2gl7 - Revision history

OCA at 09:28, 14 February 2024

OCA — Wed, 14 Feb 2024 09:28:35 GMT

←Older revision		Revision as of 09:28, 14 February 2024
Line 3:		Line 3:
	<StructureSection load='2gl7' size='340' side='right'caption='[[2gl7]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='2gl7' size='340' side='right'caption='[[2gl7]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2gl7]] is a 6 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=2GL7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GL7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2gl7]] 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=2GL7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GL7 FirstGlance]. <br>
-	</td></tr><tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>CTNNB1, CTNNB ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9606 HUMAN])~~, ~~TCF7L2, TCF4 (~~[~~https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN~~]~~), BCL9 ([https://www~~.~~ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info~~&~~srchmode=5&id=9606 HUMAN])~~</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]] 2.6Å</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=2gl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gl7 OCA], [https://pdbe.org/2gl7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gl7 RCSB], [https://www.ebi.ac.uk/pdbsum/2gl7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gl7 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=2gl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gl7 OCA], [https://pdbe.org/2gl7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gl7 RCSB], [https://www.ebi.ac.uk/pdbsum/2gl7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gl7 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[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> [[https://www.uniprot.org/uniprot/BCL9_HUMAN BCL9_HUMAN]] Note=A chromosomal aberration involving BCL9 is found in a patient with precusor B-cell acute lymphoblastic leukemia (ALL). Translocation t(1;14)(q21;q32). This translocation leaves the coding region intact, but may have pathogenic effects due to alterations in the expression level of BCL9. Several cases of translocations within the 3'-UTR of BCL9 have been found in B-cell malignancies. [[https://www.uniprot.org/uniprot/TF7L2_HUMAN TF7L2_HUMAN]] Note=Constitutive activation and subsequent transactivation of target genes may lead to the maintenance of stem-cell characteristics (cycling and longevity) in cells that should normally undergo terminal differentiation and constitute the primary transforming event in colorectal cancer (CRC). Genetic variations in TCF7L2 are associated with susceptibility to non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[https://omim.org/entry/125853 125853]]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance.<ref>PMID:16415884</ref>	+	[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>
	== Function ==		== Function ==
-	[[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> [[https://www.uniprot.org/uniprot/BCL9_HUMAN BCL9_HUMAN]] Involved in signal transduction through the Wnt pathway. Promotes beta-catenin's transcriptional activity (By similarity).<ref>PMID:11955446</ref> [[https://www.uniprot.org/uniprot/TF7L2_HUMAN TF7L2_HUMAN]] Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner. Acts as repressor in the absence of CTNNB1, and as activator in its presence. Activates transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CTNNB1. Expression of dominant-negative mutants results in cell-cycle arrest in G1. Necessary for the maintenance of the epithelial stem-cell compartment of the small intestine.<ref>PMID:9727977</ref> <ref>PMID:12408868</ref> <ref>PMID:12727872</ref> <ref>PMID:19443654</ref>	+	[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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 21:		Line 21:
	</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=2gl7 ConSurf].		</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=2gl7 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The canonical Wnt pathway plays critical roles in embryonic development, stem cell growth, and tumorigenesis. Stimulation of the Wnt pathway leads to the association of beta-catenin with Tcf and BCL9 in the nucleus, resulting in the transactivation of Wnt target genes. We have determined the crystal structure of a beta-catenin/BCL9/Tcf-4 triple complex at 2.6 A resolution. Our studies reveal that the beta-catenin binding site of BCL9 is distinct from that of most other beta-catenin partners and forms a good target for developing drugs that block canonical Wnt/beta-catenin signaling. The BCL9 beta-catenin binding domain (CBD) forms an alpha helix that binds to the first armadillo repeat of beta-catenin, which can be mutated to prevent beta-catenin binding to BCL9 without affecting cadherin or alpha-catenin binding. We also demonstrate that beta-catenin Y142 phosphorylation, which has been proposed to regulate BCL9-2 binding, does not directly affect the interaction of beta-catenin with either BCL9 or BCL9-2.
-
-	Crystal structure of a beta-catenin/BCL9/Tcf4 complex.,Sampietro J, Dahlberg CL, Cho US, Hinds TR, Kimelman D, Xu W Mol Cell. 2006 Oct 20;24(2):293-300. PMID:17052462<ref>PMID:17052462</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 2gl7" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 38:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Sampietro, J]]	+	[[Category: Sampietro J]]
-	~~[[Category: Armadillo repeat]]~~	+
-	~~[[Category: Protein complex]]~~	+
-	~~[[Category: Transcription~~]]	+

