AMER1, also known as WTX, is a phosphoinositide-binding scaffold that connects APC and other canonical Wnt signaling proteins to the cytoplasmic surface of the plasma membrane. Its membrane-targeting region and protein interaction regions organize distinct complexes: it can stabilize Axin and promote beta-catenin destruction, while also facilitating Axin-associated kinase recruitment and LRP6 receptor phosphorylation during Wnt stimulation. AMER1 can also stabilize NRF2 by competing for its KEAP1 interaction, and a nuclear pool associates with WT1 and nuclear bodies. Its membrane-associated and nuclear activities vary with cellular context and alternative splicing.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:17510365 Wilms tumor suppressor WTX negatively regulates WNT/beta-cat... | MODIFY | Summary: AXIN1 association is part of destruction-complex engagement. Reason: The PMID:17510365 abstract explicitly identifies AXIN1 in the WTX-associated complex. GO:1904713 captures that supported complex association more informatively than generic protein binding. It does not imply a purified binary interaction or Axin enzymatic activity. The same term already occurs in the seeded annotations; no NEW term is required. This generic row is subsumed by the specific binding annotation already seeded from the same study, rather than contributing an additional independent assertion. Proposed replacements: beta-catenin destruction complex binding |
| GO:0005515 protein binding | IPI PMID:17510365 Wilms tumor suppressor WTX negatively regulates WNT/beta-cat... | MODIFY | Summary: APC association contributes to destruction-complex engagement. Reason: PMID:17510365 explicitly identifies APC in the WTX complex. Refine this source-specific association to beta-catenin destruction complex binding; the separate PMID:17925383 experiments establish APC membrane recruitment. A co-purified complex does not establish every possible binary contact. This generic row is subsumed by the specific binding annotation already seeded from the same study, rather than contributing an additional independent assertion. Proposed replacements: beta-catenin destruction complex binding |
| GO:0005515 protein binding | IPI PMID:17510365 Wilms tumor suppressor WTX negatively regulates WNT/beta-cat... | MODIFY | Summary: The beta-catenin interaction has a specific binding term. Reason: The partner P35222 is beta-catenin, explicitly present in the PMID:17510365 complex. The direct interaction is independently established by the REA-region experiments of PMID:21498506. Retain the original source and evidence code while using the already-seeded beta-catenin binding term. This generic row is subsumed by the specific binding annotation already seeded from the same study, rather than contributing an additional independent assertion. Proposed replacements: beta-catenin binding Supporting Evidence: PMID:21498506 Amer1 directly interacts with the armadillo repeats of Ξ²-catenin |
| GO:0005515 protein binding | IPI PMID:17510365 Wilms tumor suppressor WTX negatively regulates WNT/beta-cat... | UNDECIDED | Summary: The SKP1 interaction cannot yet be assessed at the individual experiment level. Reason: The PMID:17510365 abstract describes the destruction-complex network but does not expose this SKP1-specific experiment. The full supplementary interaction record has not been recovered. This is not evidence of a false interaction; preserve the experimental annotation without inventing a specific adaptor or ligase activity. |
| GO:0005515 protein binding | IPI PMID:17510365 Wilms tumor suppressor WTX negatively regulates WNT/beta-cat... | MODIFY | Summary: AMER1 binds the KEAP1 substrate-recognition subunit of a CUL3 ubiquitin ligase. Reason: Independent PMID:22215675 demonstrates direct binding of a human 804-residue WTX protein to KEAP1 and competition with NRF2 at its KELCH substrate-recognition domain. This supports ubiquitin protein ligase binding through the E3 complex's KEAP1 subunit; KEAP1 is not assigned standalone catalytic activity, and direct CUL3 binding was not detected. The original PMID:17510365 interaction record remains preserved, while the specific functional refinement is supported by the separately cited later study. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:22215675 WTX directly interacts with KEAP1 but not with the KEAP1-associated CUL3 protein |
