APC

Adenomatous polyposis coli protein ;
Protein APC ;
Deleted in polyposis 2.5 ;

disease:APC mutations have led to some interesting observations. (1) the great majority of the mutations found to date would result in truncation of the APC product. (2) almost all the mutations have occurred within the first half of the coding sequence, and somatic mutations in colorectal tumors are further clustered in a particular region, called MCR (mutation cluster region). (3) most identified point mutations in the APC gene are transitions from cytosine to other nucleotides. (4) the location of germline mutations tends to correlate with the number of colorectal polyps in FAP patients. Inactivation of both alleles of the APC gene seems to be required as an early event to develop most adenomas and carcinomas in the colon and rectum as well as some of those in the stomach.,disease:Defects in APC are a cause of familial adenomatous polyposis (FAP) [MIM: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.,disease:Defects in APC are a cause of hereditary desmoid disease (HDD) [MIM:135290]; also called familial infiltrative fibromatosis (FIF). It 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.,disease:Defects in APC are a cause of medulloblastoma (MDB) [MIM: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).,disease:Defects in APC are a cause of Turcot syndrome [MIM:276300]. Turcot syndrome 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.,function:Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state.,online information:APC entry,online information:Familial adenomatous polyposis (FAP) website,online information:Information about APC mutations,online information:The Singapore human mutation and polymorphism database,PTM:Phosphorylated by GSK3B.,PTM:Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is facilitated by Axin. Deubiquitinated by ZRANB1/TRABID.,similarity:Belongs to the adenomatous polyposis coli (APC) family.,similarity:Contains 7 ARM repeats.,subunit:Forms homooligomers. Interacts with DIAPH1 and DIAPH2 (By similarity). Interacts with PDZ domains of DLG1 and DLG3. Associates with catenins. Binds axin. Interacts with the N-terminus of ARHGEF4, and the C-terminus of MAPRE1, MAPRE2 and MAPRE3. Found in a complex consisting of ARHGEF4, APC and CTNNB1. Interacts with APC2.,tissue specificity:Expressed in a variety of tissues.,