OCA at 19:08, 10 March 2021

OCA — Wed, 10 Mar 2021 19:08:18 GMT

←Older revision		Revision as of 19:08, 10 March 2021
Line 1:		Line 1:

	==Crystal Structure of a beta-catenin/BCL9/Tcf4 complex==		==Crystal Structure of a beta-catenin/BCL9/Tcf4 complex==
-	<StructureSection load='2gl7' size='340' side='right' caption='[[2gl7]], [[Resolution\|resolution]] 2.60Å' scene=''>	+	<StructureSection load='2gl7' size='340' side='right'caption='[[2gl7]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2gl7]] is a 6 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=2GL7 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2GL7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2gl7]] is a 6 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=2GL7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GL7 FirstGlance]. <br>
-	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CTNNB1, CTNNB ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TCF7L2, TCF4 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BCL9 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CTNNB1, CTNNB ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TCF7L2, TCF4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BCL9 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2gl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gl7 OCA], [~~http~~://pdbe.org/2gl7 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2gl7 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2gl7 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2gl7 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=2gl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gl7 OCA], [https://pdbe.org/2gl7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gl7 RCSB], [https://www.ebi.ac.uk/pdbsum/2gl7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gl7 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/CTNB1_HUMAN CTNB1_HUMAN]] Defects in CTNNB1 are associated with colorectal cancer (CRC) [MIM:[~~http~~://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:[~~http~~://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:[~~http~~://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:[~~http~~://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:[~~http~~://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> [[~~http~~://www.uniprot.org/uniprot/BCL9_HUMAN BCL9_HUMAN]] Note=A chromosomal aberration involving BCL9 is found in a patient with precusor B-cell acute lymphoblastic leukemia (ALL). Translocation t(1;14)(q21;q32). This translocation leaves the coding region intact, but may have pathogenic effects due to alterations in the expression level of BCL9. Several cases of translocations within the 3'-UTR of BCL9 have been found in B-cell malignancies. [[~~http~~://www.uniprot.org/uniprot/TF7L2_HUMAN TF7L2_HUMAN]] Note=Constitutive activation and subsequent transactivation of target genes may lead to the maintenance of stem-cell characteristics (cycling and longevity) in cells that should normally undergo terminal differentiation and constitute the primary transforming event in colorectal cancer (CRC). Genetic variations in TCF7L2 are associated with susceptibility to non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[~~http~~://omim.org/entry/125853 125853]]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance.<ref>PMID:16415884</ref>	+	[[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> [[https://www.uniprot.org/uniprot/BCL9_HUMAN BCL9_HUMAN]] Note=A chromosomal aberration involving BCL9 is found in a patient with precusor B-cell acute lymphoblastic leukemia (ALL). Translocation t(1;14)(q21;q32). This translocation leaves the coding region intact, but may have pathogenic effects due to alterations in the expression level of BCL9. Several cases of translocations within the 3'-UTR of BCL9 have been found in B-cell malignancies. [[https://www.uniprot.org/uniprot/TF7L2_HUMAN TF7L2_HUMAN]] Note=Constitutive activation and subsequent transactivation of target genes may lead to the maintenance of stem-cell characteristics (cycling and longevity) in cells that should normally undergo terminal differentiation and constitute the primary transforming event in colorectal cancer (CRC). Genetic variations in TCF7L2 are associated with susceptibility to non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[https://omim.org/entry/125853 125853]]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance.<ref>PMID:16415884</ref>
	== Function ==		== Function ==
-	[[~~http~~://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> [[~~http~~://www.uniprot.org/uniprot/BCL9_HUMAN BCL9_HUMAN]] Involved in signal transduction through the Wnt pathway. Promotes beta-catenin's transcriptional activity (By similarity).<ref>PMID:11955446</ref> [[~~http~~://www.uniprot.org/uniprot/TF7L2_HUMAN TF7L2_HUMAN]] Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner. Acts as repressor in the absence of CTNNB1, and as activator in its presence. Activates transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CTNNB1. Expression of dominant-negative mutants results in cell-cycle arrest in G1. Necessary for the maintenance of the epithelial stem-cell compartment of the small intestine.<ref>PMID:9727977</ref> <ref>PMID:12408868</ref> <ref>PMID:12727872</ref> <ref>PMID:19443654</ref>	+	[[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> [[https://www.uniprot.org/uniprot/BCL9_HUMAN BCL9_HUMAN]] Involved in signal transduction through the Wnt pathway. Promotes beta-catenin's transcriptional activity (By similarity).<ref>PMID:11955446</ref> [[https://www.uniprot.org/uniprot/TF7L2_HUMAN TF7L2_HUMAN]] Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner. Acts as repressor in the absence of CTNNB1, and as activator in its presence. Activates transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CTNNB1. Expression of dominant-negative mutants results in cell-cycle arrest in G1. Necessary for the maintenance of the epithelial stem-cell compartment of the small intestine.<ref>PMID:9727977</ref> <ref>PMID:12408868</ref> <ref>PMID:12727872</ref> <ref>PMID:19443654</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 32:		Line 32:

