APC2 (APCL) is a large, brain-enriched APC-family protein that associates with microtubules and actin-rich structures and binds beta-catenin. Its C-terminal regions support microtubule lattice association, interactions with growing plus ends and DYNLL2-dependent clustering. These activities help organize neuronal microtubules and dendritic morphology; local stabilization can coexist with ongoing microtubule growth and shrinkage. APC2 also reduces beta-catenin abundance and beta-catenin-dependent transcription. Perinuclear, Golgi and peripheral actin-associated pools have been observed in human cells. Biallelic loss of APC2 causes a neurodevelopmental disorder with lissencephaly and subcortical heterotopia.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000226 microtubule cytoskeleton organization | IMP PMID:25753423 Loss-of-Function Mutation in APC2 Causes Sotos Syndrome Feat... | ACCEPT | Summary: Supported existing annotation. Reason: Human wild-type APC2, compared with patient-truncation and C-terminal mutants, preserves acetylated microtubules and neuronal morphology in PMID:25753423. The human construct is assayed in mouse Neuro2a/primary neuronal hosts; organization is supported without claiming a human patient-cell assay. Later human-construct PMID:30018294 measures microtubule dynamicity and proposes regrowth from local stabilizing patches; it does not reconstitute individual rescue events with purified APC2. Supporting Evidence: file:human/APC2/APC2-notes.md Wild-type protein associated with microtubules and F-actin, protected acetylated microtubules from nocodazole, and increased GTP-bound Rac1 relative to control. PMID:30018294 Our results indicate that depletion of APC2 affects about half of dynamic portions of minus-end-out microtubule lattices, reducing dynamicity of those microtubules |
| GO:0001708 cell fate specification | IBA GO_REF:0000033 | UNDECIDED | Summary: Cell-fate specification remains distinct from the supported neuronal functions. Reason: Human APC2 cytoskeletal regulation, neuronal morphology and migration provide developmental context, but do not establish the cell-fate specification step asserted here. The PAINT node and supporting experimental context were not recovered, so this particular inherited process remains uncertain; the number or species of descendants is not an adverse finding. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000288612 · PTN000288612 UNRESOLVED The seeded proximate source is PANTHER:PTN000288612. Its exact IBD topology and supporting ancestral experiments were not reconstructed. Independent target evidence concerns neuronal cytoskeletal organization and migration, not a demonstrated cell-fate specification step. The applicable ancestral experimental context remains unresolved. |
| GO:0005515 protein binding | IPI PMID:10644998 EB3, a novel member of the EB1 family preferentially express... | KEEP AS NON CORE | Summary: Supported secondary activity, process or location. Reason: The original PMID:10644998 Results and Figures 4–5 show APCL binding to MAPRE1/EB1 in vitro with GST and reticulocyte-translated reagents. The same paper did not detect EB1 coimmunoprecipitation under its transient mammalian-cell conditions, unlike EB3. Retain the positive in-vitro interaction as non-core with this assay boundary; do not generalize the negative coimmunoprecipitation to absence of binding. Supporting Evidence: file:human/APC2/APC2-notes.md The paper's in-vitro assays support APCL binding to EB1 and EB3. |
| GO:0005515 protein binding | IPI PMID:10644998 EB3, a novel member of the EB1 family preferentially express... | KEEP AS NON CORE | Summary: Supported secondary activity, process or location. Reason: Original PMID:10644998 Figures 4–6 support APCL–MAPRE3/EB3 interaction by in-vitro pull-down and reciprocal coimmunoprecipitation of tagged full-length proteins in Cos-7 cells. Retain this supported interaction as non-core without converting EB3 binding into direct tubulin binding. Supporting Evidence: file:human/APC2/APC2-notes.md The paper's in-vitro assays support APCL binding to EB1 and EB3. |
| GO:0005515 protein binding | IPI PMID:10644998 EB3, a novel member of the EB1 family preferentially express... | UNDECIDED | Summary: The precise source or inference remains unresolved. Reason: The original human EB3 clone has accession AB024964 and supports APCL binding, but its exact mapping to the machine-sourced partner Q9UPY8-1 remains unresolved. Official sequence-record routes failed and the original clone must not be mapped from the current canonical label alone. Preserve this separate assertion; uncertainty concerns the exact isoform record, not evidence that this isoform lacks binding. Supporting Evidence: file:human/APC2/APC2-notes.md The paper's in-vitro assays support APCL binding to EB1 and EB3. |
