1m5i - Revision history

OCA at 13:26, 13 March 2024

2024-03-13T13:26:49Z

←Older revision		Revision as of 13:26, 13 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1m5i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M5I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M5I FirstGlance]. <br>		<table><tr><td colspan='2'>[[1m5i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M5I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M5I 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=1m5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m5i OCA], [https://pdbe.org/1m5i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m5i RCSB], [https://www.ebi.ac.uk/pdbsum/1m5i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m5i 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=1m5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m5i OCA], [https://pdbe.org/1m5i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m5i RCSB], [https://www.ebi.ac.uk/pdbsum/1m5i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m5i ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/APC_HUMAN APC_HUMAN]] Defects in APC are a cause of familial adenomatous polyposis (FAP) [MIM:[https://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:[https://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:[https://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:[https://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:[https://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:[https://omim.org/entry/114550 114550]]. This defect includes also the disease entity termed hepatoblastoma.<ref>PMID:8940264</ref> <ref>PMID:10782927</ref>	+	[https://www.uniprot.org/uniprot/APC_HUMAN APC_HUMAN] Defects in APC are a cause of familial adenomatous polyposis (FAP) [MIM:[https://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:[https://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:[https://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:[https://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:[https://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:[https://omim.org/entry/114550 114550]. This defect includes also the disease entity termed hepatoblastoma.<ref>PMID:8940264</ref> <ref>PMID:10782927</ref>
	== Function ==		== Function ==
-	[[https://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/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>

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

OCA at 17:00, 7 September 2022

2022-09-07T17:00:18Z

←Older revision		Revision as of 17:00, 7 September 2022
Line 3:		Line 3:
	<StructureSection load='1m5i' size='340' side='right'caption='[[1m5i]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='1m5i' size='340' side='right'caption='[[1m5i]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1m5i]] is a 1 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=1M5I OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=1M5I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1m5i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M5I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M5I FirstGlance]. <br>
-	</td></tr>~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">APC ([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=1m5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m5i OCA], [https://pdbe.org/1m5i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m5i RCSB], [https://www.ebi.ac.uk/pdbsum/1m5i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m5i ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=1m5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m5i OCA], [~~http~~://pdbe.org/1m5i PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1m5i RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1m5i PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1m5i ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== 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>	+	[[https://www.uniprot.org/uniprot/APC_HUMAN APC_HUMAN]] Defects in APC are a cause of familial adenomatous polyposis (FAP) [MIM:[https://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:[https://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:[https://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:[https://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:[https://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:[https://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/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/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 APC (adenomatous polyposis coli) tumor suppressor protein has many different intracellular functions including a nuclear export activity. Only little is known about the molecular architecture of the 2843-amino acid APC protein. Guided by secondary structure predictions we identified a fragment close to the N-terminal end, termed APC-(129-250), as a soluble and protease-resistant domain. We solved the crystal structure of APC-(129-250), which is monomeric and consists of three alpha-helices forming two separate antiparallel coiled coils. APC-(129-250) includes the nuclear export signal NES-(165-174) at the C-terminal end of the first helix. Surprisingly, the conserved hydrophobic amino acids of NES-(165-174) are buried in one of the coiled coils and are thus not accessible for interaction with other proteins. We demonstrate the direct interaction of APC-(129-250) with the nuclear export factor chromosome maintenance region 1 (Crm-1). This interaction is enhanced by the small GTPase Ran in its activated GTP-bound form and also by a double mutation in APC-(129-250), which deletes two amino acids forming two of the major interhelical interactions within the coiled coil. These observations hint to a regulatory mechanism of the APC nuclear export activity by NES masking.	+

-	The coiled coil region (amino acids 129-250) of the tumor suppressor protein adenomatous polyposis coli (APC). Its structure and its interaction with chromosome maintenance region 1 (Crm-1).,Tickenbrock L, Cramer J, Vetter IR, Muller O J Biol Chem. 2002 Aug 30;277(35):32332-8. Epub 2002 Jun 17. PMID:12070164<ref>PMID:12070164</ref>	+	==See Also==
-		+	*[[Adenomatous polyposis coli\|Adenomatous polyposis coli]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class~~=~~"pdbe-citations 1m5i" style~~=~~"background-color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cramer, J]]	+	[[Category: Cramer J]]
-	[[Category: Mueller, O]]	+	[[Category: Mueller O]]
-	[[Category: Tickenbrock, L]]	+	[[Category: Tickenbrock L]]
-	[[Category: Vetter~~, I R]]~~	+	[[Category: Vetter IR]]
-	~~[[Category: Antitumor protein]]~~	+
-	~~[[Category: Coiled-coil~~]]	+

