]]
[[Category: Aalten, D M.F Van]]
[[Category: Alessi DR]]
[[Category: Alessi, D R]]
[[Category: Deak M]]
[[Category: Deak, M]]
[[Category: Goebel J]]
[[Category: Goebel, J]]
[[Category: Rafiqi FH]]
[[Category: Rafiqi, F H]]
[[Category: Thastrup J]]
[[Category: Thastrup, J]]
[[Category: Villa F]]
[[Category: Villa, F]]
[[Category: Van Aalten DMF]]
[[Category: Atp-binding]]
[[Category: Kinase]]
[[Category: Magnesium]]
[[Category: Metal-binding]]
[[Category: Nucleotide-binding]]
[[Category: Phosphorylation]]
[[Category: Serine/threonine-protein kinase]]
[[Category: Transferase]]

Latest revision as of 09:54, 9 May 2024

Structural insights into the recognition of substrates and activators by the OSR1 kinase

2v3s, resolution 1.70Å

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