| GO:0005515 protein binding | IPI PMID:10646860 APCL, a central nervous system-specific homologue of adenoma... | KEEP AS NON CORE | Summary: Supported secondary activity, process or location. Reason: The complete PMID:10646860 abstract reports APCL binding to TP53BP2 through its SH3 and ankyrin-repeat regions, with redistribution toward the perinucleus. This association is supported and retained as non-core; the proposed p53/BCL2 signaling implication does not establish a more specific molecular activity. Supporting Evidence: PMID:10646860 the Src-homology-3 domain and the ankyrin-repeat domain of 53BP2 were both required for binding to the COOH-terminus of APCL. |
| GO:0005737 cytoplasm | IDA PMID:11691822 Human APC2 localization and allelic imbalance. | ACCEPT | Summary: Supported existing annotation. Reason: Actual PMID:11691822 human endogenous antibody localization and specificity controls support cytoplasmic APC2; this broad site is consistent with independently assayed cytoskeletal and Wnt-related functions. Supporting Evidence: PMID:11691822 endogenous APC2 is diffusely distributed in the cytoplasm and colocalizes with both the Golgi apparatus and actin filaments. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Supported existing annotation. Reason: The cytoplasmic electronic location is independently supported by actual human endogenous PMID:11691822 localization. This validates the biological assertion, not every ARBA rule premise. Supporting Evidence: PMID:11691822 endogenous APC2 is diffusely distributed in the cytoplasm and colocalizes with both the Golgi apparatus and actin filaments. |
| GO:0005794 Golgi apparatus | IDA PMID:11691822 Human APC2 localization and allelic imbalance. | KEEP AS NON CORE | Summary: Supported secondary activity, process or location. Reason: Actual PMID:11691822 endogenous human-cell observations include a Golgi-associated pool with Golgi-marker context. Retain this observed secondary compartment without assigning a Golgi-specific molecular function. Supporting Evidence: PMID:11691822 endogenous APC2 is diffusely distributed in the cytoplasm and colocalizes with both the Golgi apparatus and actin filaments. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Supported secondary activity, process or location. Reason: The Swiss-Prot subcellular mapping to Golgi is consistent with the original human localization observations. Retain a secondary location, not a proposed Golgi mechanism. Supporting Evidence: PMID:11691822 endogenous APC2 is diffusely distributed in the cytoplasm and colocalizes with both the Golgi apparatus and actin filaments. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Supported existing annotation. Reason: The official HPA APC2 page identifies supported cytosolic localization, including U2OS and additional human cell contexts, with antibody HPA078002. Retain this measured broad compartment; no new cytokinetic function follows from localization alone. Supporting Evidence: file:human/APC2/APC2-notes.md The official [HPA APC2 subcellular page](https://www.proteinatlas.org/ENSG00000115266-APC2/subcellular) reports supported cytokinetic-bridge staining in SH-SY5Y and U2OS cells and supported cytosolic signal. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: Supported existing annotation. Reason: Human APC2 associates with both microtubule and actin structures in PMID:11691822/PMID:25753423 and targeted human-construct PMID:30018294 experiments, supporting the broad cytoskeleton location. Supporting Evidence: PMID:11691822 endogenous APC2 is diffusely distributed in the cytoplasm and colocalizes with both the Golgi apparatus and actin filaments. PMID:30018294 our results highlight three cytoskeleton interacting domains within the C-terminus of APC2: an extended S microtubule binding domain, an actin binding domain and a +TIP binding domain. |
| GO:0005881 cytoplasmic microtubule | IBA GO_REF:0000033 | ACCEPT | Summary: Supported existing annotation. Reason: Human APC2 microtubule localization is independently supported by target experiments. The target itself among the PAINT descendant evidences is expected grounding, not circularity. Exact ancestral placement is not separately reconstructed here. Supporting Evidence: PMID:11691822 endogenous APC2 is diffusely distributed in the cytoplasm and colocalizes with both the Golgi apparatus and actin filaments. PMID:30018294 the S domain extended on both sides (RFP-APC2-S2) is the minimum necessary sequence for microtubule interaction |