OCA at 08:33, 2 December 2020

2020-12-02T08:33:45Z

←Older revision		Revision as of 08:33, 2 December 2020
Line 1:		Line 1:

	==Crystal Structure of the coiled coil region 129-250 of the tumor suppressor gene product APC==		==Crystal Structure of the coiled coil region 129-250 of the tumor suppressor gene product APC==
-	<StructureSection load='1m5i' size='340' side='right' caption='[[1m5i]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='1m5i' size='340' side='right'caption='[[1m5i]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1m5i]] is a 1 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=1M5I OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1M5I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1m5i]] is a 1 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=1M5I OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1M5I FirstGlance]. <br>
	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">APC ([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">APC ([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=1m5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m5i OCA], [http://pdbe.org/1m5i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1m5i RCSB], [http://www.ebi.ac.uk/pdbsum/1m5i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1m5i ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1m5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m5i OCA], [http://pdbe.org/1m5i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1m5i RCSB], [http://www.ebi.ac.uk/pdbsum/1m5i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1m5i ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 25:		Line 25:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Cramer, J]]		[[Category: Cramer, J]]
	[[Category: Mueller, O]]		[[Category: Mueller, O]]

OCA at 10:43, 18 October 2017

2017-10-18T10:43:32Z

←Older revision		Revision as of 10:43, 18 October 2017
Line 1:		Line 1:
		+
	==Crystal Structure of the coiled coil region 129-250 of the tumor suppressor gene product APC==		==Crystal Structure of the coiled coil region 129-250 of the tumor suppressor gene product APC==
	<StructureSection load='1m5i' size='340' side='right' caption='[[1m5i]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='1m5i' size='340' side='right' caption='[[1m5i]], [[Resolution\|resolution]] 2.00Å' scene=''>
Line 4:		Line 5:
	<table><tr><td colspan='2'>[[1m5i]] is a 1 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=1M5I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1M5I FirstGlance]. <br>		<table><tr><td colspan='2'>[[1m5i]] is a 1 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=1M5I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1M5I FirstGlance]. <br>
	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">APC ([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">APC ([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=1m5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m5i OCA], [http://pdbe.org/1m5i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1m5i RCSB], [http://www.ebi.ac.uk/pdbsum/1m5i 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=1m5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m5i OCA], [http://pdbe.org/1m5i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1m5i RCSB], [http://www.ebi.ac.uk/pdbsum/1m5i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1m5i ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==

OCA at 17:29, 11 September 2015

2015-09-11T17:29:40Z

←Older revision		Revision as of 17:29, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='1m5i' size='340' side='right' caption='[[1m5i]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='1m5i' size='340' side='right' caption='[[1m5i]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1m5i]] is a 1 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=1M5I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1M5I FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1m5i]] is a 1 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=1M5I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1M5I FirstGlance]. <br>
-	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">APC ([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">APC ([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=1m5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m5i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1m5i RCSB], [http://www.ebi.ac.uk/pdbsum/1m5i 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=1m5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m5i OCA], [http://pdbe.org/1m5i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1m5i RCSB], [http://www.ebi.ac.uk/pdbsum/1m5i PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 18:		Line 18:
	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 1m5i" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Cramer, J]]		[[Category: Cramer, J]]
	[[Category: Mueller, O]]		[[Category: Mueller, O]]

