View source for 3qhe


==Crystal structure of the complex between the armadillo repeat domain of adenomatous polyposis coli and the tyrosine-rich domain of Sam68==
<StructureSection load='3qhe' size='340' side='right'caption='[[3qhe]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3qhe]] is a 4 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=3QHE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QHE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</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=3qhe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qhe OCA], [https://pdbe.org/3qhe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qhe RCSB], [https://www.ebi.ac.uk/pdbsum/3qhe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qhe ProSAT]</span></td></tr>
</table>
== 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> 
== 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Adenomatous polyposis coli (APC) is a tumor suppressor protein commonly mutated in colorectal tumors. APC plays important roles in Wnt signaling and other cellular processes. Here, we present the crystal structure of the armadillo repeat (Arm) domain of APC, which facilitates the binding of APC to various proteins. APC-Arm forms a superhelix with a positively charged groove. We also determined the structure of the complex of APC-Arm with the tyrosine-rich (YY) domain of the Src-associated in mitosis, 68 kDa protein (Sam68), which regulates TCF-1 alternative splicing. Sam68-YY forms numerous interactions with the residues on the groove and is thereby fixed in a bent conformation. We assessed the effects of mutations and phosphorylation on complex formation between APC-Arm and Sam68-YY. Structural comparisons revealed different modes of ligand recognition between the Arm domains of APC and other Arm-containing proteins.

Crystal structures of the armadillo repeat domain of adenomatous polyposis coli and its complex with the tyrosine-rich domain of sam68.,Morishita EC, Murayama K, Kato-Murayama M, Ishizuka-Katsura Y, Tomabechi Y, Hayashi T, Terada T, Handa N, Shirouzu M, Akiyama T, Yokoyama S Structure. 2011 Oct 12;19(10):1496-508. PMID:22000517<ref>PMID:22000517</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3qhe" style="background-color:#fffaf0;"></div>

==See Also==
*[[Adenomatous polyposis coli|Adenomatous polyposis coli]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Akiyama T]]
[[Category: Handa N]]
[[Category: Ishizuku-Katsura Y]]
[[Category: Kato-Murayama M]]
[[Category: Morishita ECJ]]
[[Category: Murayama K]]
[[Category: Shirouzu M]]
[[Category: Terada T]]
[[Category: Tomabechi Y]]
[[Category: Yokoyama S]]