| GO:0005515 protein binding | IPI PMID:17510365 Wilms tumor suppressor WTX negatively regulates WNT/beta-cat... | MODIFY | Summary: FBXW11 association is linked to the destruction complex. Reason: Q9UKB1 is beta-TrCP2/FBXW11, explicitly named in the PMID:17510365 abstract. Refine the generic interaction to the already-seeded beta-catenin destruction complex binding term. AMER1 facilitates substrate processing by the complex but is not thereby an E3 ubiquitin ligase. This generic row is subsumed by the specific binding annotation already seeded from the same study, rather than contributing an additional independent assertion. Proposed replacements: beta-catenin destruction complex binding |
| GO:0005515 protein binding | IPI PMID:17510365 Wilms tumor suppressor WTX negatively regulates WNT/beta-cat... | MODIFY | Summary: The BTRC interaction contributes to destruction-complex engagement. Reason: Indexed original PMID:17510365 Results/Fig. 2C explicitly report purified recombinant WTX binding to beta-TrCP1/BTRC, distinct from beta-TrCP2/FBXW11 named in the abstract. This resolves the paralog-specific uncertainty. Use the already-seeded beta-catenin destruction complex binding term for its pathway context; the direct interaction does not make AMER1 an E3 ligase. The historical human 804-residue reagent is not silently equated to every current AMER1 isoform. This generic row is subsumed by the specific binding annotation already seeded from the same study, rather than contributing an additional independent assertion. Proposed replacements: beta-catenin destruction complex binding |
| GO:0005515 protein binding | IPI PMID:17925383 AMER1 regulates the distribution of the tumor suppressor APC... | MODIFY | Summary: APC binding enables recruitment to the plasma membrane. Reason: PMID:17925383 tests membrane targeting and APC association together, using binding-region mutants and recruitment experiments. Protein-membrane adaptor activity captures the measured role and subsumes the generic APC-binding row. Proposed replacements: protein-membrane adaptor activity Supporting Evidence: PMID:17925383 APC is recruited to the plasma membrane by binding to APC membrane recruitment 1 (AMER1) |
| GO:0005515 protein binding | IPI PMID:21304492 Amer1/WTX couples Wnt-induced formation of PtdIns(4,5)P2 to ... | MODIFY | Summary: LRP6 association participates in membrane scaffolding. Reason: PMID:21304492 shows AMER1 association with LRP6 and recruitment of Axin and associated kinases to the membrane. Protein-membrane adaptor activity captures this organization of receptor-proximal complexes. Proposed replacements: protein-membrane adaptor activity Supporting Evidence: PMID:21304492 Amer1 binds CK1Ξ³, recruits Axin and GSK3Ξ² to the plasma membrane and promotes complex formation between Axin and LRP6. |
| GO:0005515 protein binding | IPI PMID:22682247 Wnt signaling through inhibition of Ξ²-catenin degradation in... | MODIFY | Summary: AXIN1 association contributes to beta-catenin destruction-complex binding. Reason: Independent PMID:21498506 establishes AMER1-mediated recruitment of APC and Axin into the beta-catenin destruction complex. This substantiates the biological interaction and its specific complex-binding role, making generic protein binding uninformative. The original PMID:22682247 pair record has not been independently reconstructed; the refinement relies on the separately cited mechanistic evidence and is subsumed by the specific complex-binding annotation already present. Proposed replacements: beta-catenin destruction complex binding Supporting Evidence: PMID:21498506 Amer1 assembles the Ξ²-catenin destruction complex at the plasma membrane by recruiting Ξ²-catenin, adenomatous polyposis coli, and Axin/Conductin. |
| GO:0005515 protein binding | IPI PMID:24251807 Adenomatous polyposis coli (APC) membrane recruitment 3, a m... | MODIFY | Summary: APC association contributes to beta-catenin destruction-complex binding. Reason: Independent PMID:21498506 establishes AMER1-mediated recruitment of APC and Axin into the beta-catenin destruction complex. This substantiates the biological interaction and its specific complex-binding role, making generic protein binding uninformative. The original PMID:24251807 pair record has not been independently reconstructed; the refinement relies on the separately cited mechanistic evidence and is subsumed by the specific complex-binding annotation already present. Proposed replacements: beta-catenin destruction complex binding Supporting Evidence: PMID:21498506 Amer1 assembles the Ξ²-catenin destruction complex at the plasma membrane by recruiting Ξ²-catenin, adenomatous polyposis coli, and Axin/Conductin. |
