4g69 - Revision history

OCA at 15:39, 14 March 2024

OCA — Thu, 14 Mar 2024 15:39:42 GMT

←Older revision		Revision as of 15:39, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4g69]] 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=4G69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G69 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4g69]] 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=4G69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G69 FirstGlance]. <br>
-	</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=4g69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g69 OCA], [https://pdbe.org/4g69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g69 RCSB], [https://www.ebi.ac.uk/pdbsum/4g69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g69 ProSAT]</span></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]] 2Å</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=4g69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g69 OCA], [https://pdbe.org/4g69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g69 RCSB], [https://www.ebi.ac.uk/pdbsum/4g69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g69 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/DLG1_HUMAN DLG1_HUMAN] Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel.<ref>PMID:10656683</ref> <ref>PMID:12445884</ref> <ref>PMID:14699157</ref> <ref>PMID:15263016</ref> <ref>PMID:19213956</ref> <ref>PMID:20605917</ref>		[https://www.uniprot.org/uniprot/DLG1_HUMAN DLG1_HUMAN] Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel.<ref>PMID:10656683</ref> <ref>PMID:12445884</ref> <ref>PMID:14699157</ref> <ref>PMID:15263016</ref> <ref>PMID:19213956</ref> <ref>PMID:20605917</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The membrane associated guanylate kinase (MAGUK) family member, human Discs Large 1 (hDlg1) uses a PDZ domain array to interact with the polarity determinant, the Adenomatous Polyposis Coli (APC) microtubule plus end binding protein. The hDLG1-APC complex mediates a dynamic attachment between microtubule plus ends and polarized cortical determinants in epithelial cells, stem cells, and neuronal synapses. Using its multi-domain architecture, hDlg1 both scaffolds and regulates the polarity factors it engages. Molecular details underlying the hDlg1-APC interaction and insight into how the hDlg1 PDZ array may cluster and regulate its binding factors remain to be determined. Here, I present the crystal structure of the hDlg1 PDZ2-APC complex and the molecular determinants that mediate APC binding. The hDlg1 PDZ2-APC complex also provides insight into potential modes of ligand-dependent PDZ domain clustering that may parallel Dlg scaffold regulatory mechanisms. The hDlg1 PDZ2-APC complex presented here represents a core biological complex that bridges polarized cortical determinants with the dynamic microtubule cytoskeleton.
-
-	Structure of the Human Discs Large 1 PDZ2- Adenomatous Polyposis Coli Cytoskeletal Polarity Complex: Insight into Peptide Engagement and PDZ Clustering.,Slep KC PLoS One. 2012;7(11):e50097. doi: 10.1371/journal.pone.0050097. Epub 2012 Nov 19. PMID:23185543<ref>PMID:23185543</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4g69" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 20:26, 19 October 2022

OCA — Wed, 19 Oct 2022 20:26:30 GMT

←Older revision		Revision as of 20:26, 19 October 2022
Line 1:		Line 1:

	==Structure of the Human Discs Large 1 PDZ2 - Adenomatous Polyposis Coli Cytoskeletal Polarity Complex==		==Structure of the Human Discs Large 1 PDZ2 - Adenomatous Polyposis Coli Cytoskeletal Polarity Complex==
-	<StructureSection load='4g69' size='340' side='right' caption='[[4g69]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='4g69' size='340' side='right'caption='[[4g69]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4g69]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G69 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4G69 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4g69]] 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=4G69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G69 FirstGlance]. <br>
-	</td></tr>~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DLG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+	</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=4g69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g69 OCA], [https://pdbe.org/4g69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g69 RCSB], [https://www.ebi.ac.uk/pdbsum/4g69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g69 ProSAT]</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=4g69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g69 OCA], [~~http~~://pdbe.org/4g69 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4g69 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4g69 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4g69 ProSAT]</span></td></tr>	+
	</table>		</table>
-	== Disease ==
-	[[http://www.uniprot.org/uniprot/APC_HUMAN APC_HUMAN]] Defects in APC are a cause of familial adenomatous polyposis (FAP) [MIM:[http://omim.org/entry/175100 175100]]; which includes also Gardner syndrome (GS). FAP and GS contribute to tumor development in patients with uninherited forms of colorectal cancer. FAP is characterized by adenomatous polyps of the colon and rectum, but also of upper gastrointestinal tract (ampullary, duodenal and gastric adenomas). This is a viciously premalignant disease with one or more polyps progressing through dysplasia to malignancy in untreated gene carriers with a median age at diagnosis of 40 years.<ref>PMID:8940264</ref> <ref>PMID:10782927</ref> <ref>PMID:1651563</ref> <ref>PMID:1338904</ref> <ref>PMID:1338691</ref> <ref>PMID:1338764</ref> <ref>PMID:7833149</ref> <ref>PMID:7833931</ref> <ref>PMID:8990002</ref> <ref>PMID:10470088</ref> Defects in APC are a cause of hereditary desmoid disease (HDD) [MIM:[http://omim.org/entry/135290 135290]]; also known as familial infiltrative fibromatosis (FIF). HDD is an autosomal dominant trait with 100% penetrance and possible variable expression among affected relatives. HDD patients show multifocal fibromatosis of the paraspinal muscles, breast, occiput, arms, lower ribs, abdominal wall, and mesentery. Desmoid tumors appears also as a complication of familial adenomatous polyposis.<ref>PMID:8940264</ref> <ref>PMID:10782927</ref> Defects in APC 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. Although the majority of medulloblastomas occur sporadically, some manifest within familial cancer syndromes such as Turcot syndrome and basal cell nevus syndrome (Gorlin syndrome).<ref>PMID:8940264</ref> <ref>PMID:10782927</ref> <ref>PMID:10666372</ref> Defects in APC are a cause of mismatch repair cancer syndrome (MMRCS) [MIM:[http://omim.org/entry/276300 276300]]; also known as Turcot syndrome or brain tumor-polyposis syndrome 1 (BTPS1). MMRCS is an autosomal dominant disorder characterized by malignant tumors of the brain associated with multiple colorectal adenomas. Skin features include sebaceous cysts, hyperpigmented and cafe au lait spots.<ref>PMID:8940264</ref> <ref>PMID:10782927</ref> <ref>PMID:7661930</ref> Defects in APC are a cause of gastric cancer (GASC) [MIM:[http://omim.org/entry/613659 613659]]; also called gastric cancer intestinal or stomach cancer. Gastric cancer is a malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.<ref>PMID:8940264</ref> <ref>PMID:10782927</ref> Defects in APC are a cause of hepatocellular carcinoma (HCC) [MIM:[http://omim.org/entry/114550 114550]]. This defect includes also the disease entity termed hepatoblastoma.<ref>PMID:8940264</ref> <ref>PMID:10782927</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/DLG1_HUMAN DLG1_HUMAN]] Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel.<ref>PMID:10656683</ref> <ref>PMID:12445884</ref> <ref>PMID:14699157</ref> <ref>PMID:15263016</ref> <ref>PMID:19213956</ref> <ref>PMID:20605917</ref> [[http://www.uniprot.org/uniprot/APC_HUMAN APC_HUMAN]] Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane and this localization of MACF1 is critical for its function in microtubule stabilization.<ref>PMID:10947987</ref> <ref>PMID:17599059</ref> <ref>PMID:19893577</ref> <ref>PMID:19151759</ref> <ref>PMID:20937854</ref>	+	[https://www.uniprot.org/uniprot/DLG1_HUMAN DLG1_HUMAN] Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel.<ref>PMID:10656683</ref> <ref>PMID:12445884</ref> <ref>PMID:14699157</ref> <ref>PMID:15263016</ref> <ref>PMID:19213956</ref> <ref>PMID:20605917</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 21:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Slep, K C~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Adenomatous polyposis coli]]~~	+	[[Category: Slep KC]]
-	~~[[Category: Adherens junction]]~~	+
-	~~[[Category: Maguk]]~~	+
-	~~[[Category: Membrane protein-signaling protein complex]]~~	+
-	~~[[Category: Pdz]]~~	+
-	~~[[Category: Polarity]]~~	+
-	~~[[Category: Tetramethylrhodamine~~]]	+