cell cycle checkpoint, regulation of cyclin-dependent protein kinase activity, M phase of mitotic cell cycle, mitotic cell cycle, M phase, nuclear division, cytokinesis after mitosis, cell morphogenesis, cell morphogenesis involved in differentiation, cytokinesis, eye development, urogenital system development, cell activation, kidney development,hair follicle development, immune system development, leukocyte differentiation, regulation of myeloid leukocyte differentiation, regionalization, protein complex assembly, negative regulation of protein kinase activity, cell motion,response to DNA damage stimulus, negative regulation of microtubule depolymerization, cell-cell junction assembly,cell cycle, cell cycle arrest, mitosis, regulation of mitosis, mitotic metaphase/anaphase transition, mitotic cell cycle checkpoint, mitotic cell cycle spindle assembly checkpoint, cell adhesion, establishment or maintenance of cell polarity,cell surface receptor linked signal transduction, regulation of mitotic cell cycle, pattern specification process, ectoderm development, axonogenesis, sensory organ development, negative regulation of cell proliferation, epidermis development, axis specification, regulation of catabolic process, positive regulation of catabolic process,anterior/posterior pattern formation, dorsal/ventral pattern formation, proximal/distal pattern formation, negative regulation of signal transduction, regulation of cell cycle process, positive regulation of macromolecule metabolic process, regulation of protein kinase cascade, positive regulation of organelle organization, negative regulation of organelle organization, negative regulation of cell communication, negative regulation of protein kinase cascade,regulation of cell death, positive regulation of cell death, negative regulation of cell cycle process, Wnt receptor signaling pathway, cell migration, regulation of phosphate metabolic process, cellular homeostasis, stem cell maintenance, cell cycle process, cell cycle phase, molting cycle process, hair cycle process, biological adhesion, cell projection organization, regulation of mitotic metaphase/anaphase transition, hemopoiesis, lymphocyte differentiation,regulation of Wnt receptor signaling pathway, regulation of cell adhesion, negative regulation of Wnt receptor signaling pathway, neuron differentiation, T cell differentiation, regulation of ossification, regulation of cell migration,positive regulation of cell migration, regulation of epithelial cell differentiation, positive regulation of epithelial cell differentiation, regulation of microtubule polymerization or depolymerization, negative regulation of microtubule polymerization or depolymerization, positive regulation of microtubule polymerization or depolymerization, regulation of microtubule polymerization, regulation of microtubule depolymerization, positive regulation of microtubule polymerization, neuron projection development, regulation of pseudopodium assembly, positive regulation of pseudopodium assembly, positive regulation of protein complex assembly, regulation of cell projection organization,positive regulation of cell projection organization, spindle checkpoint, regulation of protein polymerization, positive regulation of protein polymerization, regulation of protein localization, regulation of microtubule-based process,cellular component morphogenesis, cell part morphogenesis, regulation of organelle organization, T cell differentiation in the thymus, cytokinesis during cell cycle, cellular response to stress, negative regulation of kinase activity, cell junction assembly, cell junction organization, somatic stem cell maintenance, regulation of locomotion, positive regulation of locomotion, T cell activation, regulation of cell proliferation, regulation of protein catabolic process,molting cycle, regulation of phosphorylation, regulation of odontogenesis, negative regulation of odontogenesis,response to drug, homeostatic process, hair cycle, regulation of apoptosis, camera-type eye development, positive regulation of apoptosis, negative regulation of apoptosis, regulation of programmed cell death, positive regulation of programmed cell death, negative regulation of programmed cell death, negative regulation of catalytic activity,negative regulation of protein complex disassembly, regulation of protein complex disassembly, regulation of protein complex assembly, apical junction assembly, regulation of MAPKKK cascade, negative regulation of MAPKKK cascade,regulation of kinase activity, skin development, macromolecular complex subunit organization, regulation of cellular component biogenesis, negative regulation of molecular function, cell-cell junction organization, leukocyte activation,negative regulation of cell differentiation, positive regulation of cell differentiation, regulation of myeloid cell differentiation, regulation of osteoblast differentiation, regulation of osteoclast differentiation, positive regulation of protein catabolic process, negative regulation of cyclin-dependent protein kinase activity, positive regulation of cell adhesion, negative regulation of cell cycle, negative regulation of mitosis, negative regulation of mitotic metaphase/anaphase transition, regulation of protein kinase activity, lymphocyte activation, muscle maintenance,organelle fission, hemopoietic or lymphoid organ development, thymus development, neuron development, cell morphogenesis involved in neuron differentiation, neuron projection morphogenesis, cell projection morphogenesis,stem cell differentiation, stem cell development, cell motility, regulation of epithelial cell proliferation, negative regulation of epithelial cell proliferation, positive regulation of developmental process, negative regulation of cellular component organization, positive regulation of cellular component organization, regulation of phosphorus metabolic process, positive regulation of protein metabolic process, regulation of cell motion, positive regulation of cell motion,chromosome organization, cell division, regulation of cell division, regulation of transferase activity, negative regulation of transferase activity, regulation of cytoskeleton organization, negative regulation of cytoskeleton organization, positive regulation of cytoskeleton organization, localization of cell, regulation of cell cycle, positive regulation of cell division, regulation of nuclear division, negative regulation of nuclear division, regulation of chromosome segregation, regulation of attachment of spindle microtubules to kinetochore, retina development in camera-type eye, Wnt receptor signaling pathway through beta-catenin, anatomical structure homeostasis, regulation of cellular localization, regulation of cell projection assembly, negative regulation of cell death, macromolecular complex assembly, protein complex biogenesis, regulation of microtubule cytoskeleton organization, tight junction assembly,

Cell junction, adherens junction . Cytoplasm, cytoskeleton . Cell projection, lamellipodium . Cell projection, ruffle membrane . Cytoplasm . Cell membrane . Associated with the microtubule network at the growing distal tip of microtubules (PubMed:19632184). Accumulates in the lamellipodium and ruffle membrane in response to hepatocyte growth factor (HGF) treatment (PubMed:19151759). The MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the phosphorylated form to the cell membrane (PubMed:20937854). .

Expressed in a variety of tissues: brain, small intestine, colon, thymus, skeletal muscle, heart, prostate, lung, spleen, ovary, testis kidney, placenta, blood and liver (PubMed:21643010, PubMed:27217144). Isoform 1A: Very strongly expressed in brain but has relatively low expression levels in other tissues (PubMed:19527921, PubMed:21643010, PubMed:27217144). Isoform 1B: Predominant form in all tissues except for brain, including gastric mucosa and blood (PubMed:19527921, PubMed:21643010, PubMed:27217144).