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{{STRUCTURE_4kk1|  PDB=4kk1  |  SCENE=  }}
===Crystal Structure of TSC1 core domain from S. pombe===


==Function==
==Crystal Structure of TSC1 core domain from S. pombe==
[[http://www.uniprot.org/uniprot/TSC1_SCHPO TSC1_SCHPO]] Together with tsc2, required for uptake of various amino-acids from the environment and for proper conjugation. Involved in induction of gene expression of permeases and genes required for meiosis upon nitrogen starvation. May act as a GTPase-activating protein (GAP) for the small GTPase rhb1.<ref>PMID:12136010</ref> <ref>PMID:14718525</ref> <ref>PMID:16624901</ref>
<StructureSection load='4kk1' size='340' side='right'caption='[[4kk1]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4kk1]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Schizosaccharomyces_pombe_972h- Schizosaccharomyces pombe 972h-]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KK1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KK1 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]] 3.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=4kk1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kk1 OCA], [https://pdbe.org/4kk1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kk1 RCSB], [https://www.ebi.ac.uk/pdbsum/4kk1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kk1 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TSC1_SCHPO TSC1_SCHPO] Together with tsc2, required for uptake of various amino-acids from the environment and for proper conjugation. Involved in induction of gene expression of permeases and genes required for meiosis upon nitrogen starvation. May act as a GTPase-activating protein (GAP) for the small GTPase rhb1.<ref>PMID:12136010</ref> <ref>PMID:14718525</ref> <ref>PMID:16624901</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Tuberous sclerosis complex is a disease caused by mutations in two tumor-suppressor genes, TSC1 and TSC2. The TSC1 protein, also known as hamartin, has a critical role in controlling mTOR signalling. TSC1 does not bear apparent sequence homology with other proteins. Here we show that the N-terminal half of yeast TSC1 forms a protease-resistant domain, which is evolutionarily conserved. The crystal structure of this yeast TSC1 core domain shows that it contains a pseudo-HEAT repeat fold with its C-terminal end capped by a helical subdomain. This allows us to model the three-dimensional structure of the human TSC1 N-terminal domain (TSC1-NTD), which anchors essentially all pathogenic TSC1 missense mutations found in tuberous sclerosis patients. Interestingly, most pathogenic mutations map inside of the folded TSC1-NTD structure, whereas most non-pathogenic variants are on the structural surface. This indicates that the disruption of the TSC1-NTD globular structure is a major cause of tuberous sclerosis.


==About this Structure==
Crystal structure of the yeast TSC1 core domain and implications for tuberous sclerosis pathological mutations.,Sun W, Zhu YJ, Wang Z, Zhong Q, Gao F, Lou J, Gong W, Xu W Nat Commun. 2013 Jul 16;4:2135. doi: 10.1038/ncomms3135. PMID:23857276<ref>PMID:23857276</ref>
[[4kk1]] is a 20 chain structure with sequence from [http://en.wikipedia.org/wiki/Schizosaccharomyces_pombe_972h- Schizosaccharomyces pombe 972h-]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KK1 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
<references group="xtra"/><references/>
</div>
<div class="pdbe-citations 4kk1" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Schizosaccharomyces pombe 972h-]]
[[Category: Schizosaccharomyces pombe 972h-]]
[[Category: Gao, F.]]
[[Category: Gao F]]
[[Category: Gong, W M.]]
[[Category: Gong WM]]
[[Category: Lou, J Z.]]
[[Category: Lou JZ]]
[[Category: Sun, W.]]
[[Category: Sun W]]
[[Category: Wang, Z Z.]]
[[Category: Wang ZZ]]
[[Category: Xu, W Q.]]
[[Category: Xu WQ]]
[[Category: Zhong, Q.]]
[[Category: Zhong Q]]
[[Category: Zhu, Y.]]
[[Category: Zhu Y]]
[[Category: Heat repeat]]
[[Category: Immune system]]
[[Category: Tumor suppressor]]
Retrieved from "https://proteopedia.org/4kk1"