OCA at 08:26, 5 August 2016

OCA — Fri, 05 Aug 2016 08:26:43 GMT

←Older revision		Revision as of 08:26, 5 August 2016
Line 1:		Line 1:
		+
	==Structure of the Human Discs Large 1 PDZ2 - Adenomatous Polyposis Coli Cytoskeletal Polarity Complex==		==Structure of the Human Discs Large 1 PDZ2 - Adenomatous Polyposis Coli Cytoskeletal Polarity Complex==
	<StructureSection load='4g69' size='340' side='right' caption='[[4g69]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='4g69' size='340' side='right' caption='[[4g69]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4g69]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G69 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G69 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4g69]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G69 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G69 FirstGlance]. <br>
-	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DLG1 ([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">DLG1 ([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=4g69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g69 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4g69 RCSB], [http://www.ebi.ac.uk/pdbsum/4g69 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=4g69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g69 OCA], [http://pdbe.org/4g69 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4g69 RCSB], [http://www.ebi.ac.uk/pdbsum/4g69 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4g69 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 18:		Line 19:
	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 4g69" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Slep, K C]]		[[Category: Slep, K C]]
	[[Category: Adenomatous polyposis coli]]		[[Category: Adenomatous polyposis coli]]

OCA at 11:11, 21 December 2014

OCA — Sun, 21 Dec 2014 11:11:26 GMT

←Older revision		Revision as of 11:11, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4g69\| PDB=4g69 \| SCENE= }}~~	+	==Structure of the Human Discs Large 1 PDZ2 - Adenomatous Polyposis Coli Cytoskeletal Polarity Complex==
-	===Structure of the Human Discs Large 1 PDZ2 - Adenomatous Polyposis Coli Cytoskeletal Polarity Complex===	+	<StructureSection load='4g69' size='340' side='right' caption='[[4g69]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23185543}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4g69]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G69 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G69 FirstGlance]. <br>
		+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DLG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4g69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g69 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4g69 RCSB], [http://www.ebi.ac.uk/pdbsum/4g69 PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/APC_HUMAN APC_HUMAN]] Defects in APC are a cause of familial adenomatous polyposis (FAP) [MIM:[http://omim.org/entry/175100 175100]]; which includes also Gardner syndrome (GS). FAP and GS contribute to tumor development in patients with uninherited forms of colorectal cancer. FAP is characterized by adenomatous polyps of the colon and rectum, but also of upper gastrointestinal tract (ampullary, duodenal and gastric adenomas). This is a viciously premalignant disease with one or more polyps progressing through dysplasia to malignancy in untreated gene carriers with a median age at diagnosis of 40 years.