	==See Also==		==See Also==
-	*[[Catenin\|Catenin]]	+	*[[B-cell lymphoma proteins 3D structures\|B-cell lymphoma proteins 3D structures]]
		+	*[[Catenin 3D structures\|Catenin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 38:		Line 39:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Sampietro, J]]		[[Category: Sampietro, J]]
	[[Category: Armadillo repeat]]		[[Category: Armadillo repeat]]
	[[Category: Protein complex]]		[[Category: Protein complex]]
	[[Category: Transcription]]		[[Category: Transcription]]

OCA at 06:45, 20 June 2018

OCA — Wed, 20 Jun 2018 06:45:24 GMT

←Older revision		Revision as of 06:45, 20 June 2018
Line 1:		Line 1:
		+
	==Crystal Structure of a beta-catenin/BCL9/Tcf4 complex==		==Crystal Structure of a beta-catenin/BCL9/Tcf4 complex==
	<StructureSection load='2gl7' size='340' side='right' caption='[[2gl7]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='2gl7' size='340' side='right' caption='[[2gl7]], [[Resolution\|resolution]] 2.60Å' scene=''>
Line 4:		Line 5:
	<table><tr><td colspan='2'>[[2gl7]] is a 6 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=2GL7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GL7 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2gl7]] is a 6 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=2GL7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GL7 FirstGlance]. <br>
	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CTNNB1, CTNNB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TCF7L2, TCF4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BCL9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CTNNB1, CTNNB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TCF7L2, TCF4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BCL9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2gl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gl7 OCA], [http://pdbe.org/2gl7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2gl7 RCSB], [http://www.ebi.ac.uk/pdbsum/2gl7 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=2gl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gl7 OCA], [http://pdbe.org/2gl7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2gl7 RCSB], [http://www.ebi.ac.uk/pdbsum/2gl7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2gl7 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 14:		Line 15:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gl/2gl7_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gl/2gl7_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>

OCA at 14:25, 9 February 2016

OCA — Tue, 09 Feb 2016 14:25:18 GMT

←Older revision		Revision as of 14:25, 9 February 2016
Line 18:		Line 18:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</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/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</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=2gl7 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 23:07, 10 September 2015

