Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
The APC-hDLG complex negatively regulates cell cycle progression from the G0/G1 to S phase.
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APC–DLG interaction contributes to cell-cycle suppression; perturbing the APC C-terminal motif weakens the effect.
"mutant APC lacking the S/TXV motif exhibited
weaker cell cycle blocking activity than the intact APC"
Regulation and function of the interaction between the APC tumour suppressor protein and EB1.
Structural basis of the Axin-adenomatous polyposis coli interaction.
Asef, a link between the tumor suppressor APC and G-protein signaling.
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APC binding enhances Asef nucleotide-exchange activity; APC is the regulator, not the exchange catalyst.
"APC enhanced the
GEF activity of Asef"
Adenomatous polyposis coli protein contains two nuclear export signals and shuttles between the nucleus and cytoplasm.
Binding of the adenomatous polyposis coli protein to microtubules increases microtubule stability and is regulated by GSK3 beta phosphorylation.
A role for the Adenomatous Polyposis Coli protein in chromosome segregation.
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APC participates in kinetochore-associated microtubule organization and associates with checkpoint components.
"APC localizes to the ends of microtubules embedded in kinetochores and
forms a complex with the checkpoint proteins Bub1 and Bub3"
Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein.
Synergistic activation of the Wnt signaling pathway by Dvl and casein kinase Iepsilon.
Pin1 regulates turnover and subcellular localization of beta-catenin by inhibiting its interaction with APC.
Involvement of the telomeric protein Pin2/TRF1 in the regulation of the mitotic spindle.
Association and regulation of casein kinase 2 activity by adenomatous polyposis coli protein.
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An APC C-terminal region inhibits CK2 in vitro; binding and kinase regulation are distinct from APC being phosphorylated.
"the inhibitory region was localized to
the C terminus of APC between residues 2086 and 2394"
Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon.
Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation.
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Wnt5a can promote an APC-dependent beta-catenin degradation pathway that differs from canonical destruction-complex kinase requirements.
"This pathway
is Siah2 and APC dependent, but GSK-3 and beta-TrCP independent"
Nuclear accumulation of full-length and truncated adenomatous polyposis coli protein in tumor cells depends on proliferation.
N-methyl-N'-nitro-N-nitrosoguanidine-induced senescence-like growth arrest in colon cancer cells is associated with loss of adenomatous polyposis coli protein, microtubule organization, and telomeric DNA.
Comprehensive proteomic analysis of interphase and mitotic 14-3-3-binding proteins.
Mechanism of phosphorylation-dependent binding of APC to beta-catenin and its role in beta-catenin degradation.
Crystal structure of a beta-catenin/APC complex reveals a critical role for APC phosphorylation in APC function.
The adenomatous polyposis coli protein (APC) exists in two distinct soluble complexes with different functions.
Biosensor-based micro-affinity purification for the proteomic analysis of protein complexes.
Thermodynamics of beta-catenin-ligand interactions: the roles of the N- and C-terminal tails in modulating binding affinity.
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ITC resolves direct APC–beta-catenin binding and its phosphorylation dependence.
"The thermodynamics of beta-catenin binding to E-cadherin,
Lef-1, APC, axin, and the transcriptional inhibitor ICAT have been determined by
isothermal titration calorimetry"
Differential use of functional domains by coiled-coil coactivator in its synergistic coactivator function with beta-catenin or GRIP1.
Human scribble, a novel tumor suppressor identified as a target of high-risk HPV E6 for ubiquitin-mediated degradation, interacts with adenomatous polyposis coli.
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APC binds SCRIB through its C-terminal motif and SCRIB PDZ1/4; the interaction also affects junctional APC localization.
"Interaction between hScrib and APC is mediated by the PDZ domains 1 and 4
of hScrib"
The third 20 amino acid repeat is the tightest binding site of APC for beta-catenin.
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APC repeats differ in beta-catenin affinity, with the third 20-aa repeat especially strong.
"the binding
affinities of beta-catenin with an APC 15aa repeat fragment and each of the
seven 20aa repeats"
Asef2 functions as a Cdc42 exchange factor and is stimulated by the release of an autoinhibitory module from a concealed C-terminal activation element.
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APC binding relieves Asef2 autoinhibition, allowing Asef2 to catalyze nucleotide exchange.
"Asef2 activation involves APC
releasing the ABRSH3 from the C-terminal tail"
Lack of adenomatous polyposis coli protein correlates with a decrease in cell migration and overall changes in microtubule stability.
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APC loss alters microtubule stability, protrusions and migration.
"loss of
APC results in disappearance of cellular protrusions and decreased cell
migration"
Modeling of a human circadian mutation yields insights into clock regulation by PER2.
Loss of APC induces polyploidy as a result of a combination of defects in mitosis and apoptosis.
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Human-cell APC depletion affects kinetochore tension, checkpoint recruitment and mitotic progression.
"inhibition of APC in U2OS cells
compromises the mitotic spindle checkpoint"
Energetics of peptide recognition by the second PDZ domain of human protein tyrosine phosphatase 1E.
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The APC C terminus binds human PTP1E PDZ2, with weaker affinity than earlier estimates.