<ref>PMID:8940264</ref> <ref>PMID:10782927</ref> <ref>PMID:1651563</ref> <ref>PMID:1338904</ref> <ref>PMID:1338691</ref> <ref>PMID:1338764</ref> <ref>PMID:7833149</ref> <ref>PMID:7833931</ref> <ref>PMID:8990002</ref> <ref>PMID:10470088</ref> Defects in APC are a cause of hereditary desmoid disease (HDD) [MIM:[http://omim.org/entry/135290 135290]]; also known as familial infiltrative fibromatosis (FIF). HDD is an autosomal dominant trait with 100% penetrance and possible variable expression among affected relatives. HDD patients show multifocal fibromatosis of the paraspinal muscles, breast, occiput, arms, lower ribs, abdominal wall, and mesentery. Desmoid tumors appears also as a complication of familial adenomatous polyposis.<ref>PMID:8940264</ref> <ref>PMID:10782927</ref> Defects in APC 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. Although the majority of medulloblastomas occur sporadically, some manifest within familial cancer syndromes such as Turcot syndrome and basal cell nevus syndrome (Gorlin syndrome).<ref>PMID:8940264</ref> <ref>PMID:10782927</ref> <ref>PMID:10666372</ref> Defects in APC are a cause of mismatch repair cancer syndrome (MMRCS) [MIM:[http://omim.org/entry/276300 276300]]; also known as Turcot syndrome or brain tumor-polyposis syndrome 1 (BTPS1). MMRCS is an autosomal dominant disorder characterized by malignant tumors of the brain associated with multiple colorectal adenomas. Skin features include sebaceous cysts, hyperpigmented and cafe au lait spots.<ref>PMID:8940264</ref> <ref>PMID:10782927</ref> <ref>PMID:7661930</ref> Defects in APC are a cause of gastric cancer (GASC) [MIM:[http://omim.org/entry/613659 613659]]; also called gastric cancer intestinal or stomach cancer. Gastric cancer is a malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.<ref>PMID:8940264</ref> <ref>PMID:10782927</ref> Defects in APC are a cause of hepatocellular carcinoma (HCC) [MIM:[http://omim.org/entry/114550 114550]]. This defect includes also the disease entity termed hepatoblastoma.<ref>PMID:8940264</ref> <ref>PMID:10782927</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/DLG1_HUMAN DLG1_HUMAN]] Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel.<ref>PMID:10656683</ref> <ref>PMID:12445884</ref> <ref>PMID:14699157</ref> <ref>PMID:15263016</ref> <ref>PMID:19213956</ref> <ref>PMID:20605917</ref> [[http://www.uniprot.org/uniprot/APC_HUMAN APC_HUMAN]] Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane and this localization of MACF1 is critical for its function in microtubule stabilization.<ref>PMID:10947987</ref> <ref>PMID:17599059</ref> <ref>PMID:19893577</ref> <ref>PMID:19151759</ref> <ref>PMID:20937854</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The membrane associated guanylate kinase (MAGUK) family member, human Discs Large 1 (hDlg1) uses a PDZ domain array to interact with the polarity determinant, the Adenomatous Polyposis Coli (APC) microtubule plus end binding protein. The hDLG1-APC complex mediates a dynamic attachment between microtubule plus ends and polarized cortical determinants in epithelial cells, stem cells, and neuronal synapses. Using its multi-domain architecture, hDlg1 both scaffolds and regulates the polarity factors it engages. Molecular details underlying the hDlg1-APC interaction and insight into how the hDlg1 PDZ array may cluster and regulate its binding factors remain to be determined. Here, I present the crystal structure of the hDlg1 PDZ2-APC complex and the molecular determinants that mediate APC binding. The hDlg1 PDZ2-APC complex also provides insight into potential modes of ligand-dependent PDZ domain clustering that may parallel Dlg scaffold regulatory mechanisms. The hDlg1 PDZ2-APC complex presented here represents a core biological complex that bridges polarized cortical determinants with the dynamic microtubule cytoskeleton.

