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==Solution structure of the second WW domain from mouse salvador homolog 1 protein (mWW45)==
==Solution structure of the second WW domain from mouse salvador homolog 1 protein (mWW45)==
<StructureSection load='2dwv' size='340' side='right'caption='[[2dwv]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
<StructureSection load='2dwv' size='340' side='right'caption='[[2dwv]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2dwv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DWV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DWV FirstGlance]. <br>
<table><tr><td colspan='2'>[[2dwv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DWV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DWV FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Sav1, Ww45, Wwp3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2dwv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dwv OCA], [https://pdbe.org/2dwv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dwv RCSB], [https://www.ebi.ac.uk/pdbsum/2dwv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dwv ProSAT], [https://www.topsan.org/Proteins/RSGI/2dwv TOPSAN]</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=2dwv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dwv OCA], [https://pdbe.org/2dwv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dwv RCSB], [https://www.ebi.ac.uk/pdbsum/2dwv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dwv ProSAT], [https://www.topsan.org/Proteins/RSGI/2dwv TOPSAN]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/SAV1_MOUSE SAV1_MOUSE]] Regulator of STK3/MST2 and STK4/MST1 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. SAV1 is required for STK3/MST2 and STK4/MST1 activation and promotes cell-cycle exit and terminal differentiation in developing epithelial tissues. Plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosomes, and its ability to phosphorylate CROCC and CEP250. In conjunction with STK3/MST2, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation (By similarity).<ref>PMID:18369314</ref> <ref>PMID:20080689</ref>
[https://www.uniprot.org/uniprot/SAV1_MOUSE SAV1_MOUSE] Regulator of STK3/MST2 and STK4/MST1 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. SAV1 is required for STK3/MST2 and STK4/MST1 activation and promotes cell-cycle exit and terminal differentiation in developing epithelial tissues. Plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosomes, and its ability to phosphorylate CROCC and CEP250. In conjunction with STK3/MST2, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation (By similarity).<ref>PMID:18369314</ref> <ref>PMID:20080689</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Mus musculus]]
[[Category: Guntert, P]]
[[Category: Guntert P]]
[[Category: Harada, T]]
[[Category: Harada T]]
[[Category: Inoue, M]]
[[Category: Inoue M]]
[[Category: Kigawa, T]]
[[Category: Kigawa T]]
[[Category: Koshiba, S]]
[[Category: Koshiba S]]
[[Category: Ohnishi, S]]
[[Category: Ohnishi S]]
[[Category: Structural genomic]]
[[Category: Sato M]]
[[Category: Sato, M]]
[[Category: Tochio N]]
[[Category: Tochio, N]]
[[Category: Tomizawa T]]
[[Category: Tomizawa, T]]
[[Category: Watanabe S]]
[[Category: Watanabe, S]]
[[Category: Yokoyama S]]
[[Category: Yokoyama, S]]
[[Category: Dimer]]
[[Category: National project on protein structural and functional analyse]]
[[Category: Nppsfa]]
[[Category: Protein binding]]
[[Category: Rsgi]]
[[Category: Ww domain]]
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