| GO:0005881 cytoplasmic microtubule | IDA PMID:10644998 EB3, a novel member of the EB1 family preferentially express... | ACCEPT | Summary: Supported existing annotation. Reason: Original PMID:10644998 Figure 7 and immunofluorescence Methods show tagged human APCL in the perinuclear region with partial microtubule-network localization in Cos-7/SW480 expression contexts. The authors explicitly qualify tag/overexpression effects. Independent human APC2 studies corroborate the location. Supporting Evidence: PMID:10644998 EB3 and APCL appeared together in the perinucleus and the cytoplasmic microtubule network. PMID:30018294 the S domain extended on both sides (RFP-APC2-S2) is the minimum necessary sequence for microtubule interaction |
| GO:0005881 cytoplasmic microtubule | IDA PMID:11691822 Human APC2 localization and allelic imbalance. | ACCEPT | Summary: Supported existing annotation. Reason: In PMID:11691822 the human microtubule decoration was detected on overexpression, while endogenous pools were not visibly microtubule-decorating under that assay. Preserve that boundary; the positive location is independently corroborated by later human-construct work, so the negative endogenous observation is not generalized. Supporting Evidence: file:human/APC2/APC2-notes.md In the original paper's Figure 2D caption, overexpressed APC2 colocalizes with some microtubules in transfected human SKOV3 cells. PMID:30018294 RFP-APC2-C bound all along the microtubules and quickly deformed neuronal morphology |
| GO:0005881 cytoplasmic microtubule | IDA PMID:25753423 Loss-of-Function Mutation in APC2 Causes Sotos Syndrome Feat... | ACCEPT | Summary: Supported existing annotation. Reason: Human wild-type APC2 associates with microtubules in the actual PMID:25753423 neuronal-host experiments. Patient-related/C-terminal mutants lose that organization; host cells are mouse, not an inferred human patient-cell assay. Supporting Evidence: file:human/APC2/APC2-notes.md Wild-type protein associated with microtubules and F-actin, protected acetylated microtubules from nocodazole, and increased GTP-bound Rac1 relative to control. |
| GO:0005884 actin filament | IDA PMID:11691822 Human APC2 localization and allelic imbalance. | ACCEPT | Summary: Supported existing annotation. Reason: Actual PMID:11691822 endogenous human-cell antibody localization includes actin structures and associated membrane ruffles. Retain location at actin filaments without claiming purified direct actin binding from microscopy. Supporting Evidence: PMID:11691822 endogenous APC2 is diffusely distributed in the cytoplasm and colocalizes with both the Golgi apparatus and actin filaments. |
| GO:0007026 negative regulation of microtubule depolymerization | IBA GO_REF:0000033 | ACCEPT | Summary: Supported existing annotation. Reason: The inherited protection from depolymerization is independently corroborated by human APC2 nocodazole resistance/acetylated microtubules in PMID:25753423. This is compatible with PMID:30018294 dynamic microtubules and local rescue sites; the term is not interpreted as global arrest of growth/shrinkage. No node-loss claim is made. Supporting Evidence: file:human/APC2/APC2-notes.md Wild-type protein associated with microtubules and F-actin, protected acetylated microtubules from nocodazole, and increased GTP-bound Rac1 relative to control. PMID:30018294 both constructs are able to stabilize microtubule bundles and strongly bind to acetylated microtubule lattice |
| GO:0007389 pattern specification process | IBA GO_REF:0000033 | UNDECIDED | Summary: Pattern specification is not established by neuronal migration alone. Reason: APC2-dependent migration and brain morphology support developmental functions, but do not independently identify the pattern-specification mechanism asserted by this IBA. Relevant ancestral experiments and node placement remain uninspected. No loss or inappropriate propagation is inferred merely from the donor set. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000288612 · PTN000288612 UNRESOLVED The seeded proximate source is PANTHER:PTN000288612. Its exact IBD topology and supporting ancestral experiments were not reconstructed. Available APC2 developmental evidence concerns migration and morphology; it has not resolved the specific spatial-patterning assertion or its ancestral experimental basis. |
| GO:0007399 nervous system development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Supported secondary activity, process or location. Reason: Human APC2 loss causes neurodevelopmental abnormalities, and human-construct PMID:30018294 neuronal morphogenesis plus mouse PMID:22573669 migration provide mechanistic context. Retain the broad nervous-system-development assertion as downstream non-core biology; do not manufacture a narrower developmental process. Supporting Evidence: PMID:25753423 a homozygous frameshift mutation in the APC2 gene by whole-exome sequencing, which resulted in the loss of function of cytoskeletal regulation in neurons. PMID:22573669 BDNF-stimulated directional migration is impaired in Apc2-deficient neurons. PMID:31585108 these individuals come from eight unrelated families and have bi-allelic mutations in APC2 PMID:30018294 Early in neuronal development (DIV3), RFP-APC2 localizes with slight preference to the longest neurite, while in mature neurons RFP-APC2 overwhelmingly localizes to dendrites (DIV7 and DIV15). |
