AXIN2

Summary: Mouse Axin2 loss supports an inferred role in aortic valve development.

Reason: Retain the mouse-to-human ISS inference as a developmental role. The complete official abstract of PMID:28069701 reports abnormal aortic and mitral valve maturation in Axin2-knockout mice. This is mouse perturbation evidence and not a human valve assay or a separate molecular activity.

Summary: Mouse Axin2 loss supports an inferred role in mitral valve development.

Reason: Retain the mouse-to-human ISS inference as a mouse developmental result. Axin2-knockout mice develop enlarged, abnormal mitral valves with altered Wnt activity and extracellular matrix remodeling; the principal AXIN2 activity remains signaling-complex scaffolding.

Summary: The source-specific AXIN2–PPP2CB interaction remains unverified.

Reason: The GOA pair identifies PPP2CB/P62714. The available PMID:10698523 abstract concerns Axin-associated PP2A, but the exact human AXIN2 construct and this catalytic-subunit pair were not verified in the original experiment; attempted publisher access failed. Retain the source assertion pending those data, without claiming AXIN1-only misattribution.

Summary: Conductin binds PLK1 in the cited mitotic-checkpoint study.

Reason: The complete cited abstract explicitly reports conductin/AXIN2 binding to polo-like kinase 1 in the colon-cancer/mitotic-checkpoint study. Protein kinase binding captures the demonstrated partner class more precisely. The abstract does not establish an isolated purified interface or a universal physiological mitotic effect.

Proposed replacements: protein kinase binding

Summary: Specify the established beta-catenin interaction using the curated partner identity.

Reason: The original IPI annotation identifies beta-catenin as the partner. Defer to the experimental curator for that interaction and refine its molecular-function label, supported independently by the AXIN2–beta-catenin interaction described in PMID:22056988. The exact construct and interaction-table entry in this source remain unverified; this refinement does not claim that they were inspected or that co-complex detection establishes purified direct binding.

Proposed replacements: beta-catenin binding

Summary: The cited Results explicitly report beta-catenin binding to AXIN2.

Reason: The cited cached Results paragraph explicitly states that both wild-type and Y333F beta-catenin bind AXIN2, APC and E-cadherin, referring to Supplementary Fig10. This supports the specific beta-catenin-binding class. The supplementary panels themselves were not inspected, and the PKM2-centered title does not invalidate the AXIN2 experiment.

Proposed replacements: beta-catenin binding

Summary: Specify the established GSK3B interaction using the curated partner identity.

Reason: The original IPI annotation identifies human GSK3B/P49841, a protein kinase, as the AXIN2 partner. The complete PMID:23455922 abstract describes an AP-MS study of 32 human kinase interactomes, but does not identify this individual pair. Defer to the experimental curator for the pair attribution and refine the molecular-function label to protein kinase binding, corroborated by the AXIN2–GSK3 interaction discussion in PMID:30824926 and the GSK3-beta scaffold mechanism in PMID:20300119. The exact supplementary entry, construct and pair-specific assay in PMID:23455922 remain unverified; neither the AP-MS association nor this refinement establishes purified direct binding.

Proposed replacements: protein kinase binding

Summary: Specify the established GSK3A interaction using the curated partner identity.

Reason: The original IPI annotation identifies GSK3A as the partner. Defer to the experimental curator for that interaction and refine its molecular-function label, supported independently by AXIN2–GSK3 interaction evidence in PMID:30824926 and the centrosomal scaffold mechanism in PMID:20300119. The exact construct and interaction-table entry in this source remain unverified; this refinement does not claim that they were inspected or that co-complex detection establishes purified direct binding.

Proposed replacements: protein kinase binding

Summary: Specify the established GSK3B interaction using the curated partner identity.

Reason: The original IPI annotation identifies GSK3B as the partner. Defer to the experimental curator for that interaction and refine its molecular-function label, supported independently by AXIN2–GSK3 interaction evidence in PMID:30824926 and the centrosomal scaffold mechanism in PMID:20300119. The exact construct and interaction-table entry in this source remain unverified; this refinement does not claim that they were inspected or that co-complex detection establishes purified direct binding.

Proposed replacements: protein kinase binding

Summary: AMER3 association with AXIN2 is supported but does not establish a distinct molecular activity.

