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| | <StructureSection load='6ar2' size='340' side='right'caption='[[6ar2]], [[Resolution|resolution]] 1.55Å' scene=''> | | <StructureSection load='6ar2' size='340' side='right'caption='[[6ar2]], [[Resolution|resolution]] 1.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ar2]] 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=6AR2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AR2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ar2]] 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=6AR2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AR2 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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]] 1.55Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6ar0|6ar0]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SLMAP, KIAA1601, SLAP, UNQ1847/PRO3577 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6ar2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ar2 OCA], [https://pdbe.org/6ar2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ar2 RCSB], [https://www.ebi.ac.uk/pdbsum/6ar2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ar2 ProSAT]</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=6ar2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ar2 OCA], [http://pdbe.org/6ar2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ar2 RCSB], [http://www.ebi.ac.uk/pdbsum/6ar2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ar2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/SLMAP_HUMAN SLMAP_HUMAN]] Brugada syndrome. | + | [https://www.uniprot.org/uniprot/SLMAP_HUMAN SLMAP_HUMAN] Brugada syndrome. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SLMAP_HUMAN SLMAP_HUMAN]] May play a role during myoblast fusion. | + | [https://www.uniprot.org/uniprot/SLMAP_HUMAN SLMAP_HUMAN] May play a role during myoblast fusion. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Luo, X]] | + | [[Category: Luo X]] |
| - | [[Category: Ni, L]] | + | [[Category: Ni L]] |
| - | [[Category: Osinski, A]] | + | [[Category: Osinski A]] |
| - | [[Category: Fha]]
| + | |
| - | [[Category: Hippo]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Phospho-mst2]]
| + | |
| - | [[Category: Slmap]]
| + | |
| Structural highlights
Disease
SLMAP_HUMAN Brugada syndrome.
Function
SLMAP_HUMAN May play a role during myoblast fusion.
Publication Abstract from PubMed
The Hippo pathway controls tissue growth and homeostasis through a central MST-LATS kinase cascade. The scaffold protein SAV1 promotes the activation of this kinase cascade, but the molecular mechanisms remain unknown. Here, we discover SAV1-mediated inhibition of the PP2A complex STRIPAKSLMAP as a key mechanism of MST1/2 activation. SLMAP binding to autophosphorylated MST2 linker recruits STRIPAK and promotes PP2A-mediated dephosphorylation of MST2 at the activation loop. Our structural and biochemical studies reveal that SAV1 and MST2 heterodimerize through their SARAH domains. Two SAV1-MST2 heterodimers further dimerize through SAV1 WW domains to form a heterotetramer, in which MST2 undergoes trans-autophosphorylation. SAV1 directly binds to STRIPAK and inhibits its phosphatase activity, protecting MST2 activation-loop phosphorylation. Genetic ablation of SLMAP in human cells leads to spontaneous activation of the Hippo pathway and alleviates the need for SAV1 in Hippo signaling. Thus, SAV1 promotes Hippo activation through counteracting the STRIPAKSLMAP PP2A phosphatase complex.
SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK.,Bae SJ, Ni L, Osinski A, Tomchick DR, Brautigam CA, Luo X Elife. 2017 Oct 24;6. pii: e30278. doi: 10.7554/eLife.30278. PMID:29063833[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bae SJ, Ni L, Osinski A, Tomchick DR, Brautigam CA, Luo X. SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK. Elife. 2017 Oct 24;6. pii: e30278. doi: 10.7554/eLife.30278. PMID:29063833 doi:http://dx.doi.org/10.7554/eLife.30278
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