3wf7: Difference between revisions

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<StructureSection load='3wf7' size='340' side='right'caption='[[3wf7]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
<StructureSection load='3wf7' size='340' side='right'caption='[[3wf7]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3wf7]] is a 1 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=3WF7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WF7 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3wf7]] is a 1 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=3WF7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WF7 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FS9:1-(9H-PURIN-6-YL)-N-[3-(TRIFLUOROMETHYL)PHENYL]PIPERIDINE-4-CARBOXAMIDE'>FS9</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FS9:1-(9H-PURIN-6-YL)-N-[3-(TRIFLUOROMETHYL)PHENYL]PIPERIDINE-4-CARBOXAMIDE'>FS9</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3we4|3we4]], [[3wf5|3wf5]], [[3wf6|3wf6]], [[3wf8|3wf8]], [[3wf9|3wf9]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RPS6KB1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=3wf7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wf7 OCA], [https://pdbe.org/3wf7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wf7 RCSB], [https://www.ebi.ac.uk/pdbsum/3wf7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wf7 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=3wf7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wf7 OCA], [https://pdbe.org/3wf7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wf7 RCSB], [https://www.ebi.ac.uk/pdbsum/3wf7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wf7 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/KS6B1_HUMAN KS6B1_HUMAN]] Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the preinitiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function. Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex. The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at 'Thr-412', which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function. Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B. May be involved in cytoskeletal rearrangement through binding to neurabin.<ref>PMID:11500364</ref> <ref>PMID:12801526</ref> <ref>PMID:15341740</ref> <ref>PMID:15071500</ref> <ref>PMID:14673156</ref> <ref>PMID:16286006</ref> <ref>PMID:17052453</ref> <ref>PMID:17053147</ref> <ref>PMID:17936702</ref> <ref>PMID:18952604</ref> <ref>PMID:19085255</ref> <ref>PMID:19720745</ref> <ref>PMID:19995915</ref> <ref>PMID:19935711</ref>
[https://www.uniprot.org/uniprot/KS6B1_HUMAN KS6B1_HUMAN] Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the preinitiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function. Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex. The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at 'Thr-412', which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function. Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B. May be involved in cytoskeletal rearrangement through binding to neurabin.<ref>PMID:11500364</ref> <ref>PMID:12801526</ref> <ref>PMID:15341740</ref> <ref>PMID:15071500</ref> <ref>PMID:14673156</ref> <ref>PMID:16286006</ref> <ref>PMID:17052453</ref> <ref>PMID:17053147</ref> <ref>PMID:17936702</ref> <ref>PMID:18952604</ref> <ref>PMID:19085255</ref> <ref>PMID:19720745</ref> <ref>PMID:19995915</ref> <ref>PMID:19935711</ref>  
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<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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==See Also==
==See Also==
*[[Ribosomal protein S6 kinase|Ribosomal protein S6 kinase]]
*[[Ribosomal protein S6 kinase 3D structures|Ribosomal protein S6 kinase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Niwa H]]
[[Category: Niwa, H]]
[[Category: Shirouzu M]]
[[Category: Shirouzu, M]]
[[Category: Yokoyama S]]
[[Category: Yokoyama, S]]
[[Category: Atp-binding]]
[[Category: Phosphorylation]]
[[Category: Serine/threonine protein kinase domain]]
[[Category: Transferase]]
[[Category: Transferase-transferase inhibitor complex]]
[[Category: Zinc-binding]]

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