APC - Adenomatous polyposis coli protein - human protein (Function)
 
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APC »  Adenomatous polyposis coli protein  (Protein APC)
 
Protein also known as:  Deleted in polyposis 2.5.
Gene name:  APC
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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.  
6
  • UniProtKB
GO molecular function 
Beta-catenin bindingdefinition[GO:0008013]  
4
  • UniProtKB
  • BHF-UCL
Not  Cadherin bindingdefinition[GO:0045296]  
1
  • BHF-UCL
Gamma-catenin bindingdefinition[GO:0045295]  
1
  • BHF-UCL
Microtubule bindingdefinition[GO:0008017]  
2
  • UniProtKB
Microtubule plus-end bindingdefinition[GO:0051010]  
1
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
29
  • IntAct
  • UniProtKB
Protein kinase bindingdefinition[GO:0019901]  
1
  • UniProtKB
Protein kinase regulator activitydefinition[GO:0019887]  
1
  • UniProtKB
GO biological process 
Anterior/posterior pattern specificationdefinition[GO:0009952] silver  
1
  • Ortholog Compara
Axis specificationdefinition[GO:0009798] silver  
1
  • Ortholog Compara
Axonogenesisdefinition[GO:0007409] silver  
1
  • Ortholog Compara
Canonical Wnt signaling pathwaydefinition[GO:0060070]  
2
  • UniProtKB
Canonical Wnt signaling pathway involved in negative regulation of apoptotic processdefinition[GO:0044336] silver  
1
  • Ortholog Compara
Canonical Wnt signaling pathway involved in positive regulation of apoptotic processdefinition[GO:0044337] silver  
1
  • Ortholog Compara
Cell adhesiondefinition[GO:0007155]  
1
  • UniProtKB
Cell cycle arrestdefinition[GO:0007050]  
1
  • UniProtKB
Cell migrationdefinition[GO:0016477]  
1
  • UniProtKB
Cellular response to DNA damage stimulusdefinition[GO:0006974]  
1
  • UniProtKB
Chromosome organizationdefinition[GO:0051276] silver  
1
  • Ortholog Compara
Cytoplasmic microtubule organizationdefinition[GO:0031122] silver  
1
  • Ortholog Compara
Dorsal/ventral pattern formationdefinition[GO:0009953] silver  
1
  • Ortholog Compara
Hair follicle developmentdefinition[GO:0001942] silver  
1
  • Ortholog Compara
Kidney developmentdefinition[GO:0001822] silver  
1
  • Ortholog Compara
Metaphase/anaphase transition of mitotic cell cycledefinition[GO:0007091] silver  
1
  • Ortholog Compara
Mitotic cytokinesisdefinition[GO:0000281]  
1
  • MGI
Mitotic spindle assembly checkpointdefinition[GO:0007094]  
1
  • MGI
Muscle cell cellular homeostasisdefinition[GO:0046716] silver  
1
  • Ortholog Compara
Negative regulation of canonical Wnt signaling pathwaydefinition[GO:0090090]  
1
  • MGI
Negative regulation of cell proliferationdefinition[GO:0008285]  
1
  • UniProtKB
Negative regulation of cyclin-dependent protein serine/threonine kinase activitydefinition[GO:0045736]  
1
  • UniProtKB
Negative regulation of epithelial cell proliferation involved in prostate gland developmentdefinition[GO:0060770] silver  
1
  • Ortholog Compara
Negative regulation of MAPK cascadedefinition[GO:0043409] silver  
1
  • Ortholog Compara
Negative regulation of microtubule depolymerizationdefinition[GO:0007026]  
2
  • MGI
  • UniProtKB
Negative regulation of odontogenesisdefinition[GO:0042483] silver  
1
  • Ortholog Compara
Positive regulation of apoptotic processdefinition[GO:0043065]  
1
  • MGI
Positive regulation of cell adhesiondefinition[GO:0045785] silver  
1
  • Ortholog Compara
Positive regulation of cell divisiondefinition[GO:0051781] silver  
1
  • Ortholog Compara
Positive regulation of cell migrationdefinition[GO:0030335]  
1
  • MGI
Positive regulation of epithelial cell differentiationdefinition[GO:0030858] silver  
1
  • Ortholog Compara
Positive regulation of microtubule polymerizationdefinition[GO:0031116] silver  
1
  • Ortholog Compara
Positive regulation of protein catabolic processdefinition[GO:0045732]  
2
  • BHF-UCL
  • MGI
Positive regulation of pseudopodium assemblydefinition[GO:0031274]  
1
  • MGI
Protein complex assemblydefinition[GO:0006461]  
1
  • UniProtKB
Proximal/distal pattern formationdefinition[GO:0009954] silver  
1
  • Ortholog Compara
Regulation of attachment of spindle microtubules to kinetochoredefinition[GO:0051988]  
2
  • MGI
  • UniProtKB
Regulation of microtubule-based processdefinition[GO:0032886]  
1
  • UniProtKB
Regulation of nitrogen compound metabolic processdefinition[GO:0051171] silver  
1
  • Ortholog Compara
Regulation of osteoblast differentiationdefinition[GO:0045667] silver  
1
  • Ortholog Compara
Regulation of osteoclast differentiationdefinition[GO:0045670] silver  
1
  • Ortholog Compara
Retina development in camera-type eyedefinition[GO:0060041] silver  
1
  • Ortholog Compara
Somatic stem cell maintenancedefinition[GO:0035019] silver  
1
  • Ortholog Compara
T cell differentiation in thymusdefinition[GO:0033077] silver  
1
  • Ortholog Compara
Thymus developmentdefinition[GO:0048538] silver  
1
  • Ortholog Compara
Tight junction assemblydefinition[GO:0070830]  
1
  • UniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
Basal cell carcinoma  hsa05217+324  
Colorectal cancer  hsa05210+324  
Endometrial cancer  hsa05213+324  
HTLV-I infection  hsa05166+324  
Pathways in cancer  hsa05200+324  
Regulation of actin cytoskeleton  hsa04810+324  
Wnt signaling pathway  hsa04310+324  
According to Reactome, this protein belongs to the following pathways:
APC truncation mutants are not K63 polyubiquitinated  REACT_228143  
APC truncation mutants have impaired AXIN binding  REACT_228196  
Apoptotic cleavage of cellular proteins  REACT_107  
AXIN missense mutants destabilize the destruction complex  REACT_228285  
Beta-catenin phosphorylation cascade  REACT_11065  
deactivation of the beta-catenin transactivating complex  REACT_200731  
Degradation of beta-catenin by the destruction complex  REACT_11063  
disassembly of the destruction complex and recruitment of AXIN to the membrane  REACT_200610  
misspliced GSK3beta mutants stabilize beta-catenin  REACT_228314  
S33 mutants of beta-catenin aren't phosphorylated  REACT_228159  
S37 mutants of beta-catenin aren't phosphorylated  REACT_228251  
S45 mutants of beta-catenin aren't phosphorylated  REACT_228137  
T41 mutants of beta-catenin aren't phosphorylated  REACT_228261  
truncations of AMER1 destabilize the destruction complex  REACT_228060  
 
More information is available from:
Note 
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.  
1
  • UniProtKB
 

Keywords

Biological process 
Wnt signaling pathway  definition   [KW-0879]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: Adenomatous_polyposis_coli
GenomeRNAi: 324
PRO: PR:P25054