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. Associates with both microtubules and actin filaments, components of the cytoskeleton (PubMed:17293347). Plays a role in mediating the organization of F-actin into ordered bundles (PubMed:17293347). Functions downstream of Rho GTPases and DIAPH1 to selectively stabilize microtubules (By similarity). 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.SUBUNIT Forms homooligomers (Probable). Found in a complex consisting of ARHGEF4, APC and CTNNB1 (PubMed:10947987). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B (By similarity). The complex composed, at least, of APC, CTNNB1 and GSK3B interacts with JPT1; the interaction requires the inactive form of GSK3B (phosphorylated at 'Ser-9') (PubMed:25169422). Interacts with APC2 (PubMed:11691822). Interacts with DLG1 (via PDZ domains) and DLG3 (via PDZ domains) (PubMed:8638125, PubMed:9188857). Interacts with alpha- and beta-catenins (PubMed:8259519). Interacts with AXIN1 (via RGS domain) (PubMed:10811618). Interacts with ARHGEF4 (via N-terminus) (PubMed:10947987). Interacts (via C-terminal residues 2674-2843) with MAPRE1 (via C-terminal residues 206-211); the interaction inhibits association with and bundling of F-actin (PubMed:14514668, PubMed:17293347, PubMed:19632184). Interacts with MAPRE2 and MAPRE3 (via C-terminus) (PubMed:14514668). Interacts with DIAPH1; DIAPH1 acts as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration (By similarity). Interacts with DIAPH2 (By similarity). Interacts with SCRIB; may mediate APC targeting to adherens junctions of epithelial cells (PubMed:16611247). Interacts with SPATA13 (via N-terminus and SH3 domain) (PubMed:17599059). Interacts with ASAP1 (via SH3 domain) (PubMed:20509626). Interacts (at the cell membrane) with AMER1 and AMER2 (via ARM repeats) (PubMed:21498506, PubMed:22128170). Interacts with KHDRBS1 (PubMed:22000517). Interacts with actin; binds both to F-actin and actin filament bundles (PubMed:17293347).INTERACTION Associated with the microtubule network at the growing distal tip of microtubules (PubMed:19632184). MAPRE1 may be required for targeting to the growing microtubule plus ends (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).ALTERNATIVE PRODUCTS 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).DOMAIN The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to the growing microtubule plus ends.DOMAIN The basic region (residues 2167-2674) mediates the association with both microtubule and actin proteins and promotes the bundling of F-actin.PTM Phosphorylated; phosphorylation enhances the F-actin bundling activity (PubMed:17293347). Phosphorylated by GSK3B.PTM Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is facilitated by Axin. Deubiquitinated by ZRANB1/TRABID.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The gene represented in this entry may be involved in disease pathogenesis.DISEASE The gene represented in this entry may be involved in disease pathogenesis.DISEASE The gene represented in this entry may be involved in disease pathogenesis.DISEASE The gene represented in this entry may be involved in disease pathogenesis.MISCELLANEOUS 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 FAP1 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.MISCELLANEOUS Produced by alternative promoter usage.SIMILARITY Belongs to the adenomatous polyposis coli (APC) family.ONLINE INFORMATION Leiden Open Variation Database (LOVD)