OCA at 11:54, 18 December 2014

2014-12-18T11:54:14Z

←Older revision		Revision as of 11:54, 18 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_1m5i\| PDB=1m5i \| SCENE= }}~~	+	==Crystal Structure of the coiled coil region 129-250 of the tumor suppressor gene product APC==
-	===Crystal Structure of the coiled coil region 129-250 of the tumor suppressor gene product APC===	+	<StructureSection load='1m5i' size='340' side='right' caption='[[1m5i]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~{{ABSTRACT_PUBMED_12070164}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1m5i]] is a 1 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=1M5I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1M5I FirstGlance]. <br>
		+	</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">APC ([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=1m5i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m5i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1m5i RCSB], [http://www.ebi.ac.uk/pdbsum/1m5i 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/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 APC (adenomatous polyposis coli) tumor suppressor protein has many different intracellular functions including a nuclear export activity. Only little is known about the molecular architecture of the 2843-amino acid APC protein. Guided by secondary structure predictions we identified a fragment close to the N-terminal end, termed APC-(129-250), as a soluble and protease-resistant domain. We solved the crystal structure of APC-(129-250), which is monomeric and consists of three alpha-helices forming two separate antiparallel coiled coils. APC-(129-250) includes the nuclear export signal NES-(165-174) at the C-terminal end of the first helix. Surprisingly, the conserved hydrophobic amino acids of NES-(165-174) are buried in one of the coiled coils and are thus not accessible for interaction with other proteins. We demonstrate the direct interaction of APC-(129-250) with the nuclear export factor chromosome maintenance region 1 (Crm-1). This interaction is enhanced by the small GTPase Ran in its activated GTP-bound form and also by a double mutation in APC-(129-250), which deletes two amino acids forming two of the major interhelical interactions within the coiled coil. These observations hint to a regulatory mechanism of the APC nuclear export activity by NES masking.

-	~~==Disease==~~	+	The coiled coil region (amino acids 129-250) of the tumor suppressor protein adenomatous polyposis coli (APC). Its structure and its interaction with chromosome maintenance region 1 (Crm-1).,Tickenbrock L, Cramer J, Vetter IR, Muller O J Biol Chem. 2002 Aug 30;277(35):32332-8. Epub 2002 Jun 17. PMID:12070164<ref>PMID:12070164</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/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/>
-	[[1m5i]] is a 1 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=1M5I OCA].	+	__TOC__
-		+	</StructureSection>
-	~~==Reference~~==	+
-	~~<ref group="xtra">PMID:012070164</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Cramer, J.]]	+	[[Category: Cramer, J]]
-	[[Category: Mueller, O.]]	+	[[Category: Mueller, O]]
-	[[Category: Tickenbrock, L.]]	+	[[Category: Tickenbrock, L]]
-	[[Category: Vetter, I R.]]	+	[[Category: Vetter, I R]]
	[[Category: Antitumor protein]]		[[Category: Antitumor protein]]
	[[Category: Coiled-coil]]		[[Category: Coiled-coil]]

OCA at 00:05, 25 March 2013

2013-03-25T00:05:54Z

←Older revision		Revision as of 00:05, 25 March 2013
Line 1:		Line 1:
-	[[Image:1m5i.png\|left\|200px]]
-
	{{STRUCTURE_1m5i\| PDB=1m5i \| SCENE= }}		{{STRUCTURE_1m5i\| PDB=1m5i \| SCENE= }}
-
	===Crystal Structure of the coiled coil region 129-250 of the tumor suppressor gene product APC===		===Crystal Structure of the coiled coil region 129-250 of the tumor suppressor gene product APC===
		+	{{ABSTRACT_PUBMED_12070164}}

-	~~{{ABSTRACT_PUBMED_12070164}}~~	+	==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/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==
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	==Reference==		==Reference==
-	<ref group="xtra">PMID:012070164</ref><references group="xtra"/>	+	<ref group="xtra">PMID:012070164</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Cramer, J.]]		[[Category: Cramer, J.]]

OCA: Protected "1m5i" [edit=sysop:move=sysop]

2012-08-14T17:47:02Z

Protected "1m5i" [edit=sysop:move=sysop]

←Older revision

Revision as of 17:47, 14 August 2012

OCA at 17:47, 14 August 2012

2012-08-14T17:47:00Z

←Older revision		Revision as of 17:47, 14 August 2012
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	[[Image:1m5i.png\|left\|200px]]		[[Image:1m5i.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_1m5i", creates the "Structure Box" on the page.
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	{{STRUCTURE_1m5i\| PDB=1m5i \| SCENE= }}		{{STRUCTURE_1m5i\| PDB=1m5i \| SCENE= }}