| GO:0008013 beta-catenin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Supported existing annotation. Reason: Direct human APCL fragment binding to beta-catenin in PMID:9823329 independently grounds the inherited molecular function. Target self-inclusion is expected descendant evidence; the original phylogenetic fields remain intact. Supporting Evidence: PMID:9823329 Like APC, this domain of APCL was able to bind to beta-catenin and deplete the intracellular beta-catenin pool. |
| GO:0008013 beta-catenin binding | IDA PMID:9823329 Identification of a brain-specific APC homologue, APCL, and ... | ACCEPT | Summary: Supported existing annotation. Reason: Original functional Methods/Results and Figure5 caption show human APCL627–1666 binding beta-catenin in the GST/reticulocyte experiment. This supports beta-catenin binding with fragment scope and does not establish cadherin-complex incorporation. Supporting Evidence: PMID:9823329 Like APC, this domain of APCL was able to bind to beta-catenin and deplete the intracellular beta-catenin pool. |
| GO:0008013 beta-catenin binding | IEA GO_REF:0000120 | ACCEPT | Summary: Supported existing annotation. Reason: The electronic beta-catenin-binding prediction agrees with the actual human APCL binding experiment. Domain/rule provenance is retained without treating a domain match alone as an independent physical assay. Supporting Evidence: PMID:9823329 Like APC, this domain of APCL was able to bind to beta-catenin and deplete the intracellular beta-catenin pool. |
| GO:0008017 microtubule binding | IBA GO_REF:0000033 | ACCEPT | Summary: Supported existing annotation. Reason: Target human APC2 microtubule-binding regions and live microtubule association in PMID:30018294, together with PMID:25753423 cytoskeletal assays, support the inherited binding function. Independent target evidence supports acceptance while the exact PAINT tree remains unread. Supporting Evidence: PMID:30018294 the S domain extended on both sides (RFP-APC2-S2) is the minimum necessary sequence for microtubule interaction |
| GO:0008017 microtubule binding | IEA GO_REF:0000002 | ACCEPT | Summary: Supported existing annotation. Reason: The InterPro-derived microtubule-binding assertion is corroborated by actual human APC2 domains/constructs in PMID:30018294. Retain the broad function; the distinct lattice and EB3-dependent plus-end interactions need not be collapsed into a single direct contact mechanism. Supporting Evidence: PMID:30018294 the S domain extended on both sides (RFP-APC2-S2) is the minimum necessary sequence for microtubule interaction |
| GO:0015630 microtubule cytoskeleton | IDA PMID:10644998 EB3, a novel member of the EB1 family preferentially express... | ACCEPT | Summary: Supported existing annotation. Reason: Original PMID:10644998 tagged-cell microscopy supports partial APCL localization to the microtubule network, with tag/overexpression limitations. Accept this broad cellular component with independent human APC2 corroboration; no purified microtubule-binding experiment is attributed to the original paper. Supporting Evidence: PMID:10644998 EB3 and APCL appeared together in the perinucleus and the cytoplasmic microtubule network. PMID:30018294 the S domain extended on both sides (RFP-APC2-S2) is the minimum necessary sequence for microtubule interaction |
| GO:0015630 microtubule cytoskeleton | IEA GO_REF:0000117 | ACCEPT | Summary: Supported existing annotation. Reason: The ARBA microtubule-cytoskeleton prediction is independently consistent with target-specific localization and functional assays. The opaque rule is not reinterpreted as primary evidence. Supporting Evidence: PMID:30018294 the S domain extended on both sides (RFP-APC2-S2) is the minimum necessary sequence for microtubule interaction |
| GO:0016055 Wnt signaling pathway | IEA GO_REF:0000002 | ACCEPT | Summary: Supported existing annotation. Reason: Human APCL binding, beta-catenin depletion and reduced TCF reporter activity in PMID:9823329 establish participation in Wnt regulation. Retain the broad existing process as supported; no new redundant process is proposed. Supporting Evidence: PMID:9823329 Like APC, this domain of APCL was able to bind to beta-catenin and deplete the intracellular beta-catenin pool. |