Reason: The complete PMID:24251807 abstract explicitly reports AMER3 interaction with AXIN1, AXIN2 and beta-catenin. Retain this supported generic interaction as non-core; the abstract does not establish a more specific AXIN2 molecular activity mediated by AMER3. Genericity alone is not evidence for REMOVE.

Summary: TGIF1 associates with AXIN2 in a context of nuclear sequestration.

Reason: The complete abstract and selected cached Discussion of PMID:25873176 describe TGIF association with AXIN1/AXIN2 and nuclear sequestration of the destruction-complex scaffolds. Retain the interaction with TGIF1/Q15583 as non-core, without assigning TGIF transcriptional activity to AXIN2. The partial HTML cache does not supply complete Results/Methods.

Summary: Specify the established GSK3B interaction using the curated partner identity.

Reason: The original IPI annotation identifies GSK3B as the partner. Defer to the experimental curator for that interaction and refine its molecular-function label, supported independently by AXIN2–GSK3 interaction evidence in PMID:30824926 and the centrosomal scaffold mechanism in PMID:20300119. The exact construct and interaction-table entry in this source remain unverified; this refinement does not claim that they were inspected or that co-complex detection establishes purified direct binding.

Proposed replacements: protein kinase binding

Summary: Human testis interaction data support AXIN2 binding to a GSK3 kinase.

Reason: The cited Discussion explicitly reports an AXIN2–GSK3 interaction identified in human testis and describes the testis yeast-two-hybrid and sperm co-immunoprecipitation strategies. GOA specifies GSK3A/P49840; defer to that curated pair while refining its partner class to protein kinase binding. The exact supplement row was not read, and neither an AXIN2 sperm-motility function nor GSK3A-exclusive binding is inferred.

Proposed replacements: protein kinase binding

Summary: The HuRI interaction with UniProtKB:A2BDD9 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:A2BDD9; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:O75558 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:O75558; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:O75638-2 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:O75638-2; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:O95985 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:O95985; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:P09067 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:P09067; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:P40222 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:P40222; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:P49721 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:P49721; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:P60014 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:P60014; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:P60410 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:P60410; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q13895 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q13895; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q14241 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q14241; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q15172 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q15172; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q15560 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q15560; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q15973 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q15973; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q2NKX9 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q2NKX9; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q2TBE0 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q2TBE0; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q3B820 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q3B820; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q5T619 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q5T619; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q8N3L3 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q8N3L3; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q8N8B7-2 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q8N8B7-2; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q8NEF3-2 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q8NEF3-2; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q8TAU3 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q8TAU3; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q8TBB1 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q8TBB1; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q96EZ8 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q96EZ8; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q96SQ5 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q96SQ5; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q99728 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q99728; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q9BVG8-5 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q9BVG8-5; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q9BWG6 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q9BWG6; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q9BXS5 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q9BXS5; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q9BYQ4 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q9BYQ4; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q9BYR2 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q9BYR2; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q9BZW7 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q9BZW7; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q9UKJ5 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q9UKJ5; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q9Y297 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q9Y297; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: The HuRI interaction with UniProtKB:Q9Y6W3 remains unverified at the target-assay level.

Reason: The HuRI source explicitly records the partner UniProtKB:Q9Y6W3; its identity is known. The complete scientific abstract describes the interaction-map resource, but the target pair, tested constructs and validation evidence were not inspected in the source dataset. Preserve this IPI assertion as source-specific uncertainty, with no claim that the partner is absent, the interaction is false, or generic binding itself warrants removal.

Summary: Specify the established GSK3B interaction using the curated partner identity.

Reason: The original IPI annotation identifies GSK3B as the partner. Defer to the experimental curator for that interaction and refine its molecular-function label, supported independently by AXIN2–GSK3 interaction evidence in PMID:30824926 and the centrosomal scaffold mechanism in PMID:20300119. The exact construct and interaction-table entry in this source remain unverified; this refinement does not claim that they were inspected or that co-complex detection establishes purified direct binding.

Proposed replacements: protein kinase binding

Summary: Specify the established GSK3A interaction using the curated partner identity.

Reason: The original IPI annotation identifies GSK3A as the partner. Defer to the experimental curator for that interaction and refine its molecular-function label, supported independently by AXIN2–GSK3 interaction evidence in PMID:30824926 and the centrosomal scaffold mechanism in PMID:20300119. The exact construct and interaction-table entry in this source remain unverified; this refinement does not claim that they were inspected or that co-complex detection establishes purified direct binding.