OCA — Thu, 10 Sep 2015 23:07:54 GMT

←Older revision		Revision as of 23:07, 10 September 2015
Line 2:		Line 2:
	<StructureSection load='2gl7' size='340' side='right' caption='[[2gl7]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='2gl7' size='340' side='right' caption='[[2gl7]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2gl7]] is a 6 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=2GL7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GL7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2gl7]] is a 6 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=2GL7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GL7 FirstGlance]. <br>
-	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CTNNB1, CTNNB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~]), TCF7L2, TCF4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~]), BCL9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CTNNB1, CTNNB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TCF7L2, TCF4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), BCL9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2gl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gl7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2gl7 RCSB], [http://www.ebi.ac.uk/pdbsum/2gl7 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=2gl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gl7 OCA], [http://pdbe.org/2gl7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2gl7 RCSB], [http://www.ebi.ac.uk/pdbsum/2gl7 PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 28:		Line 28:
	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 2gl7" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 35:		Line 36:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Sampietro, J]]		[[Category: Sampietro, J]]
	[[Category: Armadillo repeat]]		[[Category: Armadillo repeat]]
	[[Category: Protein complex]]		[[Category: Protein complex]]
	[[Category: Transcription]]		[[Category: Transcription]]

OCA at 08:50, 16 January 2015

OCA — Fri, 16 Jan 2015 08:50:57 GMT

←Older revision		Revision as of 08:50, 16 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2gl7]] is a 6 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=2GL7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GL7 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2gl7]] is a 6 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=2GL7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GL7 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CTNNB1, CTNNB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), TCF7L2, TCF4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), BCL9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>	+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CTNNB1, CTNNB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), TCF7L2, TCF4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), BCL9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gl7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2gl7 RCSB], [http://www.ebi.ac.uk/pdbsum/2gl7 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=2gl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gl7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2gl7 RCSB], [http://www.ebi.ac.uk/pdbsum/2gl7 PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/CTNB1_HUMAN CTNB1_HUMAN]] Defects in CTNNB1 are associated with colorectal cancer (CRC) [MIM:[http://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:[http://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:[http://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:[http://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:[http://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> [[http://www.uniprot.org/uniprot/BCL9_HUMAN BCL9_HUMAN]] Note=A chromosomal aberration involving BCL9 is found in a patient with precusor B-cell acute lymphoblastic leukemia (ALL). Translocation t(1;14)(q21;q32). This translocation leaves the coding region intact, but may have pathogenic effects due to alterations in the expression level of BCL9. Several cases of translocations within the 3'-UTR of BCL9 have been found in B-cell malignancies. [[http://www.uniprot.org/uniprot/TF7L2_HUMAN TF7L2_HUMAN]] Note=Constitutive activation and subsequent transactivation of target genes may lead to the maintenance of stem-cell characteristics (cycling and longevity) in cells that should normally undergo terminal differentiation and constitute the primary transforming event in colorectal cancer (CRC). Genetic variations in TCF7L2 are associated with susceptibility to non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[http://omim.org/entry/125853 125853]]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance.<ref>PMID:16415884</ref>		[[http://www.uniprot.org/uniprot/CTNB1_HUMAN CTNB1_HUMAN]] Defects in CTNNB1 are associated with colorectal cancer (CRC) [MIM:[http://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:[http://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:[http://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:[http://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:[http://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> [[http://www.uniprot.org/uniprot/BCL9_HUMAN BCL9_HUMAN]] Note=A chromosomal aberration involving BCL9 is found in a patient with precusor B-cell acute lymphoblastic leukemia (ALL). Translocation t(1;14)(q21;q32). This translocation leaves the coding region intact, but may have pathogenic effects due to alterations in the expression level of BCL9. Several cases of translocations within the 3'-UTR of BCL9 have been found in B-cell malignancies. [[http://www.uniprot.org/uniprot/TF7L2_HUMAN TF7L2_HUMAN]] Note=Constitutive activation and subsequent transactivation of target genes may lead to the maintenance of stem-cell characteristics (cycling and longevity) in cells that should normally undergo terminal differentiation and constitute the primary transforming event in colorectal cancer (CRC). Genetic variations in TCF7L2 are associated with susceptibility to non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[http://omim.org/entry/125853 125853]]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance.<ref>PMID:16415884</ref>
Line 36:		Line 36:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Sampietro, J.]]	+	[[Category: Sampietro, J]]
	[[Category: Armadillo repeat]]		[[Category: Armadillo repeat]]
	[[Category: Protein complex]]		[[Category: Protein complex]]
	[[Category: Transcription]]		[[Category: Transcription]]