| GO:0016342 catenin complex | IBA GO_REF:0000033 | UNDECIDED | Summary: The inherited cadherin-associated complex assertion remains unresolved. Reason: GO:0016342 denotes the cadherin-linked alpha/beta/gamma-catenin assembly. Human APC2 beta-catenin binding and the SAMP/conductin destruction-complex mechanism do not establish membership in that adhesion complex. This differs from the specifically over-annotated PMID:9823329 assignment: other evidence behind the IBA has not been inspected. Target incorporation into the cadherin assembly or an applicable experimentally supported ancestral placement would resolve the uncertainty. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000288612 · PTN000288612 UNRESOLVED The seeded proximate source is PANTHER:PTN000288612. Its exact IBD topology and supporting ancestral experiments were not reconstructed. The target beta-catenin experiments support signaling/destruction-complex biology, not the cadherin-associated assembly. Other descendant experiments and the corresponding IBD placement remain uninspected; target self-inclusion is legitimate, not circular. Supporting Evidence: PMID:9823329 Like APC, this domain of APCL was able to bind to beta-catenin and deplete the intracellular beta-catenin pool. |
| GO:0016342 catenin complex | IDA PMID:9823329 Identification of a brain-specific APC homologue, APCL, and ... | MARK AS OVER ANNOTATED | Summary: The source does not establish the specific cadherin-associated complex. Reason: The actual PMID:9823329 functional experiments assay human APCL fragment–beta-catenin binding, beta-catenin abundance and TCF output. They do not place APCL in the cadherin-associated assembly defined by GO:0016342. This source-specific CC is broader than the demonstrated complex context; retain the true binding/Wnt observations in their own accepted rows. No global exclusion from adhesion sites is asserted. Supporting Evidence: PMID:9823329 Like APC, this domain of APCL was able to bind to beta-catenin and deplete the intracellular beta-catenin pool. file:human/APC2/APC2-notes.md The cadherin-associated catenin-complex assertion from PMID:9823329 is over-annotated relative to its actual human APCL fragment binding and beta-catenin/TCF experiments. |
| GO:0016342 catenin complex | IEA GO_REF:0000117 | UNDECIDED | Summary: The precise source or inference remains unresolved. Reason: The ARBA assertion concerns the cadherin-associated catenin complex, which is distinct from the supported beta-catenin destruction complex. Its exact rule conditions and supporting annotations remain uninspected. Direct target incorporation into the cadherin assembly, or a resolved applicable source behind the rule, would be informative; beta-catenin binding alone does not settle this location. Supporting Evidence: PMID:9823329 Like APC, this domain of APCL was able to bind to beta-catenin and deplete the intracellular beta-catenin pool. |
| GO:0016477 cell migration | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Supported secondary activity, process or location. Reason: The inherited migration role is consistent with mouse Apc2-dependent directional neuronal migration in PMID:22573669 and human APC2 cytoskeletal/developmental evidence. Retain downstream non-core process with mouse ortholog/human-construct contexts distinct; no source tree reconstruction is claimed. Supporting Evidence: PMID:22573669 BDNF-stimulated directional migration is impaired in Apc2-deficient neurons. PMID:31585108 these individuals come from eight unrelated families and have bi-allelic mutations in APC2 |
| GO:0030178 negative regulation of Wnt signaling pathway | IEA GO_REF:0000002 | ACCEPT | Summary: Supported existing annotation. Reason: The existing negative-Wnt prediction agrees with actual human APCL suppression of beta-catenin/TCF output. This is an existing broad regulatory assertion, not a new unqualified mechanism or a claim that all tissues use identical regulation. Supporting Evidence: PMID:9823329 Like APC, this domain of APCL was able to bind to beta-catenin and deplete the intracellular beta-catenin pool. PMID:31291912 APC2-deficiency resulted in activation of ovarian WNT signalling |
| GO:0030877 beta-catenin destruction complex | IBA GO_REF:0000033 | ACCEPT | Summary: The inherited destruction-complex assignment is supported by combined APC2 evidence. Reason: Mammalian APC2 has two SAMP domains required for conductin binding in PMID:10021369. Together with the human APCL fragment binding, beta-catenin depletion and TCF suppression established in PMID:9823329, this supports the existing inherited destruction-complex assignment. Acceptance is a synthesis of target-relevant mechanism and the curated PAINT assertion; the precise 1999 construct species/isoform and IBD placement remain uninspected. It does not claim that the available abstract alone establishes a complete human complex. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000288612 · PTN000288612 UNRESOLVED The seeded proximate source is PANTHER:PTN000288612. Its exact IBD topology and supporting ancestral experiments were not reconstructed. Human APC2 is in the verified APC family. Mammalian APC2 SAMP-dependent conductin binding and independent human beta-catenin regulation corroborate this existing inherited complex function. The exact IBD/tree was not reconstructed; no node-level validation is claimed. Supporting Evidence: PMID:10021369 shown to contain two SAMP domains, both of which are required for binding to conductin. PMID:9823329 Like APC, this domain of APCL was able to bind to beta-catenin and deplete the intracellular beta-catenin pool. |