| GO:0005515 protein binding | IPI PMID:24251807 Adenomatous polyposis coli (APC) membrane recruitment 3, a m... | UNDECIDED | Summary: AMER1βAMER3 binding is reported, but a specific molecular role remains unresolved. Reason: The PMID:24251807 abstract explicitly identifies AMER1 as an AMER3 binding partner. This is not a wrong-gene citation. The complete interaction experiment and stoichiometry were not inspected, and binding alone does not warrant heterodimerization or a distinct adaptor activity. Generic protein binding is therefore retained as unresolved rather than promoted to the compact core. Supporting Evidence: PMID:24251807 we identified Amer1 as binding partner of Amer3. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: AXIN1 association contributes to beta-catenin destruction-complex binding. Reason: Independent PMID:21498506 establishes AMER1-mediated recruitment of APC and Axin into the beta-catenin destruction complex. This substantiates the biological interaction and its specific complex-binding role, making generic protein binding uninformative. The original PMID:26496610 pair record has not been independently reconstructed; the refinement relies on the separately cited mechanistic evidence and is subsumed by the specific complex-binding annotation already present. Proposed replacements: beta-catenin destruction complex binding Supporting Evidence: PMID:21498506 Amer1 assembles the Ξ²-catenin destruction complex at the plasma membrane by recruiting Ξ²-catenin, adenomatous polyposis coli, and Axin/Conductin. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: APC association contributes to beta-catenin destruction-complex binding. Reason: Independent PMID:21498506 establishes AMER1-mediated recruitment of APC and Axin into the beta-catenin destruction complex. This substantiates the biological interaction and its specific complex-binding role, making generic protein binding uninformative. The original PMID:26496610 pair record has not been independently reconstructed; the refinement relies on the separately cited mechanistic evidence and is subsumed by the specific complex-binding annotation already present. Proposed replacements: beta-catenin destruction complex binding Supporting Evidence: PMID:21498506 Amer1 assembles the Ξ²-catenin destruction complex at the plasma membrane by recruiting Ξ²-catenin, adenomatous polyposis coli, and Axin/Conductin. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: The beta-catenin association has a specific, independently established binding function. Reason: PMID:21498506 directly demonstrates AMER1 binding to beta-catenin armadillo repeats. Refine the generic PMID:26496610 annotation to the already-present beta-catenin binding term on that independent evidence. This does not reconstruct the original screen's pair record or assign its assay conditions to the later study. Proposed replacements: beta-catenin binding Supporting Evidence: PMID:21498506 Amer1 directly interacts with the armadillo repeats of Ξ²-catenin |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: FBXW11 association supports destruction-complex engagement. Reason: PMID:22215675 independently establishes the interaction with FBXW11; PMID:17510365 places the beta-TrCP partners in the WTX-associated beta-catenin destruction network. These mechanistic data support the existing beta-catenin destruction complex binding term. The original PMID:33961781 pair-level assay remains uninspected, so its bait direction, confidence and construct are not inferred from the supplemental evidence. This refinement is subsumed by the existing specific complex-binding assertion. Proposed replacements: beta-catenin destruction complex binding Supporting Evidence: PMID:22215675 WTX binds KEAP1 and FBXW11 through separable domains. PMID:17510365 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 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: BTRC association supports destruction-complex engagement. Reason: The inspected Fig. 2C of PMID:17510365 directly demonstrates WTX binding to beta-TrCP1/BTRC; the PMID:22215675 Discussion corroborates this earlier result while newly mapping FBXW11 binding. These distinct data support beta-catenin destruction complex binding. The PMID:17510365 abstract names beta-TrCP2 and is not used as BTRC-specific proof. The original PMID:33961781 pair-level assay remains uninspected; its bait direction, confidence and construct are not inferred. This refinement is subsumed by the existing specific complex-binding assertion. Proposed replacements: beta-catenin destruction complex binding Supporting Evidence: PMID:22215675 WTX directly binds the substrate recognition modules of two different E3 ubiquitin ligases, namely BTRC and KEAP1. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: FBXW11 association supports destruction-complex engagement. Reason: PMID:22215675 independently establishes the interaction with FBXW11; PMID:17510365 places the beta-TrCP partners in the WTX-associated beta-catenin destruction network. These mechanistic data support the existing beta-catenin destruction complex binding term. The original PMID:40205054 pair-level assay remains uninspected, so its bait direction, confidence and construct are not inferred from the supplemental evidence. This refinement is subsumed by the existing specific complex-binding assertion. Proposed replacements: beta-catenin destruction complex binding Supporting Evidence: PMID:22215675 WTX binds KEAP1 and FBXW11 through separable domains. PMID:17510365 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 |
| GO:0005546 phosphatidylinositol-4,5-bisphosphate binding | IDA PMID:21304492 Amer1/WTX couples Wnt-induced formation of PtdIns(4,5)P2 to ... | ACCEPT | Summary: PtdIns(4,5)P2 binding anchors the membrane scaffold. Reason: PMID:21304492 tests phosphoinositide binding and membrane recruitment with recombinant human AMER1 fragments and cellular perturbations. PtdIns(4,5)P2 recognition supplies the membrane anchor for its scaffold function. |
| GO:0005546 phosphatidylinositol-4,5-bisphosphate binding | IMP PMID:17925383 AMER1 regulates the distribution of the tumor suppressor APC... | ACCEPT | Summary: The N-terminal region mediates PtdIns(4,5)P2-dependent targeting. Reason: PMID:17925383 combines purified GST-AMER1 lipid-strip assays with cellular phosphoinositide perturbations, supporting PtdIns(4,5)P2-dependent membrane targeting. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A nuclear pool is supported, distinct from the main membrane-scaffold role. Reason: The UniProt location mapping agrees with Human Protein Atlas nuclear-body staining and the nuclear-shuttling observations in PMID:19416806. Nuclear occupancy is biologically meaningful but does not itself establish a general DNA-binding transcription-factor activity. The membrane-associated core is recorded separately. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic localization is compatible with AMER1 scaffolding. Reason: The UniProt mapping is consistent with the experimentally observed cytoplasmic and membrane-associated pools. Retain this broad compartment annotation; the compact core describes the membrane recruitment function more specifically without declaring the wider cellular location false. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-195251 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "Assembly of the destruction complex" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-195275 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "Phosphorylation of APC component of the destruction complex" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-195280 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "Dissociation of beta-catenin from Axin and association of beta catenin with phospho-(20 aa) APC in the detruction complex" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-195283 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "Phosphorylation of phospho- (Ser45, Thr41) beta-catenin at Ser37 by GSK-3" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-195287 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "Phosphorylation of phospho-(Ser45 ) at Thr 41 by GSK-3" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-195300 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "Phosphorylation of phospho-(Ser45,Thr41,Ser37) at Ser33 by GSK-3" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-195304 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "Association of beta-catenin with the destruction complex" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-195318 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "Phosphorylation of beta-catenin at Ser45 by CK1 alpha" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-201685 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "Beta-catenin is released from the destruction complex" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2130279 