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==Crystal structure of the pleckstrin homology domain of human Sin1, a TORC2 subunit==
==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=''>
<StructureSection load='3voq' size='340' side='right'caption='[[3voq]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3voq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VOQ FirstGlance]. <br>
<table><tr><td colspan='2'>[[3voq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. 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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ulb|3ulb]], [[3ulc|3ulc]]</td></tr>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ulb|3ulb]], [[3ulc|3ulc]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SIN1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SIN1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3voq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3voq OCA], [http://pdbe.org/3voq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3voq RCSB], [http://www.ebi.ac.uk/pdbsum/3voq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3voq ProSAT]</span></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>
</table>
== Function ==
== Function ==
[[http://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>   
[[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>   
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Matsuura, Y]]
[[Category: Matsuura, Y]]
[[Category: Pan, D]]
[[Category: Pan, D]]
[[Category: Membrane protein]]
[[Category: Membrane protein]]
[[Category: Ph domain]]
[[Category: Ph domain]]
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