| GO:0030877 beta-catenin destruction complex | NAS PMID:9601641 Downregulation of beta-catenin by human Axin and its associa... | UNDECIDED | Summary: The later complex evidence does not resolve this original NAS citation. Reason: SAMP-dependent conductin binding in PMID:10021369 and human beta-catenin regulation in PMID:9823329 support APC2 destruction-complex participation. However, the full PMID:9601641 body and the source-specific NAS/ComplexPortal derivation remain unavailable. Retain that original source assignment as uncertain while accepting the independently corroborated IBA; the older abstract does not establish a wrong-gene citation. Supporting Evidence: PMID:9601641 Human Axin (hAxin) binds directly to beta-catenin, GSK3 beta, and APC in vitro PMID:10021369 shown to contain two SAMP domains, both of which are required for binding to conductin. PMID:9823329 Like APC, this domain of APCL was able to bind to beta-catenin and deplete the intracellular beta-catenin pool. |
| GO:0031256 leading edge membrane | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Supported secondary activity, process or location. Reason: The original human PMID:11691822 localization includes leading-edge actin-associated membrane ruffles and lamellipodial membrane. This supports the broad leading-edge membrane prediction as a peripheral location, not a transmembrane topology claim. Supporting Evidence: PMID:11691822 endogenous APC2 is diffusely distributed in the cytoplasm and colocalizes with both the Golgi apparatus and actin filaments. file:human/APC2/APC2-notes.md Figure 4E specifically identifies lamellipodial membrane. |
| GO:0031258 lamellipodium membrane | IDA PMID:11691822 Human APC2 localization and allelic imbalance. | KEEP AS NON CORE | Summary: Supported secondary activity, process or location. Reason: Original PMID:11691822 Figure4E explicitly identifies APC2 staining along lamellipodial membrane in human A549 cells. Retain this secondary peripheral site; no inserted membrane segment or membrane receptor role is implied. Supporting Evidence: PMID:11691822 endogenous APC2 is diffusely distributed in the cytoplasm and colocalizes with both the Golgi apparatus and actin filaments. file:human/APC2/APC2-notes.md Figure 4E specifically identifies lamellipodial membrane. |
| GO:0031941 filamentous actin | IDA PMID:25753423 Loss-of-Function Mutation in APC2 Causes Sotos Syndrome Feat... | ACCEPT | Summary: Supported existing annotation. Reason: Actual PMID:25753423 human APC2 wild-type expression colocalizes with F-actin and alters actin-rich protrusion behavior in mouse neuronal hosts. Retain filamentous-actin location; the microscopy is not recast as purified direct binding. Supporting Evidence: file:human/APC2/APC2-notes.md Wild-type protein associated with microtubules and F-actin, protected acetylated microtubules from nocodazole, and increased GTP-bound Rac1 relative to control. |
| GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process | NAS PMID:9601641 Downregulation of beta-catenin by human Axin and its associa... | UNDECIDED | Summary: Scaffold participation is plausible, but the original process citation remains unresolved. Reason: SAMP-dependent conductin binding and human beta-catenin depletion support a scaffold role in beta-catenin turnover. A scaffold can perform part of a degradative process without catalysis. Nevertheless, the relevant PMID:9601641 full body and the NAS derivation for this exact proteasome-mediated ubiquitin-dependent process remain uninspected; the later complex evidence does not retroactively establish that source-specific assertion. Supporting Evidence: PMID:9601641 Human Axin (hAxin) binds directly to beta-catenin, GSK3 beta, and APC in vitro PMID:10021369 shown to contain two SAMP domains, both of which are required for binding to conductin. PMID:9823329 Like APC, this domain of APCL was able to bind to beta-catenin and deplete the intracellular beta-catenin pool. |