Proposed replacements: protein kinase binding

Summary: Specify the established GSK3B interaction using the curated partner identity.

Reason: The original IPI annotation identifies GSK3B as the partner. Defer to the experimental curator for that interaction and refine its molecular-function label, supported independently by AXIN2–GSK3 interaction evidence in PMID:30824926 and the centrosomal scaffold mechanism in PMID:20300119. The exact construct and interaction-table entry in this source remain unverified; this refinement does not claim that they were inspected or that co-complex detection establishes purified direct binding.

Proposed replacements: protein kinase binding

Summary: The exact AXIN2–SMAD4 interaction and construct assignment remain unverified.

Reason: The curated partner is SMAD4/Q13485. The available PMID:35512704 abstract establishes the study context but the target pair and wild-type versus cancer-mutant assignment was not verified. Preserve the original assertion pending source-level inspection; no wrong-gene, contamination or false-interaction conclusion follows from the title or abstract.

Summary: Nuclear localization is a supported contextual property of AXIN2.

Reason: Retain the PAINT-inferred nuclear location as a contextual location, corroborated by the human colon study PMID:12072559. Q9Y2T1 in WITH/FROM is legitimate target experimental grounding, not circular support. The complete PAINT tree/MSA was not reconstructed.

Summary: Endogenous AXIN2 was detected in nuclei of human colonic epithelium.

Reason: The complete PMID:12072559 abstract directly reports nuclear AXIN2 in human colonic epithelial samples, with frequent loss in dysplasia. Nuclear localization is supported but is not the defining location of the cytosolic destruction-complex activity. The full histological methods were not read.

Summary: Nuclear AXIN2 is independently supported; the inspected source images use AXIN1.

Reason: Retain nuclear localization with explicit curator deference and independent AXIN2 support from PMID:12072559. In the PMID:21383061 text, the inspected localization experiments use an AXIN1-directed antibody and AXIN1 constructs; they cannot be relabeled as direct AXIN2 imaging. This bounded observation does not establish that all AXIN2 localization evidence in the source is absent.

Summary: Cytoplasmic AXIN2 is supported, with limits on target-specific imaging in this source.

Reason: Retain the broad cytoplasmic location as a supported non-core parent location, with source precision. The inspected PMID:21383061 imaging methods/results are predominantly AXIN1-specific, whereas human AXIN2 is included in the biochemical TAP experiments; independent curated cytosolic evidence supports the overall AXIN2 location. Do not claim direct AXIN2 imaging from the AXIN1 panels.

Summary: Retain the broad cytoplasmic location without narrowing all AXIN2 to cytosol.

Reason: The UniProt mapping is consistent with cytoplasmic AXIN2. Both cytosolic destruction-complex and centrosomal locations are supported. Refining the entire parent assertion to cytosol would discard the latter scope, so retain cytoplasm as a non-core parent location while the core specifies cytosol.

Summary: Conductin localizes to centrosomes through a C-Nap1-dependent mechanism.

Reason: The cited selected main text reports endogenous conductin/AXIN2 in centrosomal fractions and antibody staining reduced by AXIN2 knockdown, together with C-Nap1-dependent localization. Retain this experimentally supported contextual site, distinguished from the principal cytosolic destruction complex.

Summary: Cytosol is a principal site of AXIN2 destruction-complex function.

Reason: Accept the curator-inferred cytosolic location as a defining site of the beta-catenin destruction-complex scaffold. The GO_REF evidence is retained as supplied; it is not described as a newly performed imaging assay.

Summary: Curated pathway context supports cytosolic AXIN2 destruction-complex function.

Reason: Accept the cytosolic location attached to the curated Reactome:R-HSA-3640844 Wnt-pathway event. The complete cached summary was read; this is curated pathway context for the AXIN2 scaffold, not an independent microscopy experiment. Complex membership and cytosolic location are kept distinct.

Summary: Curated pathway context supports cytosolic AXIN2 destruction-complex function.

Reason: Accept the cytosolic location attached to the curated Reactome:R-HSA-3640858 Wnt-pathway event. The complete cached summary was read; this is curated pathway context for the AXIN2 scaffold, not an independent microscopy experiment. Complex membership and cytosolic location are kept distinct.