-	~~==Disease==~~	+	Structure of the Human Discs Large 1 PDZ2- Adenomatous Polyposis Coli Cytoskeletal Polarity Complex: Insight into Peptide Engagement and PDZ Clustering.,Slep KC PLoS One. 2012;7(11):e50097. doi: 10.1371/journal.pone.0050097. Epub 2012 Nov 19. PMID:23185543<ref>PMID:23185543</ref>
-	~~[[http://www.uniprot.org/uniprot/APC_HUMAN APC_HUMAN]] Defects in APC are a cause~~ of ~~familial adenomatous polyposis (FAP) [MIM~~:~~[http://omim.org/entry/175100 175100]]; which includes also Gardner syndrome (GS). FAP~~ and ~~GS contribute to tumor development in patients with uninherited forms of colorectal cancer~~. ~~FAP is characterized by adenomatous polyps of the colon and rectum~~, ~~but also of upper gastrointestinal tract (ampullary, duodenal and gastric adenomas)~~. This is a viciously premalignant disease with one or more polyps progressing through dysplasia to malignancy in untreated gene carriers with a median age at diagnosis of 40 years.<ref>PMID:8940264</ref><ref>PMID:10782927</ref><ref>PMID:1651563</ref><ref>PMID:1338904</ref><ref>PMID:1338691</ref><ref>PMID:1338764</ref><ref>PMID:7833149</ref><ref>PMID:7833931</ref><ref>PMID:8990002</ref><ref>PMID:10470088</ref> Defects in APC are a cause of hereditary desmoid disease (HDD) [MIM:[http://omim.org/entry/135290 135290]]; ~~also known as familial infiltrative fibromatosis~~ (~~FIF~~). HDD is an autosomal dominant trait with 100% penetrance and possible variable expression among affected relatives. HDD patients show multifocal fibromatosis of the paraspinal muscles, breast, occiput, arms, lower ribs, abdominal wall, and mesentery. Desmoid tumors appears also as a complication of familial adenomatous polyposis.<ref>PMID:~~8940264</ref><ref>PMID:10782927</ref> Defects in APC 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. Although the majority of medulloblastomas occur sporadically, some manifest within familial cancer syndromes such as Turcot syndrome and basal cell nevus syndrome (Gorlin syndrome).<ref>PMID:~~8940264</ref><ref>PMID:10782927</ref><ref>PMID:10666372</ref> Defects in APC are a cause of mismatch repair cancer syndrome (MMRCS) [MIM:[http://omim~~.~~org~~/~~entry/276300 276300]]; also known as Turcot syndrome or brain tumor-polyposis syndrome 1 (BTPS1)~~. ~~MMRCS is an autosomal dominant disorder characterized by malignant tumors of the brain associated with multiple colorectal adenomas~~. ~~Skin features include sebaceous cysts, hyperpigmented and cafe au lait spots~~.~~<ref>PMID:8940264</ref><ref>PMID:10782927</ref><ref>PMID:7661930</ref> Defects in APC are a cause of gastric cancer (GASC) [MIM:[http://omim~~.org/entry/613659 613659]]; also called gastric cancer intestinal or stomach cancer. Gastric cancer is a malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.<ref>PMID:8940264</ref><ref>PMID:10782927</ref> Defects in APC are a cause of hepatocellular carcinoma (HCC) [MIM:[http://omim.org/entry/114550 114550]]. This defect includes also the disease entity termed hepatoblastoma.<ref>PMID:8940264</ref><ref>PMID:~~10782927~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http:~~/~~/www.uniprot.org/uniprot/DLG1_HUMAN DLG1_HUMAN]] Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels~~, ~~receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play~~ a ~~role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability~~ of ~~cardiac myocytes by modulating~~ the ~~functional expression of Kv4 channels~~. ~~Functional regulator of Kv1~~.5 channel.<ref>PMID:10656683</ref><ref>PMID:12445884</ref><ref>PMID:14699157</ref><ref>PMID:15263016</ref><ref>PMID:19213956</ref><ref>PMID:20605917</ref> [[http://www.uniprot.org/uniprot/APC_HUMAN APC_HUMAN]] Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane and this localization of ~~MACF1 is critical for its function in microtubule stabilization~~.<~~ref~~>~~PMID:10947987~~</~~ref~~>~~<ref>PMID:17599059</ref><ref>PMID:19893577</ref><ref>PMID:19151759</ref><ref>PMID:20937854</ref>~~	+	</div>
-		+	== References ==
-	==~~About this Structure==~~	+	<references/>
-	[[4g69]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G69 OCA].	+	__TOC__
-		+	</StructureSection>
-	~~==Reference~~==	+
-	<references ~~group="xtra"~~/><~~references~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Slep, K C.]]	+	[[Category: Slep, K C]]
	[[Category: Adenomatous polyposis coli]]		[[Category: Adenomatous polyposis coli]]
	[[Category: Adherens junction]]		[[Category: Adherens junction]]