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "Association of beta-catenin with the RBX1:SCF(beta-TrCP1) ubiquitin ligase complex" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2130282 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "Degradation of ubiquitinated beta catenin by the proteasome" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2130286 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "Multi-ubiquitination of phospho-beta-catenin by RBX1:SCF(beta-TrCP1)" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4791278 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "APC truncation mutants have impaired AXIN binding" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4827388 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "CTNNB1 S45 mutants aren't phosphorylated by CK1alpha" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4839634 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "CTNNB1 S33 mutants aren't phosphorylated by GSK3beta" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4839635 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "CTNNB1 S37 mutants aren't phosphorylated by GSK3beta" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4839638 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "CTNNB1 T41 mutants aren't phosphorylated by GSK3beta" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4839734 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "AXIN mutants destabilize the destruction complex" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5229343 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "AXIN is phosphorylated in the destruction complex" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5251557 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "Expression of AMER1 gene" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5339713 | ACCEPT | Summary: AMER1 occupies the cytosolic compartment in this Reactome context. Reason: The cytosol annotation for "Misspliced GSK3beta mutants stabilize beta-catenin levels" agrees with the cytoplasmic localization of AMER1 and the cytosolic surface of its membrane-associated complexes. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: The inferred membrane localization is experimentally grounded on AMER1. Reason: PTN001095668 includes AMER1 and AMER2 evidence. Target AMER1 appearing in WITH/FROM is expected when its experimental data helped establish the ancestral assertion, not circularity. Human AMER1 membrane localization is directly corroborated by PMID:17925383 and the 2011 studies. The actual PAINT tree was not recovered, so no node-placement defect is asserted. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas staining supports plasma-membrane localization. Reason: The current HPA AMER1 subcellular page was inspected. It reports supported plasma-membrane staining, including Rh30 cells, alongside nuclear-body and vesicular patterns in other contexts. This supports the existing IDA compartment assertion without claiming all AMER1 is membrane-bound in every cell. |
| GO:0005886 plasma membrane | IDA PMID:17925383 AMER1 regulates the distribution of the tumor suppressor APC... | ACCEPT | Summary: AMER1 localizes to the cytoplasmic side of the plasma membrane. Reason: The original PMID:17925383 localization, permeabilization and recruitment experiments support membrane association through the N-terminal lipid-binding region. Retain the seeded plasma-membrane term; no transmembrane topology or secretion is inferred. Supporting Evidence: PMID:17925383 APC is recruited to the plasma membrane by binding to APC membrane recruitment 1 (AMER1) |
| GO:0005886 plasma membrane | IDA PMID:21304492 Amer1/WTX couples Wnt-induced formation of PtdIns(4,5)P2 to ... | ACCEPT | Summary: Membrane recruitment participates in the receptor-level Wnt response. Reason: PMID:21304492 demonstrates phosphoinositide-dependent membrane targeting and isoform/construct-dependent LRP6 phosphorylation. Its named S2 deletion construct is not automatically equivalent to UniProt Q5JTC6-2; the sequence distinctions are recorded in the notes. Preserve the unqualified source row rather than adding an inferred isoform tag. Supporting Evidence: PMID:21304492 Amer1 binds CK1Ξ³, recruits Axin and GSK3Ξ² to the plasma membrane and promotes complex formation between Axin and LRP6. |