OCA at 08:28, 30 September 2014

OCA — Tue, 30 Sep 2014 08:28:24 GMT

←Older revision		Revision as of 08:28, 30 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_2gl7~~\| ~~PDB~~=2gl7 \| ~~SCENE~~= }}	+	==Crystal Structure of a beta-catenin/BCL9/Tcf4 complex==
-	===~~Crystal Structure~~ of a beta-catenin/~~BCL9~~/~~Tcf4 complex~~===	+	<StructureSection load='2gl7' size='340' side='right' caption='[[2gl7]], [[Resolution\|resolution]] 2.60Å' scene=''>
-	~~{{ABSTRACT_PUBMED_17052462}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2gl7]] is a 6 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=2GL7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GL7 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CTNNB1, CTNNB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), TCF7L2, TCF4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), BCL9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gl7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2gl7 RCSB], [http://www.ebi.ac.uk/pdbsum/2gl7 PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/CTNB1_HUMAN CTNB1_HUMAN]] Defects in CTNNB1 are associated with colorectal cancer (CRC) [MIM:[http://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:[http://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:[http://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:[http://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:[http://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> [[http://www.uniprot.org/uniprot/BCL9_HUMAN BCL9_HUMAN]] Note=A chromosomal aberration involving BCL9 is found in a patient with precusor B-cell acute lymphoblastic leukemia (ALL). Translocation t(1;14)(q21;q32). This translocation leaves the coding region intact, but may have pathogenic effects due to alterations in the expression level of BCL9. Several cases of translocations within the 3'-UTR of BCL9 have been found in B-cell malignancies. [[http://www.uniprot.org/uniprot/TF7L2_HUMAN TF7L2_HUMAN]] Note=Constitutive activation and subsequent transactivation of target genes may lead to the maintenance of stem-cell characteristics (cycling and longevity) in cells that should normally undergo terminal differentiation and constitute the primary transforming event in colorectal cancer (CRC). Genetic variations in TCF7L2 are associated with susceptibility to non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[http://omim.org/entry/125853 125853]]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance.<ref>PMID:16415884</ref>
		+	== Function ==
		+	[[http://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> [[http://www.uniprot.org/uniprot/BCL9_HUMAN BCL9_HUMAN]] Involved in signal transduction through the Wnt pathway. Promotes beta-catenin's transcriptional activity (By similarity).<ref>PMID:11955446</ref> [[http://www.uniprot.org/uniprot/TF7L2_HUMAN TF7L2_HUMAN]] Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner. Acts as repressor in the absence of CTNNB1, and as activator in its presence. Activates transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CTNNB1. Expression of dominant-negative mutants results in cell-cycle arrest in G1. Necessary for the maintenance of the epithelial stem-cell compartment of the small intestine.<ref>PMID:9727977</ref> <ref>PMID:12408868</ref> <ref>PMID:12727872</ref> <ref>PMID:19443654</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/gl/2gl7_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The canonical Wnt pathway plays critical roles in embryonic development, stem cell growth, and tumorigenesis. Stimulation of the Wnt pathway leads to the association of beta-catenin with Tcf and BCL9 in the nucleus, resulting in the transactivation of Wnt target genes. We have determined the crystal structure of a beta-catenin/BCL9/Tcf-4 triple complex at 2.6 A resolution. Our studies reveal that the beta-catenin binding site of BCL9 is distinct from that of most other beta-catenin partners and forms a good target for developing drugs that block canonical Wnt/beta-catenin signaling. The BCL9 beta-catenin binding domain (CBD) forms an alpha helix that binds to the first armadillo repeat of beta-catenin, which can be mutated to prevent beta-catenin binding to BCL9 without affecting cadherin or alpha-catenin binding. We also demonstrate that beta-catenin Y142 phosphorylation, which has been proposed to regulate BCL9-2 binding, does not directly affect the interaction of beta-catenin with either BCL9 or BCL9-2.