Summary: Curated pathway context supports cytosolic AXIN2 destruction-complex function.

Reason: Accept the cytosolic location attached to the curated Reactome:R-HSA-3640861 Wnt-pathway event. The complete cached summary was read; this is curated pathway context for the AXIN2 scaffold, not an independent microscopy experiment. Complex membership and cytosolic location are kept distinct.

Summary: Curated pathway context supports cytosolic AXIN2 destruction-complex function.

Reason: Accept the cytosolic location attached to the curated Reactome:R-HSA-3640862 Wnt-pathway event. The complete cached summary was read; this is curated pathway context for the AXIN2 scaffold, not an independent microscopy experiment. Complex membership and cytosolic location are kept distinct.

Summary: Curated pathway context supports cytosolic AXIN2 destruction-complex function.

Reason: Accept the cytosolic location attached to the curated Reactome:R-HSA-3640872 Wnt-pathway event. The complete cached summary was read; this is curated pathway context for the AXIN2 scaffold, not an independent microscopy experiment. Complex membership and cytosolic location are kept distinct.

Summary: Curated pathway context supports cytosolic AXIN2 destruction-complex function.

Reason: Accept the cytosolic location attached to the curated Reactome:R-HSA-3640874 Wnt-pathway event. The complete cached summary was read; this is curated pathway context for the AXIN2 scaffold, not an independent microscopy experiment. Complex membership and cytosolic location are kept distinct.

Summary: Curated cytosolic localization is consistent with the destruction complex; the event itself regulates AXIN2 expression.

Reason: Accept the cytosolic location in the curated Reactome:R-HSA-4411372 annotation in the context of independent destruction-complex evidence. The complete cached event concerns regulation of AXIN2 expression and does not itself constitute a direct AXIN2 localization assay or imply that AXIN2 performs transcription. The TAS source boundary is preserved.

Summary: Curated pathway context supports cytosolic AXIN2 destruction-complex function.

Reason: Accept the cytosolic location attached to the curated Reactome:R-HSA-4641129 Wnt-pathway event. The complete cached summary was read; this is curated pathway context for the AXIN2 scaffold, not an independent microscopy experiment. Complex membership and cytosolic location are kept distinct.

Summary: Curated pathway context supports cytosolic AXIN2 destruction-complex function.

Reason: Accept the cytosolic location attached to the curated Reactome:R-HSA-4641134 Wnt-pathway event. The complete cached summary was read; this is curated pathway context for the AXIN2 scaffold, not an independent microscopy experiment. Complex membership and cytosolic location are kept distinct.

Summary: Curated pathway context supports cytosolic AXIN2 destruction-complex function.

Reason: Accept the cytosolic location attached to the curated Reactome:R-HSA-4641256 Wnt-pathway event. The complete cached summary was read; this is curated pathway context for the AXIN2 scaffold, not an independent microscopy experiment. Complex membership and cytosolic location are kept distinct.

Summary: Curated cytosolic localization is consistent with the destruction complex; the event itself regulates AXIN2 expression.

Reason: Accept the cytosolic location in the curated Reactome:R-HSA-9944652 annotation in the context of independent destruction-complex evidence. The complete cached event concerns regulation of AXIN2 expression and does not itself constitute a direct AXIN2 localization assay or imply that AXIN2 performs transcription. The TAS source boundary is preserved.

Summary: Plasma-membrane recruitment is retained as a contextual Wnt-pathway location.

Reason: Retain the existing PAINT-inferred plasma-membrane location as a recruitment context for Wnt signaling. The ancestral inference is not invalidated by a study emphasizing nuclear or cytosolic AXIN2. The family tree/MSA and target-specific membrane assay were not newly inspected, so this is curator deference rather than a claim of direct human membrane measurement.

Summary: Beta-catenin binding is integral to AXIN2 destruction-complex scaffolding.

Reason: Accept inherited beta-catenin binding as an integral interaction of the destruction-complex scaffold, independently corroborated by the AXIN2-containing complexes and the cited PMID:22056988 Results paragraph. The PAINT assertion is an ancestral placement, not a pairwise donor-count argument.

Summary: Ortholog-inferred beta-catenin binding agrees with human AXIN2 evidence.

