View source for 6wx9


==SOX2 bound to Importin-alpha 5==
<StructureSection load='6wx9' size='340' side='right'caption='[[6wx9]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6wx9]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WX9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WX9 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</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=6wx9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wx9 OCA], [https://pdbe.org/6wx9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wx9 RCSB], [https://www.ebi.ac.uk/pdbsum/6wx9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wx9 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SOX2_HUMAN SOX2_HUMAN] Defects in SOX2 are the cause of microphthalmia syndromic type 3 (MCOPS3) [MIM:[https://omim.org/entry/206900 206900]. Microphthalmia is a clinically heterogeneous disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS3 is characterized by the rare association of malformations including uni- or bilateral anophthalmia or microphthalmia, and esophageal atresia with trachoesophageal fistula.<ref>PMID:12612584</ref> 
== Function ==
[https://www.uniprot.org/uniprot/SOX2_HUMAN SOX2_HUMAN] Transcription factor that forms a trimeric complex with OCT4 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206 (By similarity). Critical for early embryogenesis and for embryonic stem cell pluripotency. May function as a switch in neuronal development. Downstream SRRT target that mediates the promotion of neural stem cell self-renewal (By similarity). Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation (By similarity).<ref>PMID:18035408</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
SOX (SRY-related HMG-box) transcription factors perform critical functions in development and cell differentiation. These roles depend on precise nuclear trafficking, with mutations in the nuclear targeting regions causing developmental diseases and a range of cancers. SOX protein nuclear localization is proposed to be mediated by two nuclear localization signals (NLSs) positioned within the extremities of the DNA-binding HMG-box domain and, although mutations within either cause disease, the mechanistic basis has remained unclear. Unexpectedly, we find here that these two distantly positioned NLSs of SOX2 contribute to a contiguous interface spanning 9 of the 10 ARM domains on the nuclear import adapter IMPalpha3. We identify key binding determinants and show this interface is critical for neural stem cell maintenance and for Drosophila development. Moreover, we identify a structural basis for the preference of SOX2 binding to IMPalpha3. In addition to defining the structural basis for SOX protein localization, these results provide a platform for understanding how mutations and post-translational modifications within these regions may modulate nuclear localization and result in clinical disease, and also how other proteins containing multiple NLSs may bind IMPalpha through an extended recognition interface.

Structural basis for nuclear import selectivity of pioneer transcription factor SOX2.,Jagga B, Edwards M, Pagin M, Wagstaff KM, Aragao D, Roman N, Nanson JD, Raidal SR, Dominado N, Stewart M, Jans DA, Hime GR, Nicolis SK, Basler CF, Forwood JK Nat Commun. 2021 Jan 4;12(1):28. doi: 10.1038/s41467-020-20194-0. PMID:33397924<ref>PMID:33397924</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6wx9" style="background-color:#fffaf0;"></div>

==See Also==
*[[Importin 3D structures|Importin 3D structures]]
*[[OCT4 and SOX2 transcription factors|OCT4 and SOX2 transcription factors]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Aragao D]]
[[Category: Bikshapathi J]]
[[Category: Forwood JK]]
[[Category: Roman N]]
[[Category: Stewart M]]