-	~~==Disease==~~	+	Crystal structure of a beta-catenin/BCL9/Tcf4 complex.,Sampietro J, Dahlberg CL, Cho US, Hinds TR, Kimelman D, Xu W Mol Cell. 2006 Oct 20;24(2):293-300. PMID:17052462<ref>PMID:17052462</ref>
-	[[http://www.uniprot.org/uniprot/CTNB1_HUMAN CTNB1_HUMAN]] Defects in CTNNB1 are associated with colorectal cancer (CRC) [MIM:[http://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:[http:~~//~~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:[http://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:[http://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~~:~~[http://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> [[http://www.uniprot.org/uniprot/BCL9_HUMAN BCL9_HUMAN]] Note=A chromosomal aberration involving BCL9 is found in a patient with precusor B-cell acute lymphoblastic leukemia (ALL). Translocation t(1;14)(q21;q32). This translocation leaves the coding region intact, but may have pathogenic effects due to alterations in the expression level of BCL9. Several cases of translocations within the 3'-UTR of BCL9 have been found in B-cell malignancies. [[http://www.uniprot.org/uniprot/TF7L2_HUMAN TF7L2_HUMAN]] Note=Constitutive activation and subsequent transactivation of target genes may lead to the maintenance of stem-cell characteristics (cycling and longevity) in cells that should normally undergo terminal differentiation and constitute the primary transforming event in colorectal cancer (CRC). Genetic variations in TCF7L2 are associated with susceptibility to non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[http://omim.org/entry/125853 125853]]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance.<ref>PMID:~~16415884~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http:~~/~~/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> [[http://www.uniprot.org/uniprot/BCL9_HUMAN BCL9_HUMAN]] Involved in signal transduction through the Wnt pathway. Promotes beta-catenin's transcriptional activity (By similarity).<ref>PMID:11955446</ref> [[http://www.uniprot.org/uniprot/TF7L2_HUMAN TF7L2_HUMAN]] Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner. Acts as repressor in the absence of CTNNB1, and as activator in its presence. Activates transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CTNNB1. Expression of dominant-negative mutants results in cell-cycle arrest in G1. Necessary for the maintenance of the epithelial stem-cell compartment of the small intestine.<ref>PMID:9727977</ref><ref>PMID:12408868</ref><ref>PMID:12727872</ref><ref>PMID:19443654</ref>	+	</div>
-		+
-	~~==About this Structure==~~	+
-	[[2gl7]] is a 6 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=2GL7 OCA].	+

	==See Also==		==See Also==
	*[[Catenin\|Catenin]]		*[[Catenin\|Catenin]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:017052462</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Sampietro, J.]]		[[Category: Sampietro, J.]]

OCA at 10:41, 24 March 2013

OCA — Sun, 24 Mar 2013 10:41:33 GMT

←Older revision		Revision as of 10:41, 24 March 2013
Line 1:		Line 1:
-	[[Image:2gl7.png\|left\|200px]]
-
	{{STRUCTURE_2gl7\| PDB=2gl7 \| SCENE= }}		{{STRUCTURE_2gl7\| PDB=2gl7 \| SCENE= }}
-
	===Crystal Structure of a beta-catenin/BCL9/Tcf4 complex===		===Crystal Structure of a beta-catenin/BCL9/Tcf4 complex===
		+	{{ABSTRACT_PUBMED_17052462}}

