1jpw

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{{Seed}}
 
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[[Image:1jpw.png|left|200px]]
 
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==Crystal Structure of a Human Tcf-4 / beta-Catenin Complex==
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The line below this paragraph, containing "STRUCTURE_1jpw", creates the "Structure Box" on the page.
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<StructureSection load='1jpw' size='340' side='right'caption='[[1jpw]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1jpw]] is a 6 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=1JPW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JPW FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.5&#8491;</td></tr>
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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=1jpw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jpw OCA], [https://pdbe.org/1jpw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jpw RCSB], [https://www.ebi.ac.uk/pdbsum/1jpw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jpw ProSAT]</span></td></tr>
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{{STRUCTURE_1jpw| PDB=1jpw | SCENE= }}
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/CTNB1_HUMAN CTNB1_HUMAN] Defects in CTNNB1 are associated with colorectal cancer (CRC) [MIM:[https://omim.org/entry/114500 114500]. Note=Activating mutations in CTNNB1 have oncogenic activity resulting in tumor development. Somatic mutations are found in various tumor types, including colon cancers, ovarian and prostate carcinomas, hepatoblastoma (HB), hepatocellular carcinoma (HCC). HBs are malignant embryonal tumors mainly affecting young children in the first three years of life. Defects in CTNNB1 are a cause of pilomatrixoma (PTR) [MIM:[https://omim.org/entry/132600 132600]; a common benign skin tumor.<ref>PMID:11703283</ref> <ref>PMID:12027456</ref> <ref>PMID:10192393</ref> Defects in CTNNB1 are a cause of medulloblastoma (MDB) [MIM:[https://omim.org/entry/155255 155255]. MDB is a malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children.<ref>PMID:12027456</ref> <ref>PMID:10666372</ref> Defects in CTNNB1 are a cause of susceptibility to ovarian cancer (OC) [MIM:[https://omim.org/entry/167000 167000]. Ovarian cancer common malignancy originating from ovarian tissue. Although many histologic types of ovarian neoplasms have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Note=A chromosomal aberration involving CTNNB1 is found in salivary gland pleiomorphic adenomas, the most common benign epithelial tumors of the salivary gland. Translocation t(3;8)(p21;q12) with PLAG1. Defects in CTNNB1 may be a cause of mesothelioma malignant (MESOM) [MIM:[https://omim.org/entry/156240 156240]. An aggressive neoplasm of the serosal lining of the chest. It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos.<ref>PMID:11464291</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/CTNB1_HUMAN CTNB1_HUMAN] Key downstream component of the canonical Wnt signaling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Involved in the regulation of cell adhesion. Acts as a negative regulator of centrosome cohesion. Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization. Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2.<ref>PMID:17524503</ref> <ref>PMID:18086858</ref> <ref>PMID:18957423</ref> <ref>PMID:21262353</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/jp/1jpw_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=1jpw ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The multifunctional protein beta-catenin is important for cell adhesion, because it binds cadherins, and the Wnt signal transduction pathway, where it interacts with the Adenomatous polyposis coli (APC) protein and TCF/Lef family transcription factors. Mutations in APC or in beta-catenin are estimated to trigger formation of over 90% of all colon cancers. In colonic epithelia, these mutations produce elevated levels of Tcf4-beta-catenin, which stimulates a transcriptional response that initiates polyp formation and eventually malignant growth. Thus, disruption of the Tcf4-beta-catenin interaction may be an attractive goal for therapeutic intervention. Here we describe the crystal structure of a human Tcf4-beta-catenin complex and compare it with recent structures of beta-catenin in complex with Xenopus Tcf3 (XTcf3) and mammalian E-cadherin. The structure reveals anticipated similarities with the closely related XTcf3 complex but unexpectedly lacks one component observed in the XTcf3 structure.
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===Crystal Structure of a Human Tcf-4 / beta-Catenin Complex===
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Structure of a human Tcf4-beta-catenin complex.,Poy F, Lepourcelet M, Shivdasani RA, Eck MJ Nat Struct Biol. 2001 Dec;8(12):1053-7. PMID:11713476<ref>PMID:11713476</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1jpw" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_11713476}}, adds the Publication Abstract to the page
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*[[Catenin 3D structures|Catenin 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 11713476 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_11713476}}
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__TOC__
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</StructureSection>
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==About this Structure==
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1JPW 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=1JPW OCA].
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==Reference==
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Structure of a human Tcf4-beta-catenin complex., Poy F, Lepourcelet M, Shivdasani RA, Eck MJ, Nat Struct Biol. 2001 Dec;8(12):1053-7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11713476 11713476]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Eck, M J.]]
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[[Category: Eck MJ]]
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[[Category: Lepourcelet, M.]]
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[[Category: Lepourcelet M]]
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[[Category: Poy, F.]]
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[[Category: Poy F]]
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[[Category: Shivdasani, R A.]]
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[[Category: Shivdasani RA]]
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[[Category: Armadillo repeat]]
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[[Category: Beta-catenin]]
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[[Category: Colon cancer]]
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[[Category: Tcf]]
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[[Category: Tcf4]]
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[[Category: Transcription factor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 20:37:03 2008''
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Current revision

Crystal Structure of a Human Tcf-4 / beta-Catenin Complex

PDB ID 1jpw

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