Reason: Accept the rat-ortholog inference of beta-catenin binding, independently consistent with human AXIN2 interaction evidence. Preserve the rat protein and Ensembl WITH/FROM identifiers rather than rewriting the inference as human IDA.

Summary: Independent human evidence supports beta-catenin binding; the original NAS experiment was not reverified.

Reason: Accept beta-catenin binding as a core, independently established AXIN2 interaction while explicitly deferring to the original NAS curator. The normal PMID:11017067 record contains citation/erratum information but no scientific abstract; the original source experiment was not reverified. Independent PMID:22056988 supports the activity without repairing or replacing the original reference.

Summary: AXIN2 regulates GSK3 localization in the Snail1 signaling context.

Reason: The complete PMID:17072303 abstract describes AXIN2 as a nucleocytoplasmic regulator of GSK3 localization in the Snail1/EMT context. Retain this existing contextual process; it is not evidence that AXIN2 catalyzes transport or that every AXIN2 location is a separate core activity.

Summary: Suppression of proliferation is a contextual consequence of AXIN2 signaling.

Reason: Retain the existing ortholog inference for suppression of cell proliferation as a contextual signaling consequence, supported broadly by the AXIN2 negative-feedback role. Preserve the inference boundary and do not manufacture a new antiproliferative molecular activity.

Summary: Axis specification is retained as an ortholog-inferred developmental role.

Reason: Retain the rat-ortholog developmental inference for axis specification as non-core. The inference and established Wnt-patterning role are not disproved by the absence of a human embryo assay in this audit; no new human perturbation experiment is claimed.

Summary: AXIN2-dependent GSK3 redistribution can promote Snail1-associated epithelial–mesenchymal transition.

Reason: The cited complete abstract links AXIN2-dependent GSK3 redistribution and Snail1 protein stabilization to epithelial–mesenchymal transition in cancer models. Retain the existing context-specific positive EMT role, without changing the principal destruction-complex role into a universally positive Wnt function.

Summary: Tankyrase recognition regulates AXIN2 stability.

Reason: Retain the curated tankyrase interaction as non-core enzyme recognition. The cited abstract describes tankyrase-dependent AXIN stabilization/degradation and the normal UniProt record corroborates AXIN2–TNKS/TNKS2 interactions. AXIN2 is a tankyrase substrate/regulatory target here; enzyme binding does not make AXIN2 an ADP-ribosyltransferase.

Summary: Tankyrase recognition regulates AXIN2 stability.

Reason: Retain the curated tankyrase interaction as non-core enzyme recognition. The cited abstract describes tankyrase-dependent AXIN stabilization/degradation and the normal UniProt record corroborates AXIN2–TNKS/TNKS2 interactions. AXIN2 is a tankyrase substrate/regulatory target here; enzyme binding does not make AXIN2 an ADP-ribosyltransferase.

Summary: Human AXIN2-containing complexes associate with USP34.

Reason: The PMID:21383061 Methods and Results explicitly include human AXIN2 TAP purifications that identify USP34. Retain the enzyme-binding interaction as non-core. Complex association is supported; isolated direct binding and deubiquitinase activity by AXIN2 are not claimed.

Summary: Curated tankyrase association is consistent with regulation of AXIN2 turnover.

Reason: Retain the source-curated tankyrase interaction with explicit corroboration from the normal AXIN2 UniProt reference block, which assigns TNKS/TNKS2 interaction to PMID:21478859. The available abstract describes the PAR-dependent degradation mechanism but the exact interaction panels were not accessed. This is curator deference for enzyme recognition, not a new purified-binding or catalytic claim.

Summary: Curated tankyrase association is consistent with regulation of AXIN2 turnover.

Reason: Retain the source-curated tankyrase interaction with explicit corroboration from the normal AXIN2 UniProt reference block, which assigns TNKS/TNKS2 interaction to PMID:21478859. The available abstract describes the PAR-dependent degradation mechanism but the exact interaction panels were not accessed. This is curator deference for enzyme recognition, not a new purified-binding or catalytic claim.

Summary: Kinase binding positions the enzymes used by the AXIN2 scaffold.

Reason: Accept protein kinase binding as an integral interaction of the AXIN2 scaffold, supported by PAINT inheritance and human AXIN2-containing GSK3 complexes. The function does not imply kinase catalysis by AXIN2, and the complete ancestral tree was not reconstructed.

Summary: Ortholog-inferred kinase binding agrees with human AXIN2 complex evidence.