-	~~{{ABSTRACT_PUBMED_17052462}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/CTNB1_HUMAN CTNB1_HUMAN]] Defects in CTNNB1 are associated with colorectal cancer (CRC) [MIM:[http://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:[http://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:[http://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:[http://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:[http://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> [[http://www.uniprot.org/uniprot/BCL9_HUMAN BCL9_HUMAN]] Note=A chromosomal aberration involving BCL9 is found in a patient with precusor B-cell acute lymphoblastic leukemia (ALL). Translocation t(1;14)(q21;q32). This translocation leaves the coding region intact, but may have pathogenic effects due to alterations in the expression level of BCL9. Several cases of translocations within the 3'-UTR of BCL9 have been found in B-cell malignancies. [[http://www.uniprot.org/uniprot/TF7L2_HUMAN TF7L2_HUMAN]] Note=Constitutive activation and subsequent transactivation of target genes may lead to the maintenance of stem-cell characteristics (cycling and longevity) in cells that should normally undergo terminal differentiation and constitute the primary transforming event in colorectal cancer (CRC). Genetic variations in TCF7L2 are associated with susceptibility to non-insulin-dependent diabetes mellitus (NIDDM) [MIM:[http://omim.org/entry/125853 125853]]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance.<ref>PMID:16415884</ref>
		+
		+	==Function==
		+	[[http://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> [[http://www.uniprot.org/uniprot/BCL9_HUMAN BCL9_HUMAN]] Involved in signal transduction through the Wnt pathway. Promotes beta-catenin's transcriptional activity (By similarity).<ref>PMID:11955446</ref> [[http://www.uniprot.org/uniprot/TF7L2_HUMAN TF7L2_HUMAN]] Participates in the Wnt signaling pathway and modulates MYC expression by binding to its promoter in a sequence-specific manner. Acts as repressor in the absence of CTNNB1, and as activator in its presence. Activates transcription from promoters with several copies of the Tcf motif 5'-CCTTTGATC-3' in the presence of CTNNB1. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7L2/TCF4 and CTNNB1. Expression of dominant-negative mutants results in cell-cycle arrest in G1. Necessary for the maintenance of the epithelial stem-cell compartment of the small intestine.<ref>PMID:9727977</ref><ref>PMID:12408868</ref><ref>PMID:12727872</ref><ref>PMID:19443654</ref>

	==About this Structure==		==About this Structure==
Line 14:		Line 16:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:017052462</ref><references group="xtra"/>	+	<ref group="xtra">PMID:017052462</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Sampietro, J.]]		[[Category: Sampietro, J.]]

OCA at 14:08, 20 October 2012

OCA — Sat, 20 Oct 2012 14:08:36 GMT

←Older revision		Revision as of 14:08, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[2gl7]] is a 6 chain structure ~~of [[Catenin]]~~ 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=2GL7 OCA].	+	[[2gl7]] is a 6 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=2GL7 OCA].

	==See Also==		==See Also==

OCA at 14:11, 26 July 2012

OCA — Thu, 26 Jul 2012 14:11:26 GMT

←Older revision		Revision as of 14:11, 26 July 2012
Line 1:		Line 1:
	[[Image:2gl7.png\|left\|200px]]		[[Image:2gl7.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_2gl7", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_2gl7\| PDB=2gl7 \| SCENE= }}		{{STRUCTURE_2gl7\| PDB=2gl7 \| SCENE= }}

	===Crystal Structure of a beta-catenin/BCL9/Tcf4 complex===		===Crystal Structure of a beta-catenin/BCL9/Tcf4 complex===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_17052462}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 17052462 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_17052462}}		{{ABSTRACT_PUBMED_17052462}}

Line 22:		Line 11:

	==See Also==		==See Also==
-	*[[Catenin]]	+	*[[Catenin\|Catenin]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~17052462~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:017052462</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Sampietro, J.]]		[[Category: Sampietro, J.]]