OCA at 18:33, 24 March 2013

OCA — Sun, 24 Mar 2013 18:33:22 GMT

←Older revision		Revision as of 18:33, 24 March 2013
Line 1:		Line 1:
-	[[Image:4g69.jpg\|left\|200px]]
-
	{{STRUCTURE_4g69\| PDB=4g69 \| SCENE= }}		{{STRUCTURE_4g69\| PDB=4g69 \| SCENE= }}
-
	===Structure of the Human Discs Large 1 PDZ2 - Adenomatous Polyposis Coli Cytoskeletal Polarity Complex===		===Structure of the Human Discs Large 1 PDZ2 - Adenomatous Polyposis Coli Cytoskeletal Polarity Complex===
-
	{{ABSTRACT_PUBMED_23185543}}		{{ABSTRACT_PUBMED_23185543}}
		+
		+	==Disease==
		+	[[http://www.uniprot.org/uniprot/APC_HUMAN APC_HUMAN]] Defects in APC are a cause of familial adenomatous polyposis (FAP) [MIM:[http://omim.org/entry/175100 175100]]; which includes also Gardner syndrome (GS). FAP and GS contribute to tumor development in patients with uninherited forms of colorectal cancer. FAP is characterized by adenomatous polyps of the colon and rectum, but also of upper gastrointestinal tract (ampullary, duodenal and gastric adenomas). This is a viciously premalignant disease with one or more polyps progressing through dysplasia to malignancy in untreated gene carriers with a median age at diagnosis of 40 years.<ref>PMID:8940264</ref><ref>PMID:10782927</ref><ref>PMID:1651563</ref><ref>PMID:1338904</ref><ref>PMID:1338691</ref><ref>PMID:1338764</ref><ref>PMID:7833149</ref><ref>PMID:7833931</ref><ref>PMID:8990002</ref><ref>PMID:10470088</ref> Defects in APC are a cause of hereditary desmoid disease (HDD) [MIM:[http://omim.org/entry/135290 135290]]; also known as familial infiltrative fibromatosis (FIF). HDD is an autosomal dominant trait with 100% penetrance and possible variable expression among affected relatives. HDD patients show multifocal fibromatosis of the paraspinal muscles, breast, occiput, arms, lower ribs, abdominal wall, and mesentery. Desmoid tumors appears also as a complication of familial adenomatous polyposis.<ref>PMID:8940264</ref><ref>PMID:10782927</ref> Defects in APC 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. Although the majority of medulloblastomas occur sporadically, some manifest within familial cancer syndromes such as Turcot syndrome and basal cell nevus syndrome (Gorlin syndrome).<ref>PMID:8940264</ref><ref>PMID:10782927</ref><ref>PMID:10666372</ref> Defects in APC are a cause of mismatch repair cancer syndrome (MMRCS) [MIM:[http://omim.org/entry/276300 276300]]; also known as Turcot syndrome or brain tumor-polyposis syndrome 1 (BTPS1). MMRCS is an autosomal dominant disorder characterized by malignant tumors of the brain associated with multiple colorectal adenomas. Skin features include sebaceous cysts, hyperpigmented and cafe au lait spots.<ref>PMID:8940264</ref><ref>PMID:10782927</ref><ref>PMID:7661930</ref> Defects in APC are a cause of gastric cancer (GASC) [MIM:[http://omim.org/entry/613659 613659]]; also called gastric cancer intestinal or stomach cancer. Gastric cancer is a malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.<ref>PMID:8940264</ref><ref>PMID:10782927</ref> Defects in APC are a cause of hepatocellular carcinoma (HCC) [MIM:[http://omim.org/entry/114550 114550]]. This defect includes also the disease entity termed hepatoblastoma.<ref>PMID:8940264</ref><ref>PMID:10782927</ref>
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/DLG1_HUMAN DLG1_HUMAN]] Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel.<ref>PMID:10656683</ref><ref>PMID:12445884</ref><ref>PMID:14699157</ref><ref>PMID:15263016</ref><ref>PMID:19213956</ref><ref>PMID:20605917</ref> [[http://www.uniprot.org/uniprot/APC_HUMAN APC_HUMAN]] Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane and this localization of MACF1 is critical for its function in microtubule stabilization.<ref>PMID:10947987</ref><ref>PMID:17599059</ref><ref>PMID:19893577</ref><ref>PMID:19151759</ref><ref>PMID:20937854</ref>