Reason: Accept the rat ortholog transfer of protein kinase binding, consistent with human AXIN2–GSK3 interaction evidence. Preserve the computational source and donor identifiers rather than converting the evidence code to a direct human assay.

Summary: The supported negative Wnt-regulatory role is specific to the canonical beta-catenin branch.

Reason: The combined ARBA/rat-ortholog mapping is correct in essence but broader than the well-supported beta-catenin branch. Refine negative Wnt regulation to negative regulation of canonical Wnt signaling, already established by the destruction-complex activity; do not add a duplicate NEW annotation.

Proposed replacements: negative regulation of canonical Wnt signaling pathway

Summary: AXIN2 is a core component of the beta-catenin destruction complex.

Reason: Accept beta-catenin destruction-complex membership as central to AXIN2 function. Human AXIN2 TAP complexes in PMID:21383061 contain the expected signaling components. Retain the curated ancestral complex placement without interpreting the donor list as pairwise sequence evidence.

Summary: Independent human complex evidence supports this original NAS membership assertion.

Reason: Accept beta-catenin destruction-complex membership as central to AXIN2 function. Human AXIN2 TAP complexes in PMID:21383061 contain the expected signaling components. The PMID:11017067 cache has no scientific abstract, so retain its NAS assertion by explicit curator deference and independent complex evidence, not by claiming the original assay was read.

Summary: Independent human complex evidence supports this original NAS membership assertion.

Reason: Accept beta-catenin destruction-complex membership as central to AXIN2 function. Human AXIN2 TAP complexes in PMID:21383061 contain the expected signaling components. The PMID:9601641 abstract emphasizes Axin without resolving every human AXIN2 construct; retain its NAS assertion by curator deference and independent human AXIN2 complex evidence, not a wrong-paralog accusation.

Summary: Ubiquitin-ligase recognition is an ancillary interaction regulating AXIN2 stability.

Reason: Retain inherited ubiquitin-ligase binding as a regulatory interaction affecting AXIN2 stability. Human AXIN2 in the PAINT WITH/FROM list is legitimate experimental grounding, not circularity. Recognition of AXIN2 by an E3 ligase does not itself assign the ligase catalytic activity or a new degradation-participant process to AXIN2.

Summary: The inferred ubiquitin-ligase interaction agrees with AXIN2 turnover mechanisms.

Reason: Retain the ARBA inference of ubiquitin-ligase binding, consistent with the curated RNF146 interaction and AXIN2 turnover mechanism. This recognition interaction is ancillary to destruction-complex scaffolding; it is not evidence that AXIN2 is an E3 ligase.

Summary: RNF146 recognition targets AXIN2 for regulated degradation.

Reason: Retain the RNF146 interaction with explicit curator deference: the normal AXIN2 UniProt reference block assigns RNF146 interaction to PMID:21478859 and the available abstract gives the PAR-dependent recognition/degradation mechanism. Exact target panels were not accessed. AXIN2 is the recognized degradation substrate in this context, so no new ubiquitination process is inferred.

Summary: The experiment supporting a mismatch-repair regulatory role remains unavailable.

Reason: The normal PMID:11017067 record lacks a scientific abstract and original article access did not establish the mismatch-repair experiment. AXIN2 mutation in a mismatch-repair-defective tumor would not by itself establish a repair-regulatory role, but that distinction cannot replace inspection of the curator’s supporting experiment. Preserve the IMP assertion as uncertain; do not remove it from the title.

Summary: AXIN2 scaffolding promotes beta-catenin proteasomal turnover.

Reason: Accept positive regulation of proteasomal ubiquitin-dependent protein catabolism in the beta-catenin destruction pathway. AXIN2 performs scaffold work that enables substrate phosphorylation and subsequent turnover; this role is distinct from AXIN2 being degraded by RNF146. The PAINT inference is retained without manufacturing another NEW process.

Summary: The beta-catenin destruction complex is more informative than generic complex membership.

Reason: The generic protein-containing-complex transfer is correct but insufficiently informative. The established AXIN2 complex is the beta-catenin destruction complex, corroborated by human AXIN2 TAP experiments. Refine to that specific complex while preserving the original IEA source.

Proposed replacements: beta-catenin destruction complex

Summary: Human AXIN2 truncating variants support a developmental role in tooth formation.

