1o9u

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (08:41, 6 November 2024) (edit) (undo)
 
(12 intermediate revisions not shown.)
Line 1: Line 1:
-
{{Seed}}
 
-
[[Image:1o9u.png|left|200px]]
 
-
<!--
+
==GLYCOGEN SYNTHASE KINASE 3 BETA COMPLEXED WITH AXIN PEPTIDE==
-
The line below this paragraph, containing "STRUCTURE_1o9u", creates the "Structure Box" on the page.
+
<StructureSection load='1o9u' size='340' side='right'caption='[[1o9u]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
-
You may change the PDB parameter (which sets the PDB file loaded into the applet)
+
== Structural highlights ==
-
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+
<table><tr><td colspan='2'>[[1o9u]] 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=1O9U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1O9U FirstGlance]. <br>
-
or leave the SCENE parameter empty for the default display.
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
-
-->
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADZ:9-METHYL-9H-PURIN-6-AMINE'>ADZ</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
-
{{STRUCTURE_1o9u| PDB=1o9u | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1o9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1o9u OCA], [https://pdbe.org/1o9u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1o9u RCSB], [https://www.ebi.ac.uk/pdbsum/1o9u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1o9u ProSAT]</span></td></tr>
 +
</table>
 +
== 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>
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/o9/1o9u_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1o9u ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Glycogen synthase kinase 3beta (GSK3beta) is a serine/threonine kinase involved in insulin, growth factor and Wnt signalling. In Wnt signalling, GSK3beta is recruited to a multiprotein complex via interaction with axin, where it hyperphosphorylates beta-catenin, marking it for ubiquitylation and destruction. We have now determined the crystal structure of GSK3beta in complex with a minimal GSK3beta-binding segment of axin, at 2.4 A resolution. The structure confirms the co-localization of the binding sites for axin and FRAT in the C-terminal domain of GSK3beta, but reveals significant differences in the interactions made by axin and FRAT, mediated by conformational plasticity of the 285-299 loop in GSK3beta. Detailed comparison of the axin and FRAT GSK3beta complexes allows the generation of highly specific mutations, which abrogate binding of one or the other. Quantitative analysis suggests that the interaction of GSK3beta with the axin scaffold enhances phosphorylation of beta-catenin by &gt;20 000-fold.
-
===GLYCOGEN SYNTHASE KINASE 3 BETA COMPLEXED WITH AXIN PEPTIDE===
+
Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex.,Dajani R, Fraser E, Roe SM, Yeo M, Good VM, Thompson V, Dale TC, Pearl LH EMBO J. 2003 Feb 3;22(3):494-501. PMID:12554650<ref>PMID:12554650</ref>
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 1o9u" style="background-color:#fffaf0;"></div>
-
<!--
+
==See Also==
-
The line below this paragraph, {{ABSTRACT_PUBMED_12554650}}, adds the Publication Abstract to the page
+
*[[Glycogen synthase kinase 3 3D structures|Glycogen synthase kinase 3 3D structures]]
-
(as it appears on PubMed at http://www.pubmed.gov), where 12554650 is the PubMed ID number.
+
== References ==
-
-->
+
<references/>
-
{{ABSTRACT_PUBMED_12554650}}
+
__TOC__
-
 
+
</StructureSection>
-
==About this Structure==
+
-
1O9U is a [[Protein complex]] structure of sequences 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=1O9U OCA].
+
-
 
+
-
==Reference==
+
-
Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex., Dajani R, Fraser E, Roe SM, Yeo M, Good VM, Thompson V, Dale TC, Pearl LH, EMBO J. 2003 Feb 3;22(3):494-501. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12554650 12554650]
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Non-specific serine/threonine protein kinase]]
+
[[Category: Large Structures]]
-
[[Category: Protein complex]]
+
[[Category: Dajani R]]
-
[[Category: Dajani, R.]]
+
[[Category: Pearl LH]]
-
[[Category: Pearl, L H.]]
+
[[Category: Roe SM]]
-
[[Category: Roe, S M.]]
+
-
[[Category: Alternative splicing]]
+
-
[[Category: Anti-oncogene]]
+
-
[[Category: Apoptosis]]
+
-
[[Category: Atp-binding]]
+
-
[[Category: Developmental protein]]
+
-
[[Category: Insulin pathway]]
+
-
[[Category: Kinase]]
+
-
[[Category: Multigene family]]
+
-
[[Category: Phosphorylation]]
+
-
[[Category: Serine/threonine -protein kinase]]
+
-
[[Category: Transferase]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:36:47 2008''
+

Current revision

GLYCOGEN SYNTHASE KINASE 3 BETA COMPLEXED WITH AXIN PEPTIDE

PDB ID 1o9u

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1o9u"
Personal tools