3zdi - Revision history

OCA at 10:59, 20 December 2023

2023-12-20T10:59:34Z

←Older revision		Revision as of 10:59, 20 December 2023
Line 3:		Line 3:
	<StructureSection load='3zdi' size='340' side='right'caption='[[3zdi]], [[Resolution\|resolution]] 2.65Å' scene=''>		<StructureSection load='3zdi' size='340' side='right'caption='[[3zdi]], [[Resolution\|resolution]] 2.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3zdi]] 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=3ZDI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZDI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3zdi]] 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=3ZDI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZDI FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UGJ:3,6~~-~~DIAMINO-4-(2-CHLOROPHENYL)THIENO~~[~~2,3-B~~]~~PYRIDINE-~~2~~,5-DICARBONITRILE'>UGJ</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]] 2.645Å</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=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=UGJ:3,6-DIAMINO-4-(2-CHLOROPHENYL)THIENO[2,3-B]PYRIDINE-2,5-DICARBONITRILE'>UGJ</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=3zdi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zdi OCA], [https://pdbe.org/3zdi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zdi RCSB], [https://www.ebi.ac.uk/pdbsum/3zdi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zdi 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=3zdi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zdi OCA], [https://pdbe.org/3zdi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zdi RCSB], [https://www.ebi.ac.uk/pdbsum/3zdi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zdi ProSAT]</span></td></tr>
	</table>		</table>
-	== Disease ==
-	[[https://www.uniprot.org/uniprot/AXIN1_HUMAN AXIN1_HUMAN]] Defects in AXIN1 are involved in hepatocellular carcinoma (HCC) [MIM:[https://omim.org/entry/114550 114550]].<ref>PMID:10700176</ref> <ref>PMID:12101426</ref> Defects in AXIN1 are a cause of caudal duplication anomaly (CADUA) [MIM:[https://omim.org/entry/607864 607864]]. Caudal duplication anomaly is characterized by the occurrence of duplications of different organs in the caudal region. Note=Caudal duplication anomaly is associated with hypermethylation of the AXIN1 promoter.<ref>PMID:10700176</ref>
	== Function ==		== Function ==
-	[[https://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> [[https://www.uniprot.org/uniprot/AXIN1_HUMAN AXIN1_HUMAN]] Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling. Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7. Also component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development.<ref>PMID:12192039</ref> <ref>PMID:16601693</ref> <ref>PMID:17210684</ref>	+	[https://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 ==
Line 28:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Oberholzer~~, A E~~]]	+	[[Category: Oberholzer AE]]
-	[[Category: Pearl~~, L H]]~~	+	[[Category: Pearl LH]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Insulin pathway]]~~	+
-	~~[[Category: Transferase serine/threonine-protein kinase]]~~	+
-	~~[[Category: Transferase-peptide complex]]~~	+
-	~~[[Category: Wnt signaling pathway~~]]	+

OCA at 05:42, 10 August 2022

2022-08-10T05:42:53Z

←Older revision		Revision as of 05:42, 10 August 2022
Line 1:		Line 1:

	==Glycogen Synthase Kinase 3 Beta complexed with Axin Peptide and Inhibitor 7d==		==Glycogen Synthase Kinase 3 Beta complexed with Axin Peptide and Inhibitor 7d==
-	<StructureSection load='3zdi' size='340' side='right' caption='[[3zdi]], [[Resolution\|resolution]] 2.65Å' scene=''>	+	<StructureSection load='3zdi' size='340' side='right'caption='[[3zdi]], [[Resolution\|resolution]] 2.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3zdi]] 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=3ZDI OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3ZDI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3zdi]] 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=3ZDI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZDI FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UGJ:3,6-DIAMINO-4-(2-CHLOROPHENYL)THIENO[2,3-B]PYRIDINE-2,5-DICARBONITRILE'>UGJ</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UGJ:3,6-DIAMINO-4-(2-CHLOROPHENYL)THIENO[2,3-B]PYRIDINE-2,5-DICARBONITRILE'>UGJ</scene></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='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='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=3zdi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zdi OCA], [~~http~~://pdbe.org/3zdi PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3zdi RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3zdi PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3zdi 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=3zdi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zdi OCA], [https://pdbe.org/3zdi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zdi RCSB], [https://www.ebi.ac.uk/pdbsum/3zdi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zdi ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/AXIN1_HUMAN AXIN1_HUMAN]] Defects in AXIN1 are involved in hepatocellular carcinoma (HCC) [MIM:[~~http~~://omim.org/entry/114550 114550]].<ref>PMID:10700176</ref> <ref>PMID:12101426</ref> Defects in AXIN1 are a cause of caudal duplication anomaly (CADUA) [MIM:[~~http~~://omim.org/entry/607864 607864]]. Caudal duplication anomaly is characterized by the occurrence of duplications of different organs in the caudal region. Note=Caudal duplication anomaly is associated with hypermethylation of the AXIN1 promoter.<ref>PMID:10700176</ref>	+	[[https://www.uniprot.org/uniprot/AXIN1_HUMAN AXIN1_HUMAN]] Defects in AXIN1 are involved in hepatocellular carcinoma (HCC) [MIM:[https://omim.org/entry/114550 114550]].<ref>PMID:10700176</ref> <ref>PMID:12101426</ref> Defects in AXIN1 are a cause of caudal duplication anomaly (CADUA) [MIM:[https://omim.org/entry/607864 607864]]. Caudal duplication anomaly is characterized by the occurrence of duplications of different organs in the caudal region. Note=Caudal duplication anomaly is associated with hypermethylation of the AXIN1 promoter.<ref>PMID:10700176</ref>
	== Function ==		== 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> [[~~http~~://www.uniprot.org/uniprot/AXIN1_HUMAN AXIN1_HUMAN]] Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling. Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7. Also component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development.<ref>PMID:12192039</ref> <ref>PMID:16601693</ref> <ref>PMID:17210684</ref>	+	[[https://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> [[https://www.uniprot.org/uniprot/AXIN1_HUMAN AXIN1_HUMAN]] Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling. Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7. Also component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development.<ref>PMID:12192039</ref> <ref>PMID:16601693</ref> <ref>PMID:17210684</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 23:

	==See Also==		==See Also==
-	*[[Glycogen synthase kinase 3\|Glycogen synthase kinase 3]]	+	*[[Glycogen synthase kinase 3 3D structures\|Glycogen synthase kinase 3 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 29:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Oberholzer, A E]]		[[Category: Oberholzer, A E]]
	[[Category: Pearl, L H]]		[[Category: Pearl, L H]]

OCA at 03:10, 5 August 2016

2016-08-05T03:10:28Z

←Older revision		Revision as of 03:10, 5 August 2016
Line 1:		Line 1:
		+
	==Glycogen Synthase Kinase 3 Beta complexed with Axin Peptide and Inhibitor 7d==		==Glycogen Synthase Kinase 3 Beta complexed with Axin Peptide and Inhibitor 7d==
	<StructureSection load='3zdi' size='340' side='right' caption='[[3zdi]], [[Resolution\|resolution]] 2.65Å' scene=''>		<StructureSection load='3zdi' size='340' side='right' caption='[[3zdi]], [[Resolution\|resolution]] 2.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3zdi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZDI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZDI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3zdi]] 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=3ZDI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZDI FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UGJ:3,6-DIAMINO-4-(2-CHLOROPHENYL)THIENO[2,3-B]PYRIDINE-2,5-DICARBONITRILE'>UGJ</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UGJ:3,6-DIAMINO-4-(2-CHLOROPHENYL)THIENO[2,3-B]PYRIDINE-2,5-DICARBONITRILE'>UGJ</scene></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='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='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=3zdi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zdi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zdi RCSB], [http://www.ebi.ac.uk/pdbsum/3zdi PDBsum]</span></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=3zdi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zdi OCA], [http://pdbe.org/3zdi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3zdi RCSB], [http://www.ebi.ac.uk/pdbsum/3zdi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3zdi ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3zdi" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Oberholzer, A E]]		[[Category: Oberholzer, A E]]
	[[Category: Pearl, L H]]		[[Category: Pearl, L H]]