"the C-terminal segment
of the tumor suppressor APC binds much less tightly to PDZ2"
Bcr-Abl stabilizes beta-catenin in chronic myeloid leukemia through its tyrosine phosphorylation.
Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling.
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WTX associates with a destruction-complex network containing APC and contributes to beta-catenin turnover.
"WTX, a protein encoded by a gene
mutated in Wilms tumors, forms a complex with beta-catenin, AXIN1, beta-TrCP2
(beta-transducin repeat-containing protein 2), and APC (adenomatous polyposis
coli)"
APC inactivation associates with abnormal mitosis completion and concomitant BUB1B/MAD2L1 up-regulation.
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APC perturbation affects completion of cytokinesis in human samples and defined mouse models.
"Mutations in APC were associated with an increased incidence in cell
cycle defects during the completion of cytokinesis"
Htid-1, the human homolog of the Drosophila melanogaster l(2)tid tumor suppressor, defines a novel physiological role of APC.
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Cytosolic Tid/DNAJA3 forms an APC-associated complex separable from the beta-catenin-destruction context.
"the
N-terminal region including the Armadillo domain (ARM) of APC is sufficient to
bind the Tid molecules"
Identification and characterization of Asef2, a guanine-nucleotide exchange factor specific for Rac1 and Cdc42.
AMER1 regulates the distribution of the tumor suppressor APC between microtubules and the plasma membrane.
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AMER1 recruits APC to the plasma membrane and influences its distribution between cortical and microtubule pools.
"APC is recruited to the plasma membrane by binding to APC
membrane recruitment 1 (AMER1)"
Putative tumor suppressor EDD interacts with and up-regulates APC.
Trabid, a new positive regulator of Wnt-induced transcription with preference for binding and cleaving K63-linked ubiquitin chains.
The armadillo repeat domain of the APC tumor suppressor protein interacts with Striatin family members.
Activated protein C ligation of ApoER2 (LRP8) causes Dab1-dependent signaling in U937 cells.
The Axin1 scaffold protein promotes formation of a degradation complex for c-Myc.
Asef2 and Neurabin2 cooperatively regulate actin cytoskeletal organization and are involved in HGF-induced cell migration.
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HGF induces APC/Asef2/Neurabin2 accumulation in protrusions during migration.
"Asef2, Neurabin2 and APC were induced to
accumulate and colocalize in lamellipodia and membrane ruffles"
An EB1-binding motif acts as a microtubule tip localization signal.
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APC contains an EB1-recognized SxIP microtubule-tip localization motif.
"we demonstrate that a short polypeptide motif, Ser-x-Ile-Pro (SxIP), is
used by numerous +TIPs, including the tumor suppressor APC, the transmembrane
protein STIM1, and the kinesin MCAK, for localization to microtubule tips in an
EB1-dependent manner"
Binding of APC and dishevelled mediates Wnt5a-regulated focal adhesion dynamics in migrating cells.
A human MAP kinase interactome.
ErbB2 receptor controls microtubule capture by recruiting ACF7 to the plasma membrane of migrating cells.
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APC recruitment participates in cortical microtubule capture downstream of ErbB2 signaling.
"allows the relocalization of APC (adenomatous polyposis coli)
and cytoplasmic linker-associated protein 2 (CLASP2), known MT-associated
proteins, to the plasma membrane and ruffles"
Rho GTPase Cdc42 is a direct interacting partner of Adenomatous Polyposis Coli protein and can alter its cellular localization.
Deconstructing the ßcatenin destruction complex: mechanistic roles for the tumor suppressor APC in regulating Wnt signaling.
Molecular basis for the recognition of adenomatous polyposis coli by the Discs Large 1 protein.
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The APC C-terminal peptide binds DLG1 PDZ domains, supported by structures, pull-down and ITC.
"the crystal structures of the PDZ1
and PDZ2 domains of DLG1 each in complex with the C-terminal 11-residue peptide
of APC"
Crystal structures of the armadillo repeat domain of adenomatous polyposis coli and its complex with the tyrosine-rich domain of Sam68.
Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation.
Amer2 protein is a novel negative regulator of Wnt/β-catenin signaling involved in neuroectodermal patterning.
Wnt signaling through inhibition of β-catenin degradation in an intact Axin1 complex.
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An intact AXIN1-complex model places beta-catenin processing within a persistent assembly.
"β-catenin is not only phosphorylated
inside the Axin1 complex, but also ubiquinated and degraded via the proteasome"
Structure of the human discs large 1 PDZ2- adenomatous polyposis coli cytoskeletal polarity complex: insight into peptide engagement and PDZ clustering.
The regulation and deregulation of Wnt signaling by PARK genes in health and disease.
Large extent of disorder in Adenomatous Polyposis Coli offers a strategy to guard Wnt signalling against point mutations.
Adenomatous polyposis coli (APC) membrane recruitment 3, a member of the APC membrane recruitment family of APC-binding proteins, is a positive regulator of Wnt-β-catenin signalling.
Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network.
A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
Extensive metabolic disorders are present in APC(min) tumorigenesis mice.
