|
|
(One intermediate revision not shown.) |
Line 1: |
Line 1: |
| | | |
| ==Solution structure of the first WW domain from the mouse salvador homolog 1 protein (SAV1)== | | ==Solution structure of the first WW domain from the mouse salvador homolog 1 protein (SAV1)== |
- | <StructureSection load='2ysb' size='340' side='right' caption='[[2ysb]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2ysb' size='340' side='right'caption='[[2ysb]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[2ysb]] is a 1 chain structure with sequence from [http://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=2YSB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YSB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ysb]] is a 1 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=2YSB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2YSB FirstGlance]. <br> |
- | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Sav1 ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ysb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ysb OCA], [http://pdbe.org/2ysb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ysb RCSB], [http://www.ebi.ac.uk/pdbsum/2ysb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ysb ProSAT], [http://www.topsan.org/Proteins/RSGI/2ysb 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=2ysb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ysb OCA], [https://pdbe.org/2ysb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ysb RCSB], [https://www.ebi.ac.uk/pdbsum/2ysb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ysb ProSAT], [https://www.topsan.org/Proteins/RSGI/2ysb TOPSAN]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://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]] |
Line 23: |
Line 23: |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
- | [[Category: Harada, T]] | + | [[Category: Mus musculus]] |
- | [[Category: Kigawa, T]] | + | [[Category: Harada T]] |
- | [[Category: Koshiba, S]] | + | [[Category: Kigawa T]] |
- | [[Category: Ohnishi, S]] | + | [[Category: Koshiba S]] |
- | [[Category: Structural genomic]] | + | [[Category: Ohnishi S]] |
- | [[Category: Sato, M]] | + | [[Category: Sato M]] |
- | [[Category: Watanabe, S]] | + | [[Category: Watanabe S]] |
- | [[Category: Yokoyama, S]] | + | [[Category: Yokoyama S]] |
- | [[Category: National project on protein structural and functional analyse]]
| + | |
- | [[Category: Nppsfa]]
| + | |
- | [[Category: Protein binding]]
| + | |
- | [[Category: Rsgi]]
| + | |
- | [[Category: Salvador]]
| + | |
- | [[Category: Ww domain]]
| + | |
| Structural highlights
Function
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).[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Lee JH, Kim TS, Yang TH, Koo BK, Oh SP, Lee KP, Oh HJ, Lee SH, Kong YY, Kim JM, Lim DS. A crucial role of WW45 in developing epithelial tissues in the mouse. EMBO J. 2008 Apr 23;27(8):1231-42. doi: 10.1038/emboj.2008.63. Epub 2008 Mar 27. PMID:18369314 doi:http://dx.doi.org/10.1038/emboj.2008.63
- ↑ Lu L, Li Y, Kim SM, Bossuyt W, Liu P, Qiu Q, Wang Y, Halder G, Finegold MJ, Lee JS, Johnson RL. Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver. Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1437-42. doi:, 10.1073/pnas.0911427107. Epub 2010 Jan 4. PMID:20080689 doi:http://dx.doi.org/10.1073/pnas.0911427107
|