Structural highlights
Function
[SOX17_MOUSE] Acts as transcription regulator that binds target promoter DNA and bends the DNA. Binds to the sequences 5'-AACAAT-'3 or 5'-AACAAAG-3'. Modulates transcriptional regulation via WNT3A. Inhibits Wnt signaling. Promotes degradation of activated CTNNB1. Plays a key role in the regulation of embryonic development. Required for normal looping of the embryonic heart tube. Required for normal development of the definitive gut endoderm. Probable transcriptional activator in the premeiotic germ cells. Isoform 2 (T-SOX17) shows no DNA-binding activity.[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
Sox17 regulates endodermal lineage commitment and is thought to function antagonistically to the pluripotency determinant Sox2. To investigate the biochemical basis for the distinct functions of Sox2 and Sox17, we solved the crystal structure of the high mobility group domain of Sox17 bound to a DNA element derived from the Lama1 enhancer using crystals diffracting to 2.7 A resolution. Sox17 targets the minor groove and bends the DNA by approximately 80 degrees . The DNA architecture closely resembles the one seen for Sox2/DNA structures, suggesting that the degree of bending is conserved between both proteins and nucleotide substitutions have only marginal effects on the bending topology. Accordingly, affinities of Sox2 and Sox17 for the Lama1 element were found to be identical. However, when the Oct1 contact interface of Sox2 is compared with the corresponding region of Sox17, a significantly altered charge distribution is observed, suggesting differential co-factor recruitment that may explain their biological distinctiveness.
The structure of Sox17 bound to DNA reveals a conserved bending topology but selective protein interaction platforms.,Palasingam P, Jauch R, Ng CK, Kolatkar PR J Mol Biol. 2009 May 8;388(3):619-30. Epub 2009 Mar 25. PMID:19328208[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Liu X, Luo M, Xie W, Wells JM, Goodheart MJ, Engelhardt JF. Sox17 modulates Wnt3A/beta-catenin-mediated transcriptional activation of the Lef-1 promoter. Am J Physiol Lung Cell Mol Physiol. 2010 Nov;299(5):L694-710. doi:, 10.1152/ajplung.00140.2010. Epub 2010 Aug 27. PMID:20802155 doi:http://dx.doi.org/10.1152/ajplung.00140.2010
- ↑ Palasingam P, Jauch R, Ng CK, Kolatkar PR. The structure of Sox17 bound to DNA reveals a conserved bending topology but selective protein interaction platforms. J Mol Biol. 2009 May 8;388(3):619-30. Epub 2009 Mar 25. PMID:19328208 doi:10.1016/j.jmb.2009.03.055
