2dwv

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

1. ↑ 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
2. ↑ 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
3. ↑ Ohnishi S, Guntert P, Koshiba S, Tomizawa T, Akasaka R, Tochio N, Sato M, Inoue M, Harada T, Watanabe S, Tanaka A, Shirouzu M, Kigawa T, Yokoyama S. Solution structure of an atypical WW domain in a novel beta-clam-like dimeric form. FEBS Lett. 2007 Feb 6;581(3):462-8. Epub 2007 Jan 16. PMID:17239860 doi:10.1016/j.febslet.2007.01.008