1dk8

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[[Image:1dk8.jpg|left|200px]]
 
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{{Structure
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==CRYSTAL STRUCTURE OF THE RGS-HOMOLOGOUS DOMAIN OF AXIN==
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|PDB= 1dk8 |SIZE=350|CAPTION= <scene name='initialview01'>1dk8</scene>, resolution 1.57&Aring;
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<StructureSection load='1dk8' size='340' side='right'caption='[[1dk8]], [[Resolution|resolution]] 1.57&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>
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<table><tr><td colspan='2'>[[1dk8]] 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=1DK8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DK8 FirstGlance]. <br>
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|ACTIVITY=
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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]] 1.57&#8491;</td></tr>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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}}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1dk8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dk8 OCA], [https://pdbe.org/1dk8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dk8 RCSB], [https://www.ebi.ac.uk/pdbsum/1dk8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dk8 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dk/1dk8_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1dk8 ConSurf].
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<div style="clear:both"></div>
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'''CRYSTAL STRUCTURE OF THE RGS-HOMOLOGOUS DOMAIN OF AXIN'''
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==See Also==
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*[[Axin 3D structures|Axin 3D structures]]
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== References ==
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==Overview==
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<references/>
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Axin and the adenomatous polyposis coli (APC) tumor suppressor protein are components of the Wnt/Wingless growth factor signaling pathway. In the absence of Wnt signal, Axin and APC regulate cytoplasmic levels of the proto-oncogene beta-catenin through the formation of a large complex containing these three proteins, glycogen synthase kinase 3beta (GSK3beta) and several other proteins. Both Axin and APC are known to be critical for beta-catenin regulation, and truncations in APC that eliminate the Axin-binding site result in human cancers. A protease-resistant domain of Axin that contains the APC-binding site is a member of the regulators of G-protein signaling (RGS) superfamily. The crystal structures of this domain alone and in complex with an Axin-binding sequence from APC reveal that the Axin-APC interaction occurs at a conserved groove on a face of the protein that is distinct from the G-protein interface of classical RGS proteins. The molecular interactions observed in the Axin-APC complex provide a rationale for the evolutionary conservation seen in both proteins.
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__TOC__
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</StructureSection>
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==Disease==
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Known diseases associated with this structure: Caudal duplication anomaly OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603816 603816]], Hepatocellular carcinoma, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603816 603816]]
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==About this Structure==
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1DK8 is a [[Single protein]] structure of 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=1DK8 OCA].
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==Reference==
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Structural basis of the Axin-adenomatous polyposis coli interaction., Spink KE, Polakis P, Weis WI, EMBO J. 2000 May 15;19(10):2270-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10811618 10811618]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Polakis, P.]]
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[[Category: Polakis P]]
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[[Category: Spink, K E.]]
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[[Category: Spink KE]]
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[[Category: Weis, W I.]]
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[[Category: Weis WI]]
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[[Category: DTT]]
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[[Category: GOL]]
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[[Category: SO4]]
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[[Category: alpha-helix]]
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[[Category: pi-helix]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:39:52 2008''
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Current revision

CRYSTAL STRUCTURE OF THE RGS-HOMOLOGOUS DOMAIN OF AXIN

PDB ID 1dk8

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