OCA at 09:33, 21 December 2014

2014-12-21T09:33:51Z

←Older revision		Revision as of 09:33, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3zdi\| PDB=3zdi \| SCENE= }}~~	+	==Glycogen Synthase Kinase 3 Beta complexed with Axin Peptide and Inhibitor 7d==
-	===Glycogen Synthase Kinase 3 Beta complexed with Axin Peptide and Inhibitor 7d===	+	<StructureSection load='3zdi' size='340' side='right' caption='[[3zdi]], [[Resolution\|resolution]] 2.65Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23214499}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3zdi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZDI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZDI FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UGJ:3,6-DIAMINO-4-(2-CHLOROPHENYL)THIENO[2,3-B]PYRIDINE-2,5-DICARBONITRILE'>UGJ</scene></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='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=3zdi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zdi OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zdi RCSB], [http://www.ebi.ac.uk/pdbsum/3zdi PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/AXIN1_HUMAN AXIN1_HUMAN]] Defects in AXIN1 are involved in hepatocellular carcinoma (HCC) [MIM:[http://omim.org/entry/114550 114550]].<ref>PMID:10700176</ref> <ref>PMID:12101426</ref> Defects in AXIN1 are a cause of caudal duplication anomaly (CADUA) [MIM:[http://omim.org/entry/607864 607864]]. Caudal duplication anomaly is characterized by the occurrence of duplications of different organs in the caudal region. Note=Caudal duplication anomaly is associated with hypermethylation of the AXIN1 promoter.<ref>PMID:10700176</ref>
		+	== 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> [[http://www.uniprot.org/uniprot/AXIN1_HUMAN AXIN1_HUMAN]] Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling. Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7. Also component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development.<ref>PMID:12192039</ref> <ref>PMID:16601693</ref> <ref>PMID:17210684</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Plasmodium falciparum is the infective agent responsible for malaria tropica. The glycogen synthase kinase-3 of the parasite (PfGSK-3) was suggested as a potential biological target for novel antimalarial drugs. Starting from hit structures identified in a high-throughput screening campaign, 3,6-diamino-4-(2-halophenyl)-2-benzoylthieno[2,3-b]pyridine-5-carbonitriles were discovered as a new class of PfGSK-3 inhibitors. Being less active on GSK-3 homologues of other species, the title compounds showed selectivity in favor of PfGSK-3. Taking into account the X-ray structure of a related molecule in complex with human GSK-3 (HsGSK-3), a model was computed for the comparison of inhibitor complexes with the plasmodial and human enzymes. It was found that subtle differences in the ATP-binding pockets are responsible for the observed PfGSK-3 vs HsGSK-3 selectivity. Representatives of the title compound class exhibited micromolar IC(50) values against P. falciparum erythrocyte stage parasites. These results suggest that inhibitors of PfGSK-3 could be developed as potential antimalarial drugs.

-	~~==Disease==~~	+	3,6-Diamino-4-(2-halophenyl)-2-benzoylthieno[2,3-b]pyridine-5-carbonitriles Are Selective Inhibitors of Plasmodium falciparum Glycogen Synthase Kinase-3.,Fugel W, Oberholzer AE, Gschloessl B, Dzikowski R, Pressburger N, Preu L, Pearl LH, Baratte B, Ratin M, Okun I, Doerig C, Kruggel S, Lemcke T, Meijer L, Kunick C J Med Chem. 2012 Dec 27. PMID:23214499<ref>PMID:23214499</ref>
-	~~[[http://www.uniprot.org/uniprot/AXIN1_HUMAN AXIN1_HUMAN]] Defects in AXIN1 are involved in hepatocellular carcinoma~~ (~~HCC~~) [~~MIM:[http://omim.org/entry/114550 114550~~]~~].<ref>PMID:10700176</ref><ref>PMID:12101426</ref> Defects in AXIN1 are a cause~~ of ~~caudal duplication anomaly (CADUA) [MIM:[http://omim~~.~~org/entry/607864 607864]]~~. Caudal duplication anomaly is characterized by the occurrence of duplications of different organs in the caudal region. Note=Caudal duplication anomaly is associated with hypermethylation of the AXIN1 promoter.<ref>PMID:~~10700176~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[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> [[http://www.uniprot.org/uniprot/AXIN1_HUMAN AXIN1_HUMAN]] Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling. Controls dorsoventral patterning via two opposing effects; ~~down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos~~, ~~but also dorsalizes embryos by activating~~ a ~~Wnt-independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation~~ of ~~CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. Facilitates~~ the ~~phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation~~. ~~Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7~~. ~~Also component~~ of ~~the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development~~.<~~ref~~>~~PMID:12192039~~</~~ref~~>~~<ref>PMID:16601693</ref><ref>PMID:17210684</ref>~~	+	</div>
-		+
-	~~==About this Structure==~~	+
-	[[3zdi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZDI OCA].	+

	==See Also==		==See Also==
	*[[Glycogen synthase kinase 3\|Glycogen synthase kinase 3]]		*[[Glycogen synthase kinase 3\|Glycogen synthase kinase 3]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Oberholzer, A E.]]	+	[[Category: Oberholzer, A E]]
-	[[Category: Pearl, L H.]]	+	[[Category: Pearl, L H]]
	[[Category: Inhibitor]]		[[Category: Inhibitor]]
	[[Category: Insulin pathway]]		[[Category: Insulin pathway]]

