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| | ==Crystal structure of murine SPAK(T243D) in complex with AMPPNP== | | ==Crystal structure of murine SPAK(T243D) in complex with AMPPNP== |
| - | <StructureSection load='5dbx' size='340' side='right' caption='[[5dbx]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='5dbx' size='340' side='right'caption='[[5dbx]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5dbx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DBX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DBX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5dbx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DBX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DBX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</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=5dbx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dbx OCA], [https://pdbe.org/5dbx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dbx RCSB], [https://www.ebi.ac.uk/pdbsum/5dbx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dbx ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Stk39, Spak ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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='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=5dbx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dbx OCA], [http://pdbe.org/5dbx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dbx RCSB], [http://www.ebi.ac.uk/pdbsum/5dbx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dbx ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/STK39_MOUSE STK39_MOUSE]] May act as a mediator of stress-activated signals. Mediates the inhibiton of SLC4A4, SLC26A6 as well as CFTR activities by the WNK scaffolds, probably through phosphorylation (PubMed:21317537, PubMed:23542070).<ref>PMID:21317537</ref> <ref>PMID:23542070</ref> | + | [https://www.uniprot.org/uniprot/STK39_MOUSE STK39_MOUSE] May act as a mediator of stress-activated signals. Mediates the inhibiton of SLC4A4, SLC26A6 as well as CFTR activities by the WNK scaffolds, probably through phosphorylation (PubMed:21317537, PubMed:23542070).<ref>PMID:21317537</ref> <ref>PMID:23542070</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5dbx" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5dbx" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Non-specific serine/threonine protein kinase]] | + | [[Category: Mus musculus]] |
| - | [[Category: Juang, Y C]] | + | [[Category: Juang Y-C]] |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Transferase]]
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| Structural highlights
Function
STK39_MOUSE May act as a mediator of stress-activated signals. Mediates the inhibiton of SLC4A4, SLC26A6 as well as CFTR activities by the WNK scaffolds, probably through phosphorylation (PubMed:21317537, PubMed:23542070).[1] [2]
Publication Abstract from PubMed
The related protein kinases SPAK and OSR1 regulate ion homeostasis in part by phosphorylating cation cotransporter family members. The structure of the kinase domain of OSR1 was determined in the unphosphorylated inactive form and, like some other Ste20 kinases, exhibited a domain-swapped activation loop. To further probe the role of domain swapping in SPAK and OSR1, we have determined the crystal structures of SPAK 63-403 at 3.1 A and SPAK 63-390 T243D at 2.5 A resolution. These structures encompass the kinase domain and different portions of the C-terminal tail, the longer without and the shorter with an activating T243D point mutation. The structure of the T243D protein reveals significant conformational differences relative to unphosphorylated SPAK and OSR1 but also has some features of an inactive kinase. Both structures are domain-swapped dimers. Sequences involved in domain swapping were identified and mutated to create a SPAK monomeric mutant with kinase activity, indicating that monomeric forms are active. The monomeric mutant is activated by WNK1 but has reduced activity toward its substrate NKCC2, suggesting regulatory roles for domain swapping. The structure of partially active SPAK T243D is consistent with a multistage activation process in which phosphorylation induces a SPAK conformation that requires further remodeling to build the active structure.
Domain-Swapping Switch Point in Ste20 Protein Kinase SPAK.,Taylor CA 4th, Juang YC, Earnest S, Sengupta S, Goldsmith EJ, Cobb MH Biochemistry. 2015 Aug 18;54(32):5063-71. doi: 10.1021/acs.biochem.5b00593. Epub , 2015 Aug 3. PMID:26208601[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yang D, Li Q, So I, Huang CL, Ando H, Mizutani A, Seki G, Mikoshiba K, Thomas PJ, Muallem S. IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK kinase pathway. J Clin Invest. 2011 Mar;121(3):956-65. doi: 10.1172/JCI43475. Epub 2011 Feb 7. PMID:21317537 doi:http://dx.doi.org/10.1172/JCI43475
- ↑ Park S, Shcheynikov N, Hong JH, Zheng C, Suh SH, Kawaai K, Ando H, Mizutani A, Abe T, Kiyonari H, Seki G, Yule D, Mikoshiba K, Muallem S. Irbit mediates synergy between ca(2+) and cAMP signaling pathways during epithelial transport in mice. Gastroenterology. 2013 Jul;145(1):232-41. doi: 10.1053/j.gastro.2013.03.047. Epub, 2013 Mar 28. PMID:23542070 doi:http://dx.doi.org/10.1053/j.gastro.2013.03.047
- ↑ Taylor CA 4th, Juang YC, Earnest S, Sengupta S, Goldsmith EJ, Cobb MH. Domain-Swapping Switch Point in Ste20 Protein Kinase SPAK. Biochemistry. 2015 Aug 18;54(32):5063-71. doi: 10.1021/acs.biochem.5b00593. Epub , 2015 Aug 3. PMID:26208601 doi:http://dx.doi.org/10.1021/acs.biochem.5b00593
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