	===Crystal Structure of the coiled coil region 129-250 of the tumor suppressor gene product APC===		===Crystal Structure of the coiled coil region 129-250 of the tumor suppressor gene product APC===

-
-	<!--
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	{{ABSTRACT_PUBMED_12070164}}		{{ABSTRACT_PUBMED_12070164}}
-
-	==Disease==
-	Known disease associated with this structure: Adenoma, periampullary OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611731 611731]], Adenomatous polyposis coli OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611731 611731]], Brain tumor-polyposis syndrome 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611731 611731]], Colorectal cancer, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611731 611731]], Desmoid disease, hereditary OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611731 611731]], Gardner syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611731 611731]], Gastric cancer, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611731 611731]], Hepatoblastoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611731 611731]]

	==About this Structure==		==About this Structure==
-	~~1M5I is a~~ [[~~Single protein~~]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M5I OCA].	+	[[1m5i]] is a 1 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=1M5I OCA].

	==Reference==		==Reference==
-	The coiled coil region (amino acids 129-250) of the tumor suppressor protein adenomatous polyposis coli (APC). Its structure and its interaction with chromosome maintenance region 1 (Crm-1)., Tickenbrock L, Cramer J, Vetter IR, Muller O, J Biol Chem. 2002 Aug 30;277(35):32332-8. Epub 2002 Jun 17. PMID:~~[http://www.ncbi.nlm.nih.gov~~/~~pubmed~~/~~12070164 12070164]~~	+	<ref group="xtra">PMID:012070164</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Single protein]]
	[[Category: Cramer, J.]]		[[Category: Cramer, J.]]
	[[Category: Mueller, O.]]		[[Category: Mueller, O.]]
	[[Category: Tickenbrock, L.]]		[[Category: Tickenbrock, L.]]
	[[Category: Vetter, I R.]]		[[Category: Vetter, I R.]]
		+	[[Category: Antitumor protein]]
	[[Category: Coiled-coil]]		[[Category: Coiled-coil]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 23:15:29 2008''

OCA at 20:15, 2 July 2008

2008-07-02T20:15:30Z

←Older revision		Revision as of 20:15, 2 July 2008
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		+	[[Image:1m5i.png\|left\|200px]]

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	{{STRUCTURE_1m5i\| PDB=1m5i \| SCENE= }}		{{STRUCTURE_1m5i\| PDB=1m5i \| SCENE= }}

-	~~'''~~Crystal Structure of the coiled coil region 129-250 of the tumor suppressor gene product APC~~'''~~	+	===Crystal Structure of the coiled coil region 129-250 of the tumor suppressor gene product APC===


-	~~==Overview==~~	+	<!--
-	The ~~APC (adenomatous polyposis coli) tumor suppressor protein has many different intracellular functions including a nuclear export activity. Only little is known about~~ the ~~molecular architecture of the 2843-amino acid APC protein. Guided by secondary structure predictions we identified a fragment close~~ to the ~~N-terminal end, termed APC-~~(~~129-250),~~ as ~~a soluble and protease-resistant domain~~. ~~We solved the crystal structure of APC-(129-250~~), ~~which~~ is ~~monomeric and consists of three alpha-helices forming two separate antiparallel coiled coils. APC-(129-250) includes~~ the ~~nuclear export signal NES-(165-174) at the C-terminal end of the first helix~~. ~~Surprisingly, the conserved hydrophobic amino acids of NES~~-~~(165~~-174) are buried in one of the coiled coils and are thus not accessible for interaction with other proteins. We demonstrate the direct interaction of APC-(129-250) with the nuclear export factor chromosome maintenance region 1 (Crm-1). This interaction is enhanced by the small GTPase Ran in its activated GTP-bound form and also by a double mutation in APC-(129-250), which deletes two amino acids forming two of the major interhelical interactions within the coiled coil. These observations hint to a regulatory mechanism of the APC nuclear export activity by NES masking.	+	The line below this paragraph, {{ABSTRACT_PUBMED_12070164}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 12070164 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_12070164}}

	==Disease==		==Disease==
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	[[Category: Vetter, I R.]]		[[Category: Vetter, I R.]]
	[[Category: Coiled-coil]]		[[Category: Coiled-coil]]
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sat May~~ ~~3 00~~:39:28 2008''	+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 23:15:29 2008''