OCA at 09:43, 24 March 2013

2013-03-24T09:43:12Z

←Older revision		Revision as of 09:43, 24 March 2013
Line 1:		Line 1:
-	[[Image:3zdi.png\|left\|200px]]
-
	{{STRUCTURE_3zdi\| PDB=3zdi \| SCENE= }}		{{STRUCTURE_3zdi\| PDB=3zdi \| SCENE= }}
-
	===Glycogen Synthase Kinase 3 Beta complexed with Axin Peptide and Inhibitor 7d===		===Glycogen Synthase Kinase 3 Beta complexed with Axin Peptide and Inhibitor 7d===
-
	{{ABSTRACT_PUBMED_23214499}}		{{ABSTRACT_PUBMED_23214499}}
		+
		+	==Disease==
		+	[[http://www.uniprot.org/uniprot/AXIN1_HUMAN AXIN1_HUMAN]] Defects in AXIN1 are involved in hepatocellular carcinoma (HCC) [MIM:[http://omim.org/entry/114550 114550]].<ref>PMID:10700176</ref><ref>PMID:12101426</ref> Defects in AXIN1 are a cause of caudal duplication anomaly (CADUA) [MIM:[http://omim.org/entry/607864 607864]]. Caudal duplication anomaly is characterized by the occurrence of duplications of different organs in the caudal region. Note=Caudal duplication anomaly is associated with hypermethylation of the AXIN1 promoter.<ref>PMID:10700176</ref>
		+
		+	==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> [[http://www.uniprot.org/uniprot/AXIN1_HUMAN AXIN1_HUMAN]] Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling. Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7. Also component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development.<ref>PMID:12192039</ref><ref>PMID:16601693</ref><ref>PMID:17210684</ref>

	==About this Structure==		==About this Structure==
Line 12:		Line 14:
	==See Also==		==See Also==
	*[[Glycogen synthase kinase 3\|Glycogen synthase kinase 3]]		*[[Glycogen synthase kinase 3\|Glycogen synthase kinase 3]]
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Oberholzer, A E.]]		[[Category: Oberholzer, A E.]]

OCA at 12:48, 30 January 2013

2013-01-30T12:48:08Z

←Older revision		Revision as of 12:48, 30 January 2013
Line 1:		Line 1:
-	[[Image:3zdi.~~jpg~~\|left\|200px]]	+	[[Image:3zdi.png\|left\|200px]]

	{{STRUCTURE_3zdi\| PDB=3zdi \| SCENE= }}		{{STRUCTURE_3zdi\| PDB=3zdi \| SCENE= }}
Line 9:		Line 9:
	==About this Structure==		==About this Structure==
	[[3zdi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZDI OCA].		[[3zdi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZDI OCA].
		+
		+	==See Also==
		+	*[[Glycogen synthase kinase 3\|Glycogen synthase kinase 3]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Oberholzer, A E.]]		[[Category: Oberholzer, A E.]]

OCA at 09:16, 2 January 2013

2013-01-02T09:16:32Z

←Older revision		Revision as of 09:16, 2 January 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3zdi.jpg\|left\|200px]]

-	~~The entry~~ 3zdi ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_3zdi\| PDB=3zdi \| SCENE= }}

-	~~Authors: Oberholzer, A.E., Pearl, L.H.~~	+	===Glycogen Synthase Kinase 3 Beta complexed with Axin Peptide and Inhibitor 7d===

-	~~Description: Glycogen Synthase Kinase 3 Beta complexed~~ with ~~Axin Peptide and~~ Inhibitor 7d	+	{{ABSTRACT_PUBMED_23214499}}
		+
		+	==About this Structure==
		+	[[3zdi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZDI OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Oberholzer, A E.]]
		+	[[Category: Pearl, L H.]]
		+	[[Category: Inhibitor]]
		+	[[Category: Insulin pathway]]
		+	[[Category: Transferase serine/threonine-protein kinase]]
		+	[[Category: Transferase-peptide complex]]
		+	[[Category: Wnt signaling pathway]]

OCA at 20:34, 12 December 2012

2012-12-12T20:34:54Z

←Older revision		Revision as of 20:34, 12 December 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3zdi is ON HOLD	+	The entry 3zdi is ON HOLD until Paper Publication

	Authors: Oberholzer, A.E., Pearl, L.H.		Authors: Oberholzer, A.E., Pearl, L.H.

	Description: Glycogen Synthase Kinase 3 Beta complexed with Axin Peptide and Inhibitor 7d		Description: Glycogen Synthase Kinase 3 Beta complexed with Axin Peptide and Inhibitor 7d

OCA: Protected "3zdi" [edit=sysop:move=sysop]

2012-12-05T10:19:23Z

Protected "3zdi" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:19, 5 December 2012

OCA: New page: '''Unreleased structure''' The entry 3zdi is ON HOLD Authors: Oberholzer, A.E., Pearl, L.H. Description: Glycogen Synthase Kinase 3 Beta complexed with Axin Peptide and Inhibitor 7d

2012-12-05T10:19:22Z

New page: '''Unreleased structure''' The entry 3zdi is ON HOLD Authors: Oberholzer, A.E., Pearl, L.H. Description: Glycogen Synthase Kinase 3 Beta complexed with Axin Peptide and Inhibitor 7d

New page

'''Unreleased structure'''

The entry 3zdi is ON HOLD

Authors: Oberholzer, A.E., Pearl, L.H.

Description: Glycogen Synthase Kinase 3 Beta complexed with Axin Peptide and Inhibitor 7d