| GO:0005886 plasma membrane | IDA PMID:21498506 Structural and functional characterization of the Wnt inhibi... | ACCEPT | Summary: Membrane targeting is required for the assayed inhibitory scaffold. Reason: The PMID:21498506 abstract and indexed primary Results describe membrane-binding mutants, artificial retargeting and splice-construct effects. They support AMER1 membrane localization and its functional importance without making every splice product equivalent. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: The electronic membrane mapping agrees with direct experiments. Reason: The UniProt location mapping is independently supported by multiple AMER1-specific localization studies. This valid mapping remains intact; its breadth does not justify removal solely because an experimental annotation also exists. |
| GO:0008013 beta-catenin binding | IDA PMID:21498506 Structural and functional characterization of the Wnt inhibi... | ACCEPT | Summary: AMER1 directly binds beta-catenin through its REA-containing region. Reason: PMID:21498506 explicitly reports binding to beta-catenin armadillo repeats and separates this region from membrane targeting. The interaction contributes to destruction-complex organization rather than beta-catenin being an AMER1 catalytic substrate. Supporting Evidence: PMID:21498506 Amer1 directly interacts with the armadillo repeats of Ξ²-catenin |
| GO:0008013 beta-catenin binding | IPI PMID:17510365 Wilms tumor suppressor WTX negatively regulates WNT/beta-cat... | ACCEPT | Summary: The beta-catenin interaction is a specific component of scaffold function. Reason: PMID:17510365 identifies beta-catenin in the WTX complex; PMID:21498506 supplies independent direct-binding evidence. Retain the curated IPI row while recognizing that affinity purification alone does not resolve direct contact for every complex partner. Supporting Evidence: PMID:21498506 Amer1 directly interacts with the armadillo repeats of Ξ²-catenin |
| GO:0016604 nuclear body | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nuclear-body localization is supported in specific human cells. Reason: The inspected Human Protein Atlas page reports supported nuclear-body staining, including CACO-2 and Rh30 cells. The nuclear-shuttling study is compatible with this distinct cellular pool. Nuclear bodies are not all the same structure, so this HPA term is not silently narrowed to a specific paraspeckle component. |
| GO:0031398 positive regulation of protein ubiquitination | IDA PMID:17510365 Wilms tumor suppressor WTX negatively regulates WNT/beta-cat... | ACCEPT | Summary: AMER1 positively regulates beta-catenin ubiquitination through scaffolding. Reason: PMID:17510365 reports enhanced beta-catenin ubiquitination. The independent recruitment and complex-assembly experiments provide a physical mechanism beyond a loss-of-function phenotype. Retain the regulatory process; SCF-associated enzymes perform ubiquitin transfer, so AMER1 is not assigned ubiquitin-ligase activity. Supporting Evidence: PMID:17510365 WTX promotes beta-catenin ubiquitination and degradation |
| GO:0043495 protein-membrane adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Protein-membrane adaptor activity describes the principal molecular function. Reason: AMER1 couples membrane lipid recognition to recruitment of APC and other Wnt-associated proteins, directly matching the inspected GO:0043495 definition. The target in the IBA WITH/FROM list reflects experimental evidence used for the phylogenetic inference. No donor-count or self-reference objection is warranted. Supporting Evidence: PMID:17925383 APC is recruited to the plasma membrane by binding to APC membrane recruitment 1 (AMER1) PMID:21304492 Amer1 binds CK1Ξ³, recruits Axin and GSK3Ξ² to the plasma membrane and promotes complex formation between Axin and LRP6. |
| GO:0045732 positive regulation of protein catabolic process | IDA PMID:17510365 Wilms tumor suppressor WTX negatively regulates WNT/beta-cat... | ACCEPT | Summary: AMER1 facilitates beta-catenin degradation as a regulatory scaffold. Reason: PMID:17510365 supports increased beta-catenin degradation; later membrane-assembly experiments give a plausible direct organizing mechanism. Retain positive regulation of protein catabolic process without assigning protease or proteasomal catalysis to AMER1. Supporting Evidence: PMID:17510365 WTX promotes beta-catenin ubiquitination and degradation |