| GO:0045171 intercellular bridge | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Supported secondary activity, process or location. Reason: The official HPA page reports supported cytokinetic-bridge APC2 staining in human SH-SY5Y and U2OS cells. Retain the observed bridge location as non-core; this location alone does not establish a new role in cytokinesis or abscission. Supporting Evidence: file:human/APC2/APC2-notes.md The official [HPA APC2 subcellular page](https://www.proteinatlas.org/ENSG00000115266-APC2/subcellular) reports supported cytokinetic-bridge staining in SH-SY5Y and U2OS cells and supported cytosolic signal. |
| GO:0045295 gamma-catenin binding | IBA GO_REF:0000033 | UNDECIDED | Summary: Gamma-catenin binding is a separate unresolved partner-specific claim. Reason: The human beta-catenin experiments establish binding to CTNNB1, whereas this IBA asserts gamma-catenin/JUP binding. No independently inspected target JUP interaction was recovered, and the relevant donor experiment and ancestral placement remain uninspected. The shared catenin name and a single APC donor neither establish this specificity nor demonstrate its loss. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000288612 · PTN000288612 UNRESOLVED The seeded proximate source is PANTHER:PTN000288612. Its exact IBD topology and supporting ancestral experiments were not reconstructed. The independent target experiments assay beta-catenin, not gamma-catenin/JUP. The partner-specific donor assay and applicable IBD placement have not been resolved; donor count does not weaken the assertion. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:10644998 EB3, a novel member of the EB1 family preferentially express... | ACCEPT | Summary: Supported existing annotation. Reason: Original PMID:10644998 Figure 7 and immunofluorescence Methods demonstrate a tagged APCL perinuclear pool in the Cos-7/SW480 expression experiments. Later endogenous human PMID:11691822 localization corroborates the compartment; the original tag/overexpression boundary remains explicit. Supporting Evidence: PMID:10644998 EB3 and APCL appeared together in the perinucleus and the cytoplasmic microtubule network. PMID:10646860 APCL and 53BP2 proteins were localized together in the perinuclei of normal mammalian cells PMID:11691822 endogenous APC2 is diffusely distributed in the cytoplasm and colocalizes with both the Golgi apparatus and actin filaments. |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:10646860 APCL, a central nervous system-specific homologue of adenoma... | ACCEPT | Summary: Supported existing annotation. Reason: The original complete PMID:10646860 abstract reports perinuclear localization/redistribution in the APCL–TP53BP2 context. This supports the location but does not establish an autonomous TP53-pathway molecular activity. Supporting Evidence: PMID:10646860 APCL and 53BP2 proteins were localized together in the perinuclei of normal mammalian cells |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:11691822 Human APC2 localization and allelic imbalance. | ACCEPT | Summary: Supported existing annotation. Reason: Actual PMID:11691822 human endogenous localization demonstrates a prominent perinuclear pool alongside Golgi and actin-associated signal. Retain the measured location without equating all perinuclear fluorescence with a single organelle. Supporting Evidence: PMID:11691822 endogenous APC2 is diffusely distributed in the cytoplasm and colocalizes with both the Golgi apparatus and actin filaments. |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Supported existing annotation. Reason: The Swiss-Prot perinuclear mapping is consistent with the actual human localization study and prior binding/redistribution abstract. Supporting Evidence: PMID:11691822 endogenous APC2 is diffusely distributed in the cytoplasm and colocalizes with both the Golgi apparatus and actin filaments. PMID:10646860 APCL and 53BP2 proteins were localized together in the perinuclei of normal mammalian cells |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Supported existing annotation. Reason: Direct human APCL fragment experiments reduce beta-catenin abundance and TCF output, independently supporting the inherited negative canonical Wnt function. Self-inclusion among descendant evidence is expected. Supporting Evidence: PMID:9823329 Like APC, this domain of APCL was able to bind to beta-catenin and deplete the intracellular beta-catenin pool. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IDA PMID:10021369 Identification of APC2, a homologue of the adenomatous polyp... | ACCEPT | Summary: Supported existing annotation. Reason: The complete PMID:10021369 abstract reports mammalian APC2 suppression of beta-catenin/Tcf signaling, and UniProt assigns this reference to the human isoform3 sequence/function record. Human target function is independently established by PMID:9823329. Accept the gene-level regulatory activity while keeping original PMID:10021369 construct/species detail unresolved pending its body; do not label the source a direct full-length human assay. Supporting Evidence: PMID:10021369 Like APC, APC2 regulates the formation of active betacatenin-Tcf complexes PMID:9823329 Like APC, this domain of APCL was able to bind to beta-catenin and deplete the intracellular beta-catenin pool. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IDA PMID:9823329 Identification of a brain-specific APC homologue, APCL, and ... | ACCEPT | Summary: Supported existing annotation. Reason: Human APCL627–1666 reduces beta-catenin staining and TCF-dependent reporter output in actual PMID:9823329 SW480 experiments. This is negative canonical Wnt regulation with explicit fragment and expression context, not a clinical phenotype inference. Supporting Evidence: PMID:9823329 Like APC, this domain of APCL was able to bind to beta-catenin and deplete the intracellular beta-catenin pool. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: Supported existing annotation. Reason: The ARBA canonical-Wnt suppression claim is independently supported by the original human APCL functional experiments. Retain the electronic source as-is, without asserting the rule conditions were individually audited. Supporting Evidence: PMID:9823329 Like APC, this domain of APCL was able to bind to beta-catenin and deplete the intracellular beta-catenin pool. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IMP PMID:26393419 A novel GSK3-regulated APC:Axin interaction regulates Wnt si... | UNDECIDED | Summary: The precise source or inference remains unresolved. Reason: Actual PMID:26393419 construct and functional passages use Drosophila APC2 and human APC1 fragments in human SW480 hosts. Endogenous human APC2 is mentioned separately; no inspected human APC2 perturbation resolves the original IMP provenance. Independent human APC2 Wnt function remains accepted in other rows, but cannot silently convert this source into a human APC2 experiment. Supporting Evidence: PMID:26393419 cells transfected with Flag-tagged truncated human APC1-1338 (see Figure 1B) or fly APC2 PMID:9823329 Like APC, this domain of APCL was able to bind to beta-catenin and deplete the intracellular beta-catenin pool. |
| GO:0090630 activation of GTPase activity | IMP PMID:25753423 Loss-of-Function Mutation in APC2 Causes Sotos Syndrome Feat... | KEEP AS NON CORE | Summary: Supported secondary activity, process or location. Reason: Original PMID:25753423 human wild-type APC2 expression increases GTP-bound Rac1 compared with disease-related/C-terminal mutants. Retain the measured activation process as downstream non-core biology, without claiming intrinsic guanine-nucleotide exchange or GTP hydrolysis by APC2. Supporting Evidence: file:human/APC2/APC2-notes.md Wild-type protein associated with microtubules and F-actin, protected acetylated microtubules from nocodazole, and increased GTP-bound Rac1 relative to control. |
| GO:0120025 plasma membrane bounded cell projection | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Supported secondary activity, process or location. Reason: Human APC2 localizes to actin-rich leading-edge/lamellipodial structures and human constructs function in neurite/dendrite contexts. Retain the existing broad cell-projection location; no new projection subtype or developmental process is manufactured. Supporting Evidence: PMID:11691822 endogenous APC2 is diffusely distributed in the cytoplasm and colocalizes with both the Golgi apparatus and actin filaments. PMID:30018294 Early in neuronal development (DIV3), RFP-APC2 localizes with slight preference to the longest neurite, while in mature neurons RFP-APC2 overwhelmingly localizes to dendrites (DIV7 and DIV15). |
Loading supporting content…
Download this section (compressed HTML)Q: What target incorporation experiments or applicable ancestral evidence establish APC2 membership in the cadherin-associated catenin complex, and what original evidence underlies the PMID:9601641 NAS assignments?
Q: Does original EB3 accession AB024964 map exactly to the partner isoform Q9UPY8-1 used by the curated interaction record?
Q: Which human APC2 isoforms and tissues use beta-catenin regulation versus microtubule organization, and how do local stabilization and dynamic regrowth interact?
Q: Can microtubule plus-tip recognition be separated experimentally from lattice binding in human APC2, and would a more specific molecular-function term describe the demonstrated interaction?
Experiment: Resolve original APC2/EB3 reagent sequences against current isoform records before assigning isoform-specific binding.
Experiment: Reconstitute human APC2 lattice and plus-tip interactions with defined proteins and image growth, catastrophe and rescue to distinguish direct microtubule association from partner-dependent recruitment.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)