6hk4: Difference between revisions

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<StructureSection load='6hk4' size='340' side='right'caption='[[6hk4]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
<StructureSection load='6hk4' size='340' side='right'caption='[[6hk4]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6hk4]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HK4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HK4 FirstGlance]. <br>
<table><tr><td colspan='2'>[[6hk4]] is a 3 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=6HK4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HK4 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=G8E:3-azanyl-6-(4-morpholin-4-ylsulfonylphenyl)-~{N}-pyridin-3-yl-pyrazine-2-carboxamide'>G8E</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</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]] 2.5&#8491;</td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=G8E:3-azanyl-6-(4-morpholin-4-ylsulfonylphenyl)-~{N}-pyridin-3-yl-pyrazine-2-carboxamide'>G8E</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></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=6hk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hk4 OCA], [http://pdbe.org/6hk4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hk4 RCSB], [http://www.ebi.ac.uk/pdbsum/6hk4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hk4 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=6hk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hk4 OCA], [https://pdbe.org/6hk4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hk4 RCSB], [https://www.ebi.ac.uk/pdbsum/6hk4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hk4 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/GSK3B_HUMAN GSK3B_HUMAN]] Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation.<ref>PMID:1846781</ref> <ref>PMID:8397507</ref> <ref>PMID:9072970</ref> <ref>PMID:9819408</ref> <ref>PMID:11430833</ref> <ref>PMID:14690523</ref> <ref>PMID:15448698</ref> <ref>PMID:18348280</ref> <ref>PMID:20932480</ref> <ref>PMID:20937854</ref> <ref>PMID:22514281</ref> <ref>PMID:12554650</ref> 
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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</div>
</div>
<div class="pdbe-citations 6hk4" style="background-color:#fffaf0;"></div>
<div class="pdbe-citations 6hk4" style="background-color:#fffaf0;"></div>
==See Also==
*[[Glycogen synthase kinase 3 3D structures|Glycogen synthase kinase 3 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Cavalli, A]]
[[Category: Cavalli A]]
[[Category: Decherchi, S]]
[[Category: Decherchi S]]
[[Category: Demitri, N]]
[[Category: Demitri N]]
[[Category: Giabbai, B]]
[[Category: Di Martino R]]
[[Category: Girotto, S]]
[[Category: Giabbai B]]
[[Category: Gobbo, D]]
[[Category: Girotto S]]
[[Category: Martino, R Di]]
[[Category: Gobbo D]]
[[Category: Piretti, V]]
[[Category: Piretti V]]
[[Category: Storici, P]]
[[Category: Storici P]]
[[Category: Tripathi, S K]]
[[Category: Tripathi SK]]
[[Category: Complex]]
[[Category: Gsk 3b]]
[[Category: Inhibitor]]
[[Category: Pyrazine]]
[[Category: Transferase]]
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