Structural highlights
Function
[SKI_HUMAN] May play a role in terminal differentiation of skeletal muscle cells but not in the determination of cells to the myogenic lineage. Functions as a repressor of TGF-beta signaling.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The nuclear protooncoprotein SKI negatively regulates transforming growth factor-beta (TGF-beta) signaling in cell growth and differentiation. It directly interacts with the Smads and, by various mechanisms, represses the transcription of TGF-beta-responsive genes. SKI is a multidomain protein that includes a domain bearing high sequence similarity with the retinal determination protein Dachshund (the Dachshund homology domain, DHD). The SKI-DHD has been implicated in SMAD-2/3, N-CoR, SKIP, and PML-RARalpha binding. The 1.65 A crystal structure of the Dachshund homology domain of human SKI is reported here. The SKI-DHD adopts a mixed alpha/beta structure which includes features found in the forkhead/winged-helix family of DNA binding proteins, although SKI-DHD is not a DNA binding domain. Residues that form a contiguous surface patch on SKI-DHD are conserved within the Ski/Sno family and with Dachshund, suggesting that this domain may mediate intermolecular interactions common to these proteins.
Crystal structure of the dachshund homology domain of human SKI.,Wilson JJ, Malakhova M, Zhang R, Joachimiak A, Hegde RS Structure. 2004 May;12(5):785-92. PMID:15130471[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Takahata M, Inoue Y, Tsuda H, Imoto I, Koinuma D, Hayashi M, Ichikura T, Yamori T, Nagasaki K, Yoshida M, Matsuoka M, Morishita K, Yuki K, Hanyu A, Miyazawa K, Inazawa J, Miyazono K, Imamura T. SKI and MEL1 cooperate to inhibit transforming growth factor-beta signal in gastric cancer cells. J Biol Chem. 2009 Jan 30;284(5):3334-44. Epub 2008 Dec 1. PMID:19049980 doi:M808989200
- ↑ Wilson JJ, Malakhova M, Zhang R, Joachimiak A, Hegde RS. Crystal structure of the dachshund homology domain of human SKI. Structure. 2004 May;12(5):785-92. PMID:15130471 doi:10.1016/j.str.2004.02.035