Reason: The complete PMID:15042511 abstract reports segregating human AXIN2 truncating mutations with severe tooth agenesis and colorectal predisposition. Retain odontogenesis as an existing developmental role of Wnt regulation, not as a distinct molecular activity or a basis for adding multiple disease processes.

Summary: The odontogenesis role is retained with independent human genetic support.

Reason: Retain odontogenesis with explicit curator deference and independent AXIN2 genetic support from PMID:15042511. The cited PMID:16432638 abstract reports variant associations and a proposed splice-regulatory consequence; it is not described here as a demonstrated cellular knockout/rescue or proven splicing mechanism. The full experimental basis of this particular IMP annotation was not re-read.

Summary: AXIN2 contributes organizing work to beta-catenin proteasomal degradation.

Reason: Accept participation in beta-catenin proteasomal turnover through destruction-complex scaffolding, with explicit deference to the original NAS citation. The PMID:9601641 abstract does not resolve every AXIN2-specific construct, but independent AXIN2 complex evidence supports the core process. This acceptance concerns work on beta-catenin, not AXIN2’s own consumption by degradation.

Summary: Tumor repeat mutations alone do not resolve the asserted DNA-repeat-maintenance function.

Reason: The complete PMID:18755497 abstract reports frameshift mutations within AXIN2 repeats in microsatellite-unstable gastric tumors; that alone does not demonstrate that AXIN2 maintains DNA repeats. The complete original experiments were not accessible in this audit, so retain source-specific uncertainty rather than infer an experimental misattribution or remove the annotation from the abstract alone.

Summary: Rat progenitor-cell experiments support an inferred adipogenic signaling role.

Reason: Retain the rat ortholog inference as a differentiation context. The complete official PMID:23996200 abstract reports dexamethasone-induced Axin2 and reduced adipogenic readouts after Axin2 knockdown in rat ROB-C26 progenitor cells. This is rat cell evidence, not a newly established human adipogenesis experiment.

Summary: The verified abstract addresses Snail1 protein stability; the mRNA-specific experiment remains unverified.

Reason: The available PMID:17072303 abstract supports stabilization of Snail1 protein through altered GSK3 localization, not an mRNA half-life measurement. The original mRNA-specific experiment was not verified; preserve the IMP annotation as uncertain rather than equating protein stabilization with mRNA stabilization or claiming the full paper lacks such data.

Summary: Cell development is a broad contextual consequence of the conserved Wnt scaffold.

Reason: Retain PAINT-inferred cell development as a broad contextual consequence of the conserved signaling scaffold. The donor list does not measure inference strength and no target-specific loss was established. This broad process is not used to create an additional core activity.

Summary: Rat glucocorticoid-response experiments support the existing ortholog inference.

Reason: Retain the rat-ortholog steroid-response inference with donor context: the official PMID:23996200 abstract reports glucocorticoid-dependent Axin2 induction and associated adipogenic effects. This does not imply steroid binding by AXIN2 or a human endocrine assay.

Summary: AXIN2 participates in canonical Wnt signaling with context-dependent downstream effects.

Reason: Accept canonical Wnt pathway involvement as a core process. The cited abstract describes a context in which AXIN2 controls GSK3 localization and Snail1 protein stability; this supports participation without making every AXIN2 effect a negative output. The process parent is retained as an existing annotation but need not duplicate the more precise negative-regulation core slot.

Summary: Conductin links Wnt/GSK3 signaling to centrosomal beta-catenin phosphorylation.

Reason: Accept canonical Wnt pathway involvement. The selected primary Results show Wnt/GSK3 perturbations altering conductin-dependent centrosomal beta-catenin phosphorylation and centrosome cohesion. Preserve that source-specific mechanism instead of relabeling centrosomal phosphorylation as AXIN2 kinase catalysis.

Summary: Integral protein-complex scaffolding more precisely describes the AXIN2 organizing activity.

Reason: The ancestral molecular-adaptor assertion captures the correct organizing role, but protein complex scaffold activity more precisely describes AXIN2 as an integral component that holds the beta-catenin destruction machinery together. Current official GO guidance distinguishes complex scaffolds from generic protein-macromolecule adaptors. Human AXIN2 TAP complexes and the conductin scaffold mechanism support this functional refinement; the original IBA object remains unchanged.

