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FLASH GENE
Symbol APC contributors: shn/pgu - updated : 05-05-2017
HGNC name adenomatosis polyposis coli
HGNC id 583
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvessel   moderately
Hearing/Equilibriumearinnercochlea highly
Lymphoid/Immunelymph node   moderately
Nervousbrain   highly
 nerve   highly
Reproductivefemale systembreastmammary gland moderately
 male systemtestis  moderately
Respiratoryrespiratory tractlarynx  moderately
Urinarybladder   moderately
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadipose  highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • seven repeats of the arm F motif (from Drosophila armadillo segment polarity gene), localizing at the tips of microtubule bundles, for CTNNB1 binding
  • an armadillo repeat domain (APC(Arm+) formed a complex with DVL2
  • fragment close to the N-terminal end, termed APC-(129-250), as a soluble and protease-resistant domain
  • a nuclear export signal NES-(165-174) at the C-terminal end
  • 20 amino acid beta-catenin binding repeats
  • SAMP motifs mediating axin binding, and binding to the SH3 domains of DDEF1 and DDEF2, providing new insights into the functions of APC in cell migration
  • conjugated PhosphoP
    mono polymer homomer , dimer
    HOMOLOGY
    interspecies ortholog to Apc, Rattus norvegicus
    ortholog to Apc, Mus musculus
    ortholog to APC, Pan troglodytes
    ortholog to apc, Danio rerio
    Homologene
    FAMILY
  • adenomatous polyposis coli (APC) family
  • CATEGORY adhesion , transcription factor , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome,kinetochore
    text
  • centriolar
  • localize at the centrosome, and in mitotic cells contributes to formation of the mitotic spindle
  • basic FUNCTION
  • tumor suppressor gene involved in cell adhesion and active cell migration
  • acts as an antagonist of the Wnt signaling pathway
  • modulating the frequency and classes of mutation leading to colon polyps
  • playing a role in the development
  • controlling retinoic acid biosynthesis and in promoting a retinoid induced program of colonocyte differentiation
  • regulates microtubule dynamics during mitosis
  • acting as a negative regulator of Wnt/Wingless signaling
  • promoting Wingless transduction through down-regulation of axin
  • acts as a cofactor of conductin/axin for beta-catenin degradation
  • functions in the Wnt signalling pathway to regulate the degradation of beta-catenin, an important regulator of cytoskeletal function, a role in kinetochore-microtubule attachment and may contribute to chromosomal instability in cancer cells
  • role in chromosome segregation
  • plays a pivotal role in polarized cell migration
  • function of APC in antagonizing beta-catenin involves C-terminal binding protein
  • implicated in the presynaptic localization of alpha7 nicotinic acetylcholine receptor
  • regulates actin cytoskeletal organization and is required for hepatocyte growth factor-induced cell migration, in cooperation with SPATA13 and PPP1R9B
  • stimulates the GEF activity of ARHGEF4 and SPATA13
  • with DVL1 mediate a WNT5A-FZD2 signal to focal adhesions to regulate cell-substrate adhesions and migration
  • multiple betacat-binding sites act additively to fine-tune signaling via cytoplasmic retention (
  • APC and CCNB3 are potentially important markers for identifying endoderm cells differentiated from human embryonic stem cells (hESCs), and they can play important roles in the differentiation of endoderm cells from hESCs or in human endoderm development for pancreas
  • is a crucial regulator of Intermediate filaments (IFs) organization, confirming its fundamental role in the coordinated regulation of cytoskeletons
  • is a negative regulator of the WNT pathway and a well known multifunctional protein
  • is a positive regulator of centrosome MT initial assembly, suggesting that this process is disrupted by cancer mutations
  • APC helps drive mitochondria to the membrane to supply energy for cellular processes such as directed cell migration, a process disrupted by cancer mutations
  • CELLULAR PROCESS cell life, cell death/apoptosis
    cell migration & motility
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling sensory transduction/vision
    a component
  • AMER2-MAPRE1-APC complex regulates cell migration by altering microtubule stability
  • SMAD7-APC complex links the TGFBR1 to the microtubule system to regulate directed cellular extension and migratory responses evoked by TGFB1
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • microtubule-associated protein RP/EB family member 1, MAPRE1 (
  • alpha-catenin, beta-catenin, and plakoglobin (
  • junction plakoglobin, JUP (
  • glycogen synthase kinase 3 beta, GSK3beta
  • neuronal and endocrine dig,NE-dlg (
  • DAP-1 (
  • CDC20 and MAD2 (
  • protein phosphatase 2A (PP2A) regulatory subunit, B56 (
  • RP1 (
  • Rac-specific guanine nucleotide exchange factor GEF
  • protein tyrosine phosphatase PTP-BL
  • budding uninhibited by benzimidazoles 1, BUB1 and budding uninhibited by benzimidazoles 3, BUB3 during mitosis
  • rotein phosphatase 2 regulatory subunit B' alpha, PPP2R5A
