2y3a

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Current revision (08:07, 23 August 2023) (edit) (undo)
 
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<StructureSection load='2y3a' size='340' side='right'caption='[[2y3a]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
<StructureSection load='2y3a' size='340' side='right'caption='[[2y3a]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2y3a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y3A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Y3A FirstGlance]. <br>
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<table><tr><td colspan='2'>[[2y3a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y3A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Y3A FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GD9:2-(1H-INDAZOL-4-YL)-6-{[4-(METHYLSULFONYL)PIPERAZIN-1-YL]METHYL}-4-MORPHOLIN-4-YL-THIENO[3,2-D]PYRIMIDINE'>GD9</scene></td></tr>
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</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>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Nicotinate_riboside_kinase Nicotinate riboside kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.173 2.7.1.173] </span></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GD9:2-(1H-INDAZOL-4-YL)-6-{[4-(METHYLSULFONYL)PIPERAZIN-1-YL]METHYL}-4-MORPHOLIN-4-YL-THIENO[3,2-D]PYRIMIDINE'>GD9</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=2y3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y3a OCA], [https://pdbe.org/2y3a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2y3a RCSB], [https://www.ebi.ac.uk/pdbsum/2y3a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2y3a 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=2y3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y3a OCA], [https://pdbe.org/2y3a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2y3a RCSB], [https://www.ebi.ac.uk/pdbsum/2y3a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2y3a ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/PK3CB_MOUSE PK3CB_MOUSE]] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Involved in the activation of AKT1 upon stimulation by G-protein coupled receptors (GPCRs) ligands such as CXCL12, sphingosine 1-phosphate, and lysophosphatidic acid. May also act downstream receptor tyrosine kinases. Required in different signaling pathways for stable platelet adhesion and aggregation. Plays a role in platelet activation signaling triggered by GPCRs, alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) and ITAM (immunoreceptor tyrosine-based activation motif)-bearing receptors such as GP6. Regulates the strength of adhesion of ITGA2B/ ITGB3 activated receptors necessary for the cellular transmission of contractile forces. Required for platelet aggregation induced by F2 (thrombin) and thromboxane A2 (TXA2). Has a role in cell survival. May have a role in cell migration. Involved in the early stage of autophagosome formation. Modulates the intracellular level of PtdIns3P (Phosphatidylinositol 3-phosphate) and activates PIK3C3 kinase activity. May act as a scaffold, independently of its lipid kinase activity to positively regulate autophagy. May have a role in insulin signaling as scaffolding protein in which the lipid kinase activity is not required. May have a kinase-independent function in regulating cell proliferation and in clathrin-mediated endocytosis. Mediator of oncogenic signal in cell lines lacking PTEN. The lipid kinase activity is necessary for its role in oncogenic transformation. Required for the growth of ERBB2 and RAS driven tumors.<ref>PMID:18594509</ref> <ref>PMID:18544649</ref> <ref>PMID:19515725</ref> <ref>PMID:20065293</ref> <ref>PMID:19940148</ref> <ref>PMID:21059846</ref> [[https://www.uniprot.org/uniprot/P85B_MOUSE P85B_MOUSE]] Regulatory subunit of phosphoinositide-3-kinase (PI3K), a kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Binds to activated (phosphorylated) protein-tyrosine kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Indirectly regulates autophagy.[UniProtKB:O00459]
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[https://www.uniprot.org/uniprot/PK3CB_MOUSE PK3CB_MOUSE] Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Involved in the activation of AKT1 upon stimulation by G-protein coupled receptors (GPCRs) ligands such as CXCL12, sphingosine 1-phosphate, and lysophosphatidic acid. May also act downstream receptor tyrosine kinases. Required in different signaling pathways for stable platelet adhesion and aggregation. Plays a role in platelet activation signaling triggered by GPCRs, alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) and ITAM (immunoreceptor tyrosine-based activation motif)-bearing receptors such as GP6. Regulates the strength of adhesion of ITGA2B/ ITGB3 activated receptors necessary for the cellular transmission of contractile forces. Required for platelet aggregation induced by F2 (thrombin) and thromboxane A2 (TXA2). Has a role in cell survival. May have a role in cell migration. Involved in the early stage of autophagosome formation. Modulates the intracellular level of PtdIns3P (Phosphatidylinositol 3-phosphate) and activates PIK3C3 kinase activity. May act as a scaffold, independently of its lipid kinase activity to positively regulate autophagy. May have a role in insulin signaling as scaffolding protein in which the lipid kinase activity is not required. May have a kinase-independent function in regulating cell proliferation and in clathrin-mediated endocytosis. Mediator of oncogenic signal in cell lines lacking PTEN. The lipid kinase activity is necessary for its role in oncogenic transformation. Required for the growth of ERBB2 and RAS driven tumors.<ref>PMID:18594509</ref> <ref>PMID:18544649</ref> <ref>PMID:19515725</ref> <ref>PMID:20065293</ref> <ref>PMID:19940148</ref> <ref>PMID:21059846</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: Large Structures]]
[[Category: Large Structures]]
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[[Category: Lk3 transgenic mice]]
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[[Category: Mus musculus]]
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[[Category: Nicotinate riboside kinase]]
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[[Category: Perisic O]]
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[[Category: Perisic, O]]
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[[Category: Vadas O]]
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[[Category: Vadas, O]]
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[[Category: Williams RL]]
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[[Category: Williams, R L]]
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[[Category: Zhang X]]
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[[Category: Zhang, X]]
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[[Category: Phosphoinositide 3-kinase]]
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[[Category: Rtk]]
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[[Category: Transferase]]
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Current revision

Crystal structure of p110beta in complex with icSH2 of p85beta and the drug GDC-0941

PDB ID 2y3a

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OCA

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