View source for 3voq


==Crystal structure of the pleckstrin homology domain of human Sin1, a TORC2 subunit==
<StructureSection load='3voq' size='340' side='right'caption='[[3voq]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3voq]] 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=3VOQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VOQ 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&#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=3voq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3voq OCA], [https://pdbe.org/3voq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3voq RCSB], [https://www.ebi.ac.uk/pdbsum/3voq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3voq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SIN1_HUMAN SIN1_HUMAN] Subunit of mTORC2, which regulates cell growth and survival in response to hormonal signals. mTORC2 is activated by growth factors, but, in contrast to mTORC1, seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'. Within mTORC2, MAPKAP1 is required for complex formation and mTORC2 kinase activity. MAPKAP1 inhibits MAP3K2 by preventing its dimerization and autophosphorylation. Inhibits HRAS and KRAS signaling. Enhances osmotic stress-induced phosphorylation of ATF2 and ATF2-mediated transcription.<ref>PMID:15988011</ref> <ref>PMID:16962653</ref> <ref>PMID:17054722</ref> <ref>PMID:17043309</ref> <ref>PMID:17303383</ref> 
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== Publication Abstract from PubMed ==
In eukaryotes, multiprotein complexes termed TOR complex 1 (TORC1) and TOR complex 2 (TORC2) function as major regulators of cell growth, metabolism and ageing. The C-terminal domain of the Saccharomyces cerevisiae TORC2 component Avo1 is required for plasma-membrane localization of TORC2 and is essential for yeast viability. X-ray crystal structures of the C-terminal domain of Avo1 and of its human orthologue Sin1 have been determined. The structures show that the C-termini of Avo1 and Sin1 both have the pleckstrin homology (PH) domain fold. Comparison with known PH-domain structures suggests a putative binding site for phosphoinositides.

Structures of the pleckstrin homology domain of Saccharomyces cerevisiae Avo1 and its human orthologue Sin1, an essential subunit of TOR complex 2.,Pan D, Matsuura Y Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Apr 1;68(Pt 4):386-92., Epub 2012 Mar 27. PMID:22505404<ref>PMID:22505404</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3voq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Matsuura Y]]
[[Category: Pan D]]