	==About this Structure==		==About this Structure==
	[[4g69]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G69 OCA].		[[4g69]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G69 OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Slep, K C.]]		[[Category: Slep, K C.]]

OCA at 21:14, 12 December 2012

OCA — Wed, 12 Dec 2012 21:14:59 GMT

←Older revision		Revision as of 21:14, 12 December 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4g69.jpg\|left\|200px]]

-	~~The entry~~ 4g69 ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4g69\| PDB=4g69 \| SCENE= }}

-	~~Authors: Slep, K.C.~~	+	===Structure of the Human Discs Large 1 PDZ2 - Adenomatous Polyposis Coli Cytoskeletal Polarity Complex===

-	~~Description:~~ Structure ~~of the Human Discs Large 1 PDZ2~~ -Adenomatous ~~Polyposis Coli Cytoskeletal~~ Polarity ~~Complex~~	+	{{ABSTRACT_PUBMED_23185543}}
		+
		+	==About this Structure==
		+	[[4g69]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G69 OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Slep, K C.]]
		+	[[Category: Adenomatous polyposis coli]]
		+	[[Category: Adherens junction]]
		+	[[Category: Maguk]]
		+	[[Category: Membrane protein-signaling protein complex]]
		+	[[Category: Pdz]]
		+	[[Category: Polarity]]
		+	[[Category: Tetramethylrhodamine]]

OCA at 06:29, 17 October 2012

OCA — Wed, 17 Oct 2012 06:29:40 GMT

←Older revision		Revision as of 06:29, 17 October 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4g69 is ON HOLD	+	The entry 4g69 is ON HOLD until Paper Publication

	Authors: Slep, K.C.		Authors: Slep, K.C.

	Description: Structure of the Human Discs Large 1 PDZ2 -Adenomatous Polyposis Coli Cytoskeletal Polarity Complex		Description: Structure of the Human Discs Large 1 PDZ2 -Adenomatous Polyposis Coli Cytoskeletal Polarity Complex

OCA: Protected "4g69" [edit=sysop:move=sysop]

OCA — Wed, 25 Jul 2012 06:53:55 GMT

Protected "4g69" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:53, 25 July 2012

OCA: New page: '''Unreleased structure''' The entry 4g69 is ON HOLD Authors: Slep, K.C. Description: Structure of the Human Discs Large 1 PDZ2 -Adenomatous Polyposis Coli Cytoskeletal Polarity Comple...

OCA — Wed, 25 Jul 2012 06:53:54 GMT

New page: '''Unreleased structure''' The entry 4g69 is ON HOLD Authors: Slep, K.C. Description: Structure of the Human Discs Large 1 PDZ2 -Adenomatous Polyposis Coli Cytoskeletal Polarity Comple...

New page

'''Unreleased structure'''

The entry 4g69 is ON HOLD

Authors: Slep, K.C.

Description: Structure of the Human Discs Large 1 PDZ2 -Adenomatous Polyposis Coli Cytoskeletal Polarity Complex