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| - | [[Image:2law.jpg|left|200px]] | |
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| - | <!--
| + | ==Structure of the second WW domain from human YAP in complex with a human Smad1 derived peptide== |
| - | The line below this paragraph, containing "STRUCTURE_2law", creates the "Structure Box" on the page.
| + | <StructureSection load='2law' size='340' side='right'caption='[[2law]]' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[2law]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LAW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LAW FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </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=2law FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2law OCA], [https://pdbe.org/2law PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2law RCSB], [https://www.ebi.ac.uk/pdbsum/2law PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2law ProSAT]</span></td></tr> |
| - | {{STRUCTURE_2law| PDB=2law | SCENE= }}
| + | </table> |
| - | | + | == Function == |
| - | ===Structure of the second WW domain from human YAP in complex with a human Smad1 derived peptide===
| + | [https://www.uniprot.org/uniprot/YAP1_HUMAN YAP1_HUMAN] Transcriptional regulator which can act both as a coactivator and a corepressor and is the critical downstream regulatory target in the Hippo signaling pathway that 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. Plays a key role to control cell proliferation in response to cell contact. 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. The presence of TEAD transcription factors are required for it to stimulate gene expression, cell growth, anchorage-independent growth, and epithelial mesenchymal transition (EMT) induction. Isoform 2 and isoform 3 can activate the C-terminal fragment (CTF) of ERBB4 (isoform 3).<ref>PMID:12807903</ref> <ref>PMID:17974916</ref> <ref>PMID:18579750</ref> <ref>PMID:18158288</ref> <ref>PMID:18280240</ref> <ref>PMID:21364637</ref> |
| - | | + | == References == |
| - | | + | <references/> |
| - | <!-- | + | __TOC__ |
| - | The line below this paragraph, {{ABSTRACT_PUBMED_21685363}}, adds the Publication Abstract to the page
| + | </StructureSection> |
| - | (as it appears on PubMed at http://www.pubmed.gov), where 21685363 is the PubMed ID number.
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| - | -->
| + | |
| - | {{ABSTRACT_PUBMED_21685363}}
| + | |
| - | | + | |
| - | ==About this Structure== | + | |
| - | [[2law]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LAW OCA]. | + | |
| - | | + | |
| - | ==Reference== | + | |
| - | <ref group="xtra">PMID:021685363</ref><references group="xtra"/> | + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Aragon, E.]] | + | [[Category: Large Structures]] |
| - | [[Category: Escobedo, A.]] | + | [[Category: Aragon E]] |
| - | [[Category: Goerner, N.]] | + | [[Category: Escobedo A]] |
| - | [[Category: Macias, M J.]] | + | [[Category: Goerner N]] |
| - | [[Category: Massague, J.]] | + | [[Category: Macias MJ]] |
| - | [[Category: Xi, Q.]] | + | [[Category: Massague J]] |
| - | [[Category: Zaromytidou, A.]] | + | [[Category: Xi Q]] |
| - | [[Category: Cdk]]
| + | [[Category: Zaromytidou A]] |
| - | [[Category: Signal transduction]]
| + | |
| - | [[Category: Signaling protein-transcription complex]]
| + | |
| - | [[Category: Smad1]]
| + | |
| - | [[Category: Yap]]
| + | |
| Structural highlights
Function
YAP1_HUMAN Transcriptional regulator which can act both as a coactivator and a corepressor and is the critical downstream regulatory target in the Hippo signaling pathway that 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. Plays a key role to control cell proliferation in response to cell contact. 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. The presence of TEAD transcription factors are required for it to stimulate gene expression, cell growth, anchorage-independent growth, and epithelial mesenchymal transition (EMT) induction. Isoform 2 and isoform 3 can activate the C-terminal fragment (CTF) of ERBB4 (isoform 3).[1] [2] [3] [4] [5] [6]
References
- ↑ Komuro A, Nagai M, Navin NE, Sudol M. WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that translocates to the nucleus. J Biol Chem. 2003 Aug 29;278(35):33334-41. Epub 2003 Jun 13. PMID:12807903 doi:10.1074/jbc.M305597200
- ↑ Zhao B, Wei X, Li W, Udan RS, Yang Q, Kim J, Xie J, Ikenoue T, Yu J, Li L, Zheng P, Ye K, Chinnaiyan A, Halder G, Lai ZC, Guan KL. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev. 2007 Nov 1;21(21):2747-61. PMID:17974916 doi:10.1101/gad.1602907
- ↑ Zhao B, Ye X, Yu J, Li L, Li W, Li S, Yu J, Lin JD, Wang CY, Chinnaiyan AM, Lai ZC, Guan KL. TEAD mediates YAP-dependent gene induction and growth control. Genes Dev. 2008 Jul 15;22(14):1962-71. Epub 2008 Jun 25. PMID:18579750 doi:10.1101/gad.1664408
- ↑ Hao Y, Chun A, Cheung K, Rashidi B, Yang X. Tumor suppressor LATS1 is a negative regulator of oncogene YAP. J Biol Chem. 2008 Feb 29;283(9):5496-509. Epub 2007 Dec 24. PMID:18158288 doi:10.1074/jbc.M709037200
- ↑ Levy D, Adamovich Y, Reuven N, Shaul Y. Yap1 phosphorylation by c-Abl is a critical step in selective activation of proapoptotic genes in response to DNA damage. Mol Cell. 2008 Feb 15;29(3):350-61. doi: 10.1016/j.molcel.2007.12.022. PMID:18280240 doi:10.1016/j.molcel.2007.12.022
- ↑ Tomlinson V, Gudmundsdottir K, Luong P, Leung KY, Knebel A, Basu S. JNK phosphorylates Yes-associated protein (YAP) to regulate apoptosis. Cell Death Dis. 2010;1:e29. doi: 10.1038/cddis.2010.7. PMID:21364637 doi:10.1038/cddis.2010.7
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