Insulin signaling regulates a functional interaction between adenomatous polyposis coli and cytoplasmic dynein.
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APC and dynein co-immunoprecipitate reciprocally from mouse-brain extracts; source-specific fragment experiments distinguish this association from APC motor catalysis.
"We reprobed a previously published dynein immunoprecipitate from WT mouse brain extracts (Gao et al., 2015) using our APC-M2 antibody and found that full-length APC coprecipitated with dynein (Figure 4B). We also found that dynein coprecipitated with APC (Figure 4C)."
Proteome-wide analysis of phospho-regulated PDZ domain interactions.
TMEM9 promotes intestinal tumorigenesis through vacuolar-ATPase-activated Wnt/β-catenin signalling.
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Loss of APC through lysosomal turnover releases its inhibitory effect on canonical Wnt signaling.
"TMEM9-v-ATPase hyperactivates
Wnt/β-catenin signalling via lysosomal degradation of adenomatous polyposis coli
(APC)"
HENA, heterogeneous network-based data set for Alzheimer's disease.
Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
OpenCell: Endogenous tagging for the cartography of human cellular organization.
Quantitative fragmentomics allow affinity mapping of interactomes.
Protein interaction studies in human induced neurons indicate convergent biology underlying autism spectrum disorders.
Proteome-scale characterisation of motif-based interactome rewiring by disease mutations.
Multimodal cell maps as a foundation for structural and functional genomics.
E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton.
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APC and cadherin form alternative beta-catenin-associated assemblies.
"E-cadherin and APC directly compete for binding to the internal,
armadillo-like repeats of beta-catenin"
The APC protein and E-cadherin form similar but independent complexes with alpha-catenin, beta-catenin, and plakoglobin.
Association of the APC gene product with beta-catenin.
The tumour suppressor gene product APC blocks cell cycle progression from G0/G1 to S phase.
Binding of APC to the human homolog of the Drosophila discs large tumor suppressor protein.
Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly.
Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta.
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AXIN binds APC and organizes a beta-catenin-regulatory complex.
"Human Axin (hAxin) binds directly to beta-catenin, GSK3 beta, and APC
in vitro"
A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals.
Assembly of the destruction complex
Phosphorylation of APC component of the destruction complex
Dissociation of beta-catenin from Axin and association of beta catenin with phospho-(20 aa) APC in the detruction complex
Phosphorylation of phospho- (Ser45, Thr41) beta-catenin at Ser37 by GSK-3
Phosphorylation of phospho-(Ser45 ) at Thr 41 by GSK-3
Phosphorylation of phospho-(Ser45,Thr41,Ser37) at Ser33 by GSK-3
Association of beta-catenin with the destruction complex
Phosphorylation of beta-catenin at Ser45 by CK1 alpha
Beta-catenin is released from the destruction complex
Caspase mediated cleavage of APC
Association of beta-catenin with the RBX1:SCF(beta-TrCP1) ubiquitin ligase complex
Degradation of ubiquitinated beta catenin by the proteasome
Multi-ubiquitination of phospho-beta-catenin by RBX1:SCF(beta-TrCP1)
beta-catenin is replaced by repression complexes at the promoter
APC promotes disassembly of beta-catenin transactivation complex
APC truncation mutants have impaired AXIN binding
CTNNB1 S45 mutants aren't phosphorylated by CK1alpha
CTNNB1 S33 mutants aren't phosphorylated by GSK3beta
CTNNB1 S37 mutants aren't phosphorylated by GSK3beta
CTNNB1 T41 mutants aren't phosphorylated by GSK3beta
AXIN mutants destabilize the destruction complex
Truncated AMER1 mutants destabilize the destruction complex
AXIN is phosphorylated in the destruction complex
APC is K63-polyubiquitinated
APC truncation mutants are not K63 polyubiquitinated
Misspliced GSK3beta mutants stabilize beta-catenin levels
Human APC is further phosphorylated by Murine GSK3beta
Human APC is further phosphorylated by Murine CKIepsilon
Human APC is initially phosphorylated by Murine CKIepsilon
Human APC is finally phosphorylated by Murine GSK3beta
Adenomatous polyposis coli protein nucleates actin assembly and synergizes with the formin mDia1.
Rocket launcher mechanism of collaborative actin assembly defined by single-molecule imaging.
Reconstitution of the destruction complex defines roles of AXIN polymers and APC in β-catenin capture, phosphorylation, and ubiquitylation.
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All-human reconstitution establishes APC-assisted beta-catenin recruitment and processing by the destruction complex.
"APC promotes β-catenin recruitment, both by direct binding and by facilitating β-catenin binding by AXIN1"
Regulated binding of adenomatous polyposis coli protein to actin.
Adenomatous polyposis coli nucleates actin assembly to drive cell migration and microtubule-induced focal adhesion turnover.
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Purified nucleation assays and human full-length separation-of-function rescue distinguish APC actin assembly from its microtubule functions.
"Silencing APC led to a significant reduction in F-actin density (fluorescence intensity per area) in cells, and these defects were rescued by expression of FL-APC (WT) but not FL-APC (m4)"