| GO:0060828 regulation of canonical Wnt signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: The inferred Wnt-regulatory role agrees with direct AMER1 evidence. Reason: The phylogenetic annotation is corroborated by the human-protein studies. Positive receptor-level regulation and negative downstream regulation are experimentally distinguished configurations, not mutually exclusive gene-level identities. The actual ancestral tree was unavailable, and there is no basis to challenge its node placement. |
| GO:0060828 regulation of canonical Wnt signaling pathway | IMP PMID:17925383 AMER1 regulates the distribution of the tumor suppressor APC... | ACCEPT | Summary: AMER1 maintains APC abundance and recruits it to the plasma membrane. Reason: PMID:17925383 shows that AMER1 overexpression increases APC abundance, while AMER1 knockdown reduces overall APC levels and redistributes it from the membrane. These changes affect an established regulator of the beta-catenin destruction complex and support the broad Wnt-regulatory annotation. Independent PMID:21304492 and PMID:21498506 distinguish receptor-level and downstream Wnt effects. Supporting Evidence: PMID:17925383 siRNA-mediated knockdown of AMER1 reduces the overall levels of APC |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IGI PMID:17510365 Wilms tumor suppressor WTX negatively regulates WNT/beta-cat... | ACCEPT | Summary: Genetic evidence supports inhibition of canonical Wnt signaling. Reason: PMID:17510365 reports functional analyses in cultured cells, Xenopus and zebrafish. Its WITH/FROM P28026 is Xenopus Wnt-8, verified against UniProt; it is not another AMER1 protein or a human ligand. The direction is independently corroborated by PMID:21498506. Precise construct-specific epistasis remains bounded by the available original evidence. Supporting Evidence: PMID:17510365 WTX promotes beta-catenin ubiquitination and degradation |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IMP PMID:21498506 Structural and functional characterization of the Wnt inhibi... | ACCEPT | Summary: The membrane scaffold can inhibit downstream canonical Wnt output. Reason: PMID:21498506 separates membrane-targeting determinants from binding determinants and shows loss of inhibition after membrane-binding disruption, with rescue by artificial targeting. Axin stabilization and complex recruitment support participation by AMER1 itself. Retain this contextual inhibitory function without assuming equivalence of all splice constructs. |
| GO:0090263 positive regulation of canonical Wnt signaling pathway | IMP PMID:21304492 Amer1/WTX couples Wnt-induced formation of PtdIns(4,5)P2 to ... | ACCEPT | Summary: AMER1 also promotes receptor-level canonical Wnt signaling. Reason: PMID:21304492 shows recruitment of Axin and associated kinases and enhanced LRP6 phosphorylation, including an engineered receptor-tail fusion. AMER1 alone can still inhibit downstream transcription. The positive and negative annotations describe different configurations; neither should be removed just to force a single direction. Supporting Evidence: PMID:21304492 Amer1 binds CK1Ξ³, recruits Axin and GSK3Ξ² to the plasma membrane and promotes complex formation between Axin and LRP6. |
| GO:1904713 beta-catenin destruction complex binding | IPI PMID:17510365 Wilms tumor suppressor WTX negatively regulates WNT/beta-cat... | ACCEPT | Summary: AMER1 binds and organizes beta-catenin destruction-complex components. Reason: PMID:17510365 identifies the associated complex, and PMID:21498506 independently demonstrates assembly with APC, beta-catenin and Axin/Conductin. Retain the specific complex-binding function. The evidence does not establish that every listed partner makes a direct binary contact with AMER1 or that AMER1 is a catalytic complex subunit. |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: How do the sequence-defined 2011 S2 deletion construct, the 804-residue WTX-PRED/short sequence and the current UniProt Q5JTC6-2 record correspond to expressed human transcripts?
Q: Which endogenous conditions switch membrane-bound AMER1 from destruction-complex stabilization to LRP6 receptor-level activation?
Q: Can the original supplementary interaction records resolve SKP1, KEAP1, the distinct beta-TrCP paralogs and the AMER1-specific high-throughput pairs without equating complex co-purification with direct binding?
Q: Which nuclear AMER1 activities are independently established at endogenous expression, and how do they relate to its membrane scaffold function?
Q: How does endogenous, sequence-defined full-length AMER1 coordinate its KEAP1/NRF2 competition with its distinct beta-TrCP/beta-catenin regulatory complexes?
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)