  • seven in absentia homolog 1, SIAH1 (
  • kinesin superfamily (KIF) 3A-KIF3B proteins, microtubule plus-end-directed motor proteins and the kinesin superfamily-associated protein 3 (KAP3)
  • nuclear export factor chromosome maintenance region 1, Crm-1
  • casein kinase 2, CK2
  • dynactin
  • mucin 1 cell surface associated, MUC1
  • transcription factor AP-2 alpha, TFAP2A (
  • C-terminal binding protein, CtBP
  • IQ motif containing GTPase activating protein 1, IQGAP1
  • budding uninhibited by benzimidazoles 1 homolog beta, BUB1B
  • 14-3-3 sigma
  • TRAF-binding protein domain, TRABID
  • ARHGEF4 and SPATA13
  • APC interacts with RANBP2, a microtubule-binding nucleoporin
  • CCNA2/CDK2 specifically associates with APC in late G2 phase and phosphorylates it at Ser-1360, located in the mutation cluster region of APC
  • bound to DVL1 directly and this complex played a role in the WNT5A-dependent formation of cell-substrate adhesions and polarized cell migration
  • Axin (
  • SMAD7 and MAPK14 mitogen-activated protein kinase together regulate the expression of APC and cell migration in prostate cancer cells in response to TGFB1 stimulation
  • involved in protein modification, ubiquitin cycle
  • HECTD1 promotes the APC-AXIN1 interaction to negatively regulate WNT signaling
  • in cancer cells, NRIP1 stimulated APC transcription and inhibited CTNNB1 activation and target gene expression
  • APC interactions with the mitochondrial kinesin-motor complex RHOT1/TRAK2 that were mediated by the APC C-terminus
  • cell & other
  • microtubule cytoskeleton (
  • REGULATION
    Phosphorylated by GSK-3beta (
    Other deubiquitylated by TRAF-binding protein domain, TRABID (
    ASSOCIATED DISORDERS
    corresponding disease(s) CHRPE , HDD , FAP , CLSS2
    related resource Adenomatous polyposis coli
    Familial Adenomatous Polyposis at GeneDis
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in prostate carcinoma
    tumoral   LOH    
    in pancreatoblastoma
    tumoral       loss of function
    in colon, thyroid, stomach, intestine cancer, hepatocellular carcinoma, in progression
    constitutional     --low  
    in lung carcinoma
    tumoral     --other  
    loss of APC through aberrant methylation is associated with the aggressive behavior of both sporadic and familial breast cancer
    constitutional       loss of function
    tissue-dependent consequences of APC inactivation on proliferation and differentiation of ciliated cell progenitors by coordinating WNT and NOTCH1 signaling
    Susceptibility to autism spectrum disorder
    Variant & Polymorphism SNP SNP 8636C>A in the 3'-untranslated region associated with autism spectrum disorder (ASD)
    Candidate gene
    Marker
  • APC I1307K variant is a reliable marker for overall cancer risk
  • strong associations between APC, GSTP1 and SOCS1 gene promoter methylation and the risk of HCC, suggesting these to be promising biomarkers for hepatocellular carcinoma (HCC)
  • APC promoter methylation may be the potential testing for prostate cancer diagnosis
  • Therapy target
    ANIMAL & CELL MODELS
  • Mice with Apc nonsense mutation have multiple intestinal neoplasia
  • mice with homozygous truncated mutation in Apc gene die in utero before day 8 of gestation. Heterozygous mice develop multiple polyps mostly in the small intestine
  • chain-termination mutation in exon 15 of the mouse Apc gene leads to development of intestinal tumors
  • predisposes to mammary carcinomas and focal alveolar hyperplasias in mice harboring Apc gene point mutation
  • Dpc4 mutation into the Apc(delta716) knockout mice lead to development of intestinal polyps and more malignant tumors
  • treatment of Apc delta716 mice with a novel COX-2 inhibitor reduced the polyp number suggesting that COX-2 can a therapeutic agent for colorectal polyposis and cancer
  • cells carrying a truncated APC gene (Min) are defective in chromosome segregation
  • COX-2 inhibits intestinal polyps in Apc(Delta716) mice and may be useful as chemopreventive and therapeutic agents in humans at risk for colorectal neoplasia
  • mouse embryonic stem cells homozygous for multiple intestinal neoplasia or Apc1638T alleles display extensive chromosome and spindle aberrations
  • Apc+/Delta716 Cdx2+/- compound mutant mice develop six times more adenomatous polyps
  • zebrafish with truncation of apc gene have excessive endocardial cushions
  • BubR1(+/-)Apc(Min)(/+) compound mutant mice develop ten times more colonic tumors
  • Apc-deficient zebrafish display developmental abnormalities of both the lens and retina
  • rat carrying a knockout allele in apc gene develops multiple neoplasms with a distribution between the colon and small intestine
  • simultaneous deletion of both Apc and Myc in the adult murine small intestine rescued the phenotypes of perturbed differentiation, migration, proliferation and apoptosis, which occur on deletion of Apc
  • hematopoietic system of mice with the Apc(min) allele showed no abnormality in steady state hematopoiesis, bone marrow from Apc(min) mice showed enhanced repopulation potential but was unable to repopulate secondary recipients because of loss of the quiescent HSC population