InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: APC

Summary

InnateDB Protein

IDBP-485228.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

APC

Protein Name

adenomatous polyposis coli

Synonyms

BTPS2; DP2; DP2.5; DP3; GS; PPP1R46;

Species

Homo sapiens

Ensembl Protein

ENSP00000427089

InnateDB Gene

IDBG-37007 (APC)

Protein Structure

UniProt Annotation

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. 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. {ECO:0000269PubMed:10947987, ECO:0000269PubMed:17599059, ECO:0000269PubMed:19151759, ECO:0000269PubMed:19893577, ECO:0000269PubMed:20937854}.

Subcellular Localization

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

Disease Associations

Familial adenomatous polyposis (FAP) [MIM:175100]: A cancer predisposition syndrome 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. {ECO:0000269PubMed:10470088, ECO:0000269PubMed:1338691, ECO:0000269PubMed:1338764, ECO:0000269PubMed:1338904, ECO:0000269PubMed:1651563, ECO:0000269PubMed:7833149, ECO:0000269PubMed:7833931, ECO:0000269PubMed:8990002}. Note=The disease is caused by mutations affecting the gene represented in this entry.Hereditary desmoid disease (HDD) [MIM:135290]: 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. {ECO:0000269PubMed:10782927, ECO:0000269PubMed:8940264}. Note=The disease is caused by mutations affecting the gene represented in this entry.Medulloblastoma (MDB) [MIM:155255]: Malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children. {ECO:0000269PubMed:10666372}. Note=The gene represented in this entry may be involved in disease pathogenesis.Mismatch repair cancer syndrome (MMRCS) [MIM:276300]: An autosomal recessive, rare, childhood cancer predisposition syndrome encompassing a broad tumor spectrum. This includes hematological malignancies, central nervous system tumors, Lynch syndrome-associated malignancies such as colorectal tumors as well as multiple intestinal polyps, embryonic tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature reminiscent of neurofibromatosis type 1, are often found as first manifestation of the underlying cancer. Areas of skin hypopigmentation have also been reported in MMRCS patients. {ECO:0000269PubMed:7661930}. Note=The gene represented in this entry may be involved in disease pathogenesis.Gastric cancer (GASC) [MIM:613659]: 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. Note=The gene represented in this entry may be involved in disease pathogenesis.Hepatocellular carcinoma (HCC) [MIM:114550]: A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. Note=The gene represented in this entry may be involved in disease pathogenesis.

Tissue Specificity

Expressed in a variety of tissues.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 194 experimentally validated interaction(s) in this database.
They are also associated with 44 interaction(s) predicted by orthology.

Experimentally validated
Total	194 [view]
Protein-Protein	192 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	44 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005488	binding
GO:0005515	protein binding
GO:0008013	beta-catenin binding
GO:0008017	microtubule binding
GO:0019887	protein kinase regulator activity
GO:0019901	protein kinase binding
GO:0045295	gamma-catenin binding
GO:0051010	microtubule plus-end binding

Biological Process

GO:0000281	mitotic cytokinesis
GO:0006461	protein complex assembly
GO:0006915	apoptotic process
GO:0006921	cellular component disassembly involved in execution phase of apoptosis
GO:0006974	cellular response to DNA damage stimulus
GO:0007026	negative regulation of microtubule depolymerization
GO:0007050	cell cycle arrest
GO:0007094	mitotic spindle assembly checkpoint
GO:0007155	cell adhesion
GO:0008285	negative regulation of cell proliferation
GO:0016055	Wnt signaling pathway
GO:0016477	cell migration
GO:0030335	positive regulation of cell migration
GO:0031274	positive regulation of pseudopodium assembly
GO:0032886	regulation of microtubule-based process
GO:0043065	positive regulation of apoptotic process
GO:0045732	positive regulation of protein catabolic process
GO:0045736	negative regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0051988	regulation of attachment of spindle microtubules to kinetochore
GO:0060070	canonical Wnt signaling pathway
GO:0070830	tight junction assembly
GO:0090090	negative regulation of canonical Wnt signaling pathway

Cellular Component

GO:0000776	kinetochore
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005813	centrosome
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005913	cell-cell adherens junction
GO:0005923	tight junction
GO:0016328	lateral plasma membrane
GO:0030027	lamellipodium
GO:0030877	beta-catenin destruction complex
GO:0032587	ruffle membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000225 Armadillo
IPR009223 Adenomatous polyposis coli protein, cysteine-rich repeat
IPR009224 SAMP
IPR009232 EB-1 binding
IPR009234 Adenomatous polyposis coli protein basic domain
IPR009240 Adenomatous polyposis coli protein, 15 residue repeat
IPR016024 Armadillo-type fold
IPR026831 Adenomatous polyposis coli domain

PFAM