Proposed replacements: protein complex scaffold activity

Summary: I-SMAD binding is retained as an ancillary inherited interaction.

Reason: Retain the PAINT-inferred I-SMAD-binding interaction as non-core, consistent with the normal UniProt subunit statement that AXIN2 interacts with SMAD7. The complete tree/MSA and the underlying target-specific interaction experiments were not newly read. No loss/divergence argument or donor-count objection was established.

Summary: The ancestral chromosome-cohesion inference remains unresolved separately from the human centrosome assay.

Reason: The IBA asserts inheritance from PTN002918815, with mouse and human experimental grounding; the human self-donor is legitimate. The available human PMID:20300119 study concerns centrosomes, whereas GO:0070602 concerns cohesion of sister chromatids at chromosomal centromeres. The underlying IBD placement/tree and other descendant experiments were not reconstructed, so the source-specific human term mismatch does not alone justify rewriting or removing the inherited assertion.

Summary: Conductin promotes interphase centriole cohesion through the centrosomal beta-catenin scaffold.

Reason: The source measures premature splitting of gamma-tubulin-marked centrosomes in asynchronous human U2OS cultures and mouse fibroblasts; its physical-linker context is interphase cohesion. Conductin loss increases splitting, and its beta-catenin/GSK3-binding region supports rescue. The appropriate refinement is positive regulation of centriole-centriole cohesion, without a mitotic-phase restriction. AXIN2 organizes GSK3-dependent phosphorylation rather than catalyzing it. This does not concern cohesion between sister chromatids at chromosomal centromeres.

Proposed replacements: positive regulation of centriole-centriole cohesion

Summary: Rat dexamethasone-response experiments support the existing ortholog inference.

Reason: Retain the rat ortholog inference for cellular response to dexamethasone, supported by the official PMID:23996200 abstract’s glucocorticoid perturbation and Axin2 knockdown experiments. It is a specific cellular response context, not a separate hormone-receptor activity or direct human experiment.

Summary: Negative canonical Wnt regulation is the principal conserved AXIN2 signaling role.

Reason: Accept the PAINT-inferred negative feedback on canonical Wnt signaling as the principal process enabled by AXIN2 destruction-complex scaffolding. The human target’s presence among descendant evidences is legitimate grounding and does not make the ancestral inference circular.

Summary: Beta-catenin/TCF-driven AXIN2 expression establishes negative Wnt feedback.

Reason: The cited complete abstract reports beta-catenin/TCF-driven conductin expression and a negative feedback loop that restrains Wnt signaling. Accept this as a defining process while retaining the original direct-assay evidence code and avoiding a new redundant feedback annotation.

Summary: The family-based negative canonical Wnt inference agrees with experimental evidence.

Reason: Accept the InterPro family mapping to negative regulation of canonical Wnt signaling, concordant with the human experimental and curated complex evidence. The mapping is not converted to experimental evidence, and no family label is guessed from memory.

Summary: Independent negative-feedback and complex evidence support the original core-function assertion.

Reason: Accept this established core function with explicit curator deference. PMID:11017067 has no scientific abstract in its available record and its original assay was not reverified; independent PMID:11940574 and human AXIN2 complex evidence support the same negative canonical Wnt role without replacing the original IMP source.

Summary: Independent evidence supports negative canonical Wnt regulation while the source-specific assay remains unread.

Reason: Accept negative canonical Wnt regulation as a core AXIN2 activity, with explicit curator deference for the source-specific IMP experiment. The PMID:16247484 abstract emphasizes conductin-associated cell-cycle and apoptotic effects; it is not treated as a complete read of the Wnt reporter assay. Independent negative-feedback and complex evidence corroborate the function.

Summary: Mouse-to-human transfer agrees with the established human negative Wnt-regulatory role.

Reason: Accept the mouse-to-human ISS inference for the conserved negative canonical Wnt role, corroborated by human AXIN2 negative-feedback and complex studies. Preserve the mouse donor and ISS evidence boundary.

Summary: Mouse valve phenotypes support an inferred role in extracellular-matrix regulation.

Reason: Retain extracellular-matrix organization as an existing mouse-to-human developmental inference. The official PMID:28069701 abstract reports altered valve matrix production/remodeling following Axin2 loss in mice; this is a tissue signaling outcome, not evidence that AXIN2 is a structural extracellular-matrix constituent.